Anti-inflammatory activity of Theobroma cacao L. stem bark ethanol extract and its fractions in experimental models.

PubMed

Oyeleke, Sabitiu A; Ajayi, Abayomi M; Umukoro, Solomon; Aderibigbe, A O; Ademowo, Olusegun George

2018-08-10

The stem bark of Theobroma cacao L. have been used for the treatment of inflammation, toothache, measles and malaria in ethnomedicine. However, the anti-inflammatory activity of Theobroma cacao stem bark has not been fully elucidated. The anti-inflammatory activity of Theobroma cacao stem bark ethanol extract and its fractions was investigated in this study. The anti-inflammatory effect of ethanol extract of Theobroma cacao stem bark (EETc) and its dichloromethane (DCMF), ethylacetate (EAF) and aqueous (AQF) fractions was investigated in erythrocytes membrane stabilizing assay and carrageenan-induced paw oedema. The anti-inflammatory activity of the EAF and EETc was investigated in carrageenan induced-granuloma air pouch models. The extract and fractions showed significant membrane stabilizing action on rat erythrocytes cell membrane. The oral administration of DCMF, EAF and AQF (250 mg/kg) significantly inhibited paw oedema induced by carrageenan (41.3%, 55.0% and 45.0%, respectively) compared to control group. The EAF (62.5, 125 and 250 mg/kg) and EETc (250 mg/kg) significantly inhibited exudates formation in carrageenan air pouch by (63.8, 71.5, 74.5, 64.3%) at 24 h and by (69.4%, 75.7%, 77.1% and 68.4%) at 72 h respectively. The EETc and EAF significantly reduced neutrophil counts, protein, nitrite, Tumor necrosis factor (TNF-α) and malondialdehyde (MDA) but increased reduced glutathione (GSH) levels compared to control in pouch exudates. The HPLC fingerprint of EAF revealed presence of caffeic acid, rutin, ferulic acid and morin. Ethanol extract of Theobroma cacao and its ethylacetate fraction demonstrated anti-inflammatory activity partly by reducing neutrophil migration and inflammatory mediator production. Copyright © 2018 Elsevier B.V. All rights reserved.

Anti-inflammatory activity of Lippia dulcis.

PubMed

Pérez, S; Meckes, M; Pérez, C; Susunaga, A; Zavala, M A

2005-10-31

Lippia dulcis hexane and ethanol extracts were tested for its anti-inflammatory activity in several animal models. Hexane extract showed to be inactive, but the ethanol extract at doses of 400 mg/kg produced significant inhibition of carrageenan-induced paw oedema and reduced the weight of cotton pellet-induced granuloma, moreover, the topical application of 0.5 mg/ear of this extract inhibited the edema induced with TPA by 49.13%, an effect which is of less intensity than that produced by indomethacine at the same dose.

Protective effects of radon inhalation on carrageenan-induced inflammatory paw edema in mice.

PubMed

Kataoka, Takahiro; Teraoka, Junichi; Sakoda, Akihiro; Nishiyama, Yuichi; Yamato, Keiko; Monden, Mayuko; Ishimori, Yuu; Nomura, Takaharu; Taguchi, Takehito; Yamaoka, Kiyonori

2012-04-01

We assessed whether radon inhalation inhibited carrageenan-induced inflammation in mice. Carrageenan (1% v/v) was injected subcutaneously into paws of mice that had or had not inhaled approximately 2,000 Bq/m(3) of radon for 24 h. Radon inhalation significantly increased superoxide dismutase (SOD) and catalase activities and significantly decreased lipid peroxide levels in mouse paws, indicating that radon inhalation activates antioxidative functions. Carrageenan administration induced paw edema and significantly increased tumor necrosis factor-alpha (TNF-α) and nitric oxide in serum. However, radon inhalation significantly reduced carrageenan-induced paw edema. Serum TNF-α levels were lower in the radon-treated mice than in sham-treated mice. In addition, SOD and catalase activities in paws were significantly higher in the radon-treated mice than in the sham-treated mice. These findings indicated that radon inhalation had anti-inflammatory effects and inhibited carrageenan-induced inflammatory paw edema.

Antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) in Rodents: possible mechanism of actions.

PubMed

Ishola, Ismail O; Olayemi, Sunday O; Oreagba, Ibrahim A; Ifeanyi, Chikaodili I; Popoola, Temidayo O

2015-12-20

The leaves of Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) is used in Traditional African medicine for the treatment of various ailments including arthritis. The present study sought to investigate the antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of Clausena anisata (HeCA). HeCA (100, 200 or 400 mg/kg, p.o.) was administered 1 h before intraplantar injection of formalin 1%v/v in saline to evaluate antinociceptive effect. Moreover, its possible mechanism of antinociceptive action was investigated through pretreatment of mice with antagonists of receptors implicated in nociception. Anti¬inflammatory effect of the extract was investigated using the carrageenan-induced paw oedema and complete Freund's adjuvant (CFA)-induced arthritis models in rats. HeCA (400 mg/kg) treatment significantly reduced the duration of paw licking/biting during both in the early (42.12%) and late (75.79%) phases of formalin-induced nociception. However, the antinociceptive effect elicited by HeCA was reverse by pretreatment of mice with naloxone, prazosin, yohimbine, ketanserin, L-arginine, and parachlorophenylalanine (PCPA). HeCA produced dose-dependent and time course decrease in carrageenan-induced paw oedema. Pre- and post-treatment of rats with HeCA ameliorated CFA-induced arthritis evidenced in the significant decrease in arthritic index comparatively similar to the effect of celecoxib. CFA- induced oxidative and nitrosative stress were attenuated by subchronic treatment with HeCA. Findings from this study shows that C. anisata possesses antinociceptive activity through possible interaction with opioidergic, noradrenergic, L-arginine-nitric oxide and serotonergic pathways as well as anti-arthritic property which could be attributed to its ability to prevent the release of inflammatory mediators and oxidative stress.

Evaluation of in-vitro antibacterial activity and anti-inflammatory activity for different extracts of Rauvolfia tetraphylla L. root bark.

PubMed

Ganga Rao, B; Umamaheswara Rao, P; Sambasiva Rao, E; Mallikarjuna Rao, T; Praneeth D, V S

2012-10-01

To assess the in-vitro antibacterial activity and anti-inflammatory activity of orally administered different extracts (Hydro-alcoholic, methanolic, ethyl acetate and hexane) of Rauvolfia tetraphylla (R. tetraphylla) root bark in Carrageenan induced acute inflammation in rats. In-vitro antibacterial activity was evaluated for extracts against four Gram positive and four Gram negative bacteria by using cylinder plate assay. Hydro-alcoholic extract (70% v/v ethanol) at 200, 400 and 800 mg/kg doses and methanolic, ethyl acetate and hexane extracts at doses 100, 200 and 400 mg/kg were tested for anti-inflammatory activity in Carrageenan induced rat paw oedema model and paw thickness was measured every one hour up to 6 hrs. All extracts of R. tetraphylla root bark showed good zone of inhibition against tested bacterial strains. In Carrageenan induced inflammation model, hydro-alcoholic and methanolic extract of R. tetraphylla root bark at three different doses produced significant (P<0.001) reduction when compared to vehicle treated control group and hexane, ethyl acetate extracts. In the present study extracts of R. tetraphylla root bark shows good in-vitro antibacterial activity and in-vivo anti-inflammatory activity in rats.

Biochemical characterization, anti-inflammatory properties and ulcerogenic traits of some cold-pressed oils in experimental animals.

PubMed

Ibrahim, Faten M; Attia, Hanan Naeim; Maklad, Yousreya Aly Aly; Ahmed, Kawkab A; Ramadan, Mohamed F

2017-12-01

Cold-pressed oils (CPO) are commercially available in the market and characterized by their health-promoting properties. Clove oil (CLO), coriander seed oil (COO) and black cumin oil (BCO) were evaluated for their bioactive lipids. Pharmacological screening was performed to evaluate acute toxicity, anti-inflammatory and ulcerogenic effects as well as histopathological changes in tissues of albino rats fed with CPO. Fatty acids, tocols and total phenolics were analyzed. The acute toxicity test for each CPO was estimated during 14 d. Carrageenan-induced rat paw oedema was used for assessment of anti-inflammatory activity of CPO. Animals were fasted overnight, and via oral gavage given indomethacin (10 mg/kg) or CPO (400 mg/kg) to investigate ulcerogenecity. Histopathological changes in liver, kidney, heart, spleen and stomach were screened. Amounts of α-, β-, γ- and δ-tocopherols in CLO were 1495, 58, 4177 and 177 mg/kg oil, respectively. In COO, α, β, γ and δ-tocopherols were 10.0, 18.2, 5.1 and 34.8%, respectively. In BCO, β-tocotrienol was the main constituent. CLO, COO and BCO contained 4.6, 4.2 and 3.6 mg GAE/g, respectively. Acute toxicity test determined that 400 mg/kg of CPO to be used. In the carrageenan model of inflammation, pretreatment of rats with indomethacin (10 mg/kg) or CLO (400 mg/kg) induced a significant (p < 0.05) reduction by 31.3 and 27.4%, respectively, in rat paw oedema as compared with the carrageenan-treated group. Indomethacin induced a significant ulcerogenic effect with an ulcer index of 19. Oral treatment of CPO showed no ulcerogenic effect, wherein no histopathological changes were observed. CPO, particularly CLO, could minimize acute inflammation.

Inhibition of chemically induced inflammation and pain by orally and topically administered leaf extract of Manihot esculenta Crantz in rodents.

PubMed

Adeyemi, Olufunmilayo O; Yemitan, Omoniyi K; Afolabi, Lateef

2008-09-02

The aqueous leaf extract of Manihot esculenta Crantz (MELE) is being used orally and topically in traditional African medicine for the treatment of inflammation and pain, and claimed to be safe. The anti-inflammatory effects of MELE (100-400 mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) were tested against carrageenan-induced paw oedema in rats as well as against xylene-induced ear oedema in mice. The analgesic effect of MELE (100-400 mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) was tested against acetic acid-induced (20 microl, 0.6%, v/v in normal saline, i.p.) and acetylcholine-induced (8.3 mg/kg, i.p.) mouse writhing models. At 100-400 mg/kg, p.o. and 1-4% (w/w), topically, MELE produced significant inhibitions of carrageenan-induced rat paw oedema and xylene-induced ear swelling in mice. Effects produced by MELE were significantly higher than those produced by indomethacin (10 mg/kg, s.c. or 1%, w/w in petroleum jelly) in the anti-inflammatory models. For the analgesic effect, MELE (100-400 mg/kg, orally) and (1-4%, w/w, topically), like aspirin (100 mg/kg, i.p.) exhibited significant (P<0.05) inhibition of acetic acid- and acetylcholine-induced mouse writhing tests, compared to untreated control. Effects produced by MELE were significantly lower than those produced by aspirin (100 mg/kg, i.p.) in the analgesic models, except for the topically administered extract on acetylcholine-induced pain. Acute oral administration up to 10 g/kg did not cause death within 14 days, but mortalities were produced in i.p. administered extract with LD(50) of 2.5+/-0.3 g/kg. Based on these, the extract may contain orally safe, topically and orally effective anti-inflammatory and analgesic principles, which justify its use in traditional African medicine.

Evaluation of in-vitro antibacterial activity and anti-inflammatory activity for different extracts of Rauvolfia tetraphylla L. root bark

PubMed Central

Ganga Rao, B.; Umamaheswara Rao, P.; Sambasiva Rao, E.; Mallikarjuna Rao, T.; Praneeth. D, V. S.

2012-01-01

Objective To assess the in-vitro antibacterial activity and anti-inflammatory activity of orally administered different extracts (Hydro-alcoholic, methanolic, ethyl acetate and hexane) of Rauvolfia tetraphylla (R. tetraphylla) root bark in Carrageenan induced acute inflammation in rats. Methods In-vitro antibacterial activity was evaluated for extracts against four Gram positive and four Gram negative bacteria by using cylinder plate assay. Hydro-alcoholic extract (70% v/v ethanol) at 200, 400 and 800 mg/kg doses and methanolic, ethyl acetate and hexane extracts at doses 100, 200 and 400 mg/kg were tested for anti-inflammatory activity in Carrageenan induced rat paw oedema model and paw thickness was measured every one hour up to 6 hrs. Results All extracts of R. tetraphylla root bark showed good zone of inhibition against tested bacterial strains. In Carrageenan induced inflammation model, hydro-alcoholic and methanolic extract of R. tetraphylla root bark at three different doses produced significant (P<0.001) reduction when compared to vehicle treated control group and hexane, ethyl acetate extracts. Conclusions In the present study extracts of R. tetraphylla root bark shows good in-vitro antibacterial activity and in-vivo anti-inflammatory activity in rats. PMID:23569853

Inhibition of Carrageenan-Induced Acute Inflammation in Mice by Oral Administration of Anthocyanin Mixture from Wild Mulberry and Cyanidin-3-Glucoside

PubMed Central

Hassimotto, Neuza Mariko Aymoto; Moreira, Vanessa; do Nascimento, Neide Galvão; Souto, Pollyana Cristina Maggio de Castro; Teixeira, Catarina; Lajolo, Franco Maria

2013-01-01

Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements. PMID:23484081

Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidin-3-glucoside.

PubMed

Hassimotto, Neuza Mariko Aymoto; Moreira, Vanessa; do Nascimento, Neide Galvão; Souto, Pollyana Cristina Maggio de Castro; Teixeira, Catarina; Lajolo, Franco Maria

2013-01-01

Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements.

Inhibition of carrageenin-induced rat paw oedema by crotapotin, a polypeptide complexed with phospholipase A2.

PubMed Central

Landucci, E C; Antunes, E; Donato, J L; Faro, R; Hyslop, S; Marangoni, S; Oliveira, B; Cirino, G; de Nucci, G

1995-01-01

1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micrograms/paw) in the rat hind-paw. The effects of crotapotin on platelet aggregation, mast cell degranulation and eicosanoid release from guinea-pig isolated lung were also investigated. 2. Subplantar co-injection of crotapotin (1 and 10 micrograms/paw) with carrageenin or injection of crotapotin (10 micrograms/paw) into the contralateral paw significantly inhibited the carrageenin-induced oedema. This inhibition was also observed when crotapotin (10-30 micrograms/paw) was administered either intraperitoneally or orally. Subplantar injection of heated crotapotin (15 min at 60 degrees C) failed to inhibit carrageenin-induced oedema. Subplantar injection of crotapotin (10 micrograms/paw) also significantly inhibited the rat paw oedema induced by compound 48/80, but it did not affect 5-HT-induced oedema. 3. In adrenalectomized animals, subplantar injection of crotapotin markedly inhibited the oedema induced by carrageenin. The inhibitory effect of crotapotin was also observed in rats depleted of histamine and 5-HT stores. 4. Crotapotin (30 micrograms/paw) had no effect on either the histamine release induced by compound 48/80 in vitro or on the platelet aggregation induced by both arachidonic acid (1 nM) and platelet activating factor (1 microM) in human platelet-rich plasma. The platelet aggregation and thromboxane B2 (TXB2) release induced by thrombin (100 mu ml-1) in washed human platelets were also not affected by crotapotin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7537590

Osthole ameliorates neurogenic and inflammatory hyperalgesia by modulation of iNOS, COX-2, and inflammatory cytokines in mice.

PubMed

Singh, Gurjit; Bhatti, Rajbir; Mannan, Rahul; Singh, Drishtant; Kesavan, Anup; Singh, Palwinder

2018-05-07

Osthole is a bioactive component reported in medicinal plants such as Angelica pubescens and Cnidium monnieri, known for analgesic activity. However, the toxicity, median effective dose (ED 50 ), and dual modulation of nitric oxide and cyclooxygenase pathways along with inflammatory cytokines of osthole are yet to be determined. The animals (mice) were assessed for general behaviour and mortality in varying doses (50, 300, and 2000 mg kg -1 ) of osthole for acute toxicity over 14 days. The analgesic activity was investigated using acetic acid and formalin-induced hyperalgesia, and anti-inflammatory activity was explored in carrageenan-induced paw oedema. ED 50 of osthole was calculated using Design Expert software. Involvement of nitric oxide and cyclooxygenase pathways was investigated by agonist challenges with L-arginine and substance P, respectively. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined in spinal sections by immunohistochemical analysis. Lipopolysaccharide (LPS) challenge was used to assess in vivo effect on inflammatory cytokines (TNFα and IL-6). Acute toxicity studies revealed no behavioural abnormality or mortality on osthole treatment and unremarkable histological findings. Osthole was found to significantly decrease acetic acid and formalin-induced hyperalgesia (ED 50  = 5.43 mg kg -1 ) and carrageenan-induced paw oedema with no toxicity symptoms. Osthole produced a marked decrease in iNOS and COX-2 expression as well as TNFα and IL-6. The findings corroborate to modulation of iNOS and COX-2 and inflammatory cytokines by osthole. This study provides promising insights and prospects for application of osthole in pain management.

The Anti-Inflammatory Effects of the Methanolic Extract and Fractions from Davilla elliptica St. Hil. (Dilleniaceae) on Bothrops jararaca Envenomation

PubMed Central

Nishijima, Catarine Massucato; Delella, Flavia Karina; Rodrigues, Clenilson Martins; Rinaldo, Daniel; Lopes-Ferreira, Monica Valdyrce dos Anjos; da Rocha, Lucia Regina Machado; Vilegas, Wagner; Felisbino, Sergio Luis; Hiruma-Lima, Clélia Akiko

2015-01-01

Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity. PMID:26042466

Salicytamide: a New Anti-inflammatory Designed Drug Candidate.

PubMed

Guedes, Karen Marinho Maciel; Borges, Rosivaldo Santos; Fontes-Júnior, Enéas Andrade; Silva, Andressa Santa Brigida; Fernandes, Luanna Melo Pereira; Cartágenes, Sabrina Carvalho; Pinto, Ana Carla Godinho; Silva, Mallone Lopes; Queiroz, Luana Melo Diogo; Vieira, José Luís Fernandes; Sousa, Pergentino José Cunha; Maia, Cristiane Socorro Ferraz

2018-04-13

Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

Anti-inflammatory and antiallergic activity in vivo of lipophilic Isatis tinctoria extracts and tryptanthrin.

PubMed

Recio, María-Carmen; Cerdá-Nicolás, Miguel; Potterat, Olivier; Hamburger, Matthias; Ríos, José-Luis

2006-05-01

The effects of a supercritical CO2 (SFE) extract, a dichloromethane (DCM) extract from Isatis tinctoria leaf and the alkaloidal constituent tryptanthrin were studied in acute and subchronic experimental models of inflammation. The SFE and DCM extracts showed anti-inflammatory activity in the carrageenan-induced acute mouse paw oedema (ED50 values of 78 mg/kg and 165 mg/kg P. O., respectively) and in the acute tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema in oral (62% and 32% oedema reduction at 100 and 125 mg/kg, respectively) and topical application (37% and 33% reduction of oedema at 0.5 mg/ear). In contrast, tryptanthrin showed no significant anti-inflammatory effect. The DCM extract inhibited oedema formation and neutrophil infiltration in subchronic inflammation in mice induced by repeated application of TPA. The extract showed activity after oral and topical administration by reducing the various parameters of the inflammatory response. The DCM extract (1 mg/ear) inhibited the delayed-type hypersensitivity (DTH) reaction induced by application of dinitrofluorobenzene (DNFB) after topical application. The response during the induction phase (24 h) was decreased by 48%, and the inflammatory phase (48 to 96 h) was reduced by 53 to 56%. The extract had no effect in this model when administered orally. The DCM extract (200 mg/kg P. O.) inhibited the acetic acid-induced writhing by 49%.

Enhancement of anti-inflammatory activity of bromelain by its encapsulation in katira gum nanoparticles.

PubMed

Bernela, Manju; Ahuja, Munish; Thakur, Rajesh

2016-06-05

Bromelain-loaded katira gum nanoparticles were synthesized using 3 level optimization process and desirability approach. Nanoparticles of the optimized batch were characterized using particle size analysis, zeta potential, transmission electron microscopy and Fourier-transform infrared spectroscopy. Investigation of their in vivo anti-inflammatory activity by employing carrageenan induced rat-paw oedema method showed that encapsulation of bromelain in katira gum nanoparticles substantially enhanced its anti-inflammatory potential. This may be attributed to enhanced absorption owing to reduced particle size or to protection of bromelain from acid proteases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-inflammatory activity of leaf essential oil from Cinnamomum longepaniculatum (Gamble) N. Chao.

PubMed

Du, Yong-Hua; Feng, Rui-Zhang; Li, Qun; Wei, Qin; Yin, Zhong-Qiong; Zhou, Li-Jun; Tao, Cui; Jia, Ren-Yong

2014-01-01

The anti-inflammatory activity of the essential oil from C. longepaniculatum was evaluated by three experimental models including the dimethyl benzene-induced ear edema in mice, the carrageenan-induced paw edema in rat and the acetic acid-induced vascular permeability in mice. The influence of the essential oil on histological changes and prostaglandin E2 (PGE2), histamine and 5-hydroxytryptamine (5-HT) production associated with carrageenan-induced rat paw edema was also investigated. The essential oil (0.5, 0.25, 0.13 ml/kg b.w.) showed significantly inhibition of inflammation along with a dose-dependent manner in the three experimental models. The anti-inflammatory activity of essential oil was occurred both in early and late phase and peaked at 4 h after carrageenan injection. The essential oil resulted in a dose dependent reduction of the paw thickness, connective tissue injury and the infiltration of inflammatory cell. The essential oil also significantly reduced the production of PGE2, histamine and 5-HT in the exudates of edema paw induced by carrageenan. Both the essential oil and indomethacin resulted relative lower percentage inhibition of histamine and 5-HT than that of PGE2 at 4 h after carrageenan injection.

Angiotensin peptides attenuate platelet-activating factor-induced inflammatory activity in rats.

PubMed

Sato, Akira; Yokoyama, Izumi; Ebina, Keiichi

2015-11-01

Angiotensin (Ang)--a peptide that is part of the renin-angiotensin system-induces vasoconstriction and a subsequent increase in blood pressure; Ang peptides, especially AngII, can also act as potent pro-inflammatory mediators. Platelet-activating factor (PAF) is a potent phospholipid mediator that is implicated in many inflammatory diseases. In this study, we investigated the effects of Ang peptides (AngII, AngIII, and AngIV) on PAF-induced inflammatory activity. In experiments using a rat hind-paw oedema model, AngII markedly and dose-dependently attenuated the paw oedema induced by PAF. The inhibitory effects of AngIII and AngIV on PAF-induced paw oedema were lower than that of AngII. Two Ang receptors, the AT1 and AT2 receptors, did not affect the AngII-mediated attenuation of PAF-induced paw oedema. Moreover, intrinsic tyrosine fluorescence studies demonstrated that AngII, AngIII, and AngIV interact with PAF, and that their affinities were closely correlated with their inhibitory effects on PAF-induced rat paw oedema. Also, AngII interacted with metabolite/precursor of PAF (lyso-PAF), and an oxidized phospholipid, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), which bears a marked structural resemblance to PAF. Furthermore, POVPC dose-dependently inhibited AngII-mediated attenuation of PAF-induced paw oedema. These results suggest that Ang peptides can attenuate PAF-induced inflammatory activity through binding to PAF and lyso-PAF in rats. Therefore, Ang peptides may be closely involved in the regulation of many inflammatory diseases caused by PAF. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization, anti-oxidative and anti-inflammatory effects of Costa Rican noni juice (Morinda citrifolia L.).

PubMed

Dussossoy, E; Brat, P; Bony, E; Boudard, F; Poucheret, P; Mertz, C; Giaimis, J; Michel, A

2011-01-07

Noni fruit (Morinda citrifolia L.) juice has been used for more than 2000 years in Polynesia as a traditional folk medicine. The aim of the present study was to finely characterize noni juice from Costa Rica and to evaluate its anti-oxidative and anti-inflammatory activities. A microfiltrated noni juice was prepared with Costarican nonis. HPLC-DAD and Electro Spray Ionization Mass Spectrometric detection (HPLC-ESI-MS) were used to identify phenolic compounds and iridoids. The anti-oxidative activity of noni juice was measured in vitro by both Oxygen Radical Absorbance Capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging methods. The anti-inflammatory effects of noni juice were investigated in vitro by: measuring its effect on nitric oxide and prostaglandin E2 production by activated macrophages, evaluating its inhibitory activities on cyclooxygenase (COX)-1 and -2 and in vivo on a carrageenan-induced paw oedema model in rats. Several polyphenols belonging to the coumarin, flavonoid and phenolic acid groups, and two iridoids were identified. Noni juice demonstrated a mean range free radical scavenging capacity. Furthermore, it also reduced carrageenan-induced paw oedema, directly inhibited cyclooxygenase COX-1 and COX-2 activities and inhibited the production of nitric oxide (NO) and prostaglandins E(2) (PGE(2)) in activated J774 cells, in a dose dependent manner. This study showed that noni's biological effects include: (1) anti-oxidant properties probably associated with phenolic compounds, iridoids and ascorbic acid and (2) anti-inflammatory action through NO and PGE(2) pathways that might also be strengthened by anti-oxidant effects. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Cytotoxic, analgesic and anti-inflammatory properties of Syzygium calophyllifolium bark.

PubMed

Chandran, Rahul; Abrahamse, Heidi; Parimelazhagan, Thangaraj

2018-04-25

The present study explores the effect of Syzygium calophyllifolium bark methanol (SCBM) extract on pain and inflammation as cancer associated symptoms. The anti-proliferative and cell death-inducing ability of the extract was analysed using MCF-7 breast cancer cells. ATP and LDH levels, along with the cell morphology were noted. The anti-proliferative ability of the extract was examined in relation to pain and inflammation. Analgesic activity was determined using a hot plate, acetic acid and formalin-induced pain models in mice. Acute anti-inflammatory activity was observed in carrageenan and egg albumin induced paw oedema in Wistar rats. Chronic inflammation was induced by placing a cotton pellet under the skin at the axial region of rats. Reduced ATP and increased LDH content indicated the cytotoxic effect of the extract. SCBM at 200 mg/kg dose depicted good activity in acetic acid (77.69%) and formalin (80.81%) induced pain models compared to the standard drug indomethacin. However, only a moderate activity was observed in the hot plate method (53.85%). The higher dose of SCBM was equally effective in anti-inflammatory models. The dose (200 mg/kg) significantly reduced the paw oedema in carrageenan (96.71%) and egg albumin models (54.24%) compared to the control. The chronic inflammation was also inhibited upto 70.46% by SCBM. These activities can be attributed to the phenolic compounds detected in HPLC. The outcome of the study states that the extract can reduce both acute and chronic inflammatory conditions and kill the cancer cells, proposing the dual role of SCBM in treating inflammatory pains in cancer. The result of these studies indicated that wild plants like Syzygium calophyllifolium could be taken forward for a detailed study to accomplish the demand for a better treatment against diseases. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Anti-inflammatory and anti-hypersensitive effects of the crude extract, fractions and triterpenes obtained from Chrysophyllum cainito leaves in mice.

PubMed

Meira, Nicole Anzanelo; Klein, Luiz Carlos; Rocha, Lilian W; Quintal, Zhelmy Martin; Monache, Franco Delle; Cechinel Filho, Valdir; Quintão, Nara Lins Meira

2014-02-03

Chrysophyllum cainito, popularly known as "star apple", caimito, "abiu-roxo" or "abiu-do-Pará", is a tree of about 25m in height. Besides its culinary use, it is also used in folk medicine for the treatment of diabetes mellitus and several inflammatory diseases. The crude methanolic extract (CME) was submitted to phytochemical studies for obtaining fractions and isolated compounds. They were monitored by thin-layer-chromatography (TLC). The biological activity was evaluated in mice using the carrageenan-induced mechanical hypersensitivity and paw oedema. Biochemical assays, such as myeloperoxidase (MPO) and activity and cytokines levels quantification, were carried out to analyse the involvement of neutrophil migration and IL-1β and TNFα production. Some adverse effects were investigated using the open-field and rota-rod tests, and it was also measured the rectal temperature. This study demonstrates, for the first time, the anti-hypersensitivity and anti-inflammatory effects of CME, fractions and two isolated triterpenes obtained from the leaves of Chrysophyllum cainito on carrageenan-induced hypersensitivity and paw-oedema. The mice treated with CME or chloroform fraction (CHCl3) presented reduction in mechanical hypersensitivity. The effect of the CME seemed to be partially related to the anti-inflammatory activity, as the paw-oedema and MPO activity were also significantly inhibited. The isolated compound Lup-20(29)-en-3β-O-hexanoate demonstrated more reduction of the hypersensitivity than 3β-Lup-20(29)-en-3-yl acetate, suggesting that this molecule might be partially responsible for the biological effects obtained with CME and CHCl3 fractions. Finally, animals treated with CME and CHCl3 did not present changes in locomotor activity, motor performance or body temperature. Our data demonstrates, for the first time, that the crude extract, fractions and pure compounds obtained from the Chrysophyllum cainito leaves possess important anti-hypersensitive properties against inflammatory pain in mice. The mechanisms through which Chrysophyllum cainito exerts its anti-hypersensitive actions are still unclear, and require further investigation; however, this could well constitute a new and attractive alternative for the management of persistent inflammatory and neuropathic pain in humans. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Neutralization of the oedematogenic activity of Bothrops jararaca venom on the mouse paw by an antibothropic fraction isolated from opossum (Didelphis marsupialis) serum.

PubMed

Perales, J; Amorim, C Z; Rocha, S L; Domont, G B; Moussatché, H

1992-11-01

The pharmacological modulation of mice paw oedema produced by Bothrops jararaca venom (BJV) has been studied. Intraplantar injection of BJV (1-30 micrograms/paw) produced a dose- and time-related oedema, which was maximal 30 min after injection, reduced gradually thereafter and disappeared over 48 h. BJV heated at 100 degrees C for 5 or 15 min blocked local hemorrhage and caused partial inhibition of its oedematogenic activity. The BJV oedema was not inhibited by the anti-histamine meclizine, the inhibitor of histamine and serotonin, cyproheptadine, PAF-acether antagonist WEB 2170 or by the anti-leukotrienes C4/D4, LY 171883. Dexamethasone, aspirin, indomethacin, and the dual cyclooxygenase and lipoxygenase inhibitor BW 755C inhibited BJV-induced oedema indicating that arachidonic acid metabolism products via the cyclooxygenase pathway participate in its genesis and/or maintenance. The antibothropic fraction (ABF) (25-200 micrograms/paw) isolated from Didelphis marsupialis serum neutralized the oedema induced by the venom with and without heating, the hemorrhage induced by BJV and partially blocked the oedema induced by bradykinin and by cellulose sulphate. The oedema produced by histamine, serotonin, PAF-acether or leukotriene C4 was not inhibited.

Effect of tumour necrosis factor-α receptor 1 genetic deletion on carrageenan-induced acute inflammation: a comparison with etanercept

PubMed Central

Mazzon, E; Esposito, E; Di Paola, R; Muià, C; Crisafulli, C; Genovese, T; Caminiti, R; Meli, R; Bramanti, P; Cuzzocrea, S

2008-01-01

In the present study, we used tumour necrosis factor-α receptor 1 knock-out mice (TNF-αR1KO) to evaluate an in vivo role of TNF-αR1 on the pathogenesis of inflammatory diseases. We used a murine model of carrageenan-induced acute inflammation (pleurisy), a preclinical model of airway inflammation. The data proved that TNF-αR1KO were resistant to carrageenan-induced acute inflammation compared with TNF-α wild-type mice. TNF-αR1KO showed a significant reduction in accumulation of pleural exudate and in the number of inflammatory cells, in lung infiltration of polymorphonuclear leucocytes and lipid peroxidation and showed a decreased production of nitrite/nitrate in pleural exudates. Furthermore, the intensity and degree of the adhesion molecule intercellular adhesion molecule-1 and P-selectin, Fas ligand (FasL), inducible nitric oxide sythase and nitrotyrosine determined by immunohistochemical analysis were reduced markedly in lung tissues from TNF-αR1KO at 4 h and 24 h after carrageenan injection. Moreover, TNF-α and interleukin-1β concentrations were reduced in inflamed areas and in pleural exudates from TNF-αR1KO. To support the results generated using pleural inflammation, carrageenan-induced paw oedema models were also performed. In order to elucidate whether the observed anti-inflammatory effects were related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on carrageenan-induced pleurisy. The treatment with etanercept (5 mg/kg subcutaneously 2 h before the carrageenan injection) reduces markedly both laboratory and histological signs of carrageenan-induced pleurisy. Our results showed that administration of etanercept resulted in the same outcome as that of deletion of the TNF-αR1 receptor, adding a new insight to TNF-α as an excellent target by therapeutic applications. PMID:18505433

Inhibition of microsomal prostaglandin E2 synthase-1 as a molecular basis for the anti-inflammatory actions of boswellic acids from frankincense

PubMed Central

Siemoneit, U; Koeberle, A; Rossi, A; Dehm, F; Verhoff, M; Reckel, S; Maier, TJ; Jauch, J; Northoff, H; Bernhard, F; Doetsch, V; Sautebin, L; Werz, O

2011-01-01

BACKGROUND AND PURPOSE Frankincense, the gum resin derived from Boswellia species, showed anti-inflammatory efficacy in animal models and in pilot clinical studies. Boswellic acids (BAs) are assumed to be responsible for these effects but their anti-inflammatory efficacy in vivo and their molecular modes of action are incompletely understood. EXPERIMENTAL APPROACH A protein fishing approach using immobilized BA and surface plasmon resonance (SPR) spectroscopy were used to reveal microsomal prostaglandin E2 synthase-1 (mPGES1) as a BA-interacting protein. Cell-free and cell-based assays were applied to confirm the functional interference of BAs with mPGES1. Carrageenan-induced mouse paw oedema and rat pleurisy models were utilized to demonstrate the efficacy of defined BAs in vivo. KEY RESULTS Human mPGES1 from A549 cells or in vitro-translated human enzyme selectively bound to BA affinity matrices and SPR spectroscopy confirmed these interactions. BAs reversibly suppressed the transformation of prostaglandin (PG)H2 to PGE2 mediated by mPGES1 (IC50 = 3–10 µM). Also, in intact A549 cells, BAs selectively inhibited PGE2 generation and, in human whole blood, β-BA reduced lipopolysaccharide-induced PGE2 biosynthesis without affecting formation of the COX-derived metabolites 6-keto PGF1α and thromboxane B2. Intraperitoneal or oral administration of β-BA (1 mg·kg−1) suppressed rat pleurisy, accompanied by impaired levels of PGE2 and β-BA (1 mg·kg−1, given i.p.) also reduced mouse paw oedema, both induced by carrageenan. CONCLUSIONS AND IMPLICATIONS Suppression of PGE2 formation by BAs via interference with mPGES1 contribute to the anti-inflammatory effectiveness of BAs and of frankincense, and may constitute a biochemical basis for their anti-inflammatory properties. PMID:20840544

Inhibition of microsomal prostaglandin E2 synthase-1 as a molecular basis for the anti-inflammatory actions of boswellic acids from frankincense.

PubMed

Siemoneit, U; Koeberle, A; Rossi, A; Dehm, F; Verhoff, M; Reckel, S; Maier, T J; Jauch, J; Northoff, H; Bernhard, F; Doetsch, V; Sautebin, L; Werz, O

2011-01-01

Frankincense, the gum resin derived from Boswellia species, showed anti-inflammatory efficacy in animal models and in pilot clinical studies. Boswellic acids (BAs) are assumed to be responsible for these effects but their anti-inflammatory efficacy in vivo and their molecular modes of action are incompletely understood. A protein fishing approach using immobilized BA and surface plasmon resonance (SPR) spectroscopy were used to reveal microsomal prostaglandin E(2) synthase-1 (mPGES1) as a BA-interacting protein. Cell-free and cell-based assays were applied to confirm the functional interference of BAs with mPGES1. Carrageenan-induced mouse paw oedema and rat pleurisy models were utilized to demonstrate the efficacy of defined BAs in vivo. Human mPGES1 from A549 cells or in vitro-translated human enzyme selectively bound to BA affinity matrices and SPR spectroscopy confirmed these interactions. BAs reversibly suppressed the transformation of prostaglandin (PG)H(2) to PGE(2) mediated by mPGES1 (IC(50) = 3-10 µM). Also, in intact A549 cells, BAs selectively inhibited PGE(2) generation and, in human whole blood, β-BA reduced lipopolysaccharide-induced PGE(2) biosynthesis without affecting formation of the COX-derived metabolites 6-keto PGF(1α) and thromboxane B(2) . Intraperitoneal or oral administration of β-BA (1 mg·kg(-1) ) suppressed rat pleurisy, accompanied by impaired levels of PGE(2) and β-BA (1 mg·kg(-1) , given i.p.) also reduced mouse paw oedema, both induced by carrageenan. Suppression of PGE(2) formation by BAs via interference with mPGES1 contribute to the anti-inflammatory effectiveness of BAs and of frankincense, and may constitute a biochemical basis for their anti-inflammatory properties. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

[Antioxidant and anti-inflammatory activities of Moroccan Erica arborea L].

PubMed

Amezouar, F; Badri, W; Hsaine, M; Bourhim, N; Fougrach, H

2013-12-01

The present study was carried out to evaluate the antioxidant and anti-inflammatory capacity, and acute toxicity of Moroccan Erica arborea leaves. Antioxidant capacity was assessed by diphenyle-picryl-hydrazyl (DPPH), phosphomolybdate (PPM) and ferric reducing antioxidant power (FRAP) tests and anti-inflammatory capacity was evaluated by hind paw oedema model using carrageenan-induced inflammation in rat. The acute toxicity was evaluated using mice. Acute toxicity of ethanolic extract of E. arborea showed no sign of toxicity at dose of 5 g/kg B.W. Our extracts have important antioxidant properties. The efficient concentration of the ethanolic extract (10.22 μg/ml) required for decreasing initial DPPH concentration by 50% was comparable to that of standard solution butyl-hydroxy-toluene (BHT) (8.87 μg/ml). The administration of ethanolic extract at doses of 200 and 400mg/kg B.W. was able to prevent plantar oedema and exhibited a significant inhibition against carrageenan-induced inflammation when compared to the control group (NaCl 0.9%) but comparable to those of diclofenac (reference drug). Our results show that the leaves of E. arborea may contain some bioactive compounds which are responsible for the antioxidant and anti-inflammatory activities observed here. Our finding may indicate the possibility of using the extracts of this plant to prevent the antioxidant and inflammatory processes. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity

PubMed Central

Madaan, Reecha; Kumar, S.

2012-01-01

Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1st h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum. PMID:23716876

Screening of Alkaloidal Fraction of Conium maculatum L. Aerial Parts for Analgesic and Antiinflammatory Activity.

PubMed

Madaan, Reecha; Kumar, S

2012-09-01

Conium maculatum Linn. (Umbelliferae) has been traditionally used in the treatment of spasmodic disorders, and to relieve nervous excitation, rheumatic pains in the old and feeble, pain in stomach, pain of gastric ulcer, nervousness and restlessness. Alkaloids have long been considered as bioactive group of constituents present in C. maculatum. Despite a long tradition of use, C. maculatum has not been evaluated pharmacologically to validate its traditional claims for analgesic and antiinflammatory activities. Thus, the present investigations were undertaken with an objective to evaluate alkaloidal fraction of C. maculatum aerial parts for analgesic and antiinflammatory activities. Test doses (100 or 200 mg/kg, p.o.) of alkaloidal fraction were evaluated for analgesic activity using tail flick test and antiinflammatory activity using carrageenan-induced paw oedema test in rats. Morphine (5 mg/kg, p.o.) and indomethacin (5 mg/kg, p.o.) were used as standard analgesic and antiinflammatory drugs, respectively. Alkaloidal fraction of the plant exhibited significant analgesic activity at a dose of 200 mg/kg as it showed significant increase in tail flicking reaction time with respect to the control during 2 h intervals of observation. It also exhibited significant antiinflammatory activity at a dose of 200 mg/kg as it inhibited paw oedema in rats to 71% and reduced the paw volume one-fourth to the control during 1(st) h of the study. The present investigations suggest that alkaloids are responsible for analgesic and antiinflammatory activities of C. maculatum.

Anti-inflammatory activity of extract and fractions from Nepeta sibthorpii Bentham.

PubMed

Miceli, N; Taviano, M F; Giuffrida, D; Trovato, A; Tzakou, O; Galati, E M

2005-02-28

Several species of Nepeta genus are utilized in folk medicine for treatment of contusions, rheumatic pains, fever, cutaneous eruptions. Some species are employed for their anti-inflammatory properties. In this paper, we report the results of phytochemical studies on aerial parts of Nepeta sibthorpii Bentham (Lamiaceae), an endemic plant of Greece. The bioassay-guided fractionation of methanol extract led to the isolation of ursolic acid and polyphenol fraction. By HPLC, we determined some phenolics: chlorogenic acid (0.315 mg/g) and the flavonoids rutin (0.091 mg/g), luteolin-7-O-glucoside (0.387 mg/g) and a luteolin derivative. We assayed the radical scavenging activity of Nepeta sibthorpii methanol extract by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. Moreover, we studied the anti-inflammatory activity of Nepeta sibthorpii methanol extract (50 mg/kg, os), ursolic acid and polyphenol fraction (dose corresponding to 50 mg/kg of methanol extract, os) in the carrageenan-induced paw oedema in rat. In this experimental model, we observed a significant inhibition of paw oedema. We suppose that the anti-inflammatory effect of methanol extract could be related to the free radical scavenging activity and that it depends on a synergic action of all the components of the methanol extract, even if ursolic acid can be considered the main responsible for this activity.

Analgesic, antioedematous and antioxidant activity of γ-butyrolactone derivatives in rodents.

PubMed

Salat, Kinga; Librowski, Tadeusz; Moniczewski, Andrzej; Stanisz-Wallis, Krystyna; Wieckowski, Krzysztof; Malawska, Barbara

2012-08-01

In this paper, the analgesic, antioedematous, motor-impairing and antioxidant properties of four γ-butyrolactone derivatives (BM113, BM113A, BM138 and BM138A) are described. Pain was induced by thermal (hot-plate test), chemical (writhing test) or mechanical (Randall-Selitto model) stimulation. All in-vivo assays were carried out in mice pretreated intraperitoneally with the test compounds, except for the evaluation of anti-inflammatory and analgesic activities in the carrageenan-induced paw oedema model, in which rats were pretreated orally with these compounds. In the hot-plate assay, BM113A and BM138A dose dependently prolonged the latency of the nociceptive reaction. Their analgesic activity, measured as a median effective dose (ED(50)=4.7 mg/kg), was similar to that of morphine (2.4 mg/kg). In the writhing test, all four compounds, in particular BM113A and BM138A, showed higher potency than the reference drug acetylsalicylic acid (the ED(50) values were 3.7, 2.3 and 46.1 mg/kg, respectively). BM138 caused a dose-dependent diminution of paw oedema (up to 49%) in the carrageenan model and BM138A at 200 mg/kg reduced mechanical hyperalgesia in the Randall-Selitto test (∼30% when compared with the control). None of the γ-butyrolactone derivatives tested at the ED(50) obtained in the hot-plate test influenced the locomotor activity of mice, although in the rotarod test at 24 rpm, BM113A and BM138 at 100 mg/kg showed some motor-impairing properties. In vitro, a concentration-dependent ABTS radical cation-scavenging activity of BM138 and BM138A (up to 80% inhibition of the radical absorbance) was observed. The results of the present study suggest that BM138 and BM138A could be of interest for future investigations as antinociceptive and antioedematous agents with potential free radical-scavenging properties.

Taraxerol, a pentacyclic triterpene from Abroma augusta leaf, attenuates acute inflammation via inhibition of NF-κB signaling.

PubMed

Khanra, Ritu; Dewanjee, Saikat; Dua, Tarun K; Bhattacharjee, Niloy

2017-04-01

Abroma augusta L. (Malvaceae) leaf is traditionally used to treat inflammatory disorders. In our laboratory, we have scientifically validated the anti-inflammatory effect of A. augusta leaf extract. In this study, it has been aimed to evaluate in vivo anti-inflammatory effect of taraxerol isolated from the methanol extract of A. augusta leaf. It was further intended to find out the probable mechanism of anti-inflammatory effect of taraxerol. The anti-inflammatory effect of taraxerol (5 and 10mg/kg, i.p.) was measured employing carrageenan-induced paw edema model of acute inflammation. The carrageenan injection resulted significant edema formation in the right paw when compared with un-injected left paw. However, taraxerol (10mg/kg) treatment could significantly (p<0.05-0.01) attenuate carrageenan induced paw edema 2h onward. The effect of taraxerol at the dose of 5mg/kg was found to be significant (p<0.05) only after 4h of carrageenan treatment. Taraxerol (10mg/kg) treatment could significantly (p<0.01) attenuate carrageenan mediated up-regulation in the levels of IL 1β, IL 6, IL 12 and TNF α in the right paw tissues. In search of molecular mechanism, taraxerol (10mg/kg) could significantly (p<0.05-0.01) reinstate carrageenan provoked NF-κB signaling and thereby caused significant down-regulation in the expressions of COX-2 (p<0.01) and iNOS (p<0.05). In conclusion, taraxerol would attenuate acute inflammation via inhibition of NF-κB signaling. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Supercritical CO₂ extract and essential oil of aerial part of Ledum palustre L.--Chemical composition and anti-inflammatory activity.

PubMed

Baananou, Sameh; Bagdonaite, Edita; Marongiu, Bruno; Piras, Alessandra; Porcedda, Silvia; Falconieri, Danilo; Boughattas, Naceur A

2015-01-01

The anti-inflammatory activity of two extracts from the aerial parts of Ledum palustre has been reported. The volatile oil was obtained by supercritical fluid extraction (SFE) and the essential oil by hydrodistillation (HD). The oils were analysed by gas chromatography-mass spectrometry to monitor their composition. Both extracts shared as main compound (41.0-43.4%) ledol (23.3-26.7%) and ascaridole (15.1-4.5%). The anti-inflammatory activity was evaluated by the subcutaneous carrageenan injection-induced hind paw oedema. The treated animals received essential oil (SFE and HD), the reference group received ketoprofen or piroxicam and the control group received NaCl 0.9%. A statistical analysis was performed by the Student t-test. The results show that L. palustre essential oil enhanced a significant inhibition of oedema (50-73%) for HD oil and (52-80%) for SFE oil. These results were similar to those obtained with piroxicam (70%) and ketoprofen (55%).

Antihyperalgesic Effects of Indomethacin, Ketorolac, and Metamizole in Rats: Effects of Metformin.

PubMed

Guzmán-Priego, Crystell Guadalupe; Méndez-Mena, Roberto; Baños-González, Manuel Alfonso; Araiza-Saldaña, Claudia Ivonne; Castañeda-Corral, Gabriela; Torres-López, Jorge Elías

2017-03-01

Preclinical Research Metformin-dependent mechanisms have been implicated in the antinociceptive effect of some non-steroidal anti-inflammatory drugs (NSAIDs). In this study, the effect of local peripheral or systemic administration of metformin on the local peripheral or systemic antinociception induced by indomethacin, ketorolac and metamizole was assessed in the rat carrageenan-induced thermal hyperalgesia model. Rats were injected with carrageenan (1%, 50 µl) into the right hindpaw which reduced paw withdrawal latency, a measure of thermal hyperalgesia. Local peripheral or systemic administration of indomethacin, ketorolac or metamizole dose-dependently reduced carrageenan-induced thermal hyperalgesia. Local peripheral pre-treatment with metformin (800 µg/paw) partially inhibited the anti-hyperalgesic effect of indomethacin (200 µg/paw) and metamizole (200 µg/paw), but not that of ketorolac (200 µg/paw). In contrast, systemic pre-treatment with metformin (200 mg/kg) attenuated the antihyperalgesic effect of metamizole (10 mg/kg), but not that observed with either indomethacin (10 mg/kg) or ketorolac (10 mg/kg). These findings suggest that some but not all NSAIDs have effects mediated by metformin-dependent mechanisms. Drug Dev Res 78 : 98-104, 2017. ©2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Anti-inflammatory effect of selenium nanoparticles on the inflammation induced in irradiated rats.

PubMed

El-Ghazaly, M A; Fadel, N; Rashed, E; El-Batal, A; Kenawy, S A

2017-02-01

Selenium (Se) has been reported to possess anti-inflammatory properties, but its bioavailability and toxicity are considerable limiting factors. The present study aimed to investigate the possible anti-inflammatory and analgesic effects of selenium nanoparticles (Nano-Se) on inflammation induced in irradiated rats. Paw volume and nociceptive threshold were measured in carrageenan-induced paw edema and hyperalgesia model. Leukocytic count, tumor necrosis factor-α (TNF-α), prostaglandin E 2 (PGE 2 ), thiobarbituric acid reactive substances (TBAR), and total nitrate/nitrite (NOx) were estimated in the exudate collected from 6 day old air pouch model. Irradiated rats were exposed to 6 Gy gamma (γ)-irradiation. Nano-Se were administered orally in a dose of 2.55 mg/kg once before carrageenan injection in the first model and twice in the second model. The paw volume but not the nociceptive response produced by carrageenan in irradiated rats was higher than that induced in non-irradiated rats. Nano-Se were effective in reducing the paw volume in non-irradiated and irradiated rats but it did not alter the nociceptive threshold. The inflammation induced in irradiated rats increased all the estimated parameters in the exudate whereas; Nano-Se decreased their elevation in non-irradiated and irradiated rats. Nano-Se possess a potential anti-inflammatory activity on inflammation induced in irradiated rats.

Vitex negundo inhibits cyclooxygenase-2 inflammatory cytokine-mediated inflammation on carrageenan-induced rat hind paw edema

PubMed Central

Chattopadhyay, Pronobesh; Hazarika, Soilyadhar; Dhiman, Sunil; Upadhyay, Aadesh; Pandey, Anurag; Karmakar, Sanjeev; Singh, Lokendra

2012-01-01

Background: Vitex negundo L. (Verbenaceae) is a hardy plant widely distributed in the Indian subcontinent and used for treatment of a wide spectrum of health disorders in traditional and folk medicine, some of which have been experimentally validated. In present study, we aimed to investigate the anti-inflammatory effects of V. negundo in carrageenan-induced paw edema in rats, and to investigate the probable mechanism of anti-inflammatory action. Materials and Methods: Paw edema was produced by injecting 1% solution of carrageenan, and the paw volume was measured before and after carrageenan injection up to 5 h. V. negundo leaf oil was extracted using a Clevenger apparatus and administered by a trans-dermal route to Wistar rats and the percentage of inhibition of inflammation was observed using a Plethysmometer by comparing a compound aerosol-based formulation with 1 mg diclofinac diethylamine BP and 7 mg methyl salicylate IP/kg body weight served as a standard drug whereas paraffin oil served as the placebo group. After withdrawing of blood, serum was separated and cyclooxygenase (COX)-1 and COX-2 inhibitory activities were measured by the enzyme immuno assay (EIA) method by using a COX inhibitor screening assay kit. Results and Discussion: V. negundo leaf oil significantly (P < 0.05) reduced the carrageenan-induced paw edema as compared to the placebo group (paraffin oil) and 1 mg diclofinac diethylamine BP and 7 mg methyl salicylate IP showed the maximum inhibition of paw edema as compared to the V. negundo leaf oil treated group and the control group. Also in the present study V. negundo leaf oil showed significantly (P < 0.05) inhibits COX-1 pathways rather than COX-2 pathways as compared to the V. negundo leaf oil treated group. Conclusion: It is suggested that the V. negundo leaf oil is a potent anti-inflammatory agent and acts via inhibition of COX-2 without much interfering COX-1 pathways. PMID:22923950

Low-level laser therapy (LLLT) reduces the COX-2 mRNA expression in both subplantar and total brain tissues in the model of peripheral inflammation induced by administration of carrageenan.

PubMed

Prianti, Antonio Carlos Guimarães; Silva, José Antonio; Dos Santos, Regiane Feliciano; Rosseti, Isabela Bueno; Costa, Maricilia Silva

2014-07-01

In the classical model of edema formation and hyperalgesia induced by carrageenan administration in rat paw, the increase in prostaglandin E2 (PGE2) production in the central nervous system (CNS) contributes to the severity of the inflammatory and pain responses. Prostaglandins are generated by the cyclooxygenase (COX). There are two distinct COX isoforms, COX-1 and COX-2. In inflammatory tissues, COX-2 is greatly expressed producing proinflammatory prostaglandins (PGs). Low-level laser therapy (LLLT) has been used in the treatment of inflammatory pathologies, reducing both pain and acute inflammatory process. Herein we studied the effect of LLLT on both COX-2 and COX-1 messenger RNA (mRNA) expression in either subplantar or brain tissues taken from rats treated with carrageenan. The experiment was designed as follows: A1 (saline), A2 (carrageenan-0.5 mg/paw), A3 (carrageenan-0.5 mg/paw + LLLT), A4 (carrageenan-1.0 mg/paw), and A5 (carrageenan-1.0 mg/paw + LLLT). Animals from the A3 and A5 groups were irradiated at 1 h after carrageenan administration, using a diode laser with an output power of 30 mW and a wavelength of 660 nm. The laser beam covered an area of 0.785 cm(2), resulting in an energy dosage of 7.5 J/cm(2). Both COX-2 and COX-1 mRNAs were measured by RT-PCR. Six hours after carrageenan administration, COX-2 mRNA expression was significantly increased both in the subplantar (2.2-4.1-fold) and total brain (8.65-13.79-fold) tissues. COX-1 mRNA expression was not changed. LLLT (7.5 J/cm(2)) reduced significantly the COX-2 mRNA expression both in the subplantar (~2.5-fold) and brain (4.84-9.67-fold) tissues. The results show that LLLT is able to reduce COX-2 mRNA expression. It is possible that the mechanism of LLLT decreasing hyperalgesia is also related to its effect in reducing the COX-2 expression in the CNS.

Protective effects of papaverine salicylate in mouse ear dermatitis and PAF-induced rat paw oedema.

PubMed

de Bernardis, E; Leonardi, G; Caruso, A; Cutuli, V M; Amico-Roxas, M

1994-08-01

Papaverine salicylate (MR-800) has been tested as a topical antiinflammatory agent in several models of skin inflammation in rodents, such as mouse ear dermatitis induced by croton oil, cantharidin or zymosan, and rat paw oedema induced by PAF. MR-800 exerted a dose-dependent inhibitory activity in all assays, when equimolar doses of sodium salicylate or papaverine were less effective, suggesting the existence of a favourable synergism between salicylate and papaverine.

Edematogenic activity of a sulfated galactan from the red marine algae Gelidium crinale.

PubMed

Assreuy, Ana Maria Sampaio; Amorim, Renata Morais Ferreira; Brizeno, Luiz André Cavalcante; de Paulo Pereira, Lívia; de Sousa, Albertina Antonielly Sydney; Aragão, Gislei Frota; Pereira, Maria Gonçalves

2012-09-01

The red algae Gelidium crinale (Turner) Gaillon (Gelidiaceae), encountered along the Southeast and Northeast Brazilian sea coast, contains a sulfated galactan presenting a similar saccharide backbone compared to λ carrageenan. Inflammatory effects of other galactans were reported, but not for that obtained from G. crinale (SG-Gc). To investigate the in vivo edematogenic effect of SG-Gc in comparison to λ carrageenan. SG-Gc was isolated by ion exchange chromatography. Paw edema was induced by subcutaneous (s.c.) intraplantar injection of SG-Gc or λ carrageenan and evaluated by hydroplethysmometry. Data were expressed as the increase in paw volume subtracted from the basal volume or area under curve-AUC. To investigate the participation of early and late-phase inflammatory mediators, rats were treated with pyrilamine, compound 48/80, indomethacin, NG-nitro-L-arginine methyl ester (L-NAME), or pentoxifylline before SG-Gc. SG-Gc edematogenic effect was initiated at 0.5 h, peaked at 2 h (1.26 ± 0.05 mL) and lasted until 6 h (0.21 ± 0.03 mL), whereas the carrageenan-induced edema started at 1 h. The first phase (1-3 h) of SG-Gc-induced edema was 176 ± 15 (AUC) versus carrageenan (114.5 ± 14), whereas the second phase (3-5 h) was 95 ± 12 (AUC) versus carrageenan (117.5 ± 11). Treatment with compound 48/80, pyrilamine, indomethacin, L-NAME, and pentoxifylline inhibited the effect of SG-Gc by 32, 40, 69, 72, and 49%, respectively. SG-Gc and λ carrageenan induce different profile of inflammatory response in the paw edema model, that involves histamine, cytokines, prostaglandins, and nitric oxide (NO), but with different degree of participation.

Bioactive phenolic derivatives from Acaena splendens methanol extract.

PubMed

Backhouse, N; Delporte, C; Negrete, R; Feliciano, S A San; López-Pérez, J L

2002-09-01

Acaena splendens H. et A. has been used in Chilean folk medicine for the treatment of fever and inflammation. A description of the in vivo reduction of bacterial pyrogen-induced fever in rabbits and carrageenan-induced paw oedema in guinea pigs is presented. The methanol extract named ME-1, obtained after succesive extractions with petroleum ether and dichloromethane, showed a strong antipyretic action (45.7% of effect), though the antiinflammatory activity was only observed after submitting this extract to column fractionation, giving a crude mixture of flavonoids named C4 with both activities (55.7% and 98.9% of antiinflammatory and antipyretic effect respectively at a dose of 600 mg/kg). The bioassay-guided fractionation by column chromatography afforded the active fraction, which contained (-,-)-epicatechin, tiliroside, 7-O-acetyl-3-O-beta-D-glucosyl-kaempferol and 7-beta-D-glucosyloxy-5-hydroxy-chromone. Copyright 2002 John Wiley & Sons, Ltd.

Contribution of mast cells to the oedema induced by Bothrops moojeni snake venom and a pharmacological assessment of the inflammatory mediators involved.

PubMed

Galvão Nascimento, Neide; Sampaio, Marlos Cortez; Amaral Olivo, Renata; Teixeira, Catarina

2010-01-01

The ability of Bothrops moojeni venom (BmV) to induce oedema in mice, the involvement of principal inflammatory mediators and mast cells (MCs) were investigated. The intraplantar injection of BmV (0.3-6 microg/paw) caused a dose- and time-dependent oedema with a peak between 30 and 60 min after venom injection (0.3-1 microg/paw), disappearing within 24h. Either MCs granule inhibition or depletion by cromoglycate or C48/80, respectively, markedly reduced BmV-induced oedema. MCs depletion by imatinib also reduced oedema. Intraperitoneal BmV injection (2.5-10 microg/site) induced MCs degranulation and release of PGD(2). Treatment with promethazine, cimetidine or thioperamide, histamine H1, H2 and H3/H4 receptor antagonists, respectively, markedly reduced the initial phase of oedema. Combined treatment with these antagonists further reduced, but not abrogated oedema. Indomethacin or eterocoxib (cyclooxygenase inhibitors) reduced oedema until 180 min, whereas zileuton (lipoxygenase inhibitor) affected this event until 60 min. Dexamethazone caused a long lasting reduction of oedema. However, L-NAME and aminoguanidine (NO synthase inhibitors) significantly increased BmV-induced oedema. In conclusion, BmV induces oedema, mediated by MCs degranulation, histamine by H1, H2, H3/H4 receptors, prostaglandins and leukotrienes, and down-regulated by NO. Partial neutralization of oedema was observed even when polyspecific bothropic antivenom was injected immediately after venom. Copyright 2009 Elsevier Ltd. All rights reserved.

Inhibitory effect of eupatilin and jaceosidin isolated from Artemisia princeps on carrageenan-induced inflammation in mice.

PubMed

Min, Sung-Won; Kim, Nam-Jae; Baek, Nam-In; Kim, Dong-Hyun

2009-09-25

Artemisia princeps Pampanini (family Asteraceae) is an herbal medicine widely used as a hepatoprotective, antioxidative, anti-inflammatory, and antibacterial agent in Korea, China, and Japan. This study aimed to elucidate the anti-inflammatory effect of the main constituents, eupatilin and jaceosidin, isolated from Artemisia princeps. We used carrageenan-induced inflammation in an air pouch on the back of mice and carrageenan-induced hind paw edema in rats to determine the anti-inflammatory effects of eupatilin and jaceosidin. Inflammatory makers, such as expression of pro-inflammatory cytokines and cyclooxygenase (COX)-2, and activation of nuclear factor-kappa B (NF-kappaB), were measured by enzyme-linked immunosorbent assays and immunoblot analyses. Eupatilin and jaceosidin blocked carrageenan-induced increase in leukocyte number and protein levels in air pouch exudates. Eupatilin and jaceosidin inhibited COX-2 expression and NF-kappaB activation, and markedly reduced TNF-alpha, IL-1beta, and prostaglandin E2 (PGE(2)) levels. They also inhibited hind paw edema induced by carrageenan. Eupatilin and jaceosidin had similar activity. These findings suggest that eupatilin and jaceosidin may reduce inflammation by inhibiting NF-kappaB activation, and that Artemisia princeps inhibits inflammation because of these constituents.

Anti-inflammatory activity of dried flower extracts of Aegle marmelos in Wistar rats.

PubMed

Kumari, K D K P; Weerakoon, T C S; Handunnetti, S M; Samarasinghe, K; Suresh, T S

2014-02-12

Almost all part of the plant Aegle marmelos (Bael tree) has been used in the traditional medicine systems of Asian countries to treat various diseases over many centuries. The water extract of the dried flowers of Aegle marmelos is a commonly used beverage among Sri Lankan population in rural areas. Although extensive investigations done on many parts of the plant there are no experimental data available on the extracts of flowers. Anti-inflammatory effect of the water extract of dried flowers of Aegle marmelos (WEAM) was evaluated in the present study. The anti-inflammatory effect of the WEAM was evaluated by inhibition of the rat paw oedema, induced by carrageenan. The mechanism of the anti-inflammatory effect was assessed by the inhibition of production of nitric oxide (NO) by rat peritoneal cells, infiltration of rat peritoneal cells, anti-histamine effect, membrane stabilization activity, the antioxidant capacity and inhibition of lipid peroxidation by the WEAM. The maximum percentage inhibition of paw oedema was exhibited by the dose of 200 mg/kg at 2 h. The WEAM showed a significant increment of rat peritoneal cell infiltration, inhibition of NO production by rat peritoneal cells and inhibition of wheal formation on the skin of the rat after injection of histamine. The WEAM protected the erythrocyte membrane from heat-induced lysis in a dose-dependent manner and showed a significant anti-oxidant effect and lipid peroxidation inhibition activity. The WEAM possesses significant anti-inflammatory effect by multiple mechanisms in Wistar rats. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema.

PubMed

Maruyama, Hiroe; Sakamoto, Takashi; Araki, Yoko; Hara, Hideaki

2010-06-23

Bee pollen, a honeybee product, is the feed for honeybees prepared themselves by pollens collecting from plants and has been consumed as a perfect food in Europe, because it is nutritionally well balanced. In this study, we aimed to investigate the anti-inflammatory effect of bee pollen from Cistus sp. of Spanish origin by a method of carrageenan-induced paw edema in rats, and to investigate the mechanism of anti-inflammatory action and also to elucidate components involved in bee pollen extracted with ethanol. The bee pollen bulk, its water extract and its ethanol extract were administered orally to rats. One hour later, paw edema was produced by injecting of 1% solution of carrageenan, and paw volume was measured before and after carrageenan injection up to 5 h. The ethanol extract and water extract were measured COX-1 and COX-2 inhibitory activities using COX inhibitor screening assay kit, and were compared for the inhibition of NO production in LPS-stimulated RAW 264.7 cells. The constituents of bee pollen were purified from the ethanol extract subjected to silica gel or LH-20 column chromatography. Each column chromatography fractions were further purified by repeated ODS or silica gel column chromatography. The bee pollen bulk mildly suppressed the carrageenan-induced paw edema and the water extract showed almost no inhibitory activity, but the ethanol extract showed relatively strong inhibition of paw edema. The ethanol extract inhibited the NO production and COX-2 but not COX-1 activity, but the water extract did not affect the NO production or COX activities. Flavonoids were isolated and purified from the ethanol extract of bee pollen, and identified at least five flavonoids and their glycosides. It is suggested that the ethanol extract of bee pollen show a potent anti-inflammatory activity and its effect acts via the inhibition of NO production, besides the inhibitory activity of COX-2. Some flavonoids included in bee pollen may partly participate in some of the anti-inflammatory action. The bee pollen would be beneficial not only as a dietary supplement but also as a functional food.

Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema

PubMed Central

2010-01-01

Background Bee pollen, a honeybee product, is the feed for honeybees prepared themselves by pollens collecting from plants and has been consumed as a perfect food in Europe, because it is nutritionally well balanced. In this study, we aimed to investigate the anti-inflammatory effect of bee pollen from Cistus sp. of Spanish origin by a method of carrageenan-induced paw edema in rats, and to investigate the mechanism of anti-inflammatory action and also to elucidate components involved in bee pollen extracted with ethanol. Methods The bee pollen bulk, its water extract and its ethanol extract were administered orally to rats. One hour later, paw edema was produced by injecting of 1% solution of carrageenan, and paw volume was measured before and after carrageenan injection up to 5 h. The ethanol extract and water extract were measured COX-1 and COX-2 inhibitory activities using COX inhibitor screening assay kit, and were compared for the inhibition of NO production in LPS-stimulated RAW 264.7 cells. The constituents of bee pollen were purified from the ethanol extract subjected to silica gel or LH-20 column chromatography. Each column chromatography fractions were further purified by repeated ODS or silica gel column chromatography. Results The bee pollen bulk mildly suppressed the carrageenan-induced paw edema and the water extract showed almost no inhibitory activity, but the ethanol extract showed relatively strong inhibition of paw edema. The ethanol extract inhibited the NO production and COX-2 but not COX-1 activity, but the water extract did not affect the NO production or COX activities. Flavonoids were isolated and purified from the ethanol extract of bee pollen, and identified at least five flavonoids and their glycosides. Conclusions It is suggested that the ethanol extract of bee pollen show a potent anti-inflammatory activity and its effect acts via the inhibition of NO production, besides the inhibitory activity of COX-2. Some flavonoids included in bee pollen may partly participate in some of the anti-inflammatory action. The bee pollen would be beneficial not only as a dietary supplement but also as a functional food. PMID:20573205

Anti-inflammatory activities of aqueous extract of Mesona procumbens in experimental mice.

PubMed

Huang, Guan-Jhong; Liao, Jung-Chun; Chiu, Chuan-Sung; Huang, Shyh-Shyun; Lin, Tsung-Hui; Deng, Jeng-Shyan

2012-04-01

Mesona procumbens is consumed as a herbal drink and jelly-type dessert in Taiwan. The aim of this study was to determine the mechanism of anti-inflammatory activities of the aqueous extract of M. procumbens (AMP) using the λ-carrageenin (Carr)-induced mouse paw oedema model. The fingerprint chromatogram of AMP was obtained by high-performance liquid chromatography (HPLC) analysis. To investigate the anti-inflammatory mechanism of AMP, the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in paw oedema were monitored. Serum nitric oxide (NO), tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also evaluated. The fingerprint chromatogram from HPLC indicated that AMP contained protocatechuic acid, chlorogenic acid, vanillic acid and caffeic acid. In the anti-inflammatory test, AMP decreased paw oedema after Carr administration and increased the CAT, SOD and GPx activities and decreased the MDA level in paw oedema at 5 h after Carr injection. AMP also affected the serum NO, TNF-α and IL-1β levels at 5 h after Carr injection. Western blotting revealed that AMP decreased the expression of Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Mesona procumbens has the potential to provide a therapeutic approach to inflammation-associated disorders. Copyright © 2011 Society of Chemical Industry.

Morinda citrifolia lipid transfer protein 1 exhibits anti-inflammatory activity by modulation of pro- and anti-inflammatory cytokines.

PubMed

Campos, Dyély C O; Costa, Andrea S; Luz, Patrícia B; Soares, Pedro M G; Alencar, Nylane M N; Oliveira, Hermógenes D

2017-10-01

Previous reports have demonstrated that a thermostable lipid transfer protein isolated from noni seeds (McLTP 1 ; 9.4kDa) displays anti-nociceptive and anti-inflammatory activities. This work aimed to investigate the underlying mechanisms of the anti-inflammatory activity of McLTP 1 in mice. The protein was solubilised in sterile saline (0.9% NaCl) immediately before the treatment of mice by oral or intraperitoneal routes at doses of 8mg/kg. Given orally or intraperitoneally, McLTP 1 significantly inhibited (p<0.05) cell migration in experimental models of carrageenan-induced peritonitis and the formation of paw oedema induced by carrageenan and dextran. Additionally, McLTP 1 demonstrated the ability to significantly inhibit the production of the cytokines IL-1β, IL-6, and TNF-α (p<0.05) and to promote an increase in the production of the anti-inflammatory cytokine IL-10. The treatment of mice with McLTP 1 by the oral or i.p route reduced pancreatic injury and activities of amylase, lipase, and pancreatitis-associated lung injury. This study suggested that the observed anti-inflammatory effects of McLTP 1 can be related to modulation of pro- and anti-inflammatory cytokine levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Antioxidant and Anti-inflammatory Activities of a Commercial Noni Juice revealed by Carrageenan-induced Paw Edema.

PubMed

Yilmazer, N; Coskun, C; Gurel-Gurevin, E; Yaylim, I; Eraltan, E H; Ikitimur-Armutak, E I

2016-09-01

This study aimed to investigate antioxidant and anti-inflammatory activities of a commercial product of noni (Morinda citrifolia) juice. Carrageenan-induced rat paw edema was employed as inflammatory model. One control and three experimental groups were formed. Experimental groups were administered noni juice alone, noni juice+carrageenan, and carrageenan alone. Oxidant and antioxidant capacity were determined by d-ROMs test and BAP test, respectively. Plasma concentrations of endothelin-1 and leptin were measured by ELISA. Measurements were performed at zero time and 2nd hour of inflammation. Oxidant capacity decreased in noni-received groups at 2nd hour (p=0.019). Antioxidant capacity of the group which received noni alone was found to be higher at 2nd hour (p=0.036). Plasma concentrations of endothelin-1 and leptin were notably lower in noni-received groups (p=0.001 and p=0.021, respectively). The results show that the commercial noni juice investigated has pronounced antioxidant and anti-inflammatory activities.

Analgesic and anti-inflammatory activities of fixed oil of Macrotyloma uniflorum (Lam.) Verdc. in mice and rats.

PubMed

Fatima, Syeda Anum; Baig, Sadia Ghousia; Hasan, Muhammad Mohtasheemul; Ahmed, Salman; Salma, -

2018-03-01

Macrotyloma uniflorum commonly known as horse gram or kulthi bean is grown as a pulse for livestock and human consumption. The beans contain about 1.3% fat, 18% protein, 15% carbohydrate along with vitamins and minerals. In traditional medicine it is used as antihyperglycemic, antioxidant, antihypertensive and diuretic. Other important medicinal uses include treatment of renal stones, obesity, piles, oedema and fever. The present study evaluated analgesic (by acetic acid induced writhing, hot plate and tail flick tests in mice) and anti-inflammatory (carrageenan induced paw edema in rats) activities of Macrotyloma uniflorum fixed oil (MUFO). Four groups were included in study: Group-I: Normal Saline Control (2ml/kg), Group-II: MUFO (2ml/kg), Group-III: MUFO (4ml/kg), and Group-IV: Standard Acetyl salicylic acid (ASA 300mg/kg). All results were significant however delayed onset of action was observed in tail flick and paw edema tests. Acute oral toxicity of the oil was also checked in mice and was found safe upto 4ml/kg dose, as no signs of toxicity and mortality were observed. It is concluded that Macrotyloma uniflorum fixed oil may possess analgesic and anti-inflammatory activity which can be related with a peripheral mechanism of action.

Influence of several peptidase inhibitors on the pro-inflammatory effects of substance P, capsaicin and collagenase.

PubMed

Damas, J; Bourdon, V; Liégeois, J F; Simmons, W H

1996-11-01

Injection of substance P (SP) in a rat hindpaw induced extravasation of 125I-labelled albumin in both hindpaws and salivation. Intravenous injection of SP dose-dependently increased vascular permeability. This latter effect was increased in rat paws by captopril, an inhibitor of angiotensin-converting enzyme (ACE), administered locally in combination with diprotin A, an inhibitor of an dipeptidyl(amino)peptidase IV (DAP IV) or phosphoramidon, an inhibitor of neutral endopeptidase (NEP). The increase in permeability induced by SP was inhibited by RP 67580, a NK-1-receptor antagonist. Intravenous injection of capsaicin induced labelled albumin extravasation in rat paws. This effect was increased by combination of captopril with diprotin A or phosphoramidon, but not by captopril associated with amastatin, an inhibitor of aminopeptidase M (AmM). It was suppressed by RP 67580. Injection of collagenase in rat paws triggered a swelling and a local plasma exudation. These responses were reduced by RP 67580 but not by RP 68651, its inactive enantiomer. They were increased by combination of captopril with diprotin A or phosphoramidon in normal rats. The potentiating effects of captopril and diprotin A were suppressed by RP 67580 in normal rats but did not develop in kininogen-deficient rats. The oedema induced by collagenase was also increased by lisinopril, another ACE inhibitor, administered locally in combination with apstatin, an inhibitor of aminopeptidase P (AmP). In rats pretreated by methysergide, collagenase-induced oedema was reduced and can be increased by captopril, by lisinopril, administered alone or by lisinopril associated with apstatin. It is concluded that SP is mainly inactivated in rat paws by ACE, DAP IV and NEP. In collagenase-induced oedema, a low amount of SP would be released from afferent nerve terminals by bradykinin formed in low amounts. Bradykinin is inactivated in rat paws by ACE and AmP. In collagenase-oedema, the pro-inflammatory effects of bradykinin are concealed by the effects of the other mediators.

Gelam Honey Attenuates Carrageenan-Induced Rat Paw Inflammation via NF-κB Pathway

PubMed Central

Hussein, Saba Zuhair; Mohd Yusoff, Kamaruddin; Makpol, Suzana; Mohd Yusof, Yasmin Anum

2013-01-01

The activation of nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of a number of inflammatory diseases. In this study, we investigated the anti-inflammatory mechanism of Gelam honey in inflammation induced rats via NF-κB signalling pathway. Rats paw edema was induced by subplantar injection of 1% carrageenan into the right hind paw. Rats were pre-treated with Gelam honey at different doses (1 or 2 g/kg, p.o.) and NSAID Indomethacin (10 mg/kg, p.o.), in two time points (1 and 7 days). Our results showed that Gelam honey at both concentrations suppressed the gene expressions of NF-κB (p65 & p50) and IκBα in inflamed rats paw tissues. In addition, Gelam honey inhibited the nuclear translocation and activation of NF-κB and decreased the cytosolic degradation of IκBα dose dependently in inflamed rats paw tissues. The immunohistochemical expressions of pro-inflammatory mediators COX-2 and TNF-α were also decreased in inflamed rats paw tissues when treated with Gelam honey. The results of our findings suggest that Gelam honey exhibits its inhibitory effects by attenuating NF-κB translocation to the nucleus and inhibiting IκBα degradation, with subsequent decrease of inflammatory mediators COX-2 and TNF-α. PMID:24015236

Anti-Inflammatory and Analgesic Effects of the Marine-Derived Compound Excavatolide B Isolated from the Culture-Type Formosan Gorgonian Briareum excavatum

PubMed Central

Lin, Yen-You; Lin, Sung-Chun; Feng, Chien-Wei; Chen, Pei-Chin; Su, Yin-Di; Li, Chi-Min; Yang, San-Nan; Jean, Yen-Hsuan; Sung, Ping-Jyun; Duh, Chang-Yih; Wen, Zhi-Hong

2015-01-01

In recent years, several marine-derived compounds have been clinically evaluated. Diterpenes are secondary metabolites from soft coral that exhibit anti-inflammatory, anti-tumor and cytotoxic activities. In the present study, we isolated a natural diterpene product, excavatolide B, from cultured Formosan gorgonian Briareum excavatum and investigated its anti-inflammatory activities. We found that excavatolide B significantly inhibited the mRNA expression of the proinflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-challenged murine macrophages (RAW 264.7). We also examined the anti-inflammatory and anti-nociceptive effects of excavatolide B on intraplantar carrageenan-induced inflammatory responses. Excavatolide B was found to significantly attenuate carrageenan-induced nociceptive behaviors, mechanical allodynia, thermal hyperalgesia, weight bearing deficits and paw edema. In addition, excavatolide B inhibited iNOS, as well as the infiltration of immune cells in carrageenan-induced inflammatory paw tissue. PMID:25923315

Antiedematogenic and antioxidant properties of high molecular weight protein sub-fraction of Calotropis procera latex in rat.

PubMed

Chaudhary, Priyanka; de Araújo Viana, Carolina; Ramos, Marcio V; Kumar, Vijay L

2015-03-01

The aim was to evaluate the effect of high molecular weight protein fraction of Calotropis procera latex on edema formation and oxidative stress in carrageenan-induced paw inflammation. A sub-plantar injection of carrageenan was given to induce edema in the hind paw of the rat. The inhibitory effect of high molecular weight protein fraction of C. procera latex was evaluated following intravenous administration (5 and 25 mg/kg body weight) and was compared with that of diclofenac given orally (5 mg/kg). The levels of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and myeloperoxidase (MPO) were measured in the inflamed paw tissue at the end of the study. The high molecular weight protein fraction obtained from the latex of C. procera produced a dose-dependent inhibition of edema formation that was accompanied by normalization of levels of oxidative stress markers (GSH and TBARS) and MPO, a marker for neutrophils in the paw tissue. The high molecular weight protein fraction of C. procera latex ameliorates acute inflammation in the paw through its antioxidant effect.

Fluorine bearing sydnones with styryl ketone group: synthesis and their possible analgesic and anti-inflammatory activities.

PubMed

Deshpande, Shreenivas Ramachandrarao; Pai, Karkala Vasantakumar

2012-04-01

In continuation of structure activity relationship studies, a panel of fluorine containing sydnones with styryl ketone group 4-[1-oxo-3-(substituted aryl)-2-propenyl]-3-(3-chloro-4-fluorophenyl)sydnones 2a-i, was synthesized as better analgesic and anti-inflammatory agents. The title compounds were formed by condensing 4-acetyl-3-(3-chloro-4-fluorophenyl)sydnone with various substituted aryl aldehydes, characterized by spectral studies and evaluated at 100 mg\\kg b.w., p.o. for analgesic, anti-inflammatory and ulcerogenic activities. Compounds 2c and 2e showed good analgesic effect in acetic acid-induced writhing while none showed significant activity in hot plate assay in mice. In carrageenan-induced rat paw oedema test, compound 2c and 2f exhibited good anti-inflammatory effect at 3rd h, whereas compounds 2c, 2e, 2d, 2g and 2h showed activity in croton oil induced ear oedema assay in mice. Compounds 2c and 2e were less ulcerogenic than ibuprofen in rats, when tested by ulcer index method. Compounds with electron attracting substituents such as 2c and 2e were found to be promising in terms of the ratio of efficacy and adverse effect. These compounds generally exhibited better activity than those of earlier series signifying fluorine substitution.

Evaluation of fatty acid amides in the carrageenan-induced paw edema model.

PubMed

Wise, Laura E; Cannavacciulo, Roberta; Cravatt, Benjamin F; Martin, Billy F; Lichtman, Aron H

2008-01-01

While it has long been recognized that Delta(9)-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, and other cannabinoid receptor agonists possess anti-inflammatory properties, their well known CNS effects have dampened enthusiasm for therapeutic development. On the other hand, genetic deletion of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of fatty acid amides, including endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA), N-palmitoyl ethanolamine (PEA), N-oleoyl ethanolamine (OEA), and oleamide, also elicits anti-edema, but does not produce any apparent cannabinoid effects. The purpose of the present study was to investigate whether exogenous administration of FAAs would augment the anti-inflammatory phenotype of FAAH (-/-) mice in the carrageenan model. Thus, we evaluated the effects of the FAAs AEA, PEA, OEA, and oleamide in wild-type and FAAH (-/-) mice. For comparison, we evaluated the anti-edema effects of THC, dexamethasone (DEX), a synthetic glucocorticoid, diclofenac (DIC), a nonselective cyclooxygenase (COX) inhibitor, in both genotypes. A final study determined if tolerance to the anti-edema effects of PEA occurs after repeated dosing. PEA, THC, DEX, DIC elicited significant decreases in carrageenan-induced paw edema in wild-type mice. In contrast OEA produced a less reliable anti-edema effect than these other drugs, and AEA and oleamide failed to produce any significant decreases in paw edema. Moreover, none of the agents evaluated augmented the anti-edema phenotype of FAAH (-/-) mice, suggesting that maximal anti-edema effects had already been established. PEA was the most effective FAA in preventing paw edema and its effects did not undergo tolerance. While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay.

Marine bioactive compounds: stereospecific anti-inflammatory activity of natural and synthetic cordiachromene A.

PubMed

Benslimane, A F; Pouchus, Y F; Verbist, J F; Petit, J Y; Khettab, E N; Welin, L; Brion, J D

1992-01-01

A new synthesis is proposed for cordiachromene A (CCA), a bioactive component of the ascidian Aplidium antillense Gravier, using a method producing a racemic mixture. The anti-inflammatory activities of a natural extract and a chemically synthetic form of CCA were assessed in vivo by carrageenan-induced rat-paw edema. The activity of synthetic CCA was confirmed by a test on kaolin-induced granuloma in the rat. Strong activities were measured for both CCA, but comparison of results of the first test suggests that only the natural optically active isomer has an anti-inflammatory effect. CCA is similar to indomethacin in its effect on carrageenan-induced rat-paw edema and ten times as active as phenylbutazone.

Release of endogenous opioids following transcutaneous electric nerve stimulation in an experimental model of acute inflammatory pain.

PubMed

Sabino, George S; Santos, Cristiane M F; Francischi, Janetti N; de Resende, Marcos Antônio

2008-02-01

Transcutaneous electric nerve stimulation (TENS) is a noninvasive treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. The aim of the present study was to investigate the action mechanism of TENS at high (HF: 130 Hz) and low (LF: 10 Hz) frequencies in an inflammation model produced by the injection of carrageenan in rat paws (Cg; 250 microg). After carrageenan administration (0 time), either HF or LF TENS was applied to the inflamed paw of rats for 20 minutes, and hyperalgesia was assessed hourly using the modified Randall-Selitto method (1957). HF and LF TENS inhibited the carrageenan-induced hyperalgesia by 100%. Pretreatment of animals with intraplantar naltrexone (Nx; 50 microg) reversed the analgesic effect of the LF TENS but did not alter the effect of HF TENS. The application of HF and LF TENS to the contralateral paw reversed the hyperalgesia of the inflamed paw similar to that observed when TENS was applied to the inflamed paw. However, LF TENS presented a longer-lasting analgesic effect than HF TENS. Our data demonstrate that HF and LF TENS induced antihyperalgesia. We also report that the antihyperalgesia provoked by LF TENS is partially due to the local release of endogenous opioids. This study offers important information about physiotherapy practices aimed at pain relieving. TENS is a noninvasive treatment that promotes analgesia in acute and chronic inflammatory conditions. Scientists, patients, and the general population may benefit from this knowledge.

Anti-inflammatory activity of Achillea and Ruscus topical gel on carrageenan-induced paw edema in rats.

PubMed

Maswadeh, Hamzah M; Semreen, Mohammad H; Naddaf, Ahmad R

2006-01-01

The anti-inflammatory activity of Achillea and Ruscus extracts was studied in comparison with diclofenac sodium topical gel (diclosal Emulgel), using the carrageenan induced paw edema model in Albino rats. Gel formulation was prepared containing 6% of each extract in gel base, namely sodium carboxymethylcellulose (NaCMC). The kinetics of drug release from the prepared formulation was studied separately in each case. Results showed that the release follows the Higuchi square root equation. The pharmacological screening revealed that the percent reduction of edema for Achillea extract and Ruscus extract were 48.1% and 18.8%, respectively, while diclosal Emulgel produced 47% reduction of edema.

Anti-inflammatory and antinociceptive properties of blueberry extract (Vaccinium corymbosum).

PubMed

Torri, Eliane; Lemos, Marivane; Caliari, Vinícius; Kassuya, Cândida A L; Bastos, Jairo K; Andrade, Sérgio F

2007-04-01

Blueberries are among the edible fruits that are recognized best for their potential health benefits. The crude extract from Vaccinium corymbosum was assessed in anti-inflammatory and antinociceptive models. The crude hydroalcoholic extract was administered orally at doses of 100, 200 or 300 mg kg (-1) for all the assays. In the carrageenan test, the crude extract reduced rat paw oedema by 9.8, 28.5 and 65.9%, respectively. For the histamine assay, the reductions of oedema were 70.1, 71.7 and 81.9%, respectively. In the myeloperoxidase (MPO) assay, 300 mg kg (-1) crude extract produced a significant inhibition of the MPO activity, at 6 h and 24 h after injection of carrageenan, by 42.8 and 46.2%, respectively. With the granulomatous tissue assay dexamethasone displayed significant activity, whereas the blueberry extract was inactive. For the abdominal constriction test, inhibitions of 49.0, 54.5, 53.5%, respectively, were observed for the crude extract, and 61.4% for indometacin. In the formalin test, the crude extract (200 and 300 mg kg (-1)) and indometacin inhibited only the second phase by 36.2, 35.3 and 45.8%, respectively. Considering that the crude extract of blueberry displayed antinociceptive and anti-inflammatory activity, its consumption may be helpful for the treatment of inflammatory disorders.

Alpinia calcarata Roscoe: a potent antiinflammatory agent.

PubMed

Arawwawala, L D A M; Arambewela, L S R; Ratnasooriya, W D

2012-02-15

Alpinia calcarata Roscoe (Family: Zingiberaceae) rhizomes are often used in Sri Lankan traditional systems of medicine as a remedy for bronchitis, cough, respiratory ailments, diabetics, asthma and arthritis. Generally drugs that are used for arthritis have antinociceptive and antiinflammatory properties. However, validity of the antiinflammatory activity has not been scientifically investigated so far. Therefore, the aim of this study was to investigate the antiinflammatory potential of Alpinia calcarata rhizomes using hot water extract (AWE) and hot ethanolic extract (AEE). The antiinflammatory activity of Alpinia calcarata was evaluated by use of the carrageenan-induced paw oedema model in rats. In addition, the mechanism/s by which Alpinia calcarata is mediated the antinflammatory activity was assessed by determining its effects on (a) membrane stabilizing, (b) antihistamine and (c) prostaglandin synthesis inhibition activity. All the tested doses of AWE and AEE (250, 500, 750, and 1000 mg/kg) produced a significant (P≤0.05) inhibition of the inflammation, most pronounced at 4h after the injection of carrageenan. The antiinflammatory effect induced by 500 mg/kg of AEE was superior than the reference drug, indomethacin at 4h. Inhibition of histamine and prostaglandin synthesis production is probable mechanisms by which Alpinia calcarata mediates its antiinflammatory action. These findings rationalize the traditional usage of Alpinia calcarata as an antiinflammatory agent for the first time. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory effects of Scoparia dulcis L. and betulinic acid.

PubMed

Tsai, Jen-Chieh; Peng, Wen-Huang; Chiu, Tai-Hui; Lai, Shang-Chih; Lee, Chao-Ying

2011-01-01

The aims of this study intended to investigate the anti-inflammatory activity of the 70% ethanol extract from Scoparia dulcis (SDE) and betulinic acid on λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of SDE and betulinic acid was examined by detecting the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and malondialdehyde (MDA) in the edema paw tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. The betulinic acid content in SDE was detected by high performance liquid chromatography (HPLC). In the anti-inflammatory model, the results showed that SDE (0.5 and 1.0 g/kg) and betulinic acid (20 and 40 mg/kg) reduced the paw edema at 3, 4 and 5 h after λ-carrageenan administration. Moreover, SDE and betulinic acid affected the levels of COX-2, NO, TNF-α and IL1-β in the λ-carrageenan-induced edema paws. The activities of SOD, GPx and GRd in the liver tissue were increased and the MDA levels in the edema paws were decreased. It is suggested that SDE and betulinic acid possessed anti-inflammatory activities and the anti-inflammatory mechanisms appear to be related to the reduction of the levels of COX-2, NO, TNF-α and IL1-β in inflamed tissues, as well as the inhibition of MDA level via increasing the activities of SOD, GPx and GRd. The analytical result showed that the content of betulinic acid in SDE was 6.25 mg/g extract.

Mulberry extract supplements ameliorate the inflammation-related hematological parameters in carrageenan-induced arthritic rats.

PubMed

Kim, Ae-Jung; Park, Soojin

2006-01-01

Mulberry fruit (Morus Lhou Koidz.), a rich source of the major anthocyanin, cyanidin 3-glucoside (C3G), has traditionally been used for the treatment of inflammatory conditions including rheumatic arthritis. In this study, we evaluated the efficacy of orally administrated methanolic mulberry fruit extract (ME) in carrageenan-induced arthritic rats, based on previously observed in vitro antioxidant and anti-inflammatory activities. A significant attenuation of hind paw inflammation characterized by fluid accumulation, uric acid production, and rheumatoid factors induced by carrageenan was observed following the intake of both ME (50 mg/kg of body weight) and C3G (10 mg/kg of body weight). Moreover, alterations in hematological parameters such as serum triglyceride, high-density lipoprotein-cholesterol, and atherogenic index following carrageenan administration were partially reversed by the administration of ME. It is concluded that dietary mulberry fruit extracts elicited protection against carrageenan-induced inflammation.

Calycophyllum spruceanum BENTH ameliorates acute inflammation in mice.

PubMed

da Silva, Ana Paula Azevedo Barros; Amorim, Renata Morais Ferreira; de Freitas Lopes, Roberta; Mota, Mário Rogério Lima; da Silva, Felipe Moura Araújo; Koolen, Hector Henrique Ferreira; Lima, Emerson Silva; Assreuy, Ana Maria S; da Cunha, Renildo Moura

2018-06-12

Calycophyllum spruceanum (Benth.) Hook. F. ex K. Schum. is widely distributed in the Amazonian region of Brazil, where it is popularly known as "mulateiro", "pau-mulato", "pau-mulato-de-várzea", "escorrega-macaco" or "pau-marfim". Preparations of C. spruceanum barks are used in the form of tea, poultice or skin patches to treat stomach diseases, skin inflammation and uterus tumors. To investigate in vivo the antinociceptive and anti-inflammatory activities of the hydroalcoholic extract of Calycophyllum spruceanum barks (HECSb) in order to validate its popular usage in inflammatory conditions. Chemical analysis of HECSb was performed using the UHPLC-MS system. Mice were treated per oral with HECSb (5-5000 mg/kg) and evaluated for acute toxicity (during 15 days); motor activity (Rota rod test); body weight (up to 72 h); antinociceptive activity: writhes induced by 0.8% acetic acid; paw licking induced by 2.5% formalin; paw withdrawal (von Frey test) induced by carrageenan (300 μg) or PGE2 (100 ng); anti-inflammatory (paw edema model). For histopathological analysis subplantar tissue fragments were collected 1 h after paw edema induction. HECSb chemical analysis revealed the presence of caffeoylquinic derivatives, small organic acids, and phenolic compounds. HECSb showed antinociceptive effect, reducing the number of acetic acid-induced writhes by 72% at 120 mg/kg, paw licking (phase 2- Formalin test) by 33% at 60 mg/kg and 49% at 120 mg/kg; and paw withdrawal elicited by carrageenan (53% at 120 mg/kg) and PGE2 (120 mg/kg) at 0.5 h (48%) and 1 h (45%). HECSb (120 mg/kg) also inhibited the paw edema elicited both by carrageenan (48%) and PGE2 (92%). Histopathological analysis (leukocyte infiltration, edema, focal areas of hemorrhage, vascular congestion) of HECSb treatment at 120 mg/kg demonstrated normal morphology [median 0 (0,1)] compared to PGE2, showing severe alterations [median 3 (2,3); p = 0,0035]. HECSb did not induce acute toxicity nor altered body mass or motor coordination. HECSb shows antinociceptive and anti-inflammatory effect in mice without inducing apparent acute toxicity. Copyright © 2018 Elsevier B.V. All rights reserved.

Antinociceptive and anti-inflammatory effects of rosmarinic acid isolated from Thunbergia laurifolia Lindl.

PubMed

Boonyarikpunchai, Wanvisa; Sukrong, Suchada; Towiwat, Pasarapa

2014-09-01

Rosmarinic acid (RA) was isolated from an ethanolic extract of Thunbergia laurifolia leaves. The antinociceptive activity of RA was assessed in mice using hot-plate, acetic acid-induced writhing, and formalin tests. The anti-inflammatory effects of RA were determined in two mouse models of carrageenan-induced paw edema and cotton pellet-induced granuloma formation. Orally administered RA (50, 100, and 150 mg/kg) showed significant (p<0.001) antinociceptive activity in the hot-plate test and this effect was reversed by naloxone. RA at doses of 50 and 100mg/kg significantly reduced acetic acid-induced writhing by 52% (p<0.01) and 85% (p<0.001), respectively, and RA at 100mg/kg also caused significant inhibition of formalin-induced pain in the early and late phases (p<0.01 and p<0.001, respectively). RA at 100mg/kg significantly suppressed carrageenan-induced paw edema at 3, 4, 5 and 6h after carrageenan injection (p<0.01, p<0.05 p<0.01, and p<0.05, respectively) and showed significant activity against PGE2-induced paw edema. RA at 100mg/kg also inhibited cotton pellet-induced granuloma formation in mice. Taken together, these results demonstrate that RA possesses both central and peripheral antinociceptive activities and has anti-inflammatory effects against acute and chronic inflammation. While further evaluation regarding the safety profile of RA is needed, these data may provide a basis for the rational use of RA and T. laurifolia for treatment of pain and inflammatory disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

PubMed

Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

2014-06-01

Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation. Finally, multiple mechanisms, including the inhibition of the production of inflammatory mediators and activation of endogenous opioid pathways, may mediate azadirachtin activities in experimental models of inflammation and pain. Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of fatty acid amides in the carrageenan-induced paw edema model

PubMed Central

Wise, Laura E.; Cannavacciulo, Roberta; Cravatt, Benjamin F.; Martin, Billy F.; Lichtman, Aron H.

2008-01-01

While it has long been recognized that Δ9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis, and other cannabinoid receptor agonists possess anti-inflammatory properties, their well known CNS effects have dampened enthusiasm for therapeutic development. On the other hand, genetic deletion of fatty acid amide hydrolase (FAAH), the enzyme responsible for degradation of fatty acid amides, including endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA), N-palmitoyl ethanolamine (PEA), N-oleoyl ethanolamine (OEA), and oleamide, also elicits anti-edema, but does not produce any apparent cannabinoid effects. The purpose of the present study was to investigate whether exogenous administration of FAAs would augment the anti-inflammatory phenotype of FAAH (-/-) mice in the carrageenan model. Thus, we evaluated the effects of the FAAs AEA, PEA, OEA, and oleamide in wild-type and FAAH (-/-) mice. For comparison, we evaluated the anti-edema effects of THC, dexamethasone (DEX), a synthetic glucocorticoid, diclofenac (DIC), a nonselective cyclooxygenase (COX) inhibitor, in both genotypes. A final study determined if tolerance to the anti-edema effects of PEA occurs after repeated dosing. PEA, THC, DEX, DIC elicited significant decreases in carrageenan-induced paw edema in wild type mice. In contrast OEA produced a less reliable anti-edema effect than these other drugs, and AEA and oleamide failed to produce any significant decreases in paw edema. Moreover, none of the agents evaluated augmented the anti-edema phenotype of FAAH (-/-) mice, suggesting that maximal anti-edema effects had already been established. PEA was the most effective FAA in preventing paw edema and its effects did not undergo tolerance. While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay. PMID:17675189

Evaluation of in vivo and in vitro biological activities of different extracts of Cuscuta arvensis.

PubMed

Koca, Ufuk; Küpeli-Akkol, Esra; Sekeroglu, Nazim

2011-10-01

In the present study, the potential effects of extracts from the whole plant of Cuscuta arvensis were studied in mice using the carrageenan-induced hind paw edema model for antiinflammatory activity and the p-benzoquinone-induced writhing reflex for the assessment of antinociceptive activity. In order to obtain the extracts, the whole plant of C. arvensis was extracted with different solvents such as n-hexane, dichloromethane, ethyl acetate, methanol and distilled water. Antioxidant activity was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The methanolic and water extracts inhibited the carrageenan-induced paw edema and p-benzoquinone-induced writhing reflex, whereas the other extracts showed only mild inhibitory antinociceptive and antiinflammatory activities in these in vivo models. Additionally, the methanol and ethyl acetate extracts had higher scavenging ability then the non polar extracts.

IN VIVO ANTI-INFLAMMATORY EFFECTS OF TARAXASTEROL AGAINST ANIMAL MODELS

PubMed Central

Wang, Ying; Li, Guan-Hao; Liu, Xin-Yu; Xu, Lu; Wang, Sha-Sha; Zhang, Xue-Mei

2017-01-01

Background: Traditional Chinese medicine Taraxacum officinale has been widely used to treat various inflammatory diseases. Taraxasterol is one of the main active components isolated from Taraxacum officinale. Recently, we have demonstrated that taraxasterol has the in vitro anti-inflammatory effects. This study aims to determine the in vivo anti-inflammatory effects of taraxasterol against animal models. Materials and Methods: Anti-inflammatory effects were assessed in four animal models by using dimethylbenzene-induced mouse ear edema, carrageenan-induced rat paw edema, acetic acid-induced mouse vascular permeability and cotton pellet-induced rat granuloma tests. Results: Our results demonstrated that taraxasterol dose-dependently attenuated dimethylbenzene-induced mouse ear edema and carrageenan-induced rat paw edema, decreased acetic acid-induced mouse vascular permeability and inhibited cotton pellet-induced rat granuloma formation. Conclusion: Our finding indicates that taraxasterol has obvious in vivo anti-inflammatory effects against animal models. It will provide experimental evidences for the traditional use of Taraxacum officinale and taraxasterol in inflammatory diseases. PMID:28480383

Anti-thrombotic and anti-inflammatory activities of protopine.

PubMed

Saeed, S A; Gilani, A H; Majoo, R U; Shah, B H

1997-07-01

The effects of protopine on human platelet aggregation and arachidonic acid (AA) metabolism via cyclooxygenase (COX) and lipoxygenase (LOP) enzymes were examined. Platelet aggregation induced by various platelet agonists (AA, ADP, collagen and PAF) was strongly inhibited by protopine in a concentration-related manner. The IC50 values (microM) of protopine (mean +/- SEM) against: AA; 12 +/- 2: ADP; 9 +/- 2: collagen; 16 +/- 2 and PAF; 11 +/- 1, were much less than those observed for aspirin. In addition, protopine selectively inhibited the synthesis of thromboxane A2 (TXA2) via COX pathway and had no effect on the LOP pathway in platelets. In vivo, pretreatment with protopine (50-100 mg kg-1) protected rabbits from the lethal effects of AA (2 mg kg-1) or PAF (11 micrograms kg-1) in dose-dependent fashion. Protopine (50-100 mg kg-1) also inhibited carrageenan-induced rat paw oedema with a potency of three-fold as compared to aspirin. These results are suggestive that protopine acts as a potent inhibitor of thromboxane synthesis and PAF with anti-inflammatory properties.

Fucoxanthin Inhibits the Inflammation Response in Paw Edema Model through Suppressing MAPKs, Akt, and NFκB.

PubMed

Choi, Jun-Hui; Kim, Na-Hyun; Kim, Sung-Jun; Lee, Hyo-Jeong; Kim, Seung

2016-03-01

Undaria pinnatifida is a well-known traditional Korean food with a variety of biological activities. Carrageenan (carr) is commonly used to induce paw edema in animal models. This study was designed to elucidate the processes underlying the anti-inflammatory effect of fucoxanthin isolated from the sporophyll of U. pinnatifida in carr-induced paw edema in ICR mice. Fucoxanthin significantly decreased carr-induced increased nitric oxide levels in the plasma of mice with carr-induced paw edema. Fucoxanthin protected catalase (CAT) and superoxide dismutase (SOD) activity against disruption in mice with carr-induced paw edema. In addition, fucoxanthin repressed carr-induced activation of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa B, as well as carr-induced phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and protein kinase B/Akt. These results suggest that fucoxanthin may have therapeutic potential as a treatment for patients with inflammatory diseases. © 2015 Wiley Periodicals, Inc.

Inhibition of pro-inflammatory mediators: role of Bacopa monniera (L.) Wettst.

PubMed

Viji, Vijayan; Helen, Antony

2011-10-01

Bacopa monniera (L.) Wettst is a renowned plant in the Ayurvedic system of medicine. The present study seeks to identify the anti-inflammatory activity of two fractions from the methanolic extract of Bacopa, viz. the triterpenoid and bacoside-enriched fractions. The ability of these two fractions to inhibit the production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 was tested using lipopolysaccharide (LPS)-activated peripheral blood mononuclear cells and peritoneal exudate cells in vitro. We found that triterpenoid and bacoside-enriched fractions significantly inhibited LPS-activated TNF-α, IL-6 and nitrite production in mononuclear cells. Significant antioxidant activity was exhibited by the bacoside enriched fraction compared to the triterpenoid fraction. Carrageenan-induced hind paw oedema assay revealed that triterpenoid and bacoside-enriched fractions exerted anti-oedematogenic effect, while in the arthritis model only the triterpenoid fraction exerted an anti-arthritic potential. The present study provides an insight into the ability of Bacopa monniera to inhibit inflammation through modulation of pro-inflammatory mediator release.

Synthesis of novel 1,2,3-triazole based benzoxazolinones: their TNF-α based molecular docking with in-vivo anti-inflammatory, antinociceptive activities and ulcerogenic risk evaluation.

PubMed

Haider, Saqlain; Alam, M Sarwar; Hamid, Hinna; Shafi, Syed; Nargotra, Amit; Mahajan, Priya; Nazreen, Syed; Kalle, Arunasree M; Kharbanda, Chetna; Ali, Yakub; Alam, Aftab; Panda, Amulya K

2013-01-01

A library of novel bis-heterocycles containing benzoxazolinone based 1,2,3-triazoles has been synthesized using click chemistry approach. The compound 3f exhibited potent selective COX-2 inhibition of 59.48% in comparison to standard drug celecoxib (66.36% inhibition). The compound 3i showed significant (p < 0.001, 50.95%), TNF-α inhibitory activity as compared to indomethacin (p < 0.001, 64.01%). The results of the carrageenan induced hind paw oedema showed that compounds 3a, 3f, 3i, 3o, and 3e exhibited potent anti-inflammatory activity in comparison to Indomethacin. The molecular docking studies revealed that 3i exhibits strong inhibitory effect due to the extra stability of the complex because of an extra π-π bond. The histopathology report showed that none of the compounds caused gastric ulceration. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Synthesis, analgesic, anti-inflammatory and anti-ulcerogenic activities of certain novel Schiff's bases as fenamate isosteres.

PubMed

Alafeefy, Ahmed M; Bakht, Mohammed A; Ganaie, Majid A; Ansarie, Mohd N; El-Sayed, Nahed N; Awaad, Amani S

2015-01-15

A series of certain novel Schiff bases as fenamate isosteres (VI:a-k) were synthesized to locate analgesic, anti-inflammatory agent with minimal ulcerogenic potential. The structures of the newly synthesized compounds were elucidated on the basis of their elemental analysis as well as IR, and NMR and mass spectroscopic data. All the compounds were evaluated for their anti-inflammatory activity by carrageenan induced paw oedema method. The compounds possessing good anti-inflammatory activity were further tested for analgesic, ulcerogenic, lipid peroxidation potentials and liver toxicity. Compounds (VI-c), (VI-f), (VI-h) and (VI-i) showed the best anti-inflammatory and significant analgesic activities at doses comparable to that of the standard drug Indomethacin. However, compounds (VI-c) and (VI-f) could be considered the most potent anti-inflammatory and analgesic molecules with maximum reduction in gastro-intestinal ulceration with no hepatocyte necrosis or liver degeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Xylopia aethiopica (Annonaceae) fruit extract suppresses Freund's adjuvant-induced arthritis in Sprague-Dawley rats.

PubMed

Obiri, David D; Osafo, Newman; Ayande, Patrick G; Antwi, Aaron O

2014-03-28

Xylopia aethiopica is used in a decoction of the dried fruit to treat bronchitis, asthma, arthritis, rheumatism, headache, neuralgia and colic pain. The aim of the study is to evaluate the anti-arthritic effects of a 70% aqueous ethanol extract of the fruit of Xylopia aethiopica in a chronic inflammatory model. Adjuvant arthritis was induced in Sprague-Dawley rats by intraplantar injection of Complete Freund's adjuvant into the right hind paw. Foot volume was measured by water displacement plethysmometry. The oedema component of inflammation was evaluated as the percentage change in paw swelling and the total oedema induced calculated as area under the time course curves. In addition to X-ray radiography, histopathology of ankle joints supported by haematological analysis was used to assess the anti-arthritic action of the extract of Xylopia aethiopica (XAE). Xylopia aethiopica extract (100, 300 and 600 mg kg(-1)) modified the time course curve significantly reducing hind paw oedema in the ipsilateral paw at all dose levels when administered both prophylactically and therapeutically. In addition XAE significantly suppressed the systemic spread of the arthritis from the ipsilateral to the contralateral limbs. The radiological pictures of the joints particularly metatarsal, phalanges and the ankle joint space of rats in the XAE-treated group showed protective effect against adjuvant-induced arthritis while histopathology revealed significant reduction in mononuclear infiltration, pannus formation and bone erosion. The haematological analysis in the test animals revealed significant improvement relative to the CFA model group. Xylopia aethiopica XAE suppresses joint inflammation and destruction in arthritic rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Gelam Honey Inhibits the Production of Proinflammatory, Mediators NO, PGE2, TNF-α, and IL-6 in Carrageenan-Induced Acute Paw Edema in Rats

PubMed Central

Hussein, Saba Zuhair; Mohd Yusoff, Kamaruddin; Makpol, Suzana; Mohd Yusof, Yasmin Anum

2012-01-01

Natural honey is well known for its therapeutic value and has been used in traditional medicine of different cultures throughout the world. The aim of this study was to investigate the anti-inflammatory effect of Malaysian Gelam honey in inflammation-induced rats. Paw edema was induced by a subplantar injection of 1% carrageenan into the rat right hind paw. Rats were treated with the nonsteroidal anti-inflammatory drug (NSAID) Indomethacin (10 mg/kg, p.o.) or Gelam honey at different doses (1 or 2 g/kg, p.o.). The increase in footpad thickness was considered to be edema, which was measured using a dial caliper. Plasma and paw tissue were collected to analyze the production of inflammatory mediators, such as NO, PGE2, TNF-α, and IL-6, as well as iNOS and COX-2. The results showed that Gelam honey could reduce edema in a dose-dependent fashion in inflamed rat paws, decrease the production of NO, PGE2, TNF-α, and IL-6 in plasma, and suppress the expression of iNOS, COX-2, TNF-α, and IL-6 in paw tissue. Oral pretreatment of Gelam honey at 2 g/kg of body weight at two time points (1 and 7 days) showed a significantly decreased production of proinflammatory cytokines, which was similar to the effect of the anti-inflammatory drug Indomethacin (NSAID), both in plasma and tissue. Thus, our results suggest that Gelam honey has anti-inflammatory effects by reducing the rat paw edema size and inhibiting the production of proinflammatory mediators. Gelam honey is potentially useful for treating inflammatory conditions. PMID:22919407

Ilex paraguariensis Promotes Orofacial Pain Relief After Formalin Injection: Involvement of Noradrenergic Pathway.

PubMed

de Carvalho, Eudislaine Fonseca; de Oliveira, Simone Kobe; Nardi, Viviane Koepp; Gelinski, Tathiana Carla; Bortoluzzi, Marcelo Carlos; Maraschin, Marcelo; Nardi, Geisson Marcos

2016-03-01

Drinking mate or chimarrão, a hot infusion of Ilex paraguariensis (ILEX) leaves, is a common habit in Southern South America that has a social and almost ritualistic role. It has been used as a stimulant beverage in South America and analgesic in regions of Argentina for treatment of headache and others painful inflammatory conditions such as arthritis and rheumatism. The aim of this study was to evaluate the pharmacological activity of I. paraguariensis infusion (ILEX) on orofacial nociception model induced by formalin, and study its mechanism of action. The analgesic effect of ILEX was assessed through writhing test, paw formalin test, paw edema induced by carrageenan, and orofacial pain induced by formalin. To study the action mechanism of ILEX, opioidergic, dopaminergic, nitrergic, and adrenergic pathways were investigated. The high-performance liquid chromatography analysis of ILEX infusion revealed caffeine and theobromine. The treatment with ILEX reduced the number of writhing. However, it was effective neither in the formalin paw test nor in the paw edema induced by carrageenan. Different from formalin paw test, ILEX was able to reduce the orofacial reactivity to formalin in 31.8% (70.4 ± 2.5 s; first phase), and 20% (127.3 ± 18.9 s; second phase). The analgesic effect of ILEX results from the modulation of noradrenergic pathways since prazosin (α1-adrenoceptor antagonist, 0.15 mg/kg; intraperitoneal) reversed the analgesic effect of ILEX. The present report demonstrates that analgesic effect of ILEX in orofacial formalin test is due mainly to modulation of noradrenergic pathways. Ilex paraguariensis (ILEX) has been used as a stimulant beverage in South America and analgesic in regions of Argentina for the treatment of headache and others painful inflammatory conditions such arthritis and rheumatism.The aim of this study was to evaluate the pharmacological activity of ILEX on orofacial nociception model induced by formalin, and study its mechanism of action.ILEX reduced the number of writhing and orofacial reactivity to formalin in mice. However, it was effective neither in the formalin paw test nor in the paw edema induced by carrageenan.The analgesic effect of ILEX results from the modulation of noradrenergic pathways. Abbreviation Used: ILEX: Infusion of Ilex paraguariensis, NSAIDs: Nonsteroidal anti-inflammatory drugs, L-NOARG: L-NG-nitro-arginine, UV: Ultraviolet, i.p.: Intraperitoneal, NOS: Nitric Oxide Synthase, Analysis of variance, S.E.M.: Standard error of mean, HPLC: High-performance liquid chromatography, NO: Nitric Oxide, v.o.: Oral route, DCQ: dicaffeoylquinic acid, BMS: Burning mouth syndrome, PBS: Phosphate-buffered saline.

Evaluation of the analgesic and anti-inflammatory effects of the essential oil of Lippia gracilis leaves.

PubMed

Mendes, S S; Bomfim, R R; Jesus, H C R; Alves, P B; Blank, A F; Estevam, C S; Antoniolli, A R; Thomazzi, S M

2010-06-16

The aim of the present study is to investigate the antinociceptive, anti-inflammatory, and antioxidant activities of essential oil (EO) of Lippia gracilis Schauer (Verbenaceae) leaves to support the medicinal uses claimed by folklore practitioners in the caatinga region (semi-arid) of Northeastern Brazil. The chemical composition and antinociceptive and anti-inflammatory activities of the EO of Lippia gracilis leaves (50-200 mg/kg) were investigated. Antinociceptive activity of the EO was evaluated by writhing test. Anti-inflammatory activity of the EO was evaluated using paw oedema and peritonitis methods. Oral treatment with the EO of Lippia gracilis leaves elicited inhibitory activity on acetic acid effect at 50, 100, and 200 mg/kg (30.33+/-2.36, 25.20+/-1.48, and 21.00+/-1.54 abdominal writhes, respectively, P<0.05), as compared with the control group (36.73+/-1.92 writhes). The compound acetylsalicylic acid (ASA, 300 mg/kg) inhibited the acetic acid-induced writhing (12.67+/-0.50 abdominal writhes, P<0.001). Carrageenan-induced oedema formation was reduced with the EO of Lippia gracilis leaves at 200 mg/kg (0.72+/-0.06 mL h, P<0.001) and by the reference compound ASA (300 mg/kg, 0.85+/-0.04 mL h, P<0.001), as compared with the control group (1.76+/-0.06 mL h). Leukocyte migration into the peritoneal cavity induced by carrageenan was reduced with the EO of Lippia gracilis leaves at 50, 100, and 200 mg/kg (13.81+/-0.61, 11.77+/-0.91, and 10.30+/-0.60 leukocytes x 10(6)/mL, respectively, P<0.01), and by the compound dexamethasone (2 mg/kg, 5.34+/-0.33 leukocytes x 10(6)/mL, P<0.001), as compared with the control group (16.71+/-0.54 leukocytes x 10(6)/mL). The analyses of the essential oil allowed the identification of Lippia gracilis as a thymol-p-cymene chemotype (32.68% and 17.82%, respectively). The EO of Lippia gracilis leaves shows antinociceptive and anti-inflammatory activities. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis.

PubMed

Bhatia, Saurabh; Sharma, Kiran; Sharma, Ajay; Nagpal, Kalpana; Bera, Tanmoy

2015-01-01

Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions.

Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis

PubMed Central

Bhatia, Saurabh; Sharma, Kiran; Sharma, Ajay; Nagpal, Kalpana; Bera, Tanmoy

2015-01-01

Objectives: Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). Materials and Methods: Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. Results: Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. Conclusions: The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions. PMID:25767759

Anti-Inflammatory Effect of Supercritical-Carbon Dioxide Fluid Extract from Flowers and Buds of Chrysanthemum indicum Linnén

PubMed Central

Li, Chu-Wen; Zhang, Xiao-Jun

2013-01-01

The aim of this study was to analyze the chemical composition and investigate the anti-inflammatory property of the supercritical-carbon dioxide extract from flowers and buds of C. indicum (CISCFE). The anti-inflammatory effect was evaluated in four animal models including xylene-induced mouse ear edema, acetic acid-induced mouse vascular permeability, carrageenan-induced mouse hind paw edema, and cotton pellet-induced rat granuloma formation. The results indicated that CISCFE significantly attenuated xylene-induced ear edema, decreased acetic acid-induced capillary permeability, reduced carrageenan-induced paw, and inhibited the cotton pellet-induced granuloma formation in a dose-dependent manner. Histopathologically, CISCFE abated inflammatory response of the edema paw. Preliminary mechanistic studies demonstrated that CISCFE decreased the MDA level via increasing the activities of anti-oxidant enzymes (SOD, GPx, and GRd), attenuated the productions of NF-κB, TNF-α, IL-1β, IL-6, PGE2 and NO, and suppressed the activities of iNOS and COX-2. In phytochemical study, 35 compounds were identified by GC-MS, and 5 compounds (chlorogenic acid, luteolin-7-glucoside, linarin, luteolin and acacetin) were reconfirmed and quantitatively determined by HPLC-PAD. This paper firstly analyzed the chemical composition by combining GC-MS with HPLC-PAD and explored possible mechanisms for the anti-inflammatory effect of CISCFE. PMID:24223056

Adenosine signalling mediates the anti-inflammatory effects of the COX-2 inhibitor nimesulide.

PubMed

Caiazzo, Elisabetta; Maione, Francesco; Morello, Silvana; Lapucci, Andrea; Paccosi, Sara; Steckel, Bodo; Lavecchia, Antonio; Parenti, Astrid; Iuvone, Teresa; Schrader, Jürgen; Ialenti, Armando; Cicala, Carla

2016-07-15

Extracellular adenosine formation from ATP is controlled by ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) and ecto-5'-nucleotidase (e-5NT/CD73); the latter converts AMP to adenosine and inorganic phosphate, representing the rate limiting step controlling the ratio between extracellular ATP and adenosine. Evidence that cellular expression and activity of CD39 and CD73 may be subject to changes under pathophysiological conditions has identified this pathway as an endogenous modulator in several diseases and was shown to be involved in the molecular mechanism of drugs, such as methotrexate, salicylates , interferon-β. We evaluated whether CD73/adenosine/A2A signalling pathway is involved in nimesulide anti-inflammatory effect, in vivo and in vitro. We found that the adenosine A2A agonist, 4-[2-[[6-amino-9-(N-ethyl-β-d-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride (CGS21680, 2mg/kg ip.), inhibited carrageenan-induced rat paw oedema and the effect was reversed by co-administration of the A2A antagonist -(2-[7-amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol (ZM241385; 3mg/kg i.p.). Nimesulide (5mg/kg i.p.) anti-inflammatory effect was inhibited by pre-treatment with ZM241385 (3mg/kg i.p.) and by local administration of the CD73 inhibitor, adenosine 5'-(α,β-methylene)diphosphate (APCP; 400μg/paw). Furthermore, we found increased activity of 5'-nucleotidase/CD73 in paws and plasma of nimesulide treated rats, 4h following oedema induction. In vitro, the inhibitory effect of nimesulide on nitrite and prostaglandin E2 production by lipopolysaccharide-activated J774 cell line was reversed by ZM241385 and APCP. Furthermore, nimesulide increased CD73 activity in J774 macrophages while it did not inhibit nitrite accumulation by lipopolysaccharide-activated SiRNA CD73 silenced J774 macrophages. Our data demonstrate that the anti-inflammatory effect of nimesulide in part is mediated by CD73-derived adenosine acting on A2A receptors. Copyright © 2016 Elsevier Inc. All rights reserved.

Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt.

PubMed

Arora, Priyanka; Mukherjee, Biswajit

2002-09-01

In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied. Copyright 2002 Wiley-Liss, Inc.

Anti-inflammatory activity of Ambrosia artemisiaefolia and Rhoeo spathacea.

PubMed

Pérez G, R M

1996-09-01

Alcoholic extracts of the leaves of Ambrosia artemisiaefolia and Rhoeo spathacea have been investigated for anti-inflammatory activity using various experimental models of inflammation (croton oil ear oedema, carrageenan-induced edema, cotton pellet granuloma and formaldehyde induced arthritis) and the results compared with phenylbutazone and bethamethasone, standard anti-inflammatory drugs. These extracts at doses of 50, 100 and 150mg/kg of A. artemisiaefolia and R. spathacea, showed significant inhibition of acute oedema in rats and mice induced by the phlogistic agents, carrageenan and croton oil, in a dose-dependant manner. The ethanol extracts reduced cotton pellet granuloma and caused a statistically significant inhibitory effect on edema in the chronic model of formaldehyde arthritis in rats. Since Ambrosia artemisiaefolia and Rhoeo spathacea were found to be effective in both acute and chronic phases of inflammation they can be considered as general anti-inflammatory agents. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

Anti-inflammatory activity of Bromelia hieronymi: comparison with bromelain.

PubMed

Errasti, María E; Caffini, Néstor O; Pelzer, Lilian E; Rotelli, Alejandra E

2013-03-01

Some plant proteases (e. g., papain, bromelain, ficin) have been used as anti-inflammatory agents for some years, and especially bromelain is still being used as alternative and/or complementary therapy to glucocorticoids, nonsteroidal antirheumatics, and immunomodulators. Bromelain is an extract rich in cysteine endopeptidases obtained from Ananas comosus. In this study the anti-inflammatory action of a partially purified extract of Bromelia hieronymi fruits, whose main components are cysteine endopeptidases, is presented. Different doses of a partially purified extract of B. hieronymi were assayed on carrageenan-induced and serotonine-induced rat paw edema, as well as in cotton pellet granuloma model. Doses with equal proteolytic activity of the partially purified extract and bromelain showed significantly similar anti-inflammatory responses. Treatment of the partially purified extract and bromelain with E-64 provoked loss of anti-inflammatory activity on carrageenan-induced paw edema, a fact which is consistent with the hypothesis that the proteolytic activity would be responsible for the anti-inflammatory action. Georg Thieme Verlag KG Stuttgart · New York.

Antioedematous and Analgesic Properties of Fertile Fronds of Drynaria quercifolia

PubMed Central

Anuja, G. I.; Latha, P. G.; Shine, V. J.; Suja, S. R.; Shikha, P.; Satheesh Kumar, K.; Rajasekharan, S.

2014-01-01

Inflammation is a complex biological response of tissue cells to harmful stimuli including trauma, tissue necrosis, and infections which plays a key role in the pathophysiology of many deadly diseases. In ethnomedicine Drynaria quercifolia fronds are used to treat inflammation as poultice on swellings and as antibacterial, hepatoprotective, and antipyretic agent. Herein, we have evaluated the antioedematous, antiproliferative, and analgesic properties of the ethanolic extract of fertile fronds of D. quercifolia (FF) by standard procedures. Oral administration of FF produced significant inhibition of carrageenan and histamine induced paw oedema in Wistar rats. FF significantly reduced both wet weight and dry weight of granuloma tissue which shows the inhibitory effect on exudative and proliferative phases of inflammation. FF significantly attenuated acute and delayed phases of formalin induced pain, acetic acid-induced writhing, capsaicin-induced nociception, and hot plate test in mice. Phytochemical analysis revealed the presence of coumarins, flavonoids, glycosides, phenolics, saponins, steroids, tannins, and terpenoids. Total phenolic content was 186 mg/g equivalent of gallic acid. The HPLC estimation showed flavanone glycoside naringin (1.2%) and its aglycone naringenin (0.02%). The presence of potent anti-inflammatory and analgesic principles in FF and their synergistic action may be the reason for the proposed therapeutic effects. PMID:24575313

Anti-inflammatory, analgesic and antipyretic effects of Lepidagathis anobrya Nees (Acanthaceae).

PubMed

Richard, Sawadogo Wamtinga; Marius, Lompo; Noya, Somé; Innocent Pierre, Guissou; Germaine, Nacoulma-Ouedraogo Odile

2011-01-01

This study investigated the general acute, anti-inflammatory, analgesic and antipyretic effects of methanol extract of Lepidagathis anobrya Nees (Acanthaceae). Carrageenan-induced rat paw edema and croton oil-induced ear edema in rats were used for the evaluation of general acute anti-inflammatory effects. Acetic acid-induced writhing response and yeast-induced hyperpyrexia in mice were used to evaluate the analgesic and antipyretic activities respectively. The extract at doses of 10, 25, 50 and 100 mgkg(-1) for carrageenan test and doses of 0.5 mg/ear for croton oil test induced a significant reduction (p < 0.001) of paw and ear edemas in rats. In the analgesic and antipyretic tests, the extract has shown a significant inhibition of writhes and hyperpyrexia with all the doses used when compared to the untreated control group. These results clearly show the anti-inflammatory, analgesic and antipyretic effects of the methanol extract of Lepidagathis anobrya and give the scientific basis for its traditional use. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.

Evaluation of antinociceptive and anti-inflammatory properties of methanolic crude extract of Lophopetalum javanicum (bark).

PubMed

Ansari, Prawej; Badhan, Sanjeeda Sarmin; Azam, Shofiul; Sultana, Nasrin; Anwar, Sabbir; Mohamed Abdurahman, Mohamed Sheikh; Hannan, J M A

2016-06-01

The aim of the current study was to investigate the scientific basis of the traditional application of Lophopetalum javanicum for measuring anti-inflammatory and analgesic activity and phytochemical screening. Present study includes the preliminary screening of the phytochemical composition and in vivo analgesic and anti-inflammatory activity of methanolic extract of L. javanicum (MELJ). Hot-plate test and tail immersion method were used to investigate acute analgesic effects of L. javanicum, and the potency in inhibition of chronic inflammation in mice was tested by carrageenan-induced paw edema and formalin-induced edema method. One hour after the administration of carrageenan, rat's paw was inflamed, and after treating it with 500 mg/kg dose, increase in the significant inhibitory effect on paw was observed. At the third hour after carrageenan injection, extreme inhibition (55.61%±0.015%; p<0.001) resulted by methanolic extract. By using hot plate method, it was found that L. javanicum increases pain tolerance time up to 17.89±0.079 min, whereas the compared standard's interval was 21.48±0.397 min. In tail immersion method, the pain threshold was 3.02±0.074 (p<0.001) at 400 mg/kg by L. javanicum at 90 min of experiment. This study manifested that the methanolic extract of L. javanicum is efficient in inhibiting pain mediators to release, and conceivably, this report should get priority while searching for a new analgesic and anti-inflammatory agent.

Anti-Inflammatory and Antimicrobial Properties of Flavonoids from Heliotropium subulatum Exudate.

PubMed

Singh, Bharat; Sharma, Ram A

2015-01-01

Heliotropium subulatum is an erect or procumbent perennial herb; leaves contain foliar trichomes and its resinous exudate is used in traditional medicine. The anti-inflammatory activity of dichloromethane fraction and isolated flavonoids was evaluated by using carrageenan and CFA-induced paw oedema models. Similarly, the disc diffusion and microdilution methods were used for the assessment of antimicrobial activity. Five isolated flavonoids were investigated for their antiinflammatory and antimicrobial activities. Eriodictyol demonstrated maximum anti-inflammatory activity (53.09%) at 30.0 mg/kg dose on 6(th) h and similarly, it inhibited the CFA-induced arthritis swelling (41.84%) with 30.0 mg/kg dose on 8(th) day respectively. As per disc diffusion and microdilution methods used for antimicrobial activity determination, the pinocembrin was found to be most active against Staphylococcus aureus (IZ=27±0.7 mm, 08 μg/ml dose) and Candida albicans (IZ=17±0.9 mm; 12 μg/ml dose). These investigated results revealed that the eriodictyol and pinocembrin showed significant anti-inflammatory and antimicrobial activities. Further studies which aimed to investigate the mechanism of action of these isolated flavonoids in the treatment of inflammations and various types of infections have been initiated.

Anti-inflammatory and antioxidant activities of ethanolic extract of aerial parts of Vernonia patula (Dryand.) Merr.

PubMed Central

Hira, Arpona; Dey, Shubhra Kanti; Howlader, Md. Sariful Islam; Ahmed, Arif; Hossain, Hemayet; Jahan, Ismet Ara

2013-01-01

Objective To investigate the inflammatory and antioxidant activities of ethanolic extract of aerial part of Vernonia patula (Dryand.) Merr (EAV). Methods The anti-inflammatory activity of EAV was studied using carrageenan and histamine-induced rat paw edema test at different doses (100, 200 and 400 mg/kg body weight). DPPH free radical scavenging, nitric oxide scavenging, reducing power and Fe2+ ion chelating ability were used for determining antioxidant activities. Results The EAV, at the dose of 400 mg/kg, showed a significant anti-inflammatory activity (P<0.01) both in the carrageenan and histamine-induced oedema test models in rats, showing 62.86% and 64.42% reduction in the paw volume comparable to that produced by the standard drug indomethacin (67.26% and 66.01%) at 5 h respectively. In DPPH free radical scavenging test, IC50 value for EAV was found fairly significant 36.59 µg/mL when compared to the IC50 value of the reference standards ascorbic acid 8.97 µg/mL. The IC50 values of the extract and ascorbic acid were 47.72 and 12.39 µg/mL, respectively in nitric oxide scavenging assay. The IC50 value of the EAV (33.59 µg/mL) as percentage of Fe2+ ion chelating ability was also found significant compared to that of EDTA (9.16 µg/mL). The maximum absorbance for reducing power assay was found to be 1.928 at 100 µg/mL when compared to 2.449 for standard ascorbic acid. The total phenolic content was 198.81 mg/g of gallic acid equivalent. Acute toxicity test showed that the plant might be safe for pharmacological uses up to a dose level of 3 200 mg/kg of body weight in rats. Conclusions Therefore, the obtained results suggest the acute anti-inflammatory and antioxidant activities of the EAV and thus provide the scientific basis for the traditional uses of this plant part as a remedy for inflammations. PMID:24075345

Antioxidant, antinociceptive and anti-inflammatory properties of the aqueous and ethanolic leaf extracts of Andrographis paniculata in some laboratory animals.

PubMed

Adedapo, Adeolu Alex; Adeoye, Bisi Olajumoke; Sofidiya, Margaret Oluwatoyin; Oyagbemi, Ademola Adetokunbo

2015-07-01

The study was designed to evaluate the anti-inflammatory, analgesic and antioxidant properties of Andrographis paniculata leaf extracts in laboratory animals. The dried and powdered leaves of the plant were subjected to phytochemical and proximate analyses. Its mineral content was also determined. Acute toxicity experiments were first performed to determine a safe dose level. The plant material was extracted using water and ethanol as solvents. These extracts were then used to test for the anti-inflammatory, analgesic and antioxidant properties of the plant. The anti-inflammatory tests included carrageenan-induced and histamine-induced paw oedema. The analgesic tests conducted were formalin paw lick test and acetic acid writhing test. The antioxidant activities of the extracts of A. paniculata were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), total polyphenol (TP) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) using ascorbic acid as standard for both DPPH and FRAP, and gallic acid as a standard for both TP and ABTS. The acute toxicity experiment demonstrated that the plant is safe at high doses even at 1600 mg/kg. It was observed that the ethanolic extract of A. paniculata had higher antioxidant activity than the aqueous extract. The experiments using both extracts may suggest that the extracts of A. paniculata leaves possess anti-inflammatory, analgesic and antioxidant properties, although the ethanolic extract seemed to have higher biological properties than the aqueous extract. The results from this study may have justified the plant's folkloric use for medicinal purpose.

Analgesic activity of a triterpene isolated from Scoparia dulcis L. (Vassourinha).

PubMed

Freire, S M; Torres, L M; Roque, N F; Souccar, C; Lapa, A J

1991-01-01

Analgesic and anti-inflammatory activities of water (WE) and ethanolic (EE) extracts of Scoparia dulcis L. were investigated in rats and mice, and compared to the effects induced by Glutinol, a triterpene isolated by purification of EE. Oral administration (p.o.) of either WE or EE (up to 2 g/kg) did not alter the normal spontaneous activity of mice and rats. The sleeping time induced by sodium pentobarbital (50 mg/kg, i.p.) was prolonged by 2 fold in mice pretreated with 0.5 g/kg EE, p.o. Neither extract altered the tail flick response of mice in immersion test, but previous administration of EE (0.5 g/kg, p.o.) reduced writhings induced by 0.8% acetic acid (0.1 ml/10 g, i.p.) in mice by 47%. EE (0.5 and 1 g/kg, p.o.) inhibited the paw edema induced by carrageenan in rats by respectively 46% and 58% after 2 h, being ineffective on the paw edema induced by dextran. No significant analgesic or anti-edema effects were detected in animals pretreated with WE (1 g/kg, p.o.). Administration of Glutinol (30 mg/kg, p.o.) reduced writhing induced by acetic acid in mice by 40% and the carrageenan induced paw edema in rats by 73%. The results indicate that the analgesic activity of S. dulcis L. may be explained by an anti-inflammatory activity probably related to the triterpene Glutinol.

Analgesic and anti-inflammatory effects of Mangifera indica L. extract (Vimang).

PubMed

Garrido, G; González, D; Delporte, C; Backhouse, N; Quintero, G; Núñez-Sellés, A J; Morales, M A

2001-02-01

Vimang is an aqueous extract of Mangifera indica used in Cuba to improve the quality of life in patients suffering from elevated stress. To assess its possible analgesic and antiinflammatory effects, the results of a standard extract evaluation are presented. Analgesia was determined using acetic acid-induced abdominal constriction and formalin-induced licking. Antiinflammatory effects were evaluated using carrageenan- and formalin-induced oedema. Vimang (50-1000 mg/kg, p.o.) exhibited a potent and dose-dependent antinociceptive effect against acetic acid test in mice. The mean potency (DE(50)) was 54.5 mg/kg and the maximal inhibition attained was 94.4%. Vimang (20-1000 mg/kg, p.o.) dose-dependently inhibited the second phase of formalin-induced pain but not the first phase. The DE(50) of the second phase was 8.4 mg/kg and the maximal inhibition was 99.5%, being more potent than indomethacin at doses of 20 mg/kg. Vimang (20-1000 mg/kg, p.o.) significantly inhibited oedema formation (p < 0.01 or p < 0.05) of both carrageenan- and formalin-induced oedema in rat, guinea-pigs and mice (maximal inhibitions: 39.5, 45.0 and 48.6, respectively). The inhibitions were similar to those produced by indomethacin and sodium naproxen, p.o. The different polyphenols found in Vimang could account for the antinociceptive and antiinflammatory actions reported here for the first time for M. indica bark aqueous extract. Copyright 2001 John Wiley & Sons, Ltd.

Pharmacology of a selective cyclooxygenase-2 inhibitor, HN-56249: a novel compound exhibiting a marked preference for the human enzyme in intact cells.

PubMed

Berg, J; Fellier, H; Christoph, T; Kremminger, P; Hartmann, M; Blaschke, H; Rovensky, F; Towart, R; Stimmeder, D

2000-04-01

HN-56249 (3-(2,4-dichlorothiophenoxy)-4-methylsulfonylamino-benzenesu lfonamide), a highly selective cyclooxygenase (COX)-2 inhibitor, is the prototype of a novel series of COX inhibitors comprising bicyclic arylethersulfonamides; of this series HN-56249 is the most potent and selective human COX-2 inhibitor. HN-56249 inhibited platelet aggregation as a measure of COX-1 activity only moderately (IC50 26.5+/-1.7 microM). In LPS-stimulated monocytic cells the release of prostaglandin (PG) F1alpha as a measure of COX-2 was markedly inhibited (IC50 0.027+/-0.001 microM). Thus, HN-56249 showed an approximately 1000-fold selectivity for COX-2 in intact cells. In whole blood assays HN-56249 showed a potent inhibitory activity for COX-2 (IC50 0.78+/-0.37 microM) only. COX-1 was only weakly inhibited (IC50 867+/-181 microM). Hence, HN-56249 exhibited a greater than 1000-fold selectivity for whole blood COX-2. HN-56249 surpassed the COX-2 selectivities of the COX-2 selective inhibitors 3-cyclohexyloxy-4-methylsulfonylamino-nitrobenzene (NS-398) and 6-(2,4-difluorophenoxy)-5-methyl-sulfonylamino-1-indanone (flosulide) in the intact cell assays by eight- and threefold, respectively, and in the whole blood assays by approximately 40-fold. Following i.v. administration HN-56249 inhibited carrageenan-induced rat paw oedema only moderately (ID50 26.2+/-5.7 mg/kg, mean +/- SEM), approximately tenfold less potent than indomethacin (ID50 2.1+/-0.2 mg/kg, mean +/- SEM). After oral administration HN-56249 reversed thermal hyperalgesia in the carrageenan-induced rat paw oedema test, however, some 30-fold less potently than diclofenac. Comparing the inhibitory potency of HN-56249 against human COX-2 with that against murine COX-2 in intact cells revealed a 300-fold selectivity for the human enzyme. Similar effects were observed with other COX-2-selective arylethersulfonamides. In contrast, non-COX-2-selective arylethersulfonamides, including a highly selective COX-1 inhibitor, inhibited human and murine COX-2 approximately equipotently. In conclusion, HN-56249 is a novel potent and highly selective COX-2 inhibitor with a marked preference for the human COX-2 enzyme in vitro. Despite excellent bioavailability and the long plasma half-life of HN-56249, anti-inflammatory effects in rodents were only moderate. We suggest these differing in vitro-in vivo effects observed could be due to significant inflammatory prostaglandin synthesis by COX-1, or to the genetic differences between human and rodent COX-2, or to both.

Anti-inflammatory activity of Pistacia lentiscus essential oil: involvement of IL-6 and TNF-alpha.

PubMed

Maxia, Andrea; Sanna, Cinzia; Frau, Maria Assunta; Piras, Alessandra; Karchuli, Manvendra Singh; Kasture, Veena

2011-10-01

The topical anti-inflammatory activity of essential oil of Pistacia lentiscus L. was studied using carrageenan induced rat paw edema and cotton pellet induced granuloma. The effect on serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in rats inserted with cotton pellet was also investigated. On topical application, the oil exhibited a significant decrease in paw edema. The oil also inhibited cotton pellet-induced granuloma, and reduced serum TNF-alpha and IL-6. It can be concluded that the essential oil of Pistacia lentiscus reduces leukocyte migration to the damaged tissue and exhibits anti-inflammatory activity.

Synthesis of novel 2-mercapto benzothiazole and 1,2,3-triazole based bis-heterocycles: their anti-inflammatory and anti-nociceptive activities.

PubMed

Shafi, Syed; Alam, Mohammad Mahboob; Mulakayala, Naveen; Mulakayala, Chaitanya; Vanaja, G; Kalle, Arunasree M; Pallu, Reddanna; Alam, M S

2012-03-01

A focused library of novel bis-heterocycles encompassing 2-mercapto benzothiazole and 1,2,3-triazoles were synthesized using click chemistry approach. The synthesized compounds have been tested for their anti-inflammatory activity by using biochemical cyclooxygenase (COX) activity assays and carrageenan-induced hind paw edema. Among the tested compounds, compound 4d demonstrated a potent selective COX-2 inhibition with COX-2/COX-1 ratio of 0.44. Results from carrageenan-induced hind paw edema showed that compounds 4a, 4d, 4e and 4f posses significant anti-inflammatory activity as compared to the standard drug Ibuprofen. The compounds showing significant activity were further subjected to anti-nociceptive activity by writhing test. These four compounds have shown comparable activity with the standard Ibuprofen. Further ulcerogenic studies shows that none of these compounds causing gastric ulceration. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Anti-inflammatory activity of hydroalcoholic extracts of Lavandula dentata L. and Lavandula stoechas L.

PubMed

Algieri, Francesca; Rodriguez-Nogales, Alba; Vezza, Teresa; Garrido-Mesa, Jose; Garrido-Mesa, Natividad; Utrilla, M Pilar; González-Tejero, M Reyes; Casares-Porcel, Manuel; Molero-Mesa, Joaquin; Del Mar Contreras, Maria; Segura-Carretero, Antonio; Pérez-Palacio, José; Diaz, Caridad; Vergara, Noemí; Vicente, Francisca; Rodriguez-Cabezas, M Elena; Galvez, Julio

2016-08-22

Plants from genus Lavandula have been used as anti-inflammatory drugs in Mediterranean traditional medicine. Nowadays, there is a growing interest for complementary medicine, including herbal remedies, to treat inflammatory bowel disease (IBD). To test the anti-inflammatory properties of Lavandula dentata and Lavandula stoechas extracts in two inflammatory experimental models: TNBS model of rat colitis and the carrageenan-induced paw edema in mice, in order to mimic the intestinal conditions and the extra-intestinal manifestations of human IBD, respectively. The extracts were characterized through the qualitative HPLC analysis. Then, they were assayed in vitro and in vivo. In vitro studies were performed in BMDMs and CMT-93 epithelial cells with different concentrations of the extracts (ranging from 0.1 to 100µg/ml). The extracts were tested in vivo in the TNBS model of rat colitis (10 and 25mg/kg) and in the carrageenan-induced paw edema in mice (10, 25 and 100mg/kg). L. dentata and L. stoechas extracts displayed immunomodulatory properties in vitro down-regulating different mediators of inflammation like cytokines and nitric oxide. They also showed anti-inflammatory effects in the TNBS model of colitis as evidenced by reduced myeloperoxidase activity and increased total glutathione content, indicating a decrease of neutrophil infiltration and an improvement of the oxidative state. Besides, both extracts modulated the expression of pro-inflammatory cytokines and chemokines, and ameliorated the altered epithelial barrier function. They also displayed anti-inflammatory effects in the carrageenan-induced paw edema in mice, since a significant reduction of the paw thickness was observed. This was associated with a down-regulation of the expression of different inducible enzymes like MMP-9, iNOS and COX-2 and pro-inflammatory cytokines, all involved in the maintenance of the inflammatory condition. L. dentata and L. stoechas extracts showed intestinal anti-inflammatory effect, confirming their potential use as herbal remedies in gastrointestinal disorders. In addition, their anti-inflammatory effect was also observed in other locations, thus suggesting a possible use for the treatment of the extra-intestinal symptoms of IBD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models.

PubMed

Hajhashemi, Valiollah; Klooshani, Vahid

2013-01-01

This study was aimed to examine the antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models. Hydroalcoholic extract of the plant leaves was prepared by percolation method. Male Swiss mice (25-35 g) and male Wistar rats (180-200 g) were randomly distributed in control, standard drug, and three experimental groups (n=6 in each group). Acetic acid-induced writhing, formalin test, and carrageenan-induced paw edema were used to assess the antinociceptive and anti-inflammatory effects. The extract dose-dependently reduced acetic acid-induced abdominal twitches. In formalin test, the extract at any of applied doses (100, 200, and 400 mg/kg) could not suppress the licking behavior of first phase while doses of 200 and 400 mg/kg significantly inhibited the second phase of formalin test. In carrageenan test, the extract at a dose of 400 mg/kg significantly inhibited the paw edema by 26%. The results confirm the folkloric use of the plant extract in painful and inflammatory conditions. Further studies are needed to characterize the active constituents and the mechanism of action of the plant extract.

Anti-inflammatory effects of aqueous extract of Mangifera indica in Wistar rats.

PubMed

Oluwole, Oluwafemi Gabriel; Esume, Celestine

2015-05-01

Recent studies in standard laboratories have indicated that a typical mango stem bark aqueous extract (Magnifera indica Linn) possess anti-malaria and anti-fever properties. Recent information also exists in the literature, suggesting its potency as a very effective anti-inflammatory plant extract. This study will therefore contribute immensely to the systemic search for a useful, less toxic and natural bioactive medicinal compound. This study investigated the anti-inflammatory effects of the aqueous extract of Mangifera indica (MI) in a carrageenin-induced rat paw oedema model of acute inflammation. Rats (n=5) were treated orally with MI (50, 100 and 200 mg/kg), acetylsalicylic acid (100 mg/kg) or distilled water (3 mL). Thirty minutes later, acute inflammation was induced with a sub-plantar injection of 0.1 mL of 1% carrageenin solution into the right hind paw of the rats. The paw oedema sizes were measured with the aid of a Vernier calliper over a period of 3 hours. The aqueous extract of MI (50-200 mg/kg, p.o.) produced a dose-dependent and significant inhibition of the acute inflammation induced by the carrageenin in rats when compared with controls. The percentage inhibition of oedema formation produced by MI (200 mg/kg, p.o.) was similar to that elicited by acetylsalicylic acid (100 mg/kg, p.o.). The results of this preliminary investigation suggest that MI contains active compounds with an anti-inflammatory activity. However, more detailed studies using additional models are necessary to further characterise the effects of MI in inflammatory disorders.

Evaluation of anti-inflammatory potential of leaf extracts of Skimmia anquetilia

PubMed Central

Kumar, Vijender; Bhat, Zulfiqar Ali; Kumar, Dinesh; Khan, NA; Chashoo, IA

2012-01-01

Objective To evaluate anti-inflammatory potential of leaf extract of Skimmia anquetilia by in-vitro and in-vivo anti-inflammatory models. Methods Acute toxicity study was carried out to determine the toxicity level of different extract using acute toxic class method as described in Organization of Economic Co-operation and Development Guidelines No.423. Carrageenan (1% w/w) was administered and inflammation was induced in rat paw. The leaf extracts of Skimmia anquetilia were evaluated for anti-inflammatory activity by in-vitro human red blood cell (HRBC) membrane stabilization method and in-vivo carrangeenan-induced rat paw edema method. Results The in-vitro membrane stabilizing test showed petroleum ether (PE), chloroform (CE), ethyl acetate (EE), methanol (ME) and aqueous extracts (AE) showed 49.44%, 59.39%, 60.15%, 68.40% and 52.18 % protection, respectively as compared to control groups. The in-vivo results of CE, EE and ME showed 58.20%, 60.17% and 67.53% inhibition of inflammation after 6h administration of test drugs in albino rats. The potency of the leaf extracts of Skimmia anquetilia were compared with standard diclofenac (10 mg/kg) which showed 74.18% protection in in-vitro HRBC membrane stabilization test and 71.64% inhibition in in-vivo carrangeenan-induced rat paw edema model. The ME showed a dose dependent significant (P< 0.01) anti-inflammatory activity in human red blood cell membrane stabilization test and reduction of edema in carrageenan induced rat paw edema. Conclusions The present investigation has confirmed the anti-inflammatory activity of Skimmia anquetilia due to presence of bioactive phytoconstitutes for the first time and provide the pharmacological evidence in favor of traditional claim of Skimmia anquetilia as an anti- inflammatory agent. PMID:23569983

Fatty acid composition and preclinical resarches on Anthemis wiedemanniana Fisch. & Mey.: Discovery of a new anti-inflammatory agent

PubMed Central

Gönenç, Tuba Mert; Akkol, Esra Küpeli; Süntar, Ipek; Erdoğan, Tuğçe Fafal; Kıvçak, Bijen

2014-01-01

Background: Anthemis species have been used for the treatment of gastrointestinal disorders, hemorrhoid, stomachache and inflammatory diseases in Turkish folk medicine. Anthemis wiedemanniana Fisch. And Mey. is an endemic plant used as painkiller, antispasmodic, sedative and for the treatment of urinary inflammations. Objective: The objective of the present study is to evaluate the anti-inflamatory activity of the extracts of A. wiedemanniana by using in vivo methods. Materials and Methods: Carrageenan-, PGE2- and serotonin-induced hind paw edema, 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema and acetic acid-induced increase in capillary permeability models were used for the anti-inflammatory activity assessment. Moreover, the fatty acid composition of A. wiedemanniana was investigated by gas chromatography (GC). Results: n-Hexane, diethyl ether and total sesquiterpene lactone extracts exhibited significant inhibition in carrageenan-induced hind paw edema and acetic acid-induced increase in capillary permeability model. n-Hexane and total sesquiterperne lactone extracts showed anti-inflammatory activity in PGE2- and serotonin-induced hind paw edema model. However none of the extracts displayed significant activity in TPA-induced ear edema model in mice. C4:0 (Buthyric acid), C20:0 (Arachidic acid) and C16:1 (Palmitoleik acid) were found to be the major fatty acids in these species. Saturated fatty acids (SFA) were found in higher amounts than monounsaturated fatty acids and polyunsaturated fatty acids. SFAs were determined as 63.17%, UFAs as 20.89% and PuFAs as 15.95%. Conclusion: This study confirms the traditional usage of A. wiedemanniana for inflammatory diseases. PMID:24696546

Antinociceptive activity of Sempervivum tectorum L. extract in rats.

PubMed

Kekesi, Gabriella; Dobos, Ildiko; Benedek, György; Horvath, Gyöngyi

2003-11-01

The extract of Sempervivum tectorum L. (Crassulaceae) containing several flavonoids is widely used as an antiinflammatory agent in folk medicine. Previous studies have demonstrated that various flavonoids or flavonoid-containing plant extracts produce significant antinociception, but no data are available concerning their antinociceptive effect especially at the spinal level. The purpose of the present study was to investigate the antinociceptive activity of Sempervivum tectorum L. extract on acute and inflammatory pain sensitivity in awake rats. The pain sensitivity was assessed by the acute tail- flick test in intact rats and by the paw withdrawal test after carrageenan-induced inflammation using heat stimulus. The plant extract was administered intraperitoneally and intrathecally in rats. The intraperitoneal injection of a high dose of the extract (1000 mg/kg) significantly (p < 0.05) increased the paw withdrawal latency of the inflamed paw. The intrathecal administration (30-300 micro g) caused a small, but significant increase (10%-15%) in tail- flick latency. In the carrageenan-induced inflammatory model, the intrathecally applied extract (30-1000 micro g) significantly decreased, but did not relieve the thermal hyperalgesia. The results suggest that the spinal cord does not seem to play an important role in the antinociceptive effects of this plant extract. Copyright 2003 John Wiley & Sons, Ltd.

Gamma-Terpinene Modulates Acute Inflammatory Response in Mice.

PubMed

Ramalho, Theresa Raquel de Oliveira; Oliveira, Maria Talita Pacheco de; Lima, Ana Luisa de Araujo; Bezerra-Santos, Claudio Roberto; Piuvezam, Marcia Regina

2015-09-01

The monoterpene gamma-terpinene is a natural compound present in essential oils of a wide variety of plants, including the Eucalyptus genus, which has been reported to possess anti-inflammatory activity. The goal of this study was to evaluate the effect of gamma-terpinene on several in vivo experimental models of acute inflammation. Swiss mice were pretreated with gamma-terpinene and subjected to protocols of paw edema with different phlogistic agents such as carrageenan, prostaglandin-E2, histamine, or bradykinin. The microvascular permeability was measured by intraperitoneal injection of acetic acid and measuring the amount of protein extravasation. Carrageenan-induced peritonitis was used to analyze the effect of gamma-terpinene on inflammatory cell migration and cytokine production. We also developed an acute lung injury protocol to define the anti-inflammatory effect of gamma-terpinene. Mice pretreated with gamma-terpinene displayed reduced paw edema induced by carrageenan from 1-24 h after challenge. A similar reduction was observed when gamma-terpinene was administered after stimulation with PGE2, bradykinin, and histamine. Treatment with gamma-terpinene also inhibited fluid extravasation in the acetic acid model of microvascular permeability. In a carrageenan-induced peritonitis model, gamma-terpinene treatment reduced neutrophil migration as well as the production of interleukin-1β and tumor necrosis factor-α when compared to nontreated animals, and in the acute lung injury protocol, gamma-terpinene diminished the neutrophil migration into lung tissue independently of the total protein extravasation in the lung. These data demonstrate that, in different models of inflammation, treatment with gamma-terpinene alleviated inflammatory parameters such as edema and pro-inflammatory cytokine production, as well as cell migration into the inflamed site, and that this monoterpene has anti-inflammatory properties. Georg Thieme Verlag KG Stuttgart · New York.

Anti-inflammatory, analgesic and ulcerogenic properties of S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin.

PubMed

Bole-Vunduk, B; Verhnjak, K; Zmitek, J

1996-11-01

The anti-inflammatory, analgesic and gastric mucosal damage-inducing activities of S-(+)-ibuproxam, and S-(+)-ibuproxam-beta-cyclodextrin, new propionic acid derivatives, and racemic ibuproxam-beta-cyclodextrin were investigated in three animal models and compared with those of racemic ibuproxam, racemic ibuprofen and its optical enantiomer S-(+)-ibuprofen. The anti-inflammatory activities of racemic ibuprofen, S-(+)-ibuprofen and racemic ibuproxam in carrageenan-induced paw oedema in rats were almost equipotent and slightly greater than those of S-(+)-ibuproxam and S-(+)-ibuproxam-beta-cyclodextrin, and significantly greater than that of racemic ibuproxam-beta-cyclodextrin. In abdominal constriction tests in mice, the analgesic effects of racemic ibuproxam, S-(+)-ibuproxam, racemic ibuproxam-beta-cyclodextrin and S-(+)-ibuproxam-beta-cyclodextrin were significantly less pronounced than those of racemic ibuprofen and S-(+)-ibuprofen. Ulcerogenic activity of S-(+)-ibuproxam-beta-cyclodextrin in rats was found to be significantly weaker than that of racemic ibuproxam-beta-cyclodextrin, racemic ibuproxam and S-(+)-ibuproxam and, most notably, weaker than those of racemic ibuprofen and S-(+)ibuprofen. These results indicate that S-(+)-ibuproxam-beta-cyclodextrin could be a novel potent anti-inflammatory and analgesic agent with a therapeutic index more favourable than that of the classical non-steroid anti-inflammatory drugs ibuprofen and ibuproxam.

Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw

PubMed Central

Medeiros, R; Passos, G F; Vitor, C E; Koepp, J; Mazzuco, T L; Pianowski, L F; Campos, M M; Calixto, J B

2007-01-01

Background and purpose: α-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of α-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. Experimental approach: The biological activities of α-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-κB and up-regulated expression of kinin B1 receptors. Key results: Treatment with either α-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-κB induced by LPS in the rat paw. However, only α-humulene significantly reduced the increase in TNF-α and IL-1β levels, paw oedema and the up-regulation of B1 receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Conclusions and Implications: Both α-humulene and trans-caryophyllene inhibit the LPS-induced NF-κB activation and neutrophil migration, although only α-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-α and IL-1β and the in vivo up-regulation of kinin B1 receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes α-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases. PMID:17471174

Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw.

PubMed

Medeiros, R; Passos, G F; Vitor, C E; Koepp, J; Mazzuco, T L; Pianowski, L F; Campos, M M; Calixto, J B

2007-07-01

alpha-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of alpha-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. The biological activities of alpha-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-kappaB and up-regulated expression of kinin B(1) receptors. Treatment with either alpha-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-kappaB induced by LPS in the rat paw. However, only alpha-humulene significantly reduced the increase in TNF-alpha and IL-1beta levels, paw oedema and the up-regulation of B(1) receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes alpha-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases.

Water-soluble phenol TS-13 combats acute but not chronic inflammation.

PubMed

Menshchikova, Elena; Tkachev, Victor; Lemza, Anna; Sharkova, Tatyana; Kandalintseva, Natalya; Vavilin, Valentin; Safronova, Olga; Zenkov, Nikolay

2014-09-01

This study was conducted to evaluate the effect of the synthetic water-soluble phenolic antioxidant TS-13 (sodium 3-(4'-methoxyphenyl)propyl thiosulfonate), an inducer of the redox-dependent Keap1/Nrf2/ARE signaling system, in experimental models of acute and chronic inflammation. Acute local inflammation was induced by intraplantar carrageenan injection into rat hind paws, and acute systemic inflammation was modeled by intravenous zymosan injection (in rats) or LPS-induced endotoxic shock (in mice). Chronic inflammation was investigated in rat models of air pouch and collagen-induced arthritis. The effects of TS-13 treatment were estimated by changes in the intensity of inflammation (paw edema, liver infiltration, animal survival, exudation, and clinical score of arthritis) and by the effects on reactive oxygen species (ROS) generation by leukocytes from peripheral blood and inflammatory exudates. We found the significant increase in expression of mRNA, content of protein and activity of a well-characterized Nrf2 target enzyme glutathione S-transferase P1, as well as nuclear extract protein binding to the ARE consensus sequence in liver of mice fed with diet containing TS-13. TS-13 markedly attenuated carrageenan-induced paw edema, reduced blood granulocyte number and volume density of liver infiltrates in the systemic zymosan-induced inflammation model, and increased mice survival after lipopolysaccharide-induced septic shock. However, TS-13 administration did not influence cell and protein exudation into air pouches and suppressed clinical manifestation of collagen-induced polyarthritis only at early stages. Nevertheless, TS-13 inhibited the generation of ROS by leukocytes in all inflammation models. The data suggest that the anti-inflammatory effects of Keap1/Nrf2/ARE system are more prominent against acute innate-mediated inflammation than chronic immune inflammation. This narrows the potential therapeutic efficacy of ARE inducers in inflammation treatment.

Gait Analysis in Rats with Single Joint Inflammation: Influence of Experimental Factors

PubMed Central

Ängeby Möller, Kristina; Kinert, Susanne; Størkson, Rolf; Berge, Odd-Geir

2012-01-01

Disability and movement-related pain are major symptoms of joint disease, motivating the development of methods to quantify motor behaviour in rodent joint pain models. We used observational scoring and automated methods to compare weight bearing during locomotion and during standing after single joint inflammation induced by Freund's complete adjuvant (0.12–8.0 mg/mL) or carrageenan (0.47–30 mg/mL). Automated gait analysis was based on video capture of prints generated by light projected into the long edge of the floor of a walkway, producing an illuminated image of the contact area of each paw with light intensity reflecting the contact pressure. Weight bearing was calculated as an area-integrated paw pressure, that is, the light intensity of all pixels activated during the contact phase of a paw placement. Automated static weight bearing was measured with the Incapacitance tester. Pharmacological sensitivity of weight-bearing during locomotion was tested in carrageenan-induced monoarthritis by administration of the commonly used analgesics diclofenac, ibuprofen, and naproxen, as well as oxycodone and paracetamol. Observational scoring and automated quantification yielded similar results. We found that the window between control rats and monoarthritic rats was greater during locomotion. The response was more pronounced for inflammation in the ankle as compared to the knee, suggesting a methodological advantage of using this injection site. The effects of both Freund's complete adjuvant and carrageenan were concentration related, but Freund's incomplete adjuvant was found to be as effective as lower, commonly used concentrations of the complete adjuvant. The results show that gait analysis can be an effective method to quantify behavioural effects of single joint inflammation in the rat, sensitive to analgesic treatment. PMID:23071540

Analgesic, Anti- inflammatory, Anti- lipoxygenase Activity and Characterization of Three Bioactive Compounds in the Most Active Fraction of Leptadenia reticulata (Retz.)Wight & Arn. – A Valuable Medicinal Plant

PubMed Central

Mohanty, Sudipta Kumar; Swamy, Mallappa Kumara; Middha, Sushil Kumar; Prakash, Lokesh; Subbanarashiman, Balasubramanya; Maniyam, Anuradha

2015-01-01

Leptadenia reticulata was reported to be used for several medicinal purposes. The present study was undertaken to evaluate anti-inflammatory, analgesic and lipid peroxidation inhibition activities of L. reticulata. The anti-inflammatory assay was performed by λ-carrageenan and formalin induced paw edema test. Pro inflammatory mediators (IL2, IL6, TNF-α) in serum of treated and control organism were analyzed by quantitative ELISA. Lipid peroxidation inhibition was measured by thiobarbituric acid reactive substances (TBARS) assay. Analysis of the most active fraction revealed the presence of one phenolic compound (p-coumaric acid), two flavonoids (rutin and quercetin) which also determined quantitatively. The ethyl acetate fraction at 600 mg/Kg significantly inhibited λ-carrageenan and formalin induced paw edema by 60.59% and 59.24% respectively. Notable reduction in percentage of writhing (76.25%), induced by acetic acid signifies the potent analgesic activity. Lower level of pro-inflammatory cytokines (IL-2, IL-6, TNF-α) in serum at the 4th hour of λ-Carrageenan injection indicated the inhibition of cyclooxigenase-2 (Cox-2), Nitric oxide (NO) and release of prostaglandin to prevent inflammation. The study also demonstrated the decrease in malonaldehyde (MDA) concentration which revealed the lipid peroxidation inhibition potential of the plant. Our finding provides evidence for potent biological activities in tested model which is supported by its characterized bioactive compounds and ethnomedicinal relevance. PMID:26330883

Novel anti-inflammatory and analgesic agents: synthesis, molecular docking and in vivo studies.

PubMed

Ugwu, David Izuchukwu; Okoro, Uchechukwu Christopher; Ukoha, Pius Onyeoziri; Gupta, Astha; Okafor, Sunday N

2018-12-01

Twelve new derivatives of benzothiazole bearing benzenesulphonamide and carboxamide were synthesised and investigated for their in vivo anti-inflammatory, analgesic and ulcerogenic activities. Molecular docking showed an excellent binding interaction of the synthesised compounds with the receptors, with 17c showing the highest binding energy (-12.50 kcal/mol). Compounds 17c and 17i inhibited carrageenan-induced rat paw oedema at 72, 76, and 80% and 64, 73, and 78% at 1 h, 2 h, and 3 h, respectively. In the analgesic activity experiment, compounds 17c, 17 g, and 17i had ED 50 (µM/kg) of 96, 127, and 84 after 0.5 h; 102, 134, and 72 after 1 h and 89, 156, and 69 µM/kg after 2 h, respectively, which were comparable with 156, 72, and 70 µM/kg for celecoxib. The ulcerogenic index of the most active derivatives 17c and 17i were 0.82 and 0.89, respectively, comparable to 0.92 for celecoxib. The physicochemical studies of the new derivatives showed that they will not have oral bioavailability problems.

Pharmacological and Toxicological Studies of Essential Oil of Lavandula stoechas subsp. luisieri.

PubMed

Arantes, Sílvia; Candeias, Fátima; Lopes, Orlando; Lima, Mónica; Pereira, Marízia; Tinoco, Teresa; Cruz-Morais, J; Martins, M Rosário

2016-09-01

The present study was carried out to evaluate the chemical and pharmacological properties of the essential oil of Lavandula stoechas subsp. luisieri, which is a spontaneous shrub widespread in Alentejo (Portugal). Oxygenated monoterpenes, such as 1,8-cineole, lavandulol, and necrodane derivatives, are the main components of essential oil. It revealed important antioxidant activity with a high ability to inhibit lipid peroxidation and showed an outstanding effect against a wide spectrum of microorganisms, such as gram-positive and gram-negative bacteria and pathogenic yeasts. The analgesic effect studied in rats was dose dependent, reaching a maximum of 67 % at 60 min with the dose of 200 mg/kg and the anti-inflammatory activity with this dose caused an inhibition in carrageenan-induced rat paw oedema (83 %) that is higher than dexamethasone 1 mg/Kg (69 %). Besides, animals exhibited normal behaviour after essential oil administration, revealing low toxicity. The essential oil of L. luisieri from Alentejo presents important pharmacological properties and low toxicity, and is a promised candidate to be used as a food supplement or in pharmaceutical applications. Georg Thieme Verlag KG Stuttgart · New York.

Synthesis of biologically active N-methyl derivatives of amidines and cyclized five-membered products of amidines with oxalyl chloride.

PubMed

Sondhi, Sham M; Dinodia, Monica; Jain, Shubhi; Kumar, Ashok

2008-12-01

A series of substituted N-methylisonicotinamidine (2a-f), N-methylpyrazine-2-carboxamidine (2g-i) derivatives were synthesized by reaction of amidine derivatives (1a-i) with methyl iodide in presence of triethylamine. Five-membered condensed dihydroimidazolylbenzenesulfonamide derivatives (3a-i) were obtained by the reaction of amidine derivatives (1a-i) with acylating agent oxalyl chloride. All the compounds, i.e. 2a-i and 3a-i were purified by crystallization. Structures of all the synthesized compounds are supported by correct IR, (1)H NMR, mass spectral and analytical data. Anti-inflammatory activity evaluation was carried out using carrageenan-induced paw oedema assay and compounds 2e, 3a and 3d exhibited good anti-inflammatory activity (44%, 31% and 37% activity at 50 mg/kg p.o., respectively). Analgesic activity evaluation was carried out using acetic acid writhing assay and compounds 2a and 3f gave 75% activity each at 100 mg/kg p.o.; on the other hand compounds 3a and 3d exhibited 60% analgesic activity each at 50 mg/kg p.o. Compounds 3a and 3d exhibited good anti-inflammatory and analgesic activities.

Immunomodulatory activity and chemical characterisation of sangre de drago (dragon's blood) from Croton lechleri.

PubMed

Risco, Ester; Ghia, Felipe; Vila, Roser; Iglesias, José; Alvarez, Elida; Cañigueral, Salvador

2003-09-01

The immunomodulatory activity of the latex from Croton lechleri (sangre de drago) was determined by in vitro assays. Classical (CP) and alternative (AP) complement pathways activities were determined in human serum. Intracellular generation of reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) and monocytes, and phagocytosis of opsonised fluorescent microspheres were measured by flow cytometry. Free radical scavenging activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Activity on proliferation of murine lymphocytes was also investigated. In addition, anti-inflammatory activity was assayed in vivo by carrageenan-induced rat paw oedema test. Some of the activities were compared with those of the isolated alkaloid taspine. Sangre de drago from Croton lechleri showed immunomodulatory activity. It exhibited a potent inhibitory activity on CP and AP of complement system and inhibited the proliferation of activated T-cells. The latex showed free radical scavenging capacity. Depending on the concentration, it showed antioxidant or prooxidant properties, and stimulated or inhibited the phagocytosis. Moreover, the latex has strong anti-inflammatory activity when administered i. p. Taspine cannot be considered the main responsible for these activities, and other constituents, probably proanthocyanidins, should be also involved.

Ethnopharmacological evaluation of some Scorzonera species: in vivo anti-inflammatory and antinociceptive effects.

PubMed

Küpeli Akkol, Esra; Bahadır Acıkara, Ozlem; Süntar, Ipek; Ergene, Burçin; Saltan Çitoğlu, Gülçin

2012-03-27

Scorzonera species are mainly used against inflammation and to relieve pain in Turkish traditional medicine. Therefore, we aimed to assess in vivo anti-inflammatory and antinociceptive activities of the aerial part and root extracts of Scorzonera acuminata, Scorzonera cana var. alpina, Scorzonera cana var. jacquiniana, Scorzonera cana var. radicosa, Scorzonera cinerea, Scorzonera eriophora, Scorzonera incisa, Scorzonera laciniata ssp. laciniata, Scorzonera parviflora and Scorzonera sublanata. For the anti-inflammatory activity evaluation carrageenan, PGE(2) and serotonin-induced hind paw edema and 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear edema models were used. p-Benzoquinone-induced abdominal constriction test was employed in mice for the assessment of antinociceptive activity. Furthermore chemical composition of the tested extracts was investigated qualitatively and quantitatively by using RP-HPLC method. Some phenolic acids and flavonoids were used as standards. Extracts prepared from the aerial parts of Scorzonera cana var. jacquiniana, Scorzonera cinerea, Scorzonera eriophora, Scorzonera incisa and Scorzonera parviflora showed significant inhibitory effect on carrageenan and PGE(2)-induced hind paw edema model as well as on p-benzoquinone-induced abdominal constriction test. The extracts did not show any remarkable activity on serotonin-induced hind paw edema and TPA-induced mouse ear edema models. Chlorogenic acid was detected as major compounds in all the species investigated. Additionally, among the tested flavonoids, luteolin-7-glucoside, hyperoside and rutin were found to be in different amounts in Scorzonera species. The experimental data revealed that Scorzonera cana var. jacquiniana, Scorzonera cinerea, Scorzonera eriophora, Scorzonera incisa and Scorzonera parviflora possess significant anti-inflammatory and antinociceptive activity. It has been suggested that flavonoids and chlorogenic acid are partly responsible for mentioned activities of Scorzonera species. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Anti-Inflammatory Activity of Polysaccharide Fraction of Curcuma longa (NR-INF-02).

PubMed

Illuri, Ramanaiah; Bethapudi, Bharathi; Anandhakumar, Senthilkumar; Murugan, Sasikumar; Joseph, Joshua Allan; Mundkinajeddu, Deepak; Agarwal, Amit; Velusami, Chandrasekaran Chinampudur

2015-04-07

The aim of the study was to investigate the safety and anti-inflammatory effects of polysaccharide fraction (F1) of Curcuma longa (NR-INF-02) in classical rodent models of inflammation. F1 was evaluated for its acute oral toxicity and found to be safe upto 5000 mg/kg body weight in rats. The anti-inflammatory activity of F1 was evaluated in acute (carrageenan - induced paw edema; xylene - induced ear edema) and chronic (cotton pellet - induced granuloma) models of inflammation. The results of the study demonstrated that F1 significantly (p ≤ 0.05) inhibited carrageenan-induced paw edema at 1 h and 3 h at doses of 11.25, 22.5 and 45 mg/kg body weight in rats. Also, F1 at doses of 15.75, 31.5 and 63 mg/kg significantly inhibited the xylene induced ear edema in mice. In a chronic model, F1 at 11.25, 22.5 and 45 mg/kg doses produced significant reduction of wet and dry weights of cotton pellets in rats. Overall results indicated that F1 of NR-INF-02 significantly attenuated acute and chronic inflammation in rodent models. This study emphasizes on the importance of Curcuma longa polysaccharide's role in acute and chronic inflammation.

Anti-Inflammatory Activity of Polysaccharide Fraction of Curcuma longa Extract (NR-INF-02).

PubMed

Illuri, Ramanaiah; Bethapudi, Bharathi; Anandakumar, Senthilkumar; Murugan, Sasikumar; Joseph, Joshua A; Mundkinajeddu, Deepak; Agarwal, Amit; Chandrasekaran, C V

2015-01-01

The aim of the study was to investigate the safety and anti-inflammatory effects of polysaccharide fraction (F1) of Curcuma longa extract (NR-INF-02) in classical rodent models of inflammation. F1 was evaluated for its acute oral toxicity and found to be safe upto 5000 mg/kg body weight in rats. The anti-inflammatory activity of F1 was evaluated in acute (carrageenan - induced paw edema; xylene - induced ear edema) and chronic (cotton pellet - induced granuloma) models of inflammation. The results of the study demonstrated that F1 significantly (p ≤ 0.05) inhibited carrageenan-induced paw edema at 1 h and 3 h at doses of 11.25, 22.5 and 45 mg/kg body weight in rats. Also, F1 at doses of 15.75, 31.5 and 63 mg/kg significantly inhibited the xylene induced ear edema in mice. In a chronic model, F1 at 11.25, 22.5 and 45 mg/kg doses produced significant reduction of wet and dry weights of cotton pellets in rats. Overall results indicated that F1 of NR-INF-02 significantly attenuated acute and chronic inflammation in rodent models. This study emphasizes on the importance of Curcuma longa polysaccharide's role in acute and chronic inflammation.

Anti-inflammatory activity of flower extract of Calendula officinalis Linn. and its possible mechanism of action.

PubMed

Preethi, Korengath Chandran; Kuttan, Girija; Kuttan, Ramadasan

2009-02-01

Calendula officinalis flower extract possessed significant anti-inflammatory activity against carrageenan and dextran-induced acute paw edema. Oral administration of 250 and 500 mg/kg body weight Calendula extract produced significant inhibition (50.6 and 65.9% respectively) in paw edema of animals induced by carrageenan and 41.9 and 42.4% respectively with inflammation produced by dextran. In chronic anti-inflammatory model using formalin, administration of 250 and 500 mg/kg body weight Calendula extract produced an inhibition of 32.9 and 62.3% respectively compared to controls. TNF-alpha production by macrophage culture treated with lipopolysaccharide (LPS) was found to be significantly inhibited by Calendula extract. Moreover, increased levels of proinflammatory cytokines IL- 1beta, IL-6, TNF-alpha and IFN-gamma and acute phase protein, C- reactive protein (CRP) in mice produced by LPS injection were inhibited significantly by the extract. LPS induced cyclooxygenase-2 (Cox-2) levels in mice spleen were also found to be inhibited by extract treatment. The results showed that potent anti-inflammatory response of C. officinalis extract may be mediated by the inhibition of proinflammatory cytokines and Cox-2 and subsequent prostaglandin synthesis.

Antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models

PubMed Central

Hajhashemi, Valiollah; Klooshani, Vahid

2013-01-01

Objective: This study was aimed to examine the antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models. Materials and Methods: Hydroalcoholic extract of the plant leaves was prepared by percolation method. Male Swiss mice (25-35 g) and male Wistar rats (180-200 g) were randomly distributed in control, standard drug, and three experimental groups (n=6 in each group). Acetic acid-induced writhing, formalin test, and carrageenan-induced paw edema were used to assess the antinociceptive and anti-inflammatory effects. Results: The extract dose-dependently reduced acetic acid-induced abdominal twitches. In formalin test, the extract at any of applied doses (100, 200, and 400 mg/kg) could not suppress the licking behavior of first phase while doses of 200 and 400 mg/kg significantly inhibited the second phase of formalin test. In carrageenan test, the extract at a dose of 400 mg/kg significantly inhibited the paw edema by 26%. Conclusion: The results confirm the folkloric use of the plant extract in painful and inflammatory conditions. Further studies are needed to characterize the active constituents and the mechanism of action of the plant extract. PMID:25050274

Anti-inflammatory activity and chemical composition of the essential oils from Senecio flammeus

PubMed Central

Xiao, Kai-Jun; Wang, Wen-Xia; Dai, Jia-Li; Zhu, Liang

2014-01-01

Many species from Senecio genus have been used in traditional medicine, and their pharmacological activities have been demonstrated. This study investigated the chemical composition and anti-inflammatory activities of essential oils from Senecio flammeus. A total of 48 components representing 98.41 % of the total oils were identified. The main compounds in the oils were α-farnesene (11.26 %), caryophyllene (8.69 %), n-hexadecanoic acid (7.23 %), and α-pinene (6.36 %). The anti-inflammatory activity of the essential oils was evaluated in rodents (10–90 mg/kg bw) in classical models of inflammation [carrageenan-induced paw edema, 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ear edema, and cotton pellet-induced granuloma]. The essential oils at doses of 10, 30, and 90 mg/kg bw significantly reduced carrageenan-induced paw edema by 17.42 % (P < 0.05), 52.90 % (P < 0.05), and 66.45 % (P < 0.05) 4 h after carrageenan injection, respectively, and significantly reduced myeloperoxidase activity (P < 0.05). The essential oils (10, 30, and 90 mg/kg) also produced a significant dose-dependent response to reduce TPA-induced ear edema by 20.27 % (P < 0.05), 33.06 % (P < 0.05), and 53.90 % (P < 0.05), respectively. The essential oils produced significant dose-response anti-inflammatory activity against cotton pellet-induced granuloma that peaked at the highest dose of 90 mg/kg (49.08 % wet weight and 47.29 % dry weight). Results demonstrate that the essential oils of S. flammeus were effective in the treatment of both acute and chronic inflammatory conditions, thereby supporting the traditional use of this herb. PMID:26417301

Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-κB and oxidative stress.

PubMed

Pinho-Ribeiro, Felipe A; Fattori, Victor; Zarpelon, Ana C; Borghi, Sergio M; Staurengo-Ferrari, Larissa; Carvalho, Thacyana T; Alves-Filho, Jose C; Cunha, Fernando Q; Cunha, Thiago M; Casagrande, Rubia; Verri, Waldiceu A

2016-06-01

We evaluated the effect of pyrrolidine dithiocarbamate (PDTC) in superoxide anion-induced inflammatory pain. Male Swiss mice were treated with PDTC and stimulated with an intraplantar or intraperitoneal injection of potassium superoxide, a superoxide anion donor. Subcutaneous PDTC treatment attenuated mechanical hyperalgesia, thermal hyperalgesia, paw oedema and leukocyte recruitment (neutrophils and macrophages). Intraplantar injection of superoxide anion activated NF-κB and increased cytokine production (IL-1β, TNF-α and IL-10) and oxidative stress (nitrite and lipid peroxidation levels) at the primary inflammatory foci and in the spinal cord (L4-L6). PDTC treatment inhibited superoxide anion-induced NF-κB activation, cytokine production and oxidative stress in the paw and spinal cord. Furthermore, intrathecal administration of PDTC successfully inhibited superoxide anion-induced mechanical hyperalgesia, thermal hyperalgesia and inflammatory response in peripheral foci (paw). These results suggest that peripheral stimulus with superoxide anion activates the local and spinal cord oxidative- and NF-κB-dependent inflammatory nociceptive mechanisms. PDTC targets these events, therefore, inhibiting superoxide anion-induced inflammatory pain in mice.

Nociception and inflammatory hyperalgesia evaluated in rodents using infrared laser stimulation after Trpv1 gene knockout or resiniferatoxin lesion.

PubMed

Mitchell, Kendall; Lebovitz, Evan E; Keller, Jason M; Mannes, Andrew J; Nemenov, Michael I; Iadarola, Michael J

2014-04-01

TRPV1 is expressed in a subpopulation of myelinated Aδ and unmyelinated C-fibers. TRPV1+ fibers are essential for the transmission of nociceptive thermal stimuli and for the establishment and maintenance of inflammatory hyperalgesia. We have previously shown that high-power, short-duration pulses from an infrared diode laser are capable of predominantly activating cutaneous TRPV1+ Aδ-fibers. Here we show that stimulating either subtype of TRPV1+ fiber in the paw during carrageenan-induced inflammation or following hind-paw incision elicits pronounced hyperalgesic responses, including prolonged paw guarding. The ultrapotent TRPV1 agonist resiniferatoxin (RTX) dose-dependently deactivates TRPV1+ fibers and blocks thermal nociceptive responses in baseline or inflamed conditions. Injecting sufficient doses of RTX peripherally renders animals unresponsive to laser stimulation even at the point of acute thermal skin damage. In contrast, Trpv1-/- mice, which are generally unresponsive to noxious thermal stimuli at lower power settings, exhibit withdrawal responses and inflammation-induced sensitization using high-power, short duration Aδ stimuli. In rats, systemic morphine suppresses paw withdrawal, inflammatory guarding, and hyperalgesia in a dose-dependent fashion using the same Aδ stimuli. The qualitative intensity of Aδ responses, the leftward shift of the stimulus-response curve, the increased guarding behaviors during carrageenan inflammation or after incision, and the reduction of Aδ responses with morphine suggest multiple roles for TRPV1+ Aδ fibers in nociceptive processes and their modulation of pathological pain conditions. Copyright © 2014. Published by Elsevier B.V.

Weight bearing of the limb as a confounding factor in assessment of mechanical allodynia in the rat.

PubMed

Kauppila, T; Kontinen, V K; Pertovaara, A

1998-01-01

Effect of weight bearing of the hindlimbs on the assessment of mechanically-induced hindlimb withdrawal threshold was determined in intact rats and in rats with various pathophysiological conditions causing allodynia or hyperalgesia. Hindlimb withdrawal was elicited by applying a series of calibrated monofilaments to the plantar or the dorsal surface of the paw. During testing the rat was either in a restraint tube with hindlimbs hanging semi-extended without weight bearing or it was standing on a metal grid (bearing its own weight). In intact rats, the withdrawal thresholds were significantly lower when the stimulus site was the dorsal hairy skin rather than the plantar glabrous skin. Also, thresholds were significantly lower when the hindlimbs were not bearing weight. Following carrageenan-induced unilateral inflammation of the plantar paw or a tibial nerve cut there was a marked threshold decrease to test stimuli applied to plantar or dorsal paw, respectively, ipsilateral to the pathological condition in standing rats. However, when the hindlimbs were not weight bearing the unilateral threshold decrease was markedly attenuated (carrageenan-treated rats) or completely abolished (tibial cut). In contrast, in rats with a unilateral spinal nerve ligation the threshold decrease ipsilateral to the nerve lesion was highly significant independent of the weight bearing of the hindlimbs. The results indicate that weight bearing of hindlimbs is an important confounding factor in the assessment of tactile allodynia in rats.

Analgesic and anti-inflammatory effects of honey: the involvement of autonomic receptors.

PubMed

Owoyele, Bamidele Victor; Oladejo, Rasheed Olajiire; Ajomale, Kayode; Ahmed, Rasheedat Omotayo; Mustapha, Abdulrasheed

2014-03-01

The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 μg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors.

Physio-pharmacological Investigations About the Anti-inflammatory and Antinociceptive Efficacy of (+)-Limonene Epoxide.

PubMed

de Almeida, Antonia Amanda Cardoso; Silva, Renan Oliveira; Nicolau, Lucas Antonio Duarte; de Brito, Tarcísio Vieira; de Sousa, Damião Pergentino; Barbosa, André Luiz Dos Reis; de Freitas, Rivelilson Mendes; Lopes, Luciano da Silva; Medeiros, Jand-Venes Rolim; Ferreira, Paulo Michel Pinheiro

2017-04-01

D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P < 0.05). At 75 mg/kg, it suppressed edema provoked by compound 48/80, histamine, prostaglandin E 2 , and serotonin and reduced permeability determined by Evans blue and MPO activity. It also reduced leukocytes, neutrophils, and IL-1β levels in the peritoneal cavity in comparison with carrageenan group (P < 0.05). (+)-Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P < 0.05). Additionally, it enlarged response times to the thermal stimulus after 60 and 90 min. In conclusion, (+)-limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.

Vinpocetine Reduces Carrageenan-Induced Inflammatory Hyperalgesia in Mice by Inhibiting Oxidative Stress, Cytokine Production and NF-κB Activation in the Paw and Spinal Cord

PubMed Central

Ruiz-Miyazawa, Kenji W.; Zarpelon, Ana C.; Pinho-Ribeiro, Felipe A.; Pavão-de-Souza, Gabriela F.; Casagrande, Rubia; Verri, Waldiceu A.

2015-01-01

Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ) and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH) levels, superoxide anion, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels, as well as nuclear factor kappa B (NF-κB) activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases), as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels. PMID:25822523

Vinpocetine reduces carrageenan-induced inflammatory hyperalgesia in mice by inhibiting oxidative stress, cytokine production and NF-κB activation in the paw and spinal cord.

PubMed

Ruiz-Miyazawa, Kenji W; Zarpelon, Ana C; Pinho-Ribeiro, Felipe A; Pavão-de-Souza, Gabriela F; Casagrande, Rubia; Verri, Waldiceu A

2015-01-01

Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ) and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH) levels, superoxide anion, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels, as well as nuclear factor kappa B (NF-κB) activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases), as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels.

Anti-Inflammatory Effects of a Stauntonia hexaphylla Fruit Extract in Lipopolysaccharide-Activated RAW-264.7 Macrophages and Rats by Carrageenan-Induced Hind Paw Swelling

PubMed Central

Kim, Jaeyong; Kim, Heesook; Choi, Hakjoon; Jo, Ara; Kang, Huwon; Yun, Hyojeong; Im, Sojeong; Choi, Chulyung

2018-01-01

The fruit of Stauntonia hexaphylla is commonly used as a traditional anthelmintic in Korea, Japan, and China. However, its anti-inflammatory activity and the underlying mechanisms have not been studied systematically. In the present study, we examined the anti-inflammatory activities of an aqueous extract of S. hexaphylla fruit (SHF) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The SHF extract contained anti-inflammatory compounds, such as neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid. The extract inhibited protein levels of inducible nitric oxide synthase and the activity of cyclooxygenase enzyme, with concomitant reductions in the production of nitric oxide and prostaglandin E2 in LPS-activated RAW 264.7 cells. Additionally, the SHF extract reduced the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The SHF extract attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing the phosphorylation of its inhibitor, IκBα. Furthermore, the SHF extract showed a significant anti-inflammatory effect in vivo by reducing the volume of carrageenan-induced paw edema in rats. Our results suggest that the SHF extract exerts potential anti-inflammatory properties against LPS-activated RAW 254.7 cells, and in an animal model of inflammation. PMID:29361789

Guava pomace: a new source of anti-inflammatory and analgesic bioactives

PubMed Central

2013-01-01

Background Guava pomace is an example of the processing waste generated after the manufacturing process from the juice industry that could be a source of bioactives. Thus, the present investigation was carried out in order to evaluate the anti-inflammatory and antinociceptive potential and determinate the main phenolic compounds of a guava pomace extract (GPE). Methods The anti-inflammatory activity was evaluated by carrageenan, dextran, serotonin, histamine-induced paw edema and neutrophils migration in the peritoneal cavity models. Acetic acid-induced abdominal writhing and formalin test were performed to investigate the antinociceptive effects. In addition, the content of total phenolic and of individual phenolic compounds was determined by GC/MS. Results GPE showed anti-inflammatory activity by carrageenan, dextran, serotonin, histamine-induced paw edema and neutrophils migration in the peritoneal cavity models (p < 0.05). GPE also demonstrated antinociceptive activity by acetic acid-induced abdominal writhing and formalin test (p < 0.05). The total phenolic value was 3.40 ± 0.09 mg GAE/g and epicatechin, quercetin, myricetin, isovanilic and gallic acids were identified by GC/MS analysis. Conclusions The presence of bioactive phenolic compounds as well as important effects demonstrated in animal models suggest that guava pomace could be an interesting source of anti-inflammatory and analgesic substances. PMID:24063346

Anti-Inflammatory Effects of a Stauntonia hexaphylla Fruit Extract in Lipopolysaccharide-Activated RAW-264.7 Macrophages and Rats by Carrageenan-Induced Hind Paw Swelling.

PubMed

Kim, Jaeyong; Kim, Heesook; Choi, Hakjoon; Jo, Ara; Kang, Huwon; Yun, Hyojeong; Im, Sojeong; Choi, Chulyung

2018-01-22

The fruit of Stauntonia hexaphylla is commonly used as a traditional anthelmintic in Korea, Japan, and China. However, its anti-inflammatory activity and the underlying mechanisms have not been studied systematically. In the present study, we examined the anti-inflammatory activities of an aqueous extract of S. hexaphylla fruit (SHF) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The SHF extract contained anti-inflammatory compounds, such as neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid. The extract inhibited protein levels of inducible nitric oxide synthase and the activity of cyclooxygenase enzyme, with concomitant reductions in the production of nitric oxide and prostaglandin E₂ in LPS-activated RAW 264.7 cells. Additionally, the SHF extract reduced the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. The SHF extract attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing the phosphorylation of its inhibitor, IκBα. Furthermore, the SHF extract showed a significant anti-inflammatory effect in vivo by reducing the volume of carrageenan-induced paw edema in rats. Our results suggest that the SHF extract exerts potential anti-inflammatory properties against LPS-activated RAW 254.7 cells, and in an animal model of inflammation.

Analgesic and Anti-Inflammatory Activities of the Methanol Extract from Pogostemon cablin

PubMed Central

Lu, Tsung-Chun; Liao, Jung-Chun; Huang, Tai-Hung; Lin, Ying-Chih; Liu, Chia-Yu; Chiu, Yung-jia; Peng, Wen-Huang

2011-01-01

Pogostemon cablin (PC) is a herbal medicine traditionally applied to treat not only common cold, nausea and diarrhea but also headache and fever. The aim of this study was to investigate the analgesic and anti-inflammatory properties of standardized PC methanol extract (PCMeOH) in vivo. Investigations were performed in mice with two analgesic models. One was acetic acid-induced writhing response and the other formalin-induced paw licking. The anti-inflammatory effect was tested by λ-carrageenan (Carr)-induced mice paw edema. These analgesic experimental results indicated that PCMeOH (1.0 g/kg) decreased the acetic acid-induced writhing responses and PCMeOH (0.5 and 1.0 g/kg) decreased the licking time in the second phase of the formalin test. Moreover, Carr-induced paw edema inflammation was significantly reduced in a dose-dependent manner when PCMeOH (0.5 and 1.0 g/kg) was administered 3 and 4 h after the Carr injection. Mechanistic studies showed that PCMeOH decreased the levels of malondialdehyde in the edema paw by increasing the activities of anti-oxidant enzymes, such as superoxide dismutase, glutathione peroxidase and glutathione reductase, in the liver and decreasing the cyclooxygenase 2 and tumor necrosis factor-α activities in the edema paw. This study has demonstrated the analgesic and anti-inflammatory effects of PCMeOH, thus verifying its popular use in traditional medicine. PMID:19933324

Effects of ethanol and water extracts of propolis (bee glue) on acute inflammatory animal models.

PubMed

Hu, Fuliang; Hepburn, H R; Li, Yinghua; Chen, M; Radloff, S E; Daya, S

2005-09-14

The anti-inflammatory effects of ethanol (EEP) and water (WSD) extracts in ICR mice and Wistar rats were analyzed. Both WSD and EEP exhibited significant anti-inflammatory effects in animal models with respect to thoracic capillary vessel leakage in mice, carrageenan-induced oedema, carrageenan-induced pleurisy, acute lung damage in rats. The mechanisms for the anti-inflammatory effects probably involve decreasing prostaglandin-E(2) (PGE(2)) and nitric oxide (NO) levels. In rats with Freund's complete adjuvant (FCA) induced arthritis, propolis extracts significantly inhibited the increase of interleukin-6 (IL-6) in inflamed tissues, but had no significant effect on levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). The results are consistent with the interpretation that EEP and WSD may exert these effects by inhibiting the activation and differentiation of mononuclear macrophages.

Anti-inflammatory activities of Aller-7, a novel polyherbal formulation for allergic rhinitis.

PubMed

Pratibha, N; Saxena, V S; Amit, A; D'Souza, P; Bagchi, M; Bagchi, D

2004-01-01

Allergic rhinitis is an immunological disorder and an inflammatory response of nasal mucosal membranes. Allergic rhinitis, a state of hypersensitivity, occurs when the body overreacts to a substance such as pollens or dust. A novel, safe polyherbal formulation (Aller-7/NR-A2) has been developed for the treatment of allergic rhinitis using a unique combination of extracts from seven medicinal plants including Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and Piper longum. Since inflammation is an integral mechanistic component of allergy, the present study aimed to determine the anti-inflammatory activity of Aller-7 in various in vivo models. The efficacy of Aller-7 was investigated in compound 48/80-induced paw edema both in Balb/c mice and Swiss Albino mice, carrageenan-induced paw edema in Wistar Albino rats and Freund's adjuvant-induced arthritis in Wistar Albino rats. The trypsin inhibitory activity of Aller-7 was also determined and compared with ovomucoid. At a dose of 250 mg/kg, Aller-7 demonstrated 62.55% inhibition against compound 48/80-induced paw edema in Balb/c mice, while under the same conditions prednisolone at an oral dose of 14 mg/kg exhibited 44.7% inhibition. Aller-7 significantly inhibited compound 48/80-induced paw edema at all three doses of 175, 225 or 275 mg/kg in Swiss Albino mice, while the most potent effect was observed at 225 mg/kg. Aller-7 (120 mg/kg, p.o.) demonstrated 31.3% inhibition against carrageenan-induced acute inflammation in Wistar Albino rats, while ibuprofen (50 mg/kg, p.o.) exerted 68.1% inhibition. Aller-7 also exhibited a dose-dependent (150-350 mg/kg) anti-inflammatory effect against Freund's adjuvant-induced arthritis in Wistar Albino rats and an approximately 63% inhibitory effect was observed at a dose of 350 mg/kg. The trypsin inhibitory activity of Aller-7 was determined, using ovomucoid as a positive control. Ovomucoid and Aller-7 demonstrated IC50 concentrations at 1.5 and 9.0 microg/ml, respectively. These results demonstrate that this novel polyherbal formulation is a potent anti-inflammatory agent that can ameliorate the symptoms of allergic rhinitis.

Antinociceptive and antiedematogenic effect of pecan (Carya illinoensis) nut shell extract in mice: a possible beneficial use for a by-product of the nut industry.

PubMed

Trevisan, Gabriela; Rossato, Mateus F; Hoffmeister, Carin; Müller, Liz G; Pase, Camila; Córdova, Marina M; Rosa, Fernanda; Tonello, Raquel; Hausen, Bruna S; Boligon, Aline A; Moresco, Rafael N; Athayde, Margareth L; Burguer, Marilise E; Santos, Adair R; Ferreira, Juliano

2014-01-27

Abstract Background: Interest in pecan (Carya illinoensis) nut shells, a by-product of the nut industry, has increased due to its anti-inflammatory and antioxidant activities. The goal of this study was to evaluate the antinociceptive and antiedematogenic activity and the mechanisms of the pecan shell aqueous extract (AE). Methods: First, we performed fingerprinting of C. illinoensis AE. The antinociceptive and antiedematogenic effects of AE intragastric (i.g.) administration in mice (male Swiss mice 20-30 g) were evaluated using the acetic acid test or after subcutaneous (s.c.) paw injection of diverse transient receptor potential ankyrin 1 (TRPA1) agonists, including hydrogen peroxide (H2O2), allyl isothiocyanate, or cinnamaldehyde. We also observed AE antinociceptive and antiedematogenic effects after carrageenan s.c. paw injection and measured H2O2 production. Moreover, we observed the development of adverse effects after AE i.g. treatment. Results: The high-performance liquid chromatography fingerprinting of AE showed the presence of rutin. AE or rutin i.g. treatment produced antinociception in the acetic acid test and reduced the nociception and edema mediated by H2O2 s.c. hind paw injection or nociception induced by other TRPA1 agonists. Moreover, AE or rutin reduced the hyperalgesia, edema, and H2O2 production induced by carrageenan s.c. paw injection. No motor, gastric, or toxicological alterations were observed after AE administration. Conclusions: Collectively, the present results show that AE and its constituent rutin produced antinociceptive and antiedematogenic action in models of acute and persistent inflammatory nociception and it seems to be related to the inhibition of TRPA1 receptor activation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saeed, Noha M.; El-Demerdash, Ebtehal; Abdel-Rahman, Hanaa M.

Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). MP and EP decreased NF-κB expression in liver and lung tissues and ameliorated histopathological changes caused by LPS.more » Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models. -- Highlights: ► Efficacy of MP and EP in combating inflammation was displayed in several models. ► MP and EP reduced carrageenan-induced rat paw edema and prostaglandin E2 level. ► MP and EP decreased TNF-α and IL-6 levels in experimental endotoxemia. ► MP and EP reduced NF-κB expression and histological changes in rat liver and lung. ► MP and EP reduced croton oil-induced ear edema and neutrophil infiltration.« less

Chemicals Compositions, Antioxidant and Anti-Inflammatory Activity of Cynara scolymus Leaves Extracts, and Analysis of Major Bioactive Polyphenols by HPLC

PubMed Central

Ben Salem, Maryem; Athmouni, Khaled; Ksouda, Kamilia; Dhouibi, Raouia; Sahnoun, Zouheir; Hammami, Serria; Zeghal, Khaled Mounir

2017-01-01

Objective. Artichoke (Cynara scolymus L.) was one of the plant remedies for primary health care. The present study was focused on the determination of chemical composition, antioxidant activities, and anti-inflammatory activity and on analyzing its major bioactive polyphenols by HPLC. Methods. Artichoke Leaves Extracts (ALE) were analyzed for proximate analysis and phytochemical and antioxidant activity by several methods such as DDPH, ABTS, FRAP, and beta-carotene bleaching test. The carrageenan (Carr) model induced paw oedema in order to investigate the anti-inflammatory activity. Identification and quantification of bioactive polyphenols compounds were done by HPLC method. The oxidative stress parameters were determined; CAT, SOD, GSH, MDA, and AOPP activities and the histopathological examination were also performed. Results. It was noted that EtOH extract of ALE contained the highest phenolic, flavonoid, and tannin contents and the strongest antioxidants activities including DDPH (94.23%), ABTS (538.75 mmol), FRAP assay (542.62 umol), and β-carotene bleaching (70.74%) compared to the other extracts of ALE. Administration of EtOH extract at dose 400 mg/kg/bw exhibited a maximum inhibition of inflammation induced by Carr for 3 and 5 hours compared to reference group Indomethacin (Indo). Conclusion. ALE displayed high potential as natural source of minerals and phytochemicals compounds with antioxidant and anti-inflammatory properties. PMID:28539965

Chemicals Compositions, Antioxidant and Anti-Inflammatory Activity of Cynara scolymus Leaves Extracts, and Analysis of Major Bioactive Polyphenols by HPLC.

PubMed

Ben Salem, Maryem; Affes, Hanen; Athmouni, Khaled; Ksouda, Kamilia; Dhouibi, Raouia; Sahnoun, Zouheir; Hammami, Serria; Zeghal, Khaled Mounir

2017-01-01

Objective . Artichoke ( Cynara scolymus L.) was one of the plant remedies for primary health care. The present study was focused on the determination of chemical composition, antioxidant activities, and anti-inflammatory activity and on analyzing its major bioactive polyphenols by HPLC. Methods . Artichoke Leaves Extracts (ALE) were analyzed for proximate analysis and phytochemical and antioxidant activity by several methods such as DDPH, ABTS, FRAP, and beta-carotene bleaching test. The carrageenan (Carr) model induced paw oedema in order to investigate the anti-inflammatory activity. Identification and quantification of bioactive polyphenols compounds were done by HPLC method. The oxidative stress parameters were determined; CAT, SOD, GSH, MDA, and AOPP activities and the histopathological examination were also performed. Results . It was noted that EtOH extract of ALE contained the highest phenolic, flavonoid, and tannin contents and the strongest antioxidants activities including DDPH (94.23%), ABTS (538.75 mmol), FRAP assay (542.62 umol), and β -carotene bleaching (70.74%) compared to the other extracts of ALE. Administration of EtOH extract at dose 400 mg/kg/bw exhibited a maximum inhibition of inflammation induced by Carr for 3 and 5 hours compared to reference group Indomethacin (Indo). Conclusion . ALE displayed high potential as natural source of minerals and phytochemicals compounds with antioxidant and anti-inflammatory properties.

Antiedematogenic activity of the indole derivative N-salicyloyltryptamine in animal models.

PubMed

Sousa-Neto, Benedito P; Gomes, Bruno S; Cunha, Francisco V M; Arcanjo, Daniel D R; Gutierrez, Stanley J C; Souza, Maria F V; Almeida, Fernanda R C; Oliveira, Francisco A

2018-01-01

The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.

Analgesic and Anti-Inflammatory Activities of Rosa taiwanensis Nakai in Mice

PubMed Central

Tsai, Der-Shiang; Huang, Mei-Hsuen; Tsai, Jen-Chieh; Chang, Yuan-Shuang; Chiu, Yung-Jia; Lin, Yen-Chang

2015-01-01

Abstract In this study, we evaluated the analgesic and anti-inflammatory activities of a 70% ethanol extract from Rosa taiwanensis Nakai (RTEtOH). The analgesic effect was determined using acetic acid-induced writhing response and formalin test. The anti-inflammatory activity was evaluated by λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of RTEtOH was examined by measuring the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and malondialdehyde (MDA) in the paw edema tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver tissue. The betulinic acid and oleanolic acid contents of RTEtOH were assayed by HPLC. The results showed that RTEtOH decreased the acetic acid-induced writhing responses (1.0 g/kg) and the late phase of the formalin-induced licking time (0.5 and 1.0 g/kg). In the anti-inflammatory models, RTEtOH (0.5 and 1.0 g/kg) reduced the paw edema at 3, 4, and 5 h after λ-carrageenan administration. Moreover, the anti-inflammatory mechanisms might be due to the decreased levels of COX-2, TNF-α, IL-1β, and IL-6, as well as the inhibition of NO and MDA levels through increasing the activities of SOD, GPx, and GRd. The contents of two active compounds, betulinic acid and oleanolic acid, were quantitatively determined. This study demonstrated the analgesic and anti-inflammatory activities of RTEtOH and provided evidence to support its therapeutic use in inflammatory diseases. PMID:25494361

Antinociceptive and anti-inflammatory effect of sulfated polysaccharide fractions from Sargassum wightii and Halophila ovalis in male Wistar rats

PubMed Central

Neelakandan, Yuvaraj; Venkatesan, Arul

2016-01-01

Aim: The aim of this objective is to evaluate the antinociceptive and anti-inflammatory potential of sulfated polysaccharide purified fractions isolated from brown seaweed Sargassum wightii and seagrass Halophila ovalis in male Wistar rats. Subjects and Methods: Crude sulfated polysaccharide from S. wightii and H. ovalis was subjected to anion exchange chromatography, and the chemical composition was investigated. The antinociceptive activity of purified fractions was investigated using formalin and hot plate test. Carrageenan-induced paw edema, peritonitis model, and Freund's Complete Adjuvant-induced arthritis model were employed to determine the anti-inflammatory activity. Results: In the formalin test, there was a significant reduction in licking time in both phases of the test at a dose of 10 mg/kg. In the hot plate test, the antinociceptive effect was observed only in animals treated with 5, 10 mg/kg suggesting that the analgesic effect occurs through a central action mechanism. Sw FrIV and Ho FrIV significantly inhibited paw edema induced by carrageenan, especially at 3 h after treatment and potentially decreased neutrophil migration at 10 mg/kg, respectively. In Freund's adjuvant-induced arthritic rats, a significant reduction in paw volume was observed in Sw FrIV and Ho FrIV-treated groups (10 mg/kg). Conclusion: Purified components from S. wightii and H. ovalis have strong antinociceptive and anti-inflammatory effect on animal model. However, to determine the molecular mechanism, it is necessary to investigate the effect of purified fractions on inhibition of nitric oxide synthase expression mediated by inhibiting the phosphorylation of various signal proteins in lipopolysaccharide-stimulated RAW264.7 cells. PMID:27721544

Anti-inflammatory potential of silk sericin.

PubMed

Aramwit, Pornanong; Towiwat, Pasarapa; Srichana, Teerapol

2013-04-01

Silk sericin was found to suppress the production of pro-inflammatory cytokines, which are related to the inflammatory reaction. The objectives of this study were to investigate the anti-inflammatory effect of sericin in vivo using the carrageenan-induced rat edema model and changes in the histology of tissues. The effects of sericin on the expression of COX-2 and iNOS were also evaluated. Sericin solutions at 0.004-0.080 mg/mL were applied topically to the top of the hind paw and carrageenan (1.0 mg) was injected subcutaneously to the plantar surface of the right hind paw. Our results indicated that sericin significantly reduced the inflammation in rats' paw compared with the negative control (water and acetone) and its effect at 0.080 mg/mL was only slightly lower than that of 1.0% w/v indomethacin. Similar numbers of polymorphonuclear and macrophage cells were found in rats' tissue treated with indomethacin and sericin solution, while the numbers were significantly higher in their absence. The gene expression results by RT-PCR showed that the COX-2 and iNOS genes were down-regulated in samples treated with sericin in a dose dependent manner. These data indicated that the anti-inflammatory properties of sericin may be partly attributable to the suppression of the COX-2 enzyme and nitric oxide production.

Inhibitory effects of proanthocyanidins from Ribes nigrum leaves on carrageenin acute inflammatory reactions induced in rats

PubMed Central

Garbacki, Nancy; Tits, Monique; Angenot, Luc; Damas, Jacques

2004-01-01

Background The anti-inflammatory effects of proanthocyanidins (PACs), isolated from blackcurrant (Ribes nigrum L.) leaves, were analysed using carrageenin-induced paw oedema and carrageenin-induced pleurisy in rats. Results Pretreatment of the animals with PACs (10, 30, 60 and 100 mg/kg, i.p.) reduced paw oedema induced by carrageenin in a dose and time-dependent manner. PACs also inhibited dose-dependently carrageenin-induced pleurisy in rats. They reduced (A) lung injury, (B) pleural exudate formation, (C) polymorphonuclear cell infiltration, (D) pleural exudate levels of TNF-α, IL-1β and CINC-1 but did not affect IL-6 and IL-10 levels. They reduced (E) pleural exudate levels of nitrite/nitrate (NOx). In indomethacin treated rats, the volume of pleural exudate was low, its content in leukocytes and its contents in TNF-α, IL-1β, IL-6 and IL-10 but not in NOx were reduced. These data suggest that the anti-inflammatory properties of PACs are achieved through a different pattern from those of indomethacin. Conclusion These results suggest that the main mechanism of the anti-inflammatory effect of PACs mainly lies in an interference with the migration of the leukocytes. Moreover, PACs inhibited in vivo nitric oxide release. PMID:15498105

Antiinflammatory activity of an herbal preparation (HemoHIM) in rats.

PubMed

Jo, Sung Kee; Lee, Hae June; Kim, Se Ra; Kim, Jong Choon; Bae, Chun Sik; Jung, Uhee; Park, Hae Ran; Jang, Jong Sik; Kim, Sung Ho

2007-07-01

This study evaluated a new herbal preparation, HemoHIM, for its antiinflammatory activity against carrageenan-induced edema, the formation of granulation tissues by cotton pellet and experimental colitis by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The HemoHIM was prepared by adding its ethanol-insoluble polysaccharide fraction to the total water extract of Angelica Radix, Cnidii Rhizoma and Paeonia Radix. The preparation (4 mg of solids/mL of drinking water, p.o., 50-100 mg/kg of body weight, i.p.) produced a dose-related inhibition of carrageenan-induced paw edema and cotton pellet-induced granuloma in rats. In addition, HemoHIM also reduced the degree of TNBS-induced colitis and improved the gross and histological changes such as thickening, dilatation, ulceration, and infiltration by polymorphonuclear leukocytes and multiple erosive lesions. These results demonstrate that the HemoHIM has a potent antiinflammatory effect. Copyright 2007 John Wiley & Sons, Ltd.

Antinociceptive and anti-edema properties of the ethyl acetate fraction obtained from extracts of Coriandrum sativum Linn. leaves.

PubMed

Begnami, Andreza Fabiana; Spindola, Humberto M; Ruiz, Ana Lucia T Gois; de Carvalho, João Ernesto; Groppo, Francisco Carlos; Rehder, Vera L Garcia

2018-07-01

This study evaluated the antinociceptive and anti-edema properties of fractions of Coriandrum sativum Linn. (Apiaceae/Umbelliferae) leaves in mice. Ethyl acetate fractions (FAc) were obtained from dichloromethane extracts prepared from dried C. sativum (CS) leaves and stems. The effects of different concentrations of FAc on mice were observed using the open-field test, formalin-, capsaicin-, and carrageenan-induced paw edema tests, and the acetic acid-induced abdominal writhing test. Results from the carrageenan-induced paw edema test were subjected to a linear regression analysis and data from other assays were subjected to the Kruskal-Wallis test (followed by the SNK post hoc test). Dihydrocoriandrin (34.5%), coriandrin (14.4%), vitamin E (4.6%), and stigmasterol (7.9%) were identified in FAc. The number of squares the mice crossed in the open field test was decreased by 100 mg/kg and 300 mg/kg FAc (i.p.). The administration of 30, 100, and 300 mg/kg FAc induced fewer abdominal writhes than the control. In the formalin test, neurogenic pain was reduced by 20 mg/kg morphine and 30 and 100 mg/kg FAc, but not 5 mg/kg dexamethasone or 10 mg/kg FAc. Formalin-induced inflammatory pain was decreased by morphine, dexamethasone, and 30 and 100 mg/kg FAc. Morphine and 30, 100, and 300 mg/kg FAc significantly decreased the reaction time during the capsaicin test. Dexamethasone reduced both early and later phases of carrageenan-induced edema. Both 30 and 300 mg/kg FAc induced less edema than the control throughout the experiment. FAc showed antinociceptive, anti-edema and anti-inflammatory properties and it may be considered as a potential phytotherapeutic agent in the future. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Antinociceptive and anti-inflammatory activities of Cuscuta chinensis seeds in mice.

PubMed

Liao, Jung-Chun; Chang, Wen-Te; Lee, Meng-Shiou; Chiu, Yung-Jia; Chao, Wei-Kai; Lin, Ying-Chih; Lin, Ming-Kuem; Peng, Wen-Huang

2014-01-01

The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the λ-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis( CC MeOH ) significantly decreased (p < 0.01 and p < 0.001, respectively) the writhing response in the acetic acid assay. Additionally, 20-500 mg/kg of CC MeOH significantly decreased licking time at the early (20 and 100 mg/kg, p < 0.001) and late phases (100 mg/kg, p < 0.01; 500 mg/kg, p < 0.001) of the formalin test, respectively. Furthermore, CC MeOH (100 and 500 mg/kg) significantly decreased (p < 0.01 and p < 0.001, respectively) edema paw volume four hours after λ-carrageenan had been injected. The results in the following study also revealed that the anti-inflammatory mechanism of CC MeOH may be due to declined levels of NO and MDA in the edema paw by increasing the activities of SOD, GPx and GRd in the liver. In addition, CC MeOH also decreased IL-1β, IL-6, NF-κB, TNF-α, and COX-2 levels. This is the first study to demonstrate the possible mechanisms for the antinociceptive and anti-inflammatory effects of CC MeOH in vivo. Thus, it provides evidence for the treatment of Cuscutae Semen in inflammatory diseases.

Synthesis, Anti-inflammatory and Antibacterial Activities of Novel Pyrazolo[4,3-g]pteridines.

PubMed

Abdel-Mohsen, Shawkat Ahmed; El-Emary, Talaat Ibrahim; El-Kashef, Hussein Salama

2016-01-01

A novel series of 6-substituted pyrazolo[3,4-g]pteridines 2-9 and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pteridin-2(3H)-one (thione) 10 and 11 was synthesized using the starting compound 3,7-dimethyl-1-phenylpyrazolo[4',3':5,6]pyrazino[2,3-d][1,3]oxazin-5(1H)-one 2. The structure of the newly synthesized compounds was elucidated by IR, (1)H-NMR, (13)C-NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity of all the newly synthesized compounds was evaluated using the carrageenan-induced paw oedema test in rats using indomethacin as the reference drug. Compound 11 and the two derivatives 7f and 8b were the most active compounds, showing an activity comparable to indomethacin. Also, the synthesized compounds were evaluated for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) using chloramphenicol as control. The pyrazolotriazolopteridin-2-thione 11, 6-hydroxyethyl- 6a, 6-(4-nitrophenyl)-7g, and 6-(phenylamino) 8b derivatives were found to be the most active compounds against the Gram-positive species. None of them showed any activity against Gram-negative species.

Antibacterial and anti-inflammatory activities of an extract, fractions, and compounds isolated from Gochnatia pulchra aerial parts

PubMed Central

Lucarini, R.; Tozatti, M.G.; Silva, M.L.A.; Gimenez, V.M.M.; Pauletti, P.M.; Groppo, M.; Turatti, I.C.C.; Cunha, W.R.; Martins, C.H.G.

2015-01-01

This paper reports on the in vitro antibacterial and in vivo anti-inflammatory properties of a hydroethanolic extract of the aerial parts of Gochnatia pulchra (HEGP). It also describes the antibacterial activity of HEGP fractions and of the isolated compounds genkwanin, scutellarin, apigenin, and 3,5-O-dicaffeoylquinic acid, as evaluated by a broth microdilution method. While HEGP and its fractions did not provide promising results, the isolated compounds exhibited pronounced antibacterial activity. The most sensitive microorganism was Streptococcus pyogenes, with minimum inhibitory concentration (MIC) values of 100, 50 and 25 µg/mL for genkwanin and the flavonoids apigenin and scutellarin, respectively. Genkwanin produced an MIC value of 25 µg/mL against Enterococcus faecalis. A paw edema model in rats and a pleurisy inflammation model in mice aided investigation of the anti-inflammatory effects of HEGP. This study also evaluated the ability of HEGP to modulate carrageenan-induced interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) production. Orally administered HEGP (250 and 500 mg/kg) inhibited carrageenan-induced paw edema. Regarding carrageenan-induced pleurisy, HEGP at 50, 100, and 250 mg/kg diminished leukocyte migration by 71.43%, 69.24%, and 73.34% (P<0.05), respectively. HEGP suppressed IL-1β and MCP-1 production by 55% and 50% at 50 mg/kg (P<0.05) and 60% and 25% at 100 mg/kg (P<0.05), respectively. HEGP abated TNF-α production by macrophages by 6.6%, 33.3%, and 53.3% at 100, 250, and 500 mg/kg (P<0.05), respectively. HEGP probably exerts anti-inflammatory effects by inhibiting production of the pro-inflammatory cytokines TNF-α, IL-1β, and MCP-1. PMID:26200228

Acute turpentine inflammation and kinin release in rat-paw thermic oedema.

PubMed Central

Limãos, E. A.; Borges, D. R.; Souza-Pinto, J. C.; Gordon, A. H.; Prado, J. L.

1981-01-01

Livers from rats at 2-3 days after s.c. injection of turpentine, when perfused, synthesized prekallikrein nearly 3 times faster than did livers from normal rats. On the other hand paw oedema, produced by heating to 46 degrees, in rats injured in this way was less marked. Likewise in such rats the amount of bradykinin release by 50 min. of coaxial perfusion of the paw was only 13.6 +/- 4.6 compared with 63.1 +/- 13.4 ng in normal rats. A possible explanation for the observed reduction in production of bradykinin may be inhibition of kallikrein due to an increased concentration of alpha 2-macroglobulin. PMID:6173056

Anti-Inflammatory Activities of Cinnamomum cassia Constituents In Vitro and In Vivo

PubMed Central

Liao, Jung-Chun; Deng, Jeng-Shyan; Chiu, Chuan-Sung; Hou, Wen-Chi; Huang, Shyh-Shyun; Shie, Pei-Hsin; Huang, Guang-Jhong

2012-01-01

We have investigated the anti-inflammatory effects of Cinnamomum cassia constituents (cinnamic aldehyde, cinnamic alcohol, cinnamic acid, and coumarin) using lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) and carrageenan (Carr)-induced mouse paw edema model. When RAW264.7 macrophages were treated with cinnamic aldehyde together with LPS, a significant concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) levels productions were detected. Western blotting revealed that cinnamic aldehyde blocked protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear transcription factor kappa B (NF-κB), and IκBα, significantly. In the anti-inflammatory test, cinnamic aldehyde decreased the paw edema after Carr administration, and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated cinnamic aldehyde attenuated the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in the edema paw after Carr injection. Cinnamic aldehyde decreased the NO, TNF-α, and PGE2 levels on the serum level after Carr injection. Western blotting revealed that cinnamic aldehyde decreased Carr-induced iNOS, COX-2, and NF-κB expressions in the edema paw. These findings demonstrated that cinnamic aldehyde has excellent anti-inflammatory activities and thus has great potential to be used as a source for natural health products. PMID:22536283

Anti-inflammatory and anti-granuloma activity of Berberis aristata DC. in experimental models of inflammation

PubMed Central

Kumar, Rohit; Gupta, Yogendra Kumar; Singh, Surender

2016-01-01

Objective: Berberis aristata (Berberidaceae) is an important medicinal plant used in traditional system of medicine for the treatment of rheumatoid arthritis and other inflammatory disorders. The aim of the present study is to scientifically validate the traditional use of BA in the treatment of inflammatory disorders. Materials and Methods: Anti-inflammatory and anti-granuloma activity of BA hydroalcoholic extract (BAHE) were evaluated in experimental models, viz., carrageenan-induced paw edema, cotton pellet-induced granuloma formation, and complete Freund's adjuvant-induced stimulation of peritoneal macrophages in rats. Expression of inflammatory mediators, viz., tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, TNF-R1, and cyclooxygenase-2 (COX-2) was carried out in serum and peritoneal macrophages to derive the plausible mechanism of BAHE in activated peritoneal macrophages. Results: Pretreatment with BAHE produced a dose-dependent reduction (P < 0.01) in carrageenan-induced paw edema and cotton pellet-induced granuloma model. BAHE treatment produced significant (P < 0.01) reduction in serum inflammatory cytokine levels as compared to control. Protein expression of pro-inflammatory markers, IL-1β, IL-6, TNF-R1, and COX-2, was found to be reduced in stimulated macrophages whereas anti-inflammatory cytokine, IL-10, was upregulated in peritoneal macrophages. Conclusion: The result of the present study thus demonstrates the anti-inflammatory and anti-granuloma activity of BAHE which may be attributed to its inhibitory activity on macrophage-derived cytokine and mediators. PMID:27114638

Anti-inflammatory effects of essential oils from Mangifera indica.

PubMed

Oliveira, R M; Dutra, T S; Simionatto, E; Ré, N; Kassuya, C A L; Cardoso, C A L

2017-03-16

Mangifera indica is widely found in Brazil, and its leaves are used as an anti-inflammatory agent in folk medicine. The aim of this study is to perform composition analysis of essential oils from the M. indica varieties, espada (EOMIL1) and coração de boi (EOMIL2), and confirm their anti-inflammatory properties. Twenty-three volatile compounds were identified via gas chromatography-mass spectrometry (GC-MS) in two essential oils from the leaves. Paw edema and myeloperoxidase (MPO) activity were evaluated using the carrageenan-induced paw model, while leukocyte migration was analyzed using the pleurisy model. At oral doses of 100 and 300 mg/kg, the essential oils significantly reduced edema formation and the increase in MPO activity induced by carrageenan in rat paws. For a dose of 300 mg/kg EOMIL1, 62 ± 8% inhibition of edema was observed, while EOMIL2 led to 51 ± 7% inhibition of edema. At a dose of 100 mg/kg, the inhibition was 54 ± 9% for EOMIL1 and 37 ± 7% for EOMIL2. EOMIL1 and EOMIL2 significantly reduced MPO activity at doses of 100 mg/kg (47 ± 5 and 23 ± 8%, respectively) and 300 mg/kg (50 ± 9 and 31 ± 7%, respectively). In the pleurisy model, inhibitions were also observed for EOMIL1 and EOMIL2 in the leukocyte migration test. The results of the present study show that essential oils from M. indica differ in chemical composition and anti-inflammatory activity in rats.

Anti-inflammatory activity of the essential oil obtained from Ocimum basilicum complexed with β-cyclodextrin (β-CD) in mice.

PubMed

Rodrigues, Lindaiane Bezerra; Martins, Anita Oliveira Brito Pereira Bezerra; Ribeiro-Filho, Jaime; Cesário, Francisco Rafael Alves Santana; E Castro, Fyama Ferreira; de Albuquerque, Thaís Rodrigues; Fernandes, Maria Neyze Martins; da Silva, Bruno Anderson Fernandes; Quintans Júnior, Lucindo José; Araújo, Adriano Antunes de Sousa; Menezes, Paula Dos Passos; Nunes, Paula Santos; Matos, Isabella Gonçalves; Coutinho, Henrique Douglas Melo; Goncalves Wanderley, Almir; de Menezes, Irwin Rose Alencar

2017-11-01

Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with β - cyclodextrin (OBEO/β-CD) in mice. The complexation with β-cyclodextrin (β-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with β-CD. The oral administration of OEOB/β-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with β-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synergistic Interaction of Matricaria Chamomilla Extract with Diclofenac and Indomethacin on Carrageenan-Induced Paw Inflammation in Rats.

PubMed

Ortiz, Mario I; Cariño-Cortés, Raquel; Ponce-Monter, Héctor A; González-García, Martha P; Castañeda-Hernández, Gilberto; Salinas-Caballero, Mireya

2017-11-01

Preclinical Research The coadministration of non-steroidal anti-inflammatory drugs (NSAIDs) with medicinal plant extracts may increase anti-inflammatory activity, thus permitting the use of lower NSAID doses and limiting the side effects. The aim of this study was to explore the interactions between an ethanolic extract of M. chamomilla extract (MCE) with two NSAIDs, diclofenac and indomethacin on carrageenan-induced paw inflammation and gastric injury in rats. Diclofenac, indomethacin and MCE, or combinations with MCE produced an anti-inflammatory effect. Effective dose (ED) values were estimated for the individual drugs, and isobolograms were constructed. The final experimental ED values were 483.7 mg/kg for diclofenac + MCE combination, and 212.6 mg/kg for indomethacin + MCE. These values were lower (p < 0.05) than the theoretical ED values (1186.9 mg/kg for diclofenac + MCE combination, and 1183.8 mg/kg for indomethacin + MCE). These data suggest that the interactions between NSAIDs and MCE that mediate the anti-inflammatory effects at the systemic level are synergistic and may have therapeutic advantages for the clinical treatment of inflammatory processes. Drug Dev Res 78 : 360-367, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Anti-inflammatory effects of polyamines in serotonin and carrageenan paw edemata - possible mechanism to increase vascular permeability inhibitory protein level which is regulated by glucocorticoids and superoxide radical.

PubMed

Oyanagui, Y

1984-02-01

Serotonin paw edema of mice and carrageenan paw edema of rats were inhibited by subcutaneously or orally administered certain polyamines. They must be given at least 2 h before serotonin challenge to get inhibitions which were blocked by the concomitant injections of cycloheximide. Thirty percent inhibitory dose (ID30) of polyamines (s.c.) 3 h before serotonin (s.c.) were: spermidine (8 mg/kg), spermine 28 mg/kg) and putrescine (55 mg/kg). Agmatine, cadaverine, ornithine, citrulline, lysine and arginine were not inhibitory even at 200 mg/kg. Three inhibitory polyamines were effective by oral administration but were not inhibitory by local administration into the paws. Intravenous injections of spermidine also required 2 h of lag period for inhibitions. Serotonin edema was inhibited by dexamethasone (1 mg/kg), prednisolone (1 mg/kg) or by superoxide dismutase (SOD, 5 mg/kg) in lag period requiring manner (s.c. and i.v.). High dose of cyclo-oxygenase inhibitors indomethacin and diclofenac sodium, lipo-oxygenase inhibitor BW755C (30 mg/kg s.c., respectively) and phospholipase A2 inhibitor quinacrine (100 mg/kg s.c.) failed to inhibit serotonin edema, suggesting that arachidonate metabolites are not participating in this model. ID30 of polyamines which were administered (s.c. and oral) to rats 3 h before carrageenan and determined at 3 h by paw weight were: spermidine (28 and 100 mg/kg), spermine (18 and 90 mg/kg) and putrescine (both greater than 200 mg/kg). Adrenalectomized rats responded to polyamines just as normal rats. Local vascular permeability, irritancy and acute toxicity were also tested in mice. Polyamines were proved to be glucocorticoid-type anti-inflammatory drugs. Polyamines may be mediators of glucocorticoids for the synthesis of the postulated vascular permeability inhibitory protein (called as 'vasoregulin' for convenience). Anti-inflammatory effect of glucocorticoid is recently explained by its capacity to induce phospholipase A2 inhibitory protein(s) (macrocortin or lipomodulin). However, this hypothesis has not yet been proved by in vivo experiment and our data suggest that there is induction by glucocorticoid of another kind of protein which does not inhibit phospholipase A2 activity.

Discovery of Ecopladib, an indole inhibitor of cytosolic phospholipase A2alpha.

PubMed

Lee, Katherine L; Foley, Megan A; Chen, Lihren; Behnke, Mark L; Lovering, Frank E; Kirincich, Steven J; Wang, Weiheng; Shim, Jaechul; Tam, Steve; Shen, Marina W H; Khor, Soopeang; Xu, Xin; Goodwin, Debra G; Ramarao, Manjunath K; Nickerson-Nutter, Cheryl; Donahue, Frances; Ku, M Sherry; Clark, James D; McKew, John C

2007-03-22

The synthesis and structure-activity relationship of a series of indole inhibitors of cytosolic phospholipase A2alpha (cPLA2alpha, type IVA phospholipase) are described. Inhibitors of cPLA2alpha are predicted to be efficacious in treating asthma as well as the signs and symptoms of osteoarthritis, rheumatoid arthritis, and pain. The introduction of a benzyl sulfonamide substituent at C2 was found to impart improved potency of these inhibitors, and the SAR of these sulfonamide analogues is disclosed. Compound 123 (Ecopladib) is a sub-micromolar inhibitor of cPLA2alpha in the GLU micelle and rat whole blood assays. Compound 123 displayed oral efficacy in the rat carrageenan air pouch and rat carrageenan-induced paw edema models.

Analgesic, antipyretic, anti-inflammatory effects of methanol, chloroform and ether extracts of Vernonia cinerea less leaf.

PubMed

Iwalewa, E O; Iwalewa, O J; Adeboye, J O

2003-06-01

The chloroform, methanolic and ether extracts of Vernonia cinerea (Asteraceae; Less) leaf (100, 200 and 400mg/kg intraperitoneally) were tested in: acetic acid-induced writhing in mice, carrageenin-induced oedema and brewer's yeast-induced pyrexia in rats to assess their analgesic, anti-inflammatory, antipyretic and behavioral activities, respectively. The changes in writhings and behavioural activities in mice, the pyrexia and paw volumes in rats were reduced significantly (P<0.05) compared to the control. There was an increase in pain threshold on the oedematous right hind limb paw of the rats. These results indicate that the extracts could possess analgesic, antipyretic and anti-inflammatory properties. All these effects and the changes in the behavioural activities could be suggested as contributory effects to the use of V. cinerea leaf in the treatment of malaria.

Antithrombotic effects of ethanol extract of Crataegus orientalis in the carrageenan-induced mice tail thrombosis model.

PubMed

Arslan, Rana; Bor, Zeynep; Bektas, Nurcan; Meriçli, Ali Hikmet; Ozturk, Yusuf

2011-03-01

Crataegus species (common name is Hawthorn) are medicinal plants, which have flavonoids, triterpene acids, proanthocyanidins, and organic acids as main constituents, used in the treatment of cardiovascular diseases. One of the main causes of multiple cardiovascular diseases is intravascular thrombosis and current agents, which are used for the treatment and prevention of thrombosis, have some side effects. Therefore, new antithrombotic and thrombolytic agents are still needed. Antithrombotic function of ethanol extract of Crataegus orientalis (COE) leaves was investigated in carrageenan-induced mice tail thrombosis model. Mice were injected with 40 μl (1%) carrageenan (Type I) dissolved in physiological saline by intraplantar administration in the right hind paw. After carrageenan injection, the extract was administered at the doses of 100, 200, and 300 mg/kg. Heparin was used as a positive control (10 and 100 IU). The length of tail-thrombosis was measured at 24th, 48th, and 72nd hours. 100mg/kg COE and 10IU heparin were not significant when compared to control groups at the time interval (24-72 h) that results was obtained. At 24th hour, both 200 and 300 mg/kg of COE showed a significant antithrombotic activity (p<0.05 and p<0.01, respectively). However, 200 mg/kg COE lost its significance and there was a decrease in the significance values of 300 mg/kg COE (p<0.05) at 48 and 72 h. From these results, it was concluded that COE significantly inhibited carrageenan-induced mice tail thrombosis in vivo. Copyright © 2010. Published by Elsevier Ltd.

Antiarthritic activity of Majoon Suranjan (a polyherbal Unani formulation) in rat

PubMed Central

Singh, Surender; Nair, Vinod; Gupta, Y.K.

2011-01-01

Background & objectives: Majoon Suranjan (MS) is a polyherbal formulation used in Unani system of medicine for the treatment of rheumatoid arthritis (RA). The present study evaluates the antiarthritic efficacy of this formulation in three different experimental models. Methods: The anti-inflammatory activity of MS (in doses of 450, 900 and 1800 mg/kg body wt) was evaluated using the turpentine oil induced paw oedema model and the antiarthritic efficacy was evaluated using the formaldehyde and complete Freund's adjuvant (CFA) induced arthritis models. Aspirin (100 mg/kg body wt) was used as the standard drug in all the models. In order to assess the safety of the test drug, oral acute and 28 day toxicity studies were also carried out. Results: MS produced a dose dependent protective effect in all the experimental models. Its antiarthritic efficacy was comparable to aspirin in formaldehyde induced arthritis and was superior to aspirin in turpentine oil induced paw oedema and CFA induced arthritis. MS also inhibited the delayed increase in joint diameter as seen in control and aspirin treated animals in CFA induced arthritis. Oral LD50 of MS was found to be >5000 mg/kg in rats. Chronic administration did not produce any significant physiological changes in the tested animals. Interpretation & conclusions: Results of the present study suggest that the antiarthritic activity of MS was due to the interplay between its anti-inflammatory and disease modifying activities, thus supporting its use in traditional medicine for the treatment of RA. PMID:21985823

Aqueous extract of Codium fragile suppressed inflammatory responses in lipopolysaccharide-stimulated RAW264.7 cells and carrageenan-induced rats.

PubMed

Lee, Seul Ah; Moon, Sung-Min; Choi, Yun Hee; Han, Seul Hee; Park, Bo-Ram; Choi, Mi Suk; Kim, Jae-Sung; Kim, Yong Hwan; Kim, Do Kyung; Kim, Chun Sung

2017-09-01

Codium fragile (Suringar) Hariot has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria and has been shown to have various biological effects. In this study, we evaluated the anti-inflammatory effects of aqueous extract of C. fragile (AECF) using in vitro and in vivo models. Nitric oxide (NO), prostaglandin E 2 (PGE 2 ), inflammatory-related mRNAs, and proteins were determined using the Griess assay, enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and western blotting, respectively. Our results indicate that pretreatment of cells with AECF (50, 100 and 200μg/mL) significantly inhibited LPS-induced secretion of NO and PGE 2 in RAW264.7 cells without cytotoxicity. We also found that AECF (100 and 200μg/mL) inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 expression in a dose-dependent manner. Additionally, pretreatment of cells with AECF (100 and 200μg/mL) inhibited LPS-induced production of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. It also prevented the nuclear translocation of nuclear factor (NF)-κB by suppressing the phosphorylation and degradation of inhibitor of NF-κB (IκB)-α. Furthermore, AECF (100 and 200μg/mL) inhibited the phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. In addition, orally administered 50, 100, and 200mg/kg body weight of AECF dose-dependently suppressed carrageenan-induced rat paw edema thickness by 6%, 31%, and 50% respectively, after 4h. Furthermore, the anti-inflammatory effect was comparable to that observed in animals treated with the standard drug diclofenac sodium (56%) in vivo. Collectively, our results suggest that AECF exerts potential anti-inflammatory effects by suppressing NF-κB activation and MAPKs pathways in vitro, as well as inhibiting carrageenan-induced rat paw edema thickness in vivo. These findings indicate that AECF could be further developed as an anti-inflammatory drug. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Ketamine-xylazine anaesthesia and orofacial administration of substance P: A lethal combination in rats.

PubMed

Francischi, Janetti N; Frade, Taíssa Iolanda C; Almeida, Marcella P A de; Queiroz, Bárbara F G de; Bakhle, Y S

2017-04-01

Ketamine+xylazine mixture is a widely used anaesthetic in animal experiments. In rats anaesthetized with this mixture, we have shown that injection of carrageenan, a standard proinflammatory stimulus, into the cheek (intra-oral injection) induced oedema. A likely mediator of this oedema is substance P (SP), a major transmitter of sensory nerves in orofacial tissue. We have assessed the effects of intra-oral injection of SP in rats. SP (50-1μg per rat) was injected intra-orally in male adult Holtzman or Wistar rats, anaesthetized with ketamine+xylazine. For comparison, histamine (50μg) and 5-HT (5μg) were similarly injected. Antagonists of SP (SR140333, 2mg/kg), of histamine (pyrilamine, 2mg/kg) or of 5-HT (pizotifen, 2mg/kg) were subcutaneously (s.c.) injected, 30min before the corresponding agonist. Oedema in the cheek was assessed by measuring tissue thickness with calipers. Intra-oral injection of SP (1-50μg per rat) in Holtzman or Wistar rats anaesthetized with ketamine+xylazine induced, dose-dependently, death within 15min, accompanied by signs of excessive salivation. Rats pretreated with SR140333 were protected against SP-induced lethality and the excessive salivation. However, intra-oral injection of either histamine or 5-HT did not induce death, only a characteristic cheek oedema. These doses of SP injected into the hindpaws of conscious Holtzman and Wistar rats only induced oedema with no deaths. In rats anaesthetized with inhaled isoflurane, intra-oral SP (50μg) induced only cheek oedema, with no deaths or excessive salivation. This oedema was prevented by pre-treating rats with SR140333, pyrilamine and pizotifen. It is likely that the deaths were due to excessive salivation induced by the particular combination of ketamine and SP. Our results are presented as a warning to other experimenters who might use these two otherwise non-toxic conditions and the consequent unexpected and needless loss of experimental animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analgesic and anti-inflammatory effects of UP1304, a botanical composite containing standardized extracts of Curcuma longa and Morus alba.

PubMed

Yimam, Mesfin; Lee, Young-Chul; Moore, Breanna; Jiao, Ping; Hong, Mei; Nam, Jeong-Bum; Kim, Mi-Ran; Hyun, Eu-Jin; Chu, Min; Brownell, Lidia; Jia, Qi

2016-01-01

Though the initial etiologies of arthritis are multifactorial, clinically, patients share the prime complaints of the disease, pain. Here the authors assessed the analgesic and anti-inflammatory effects of UP1304, a composite that contains a standardized blend of extracts from the rhizome of Curcuma longa and the root bark of Morus alba, on rats with carrageenan-induced paw edema. A plant library was screened for bradykinin receptor antagonists. In vivo, the anti-inflammatory and analgesic effects of the standardized composite, UP1304, were evaluated in rats with carrageenan-induced paw edema using oral dose ranges of 100-400 mg/kg. Ibuprofen, at a dose of 200 mg/kg, was used as a reference compound. In vitro, cyclooxygenase (COX) and lipoxygenase (LOX) inhibition assays were performed to evaluate the degree of inflammation. Statistically significant improvements in pain resistance and paw edema suppression were observed in animals treated with UP1304, when compared to vehicle-treated rats. Results from the highest dose of UP1304 (400 mg/kg) were similar to those achieved by ibuprofen treatment at 200 mg/kg. In vitro, UP1304 showed dose-dependent inhibition of the enzymatic activities of COX and LOX. A half-maximal inhibitory concentration of 9.6 μg/mL for bradykinin B1 inhibition was calculated for the organic extract of C. longa. Curcumin showed Ki values of 2.73 and 58 μg/mL for bradykinin receptors B1 and B2, respectively. Data presented here suggest that UP1304, analgesic and anti-inflammatory agent of botanical origin, acted as a bradykinin receptor B1 and B2 antagonist, and inhibited COX and LOX enzyme activities. This compound should be considered for the management of symptoms associated with arthritis.

Antioxidant, analgesic and anti-inflammatory activities of the methanolic extract of Piper betle leaves.

PubMed

Alam, Badrul; Akter, Fahima; Parvin, Nahida; Sharmin Pia, Rashna; Akter, Sharmin; Chowdhury, Jesmin; Sifath-E-Jahan, Kazi; Haque, Ekramul

2013-01-01

The present study was designed to evaluate the antioxidant, analgesic, and anti-inflammatory activities of the methanolic extract of Piper betle leaves (MPBL). MPBL was evaluated for anti-inflammatory activity using carrageenan-induced hind paw edema model. Analgesic activity of MPBL was evaluated by hot plate, writhing, and formalin tests. Total phenolic and flavonoids content, total antioxidant activity, scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, peroxynitrate (ONOO) as well as inhibition of total ROS generation, and assessment of reducing power were used to evaluate antioxidant potential of MPBL. The extract of MPBL, at the dose of 100 and 200 mg/kg, produced a significant (p<0.05) increase in pain threshold in hot plate method whereas significantly (p<0.05) reduced the writhing caused by acetic acid and the number of licks induced by formalin in a dose-dependent manner. The same ranges of doses of MPBL caused significant (p<0.05) inhibition of carrageenan-induced paw edema after 4 h in a dose-dependent manner. In DPPH, ONOO(-), and total ROS scavenging method, MPBL showed good antioxidant potentiality with the IC50 value of 16.33±1.02, 25.16±0.61 , and 41.72±0.48 µg/ml, respectively with a significant (p<0.05) good reducing power. The findings of the study suggested that MPBL has strong analgesic, anti-inflammatory, and antioxidant effects, conforming the traditional use of this plant for inflammatory pain alleviation to its antioxidant potentiality.

Evaluation of the anti-inflammatory activity of the aqueous and ethanolic extracts of the leaves of Albizzia lebbeck in rats

PubMed Central

Meshram, Girish Gulab; Kumar, Anil; Rizvi, Waseem; Tripathi, C.D.; Khan, R.A.

2015-01-01

Albizzia lebbeck Benth. (Mimosaceae) is a medicinal tree used to treat several inflammatory ailments in the Indian traditional Ayurvedic system of medicine. The aim of the present study was to evaluate the possible anti-inflammatory activity of the aqueous (AE) and ethanolic (EE) extracts of the leaves of A. lebbeck to support the ethnopharmacological claims. The study was carried out using Wistar rats (100–150 g). The AE and EE were prepared using the Soxhlet extraction process. The anti-inflammatory activity of the AE and EE of the leaves of A. lebbeck were studied using carrageenan-induced paw edema and cotton pellet-induced granuloma models. The AE and EE of the leaves of A. lebbeck at doses of 50, 100, and 200 mg/kg p.o. (oral administration) showed a dose-dependent and significant (p < 0.05) inhibition of carrageenan-induced hind paw edema with maximum percentage inhibition (PI) values of 22.34, 30.85, 39.36 and 22.53, 32.98, 42.55, respectively. The AE and EE at doses of 50, 100, 200 mg/kg p.o. significantly (p < 0.05) inhibited granuloma formation with PI values of 19.07, 27.57, 38.55 and 23.93, 32.23, 42.33, respectively. The AE and EE of the leaves of A. lebbeck showed significant (p < 0.05) anti-inflammatory activity. PMID:27114941

Evaluation of the anti-inflammatory activity of the aqueous and ethanolic extracts of the leaves of Albizzia lebbeck in rats.

PubMed

Meshram, Girish Gulab; Kumar, Anil; Rizvi, Waseem; Tripathi, C D; Khan, R A

2016-04-01

Albizzia lebbeck Benth. (Mimosaceae) is a medicinal tree used to treat several inflammatory ailments in the Indian traditional Ayurvedic system of medicine. The aim of the present study was to evaluate the possible anti-inflammatory activity of the aqueous (AE) and ethanolic (EE) extracts of the leaves of A. lebbeck to support the ethnopharmacological claims. The study was carried out using Wistar rats (100-150 g). The AE and EE were prepared using the Soxhlet extraction process. The anti-inflammatory activity of the AE and EE of the leaves of A. lebbeck were studied using carrageenan-induced paw edema and cotton pellet-induced granuloma models. The AE and EE of the leaves of A. lebbeck at doses of 50, 100, and 200 mg/kg p.o. (oral administration) showed a dose-dependent and significant (p < 0.05) inhibition of carrageenan-induced hind paw edema with maximum percentage inhibition (PI) values of 22.34, 30.85, 39.36 and 22.53, 32.98, 42.55, respectively. The AE and EE at doses of 50, 100, 200 mg/kg p.o. significantly (p < 0.05) inhibited granuloma formation with PI values of 19.07, 27.57, 38.55 and 23.93, 32.23, 42.33, respectively. The AE and EE of the leaves of A. lebbeck showed significant (p < 0.05) anti-inflammatory activity.

Anti-inflammatory activity of Arnica montana 6cH: preclinical study in animals.

PubMed

Macêdo, S B; Ferreira, L R; Perazzo, F F; Carvalho, J C

2004-04-01

The anti-inflammatory effect of Arnica montana 6cH was evaluated using acute and chronic inflammation models. In the acute, model, carrageenin-induced rat paw oedema, the group treated with Arnica montana 6cH showed 30% inhibition compared to control (P < 0.05). Treatment with Arnica 6cH, 30 min prior to carrageenin, did not produce any inhibition of the inflammatory process. In the chronic model, Nystatin-induced oedema, the group treated 3 days previously with Arnica montana 6cH had reduced inflammation 6 h after the inflammatory agent was applied (P < 0.05). When treatment was given 6 h after Nystatin treatment, there was no significant inhibitory effect. In a model based on histamine-induced increase of vascular permeability, pretreatment with Arnica montana 6cH blocked the action of histamine in increasing vascular permeability.

Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis

PubMed Central

Liu, Shu-Ling; Deng, Jeng-Shyan; Chiu, Chuan-Sung; Hou, Wen-Chi; Huang, Shyh-Shyun; Lin, Wang-Ching; Liao, Jung-Chun; Huang, Guan-Jhong

2012-01-01

Anti-inflammatory effects of the aqueous extract of Hibiscus taiwanensis (AHT) were used in lipopolysaccharide (LPS-)stimulated mouse macrophage RAW264.7 cells and carrageenan (Carr-)induced mouse paw edema model. When RAW264.7 macrophages were treated with AHT together with LPS, a concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) levels productions were detected. Western blotting revealed that AHT blocked protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and elevated heme oxygenase-1 (HO-1), significantly. In the animal test, AHT decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated AHT decreased the NO, TNF-α, and PGE2 levels on the serum level at the 5th h after the Carr injection. Western blotting revealed that AHT decreased Carr-induced iNOS, and COX-2, and increased HO-1 expressions at the 5th h in the edema paw. These findings demonstrated that AHT has excellent anti-inflammatory activities in vitro and in vivo and thus it has great potential to be used as a source for natural health products. PMID:22778769

Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis.

PubMed

Liu, Shu-Ling; Deng, Jeng-Shyan; Chiu, Chuan-Sung; Hou, Wen-Chi; Huang, Shyh-Shyun; Lin, Wang-Ching; Liao, Jung-Chun; Huang, Guan-Jhong

2012-01-01

Anti-inflammatory effects of the aqueous extract of Hibiscus taiwanensis (AHT) were used in lipopolysaccharide (LPS-)stimulated mouse macrophage RAW264.7 cells and carrageenan (Carr-)induced mouse paw edema model. When RAW264.7 macrophages were treated with AHT together with LPS, a concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE(2)) levels productions were detected. Western blotting revealed that AHT blocked protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and elevated heme oxygenase-1 (HO-1), significantly. In the animal test, AHT decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated AHT decreased the NO, TNF-α, and PGE2 levels on the serum level at the 5th h after the Carr injection. Western blotting revealed that AHT decreased Carr-induced iNOS, and COX-2, and increased HO-1 expressions at the 5th h in the edema paw. These findings demonstrated that AHT has excellent anti-inflammatory activities in vitro and in vivo and thus it has great potential to be used as a source for natural health products.

Formulation and evaluation of once-a-day transdermal gels of diclofenac diethylamine.

PubMed

Baboota, S; Shakeel, F; Kohli, K

2006-03-01

The present study was undertaken to prepare and evaluate transdermal gels of diclofenac diethylamine (DDEA) containing penetration enhancers such as olesan oil and dimethyl sulfoxide (DMSO). Transdermal gels were prepared using different polymers such as carbopol-940, polyvinyl alcohol (PVA), hydroxy propyl methyl cellulose-K(4) M, hydroxy propyl cellulose-M, and sodium carboxy methyl cellulose. The formulated gels were subjected to physicochemical studies, in vitro release studies and in vitro skin permeations studies and were evaluated for drug content, viscosity, extrudability, spreadability, and pH. The in vitro release studies of prepared gels were performed using specially designed Fites cell and in vitro skin permeation studies were performed using keshary-chien diffusion cell through rat skin. Selected formulations were evaluated for their antiinflammatory activity using the carrageenan-induced paw edema in rats. The carbopol-940 and PVA gels containing 10% DMSO showed best in vitro skin permeation of DDEA. In vivo study for the selected formulation showed a sustained reduction in inflammation in the carrageenan induced paw edema in rats. The efficacies of carbopol-940 and PVA gels were also compared with that of the marketed Voveran gel,(R) and it was found that carbopol and PVA gels produced better results than the Voveran gel. (c) 2006 Prous Science. All rights reserved. (c) 2006 Prous Science. All rights reserved.

Antioxidant, antibacterial, anti-inflammatory and wound healing effects of Artemisia campestris aqueous extract in rat.

PubMed

Ghlissi, Zohra; Sayari, Nadhim; Kallel, Rim; Bougatef, Ali; Sahnoun, Zouheir

2016-12-01

This study investigated some biological properties of Artemisia campestris aqueous extract (ACAE) as well its global chemical compositions. Twenty four rats were excised on the posterior neck skin area and divided into 4 groups, treated respectively with: sterile saline, glycerol, CICAFLORA and ACAE. The wound closure rate, histopathology evolution and the superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) level in skin tissue were evaluated. Anti-inflammatory activity was studied by carrageenan-induced rat paw edema. Animals were divided into 3 groups pre-treated respectively with sterile saline, acetylsalicylic acid (AA) and ACAE. The antibacterial activity was tested against six bacteria and the antioxidant activity was estimated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH), reducing power and β-carotene activities. Our results demonstrated a significant improvement in wound healing progression and in oxidative stress damage in the wounds tissues of ACAE-treated rats, compared to control. ACAE-treated rats revealed also a significant inhibition of carrageenan-induced hind paws edema as confirmed by the histological analysis. In addition to the antioxidant activity, ACAE showed considerable antibacterial activities. ACAE exhibited important wound healing effect probably due to the anti-inflammatory, antibacterial and antioxidant activities of its phytochemical contents. Therefore, this study confirms its popular use and highlights its promise in the development of new drugs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Red Pepper (Capsicum baccatum) Extracts Present Anti-Inflammatory Effects In Vivo and Inhibit the Production of TNF-α and NO In Vitro.

PubMed

Allemand, Alexandra; Leonardi, Bianca Franco; Zimmer, Aline Rigon; Moreno, Susana; Romão, Pedro Roosevelt Torres; Gosmann, Grace

2016-08-01

Capsicum baccatum is the most consumed red pepper species in Brazil. Our previous studies demonstrated the anti-inflammatory properties of its crude extract, whose activity is yet to be fully characterized. Herein, we examined the anti-inflammatory in vivo effects of enriched extracts obtained through bioguided fractionation as dichloromethane (DCM), butanol (BUT), and residual aqueous (RAq) extracts and its influence on inflammatory mediators produced by macrophages in vitro. We demonstrated that all C. baccatum extracts presented anti-inflammatory activity in vivo. In addition, we showed that BUT and RAq were more effective in inhibiting the neutrophil migration induced by carrageenan (Cg) to peritoneal cavity and both extracts inhibited paw edema induced by Cg, prostaglandin E2, and histamine in mice. Furthermore, the pretreatment with C. baccatum extracts significantly reduced the levels of myeloperoxidase (MPO) in the paw tissues of mice compared with the carrageenan group. Once again, RAq and BUT caused the greatest reduction in MPO levels. Moreover, it was demonstrated for the first time that C. baccatum inhibited the nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide/interferon gamma (IFN-γ)-stimulated macrophages. These anti-inflammatory effects seem to be at least, in part, independent of capsaicin. Hence, red pepper has bioactive compounds and might be used to develop food-derived extracts to treat related inflammatory diseases.

2-Pentadecyl-2-Oxazoline, the Oxazoline of Pea, Modulates Carrageenan-Induced Acute Inflammation

PubMed Central

Petrosino, Stefania; Campolo, Michela; Impellizzeri, Daniela; Paterniti, Irene; Allarà, Marco; Gugliandolo, Enrico; D’Amico, Ramona; Siracusa, Rosalba; Cordaro, Marika; Esposito, Emanuela; Di Marzo, Vincenzo; Cuzzocrea, Salvatore

2017-01-01

N-acylethanolamines (NAEs) involve a family of lipid molecules existent in animal and plant, with N-palmitoylethanolamide (PEA) that arouses great attention owing to its anti-inflammatory, analgesic and neuroprotective activities. Because PEA is produced on demand and exerts pleiotropic effects, the modulation of specific amidases for NAEs (and in particular NAE-hydrolyzing acid amidase NAAA, which is more selective for PEA) could be a condition to preserve its levels. Here we investigate the effect of 2-Pentadecyl-2-oxazoline (PEA-OXA) the oxazoline of PEA, on human recombinant NAAA in vitro and in an established model of Carrageenan (CAR)-induced rat paw inflammation. PEA-OXA dose-dependently significantly inhibited recombinant NAAA and, orally administered to rats (10 mg/kg), limiting histological damage, thermal hyperalgesia and the increase of infiltrating inflammatory cells after CAR injection in the rat right hindpaw, compared to ultramicronized PEA given orally at the same dose (10 mg/kg). These effects were accompanied by elevation of paw PEA levels. Moreover, PEA-OXA markedly reduced neutrophil infiltration and pro-inflammatory cytokine release and prevented CAR-induced IκB-α degradation, nuclear translocation of NF-κB p65, the increase of inducible nitric oxide synthase, cyclooxygenase-2, intercellular adhesion molecule-1, and mast cell activation. Experiments in PPAR-α knockout mice showed that the anti-inflammatory effects of PEA-OXA were not dependent on the presence of PPAR-α receptors. In conclusion, NAAA modulators as PEA-OXA could help to maximize the tissue availability of PEA by increasing its levels and anti-inflammatory effects. PMID:28611664

Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract of Leonotis ocymifolia (Burm.f.) Iwarsson Leaves in Rodent Models

PubMed Central

Alemu, Asnakech

2018-01-01

Background Pain and inflammation are the major health problems commonly treated with traditional remedies mainly using medicinal plants. Leonotis ocymifolia is one of such medicinal plants used in folkloric medicine of Ethiopia. However, the plant has not been scientifically evaluated. The aim of this study was to evaluate analgesic and anti-inflammatory effects of the 80% methanol leaves extract of Leonotis ocymifolia using rodent models. Method The central and peripheral analgesic effect of the extract at 100, 200, and 400 mg/kg dose levels was evaluated using hot plate and acetic acid induced writhing rodent models, whereas carrageenan induced paw edema and cotton pellet granuloma methods were used to screen anti-inflammatory effect of the extract at the same dose levels. Acute toxicity test was also done. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test and p < 0.05 was considered significant. Results The extract did not produce mortality up to 2000 mg/kg. All tested doses of the extract showed significant analgesic effect with maximum latency response of 62.8% and inhibition of acetic acid induced writhing. Maximum anti-inflammatory effect was recorded at 6 h after induction, with 75.88% reduction in carrageenan induced paw edema. Moreover, all tested doses of extract significantly inhibited the formation of inflammatory exudates and granuloma formation (p < 0.001). Conclusion The study indicated that the extract was safe in mice and it has both analgesic and anti-inflammatory effect in rodent models. PMID:29675050

Antiulcerogenic and antiinflammatory studies with shilajit.

PubMed

Goel, R K; Banerjee, R S; Acharya, S B

1990-04-01

In folk medicine, shilajit has been used to treat diverse clinical conditions ranging from peptic ulcer to bone healing. The present study was conducted to evaluate the possible antiulcerogenic and antiinflammatory activities of shilajit obtained from the rocky mountains of Zarlek, Badekshan, Afghanistan. Shilajit increased the carbohydrate/protein ratio and decreased gastric ulcer index, indicating an increased mucus barrier. Shilajit was found to have significant antiinflammatory effect in carrageenan-induced acute pedal oedema, granuloma pouch and adjuvant-induced arthritis in rats. The results of the present study thus substantiate the use of shilajit in peptic ulcer and inflammation.

Chemical characterization and pharmacological assessment of polysaccharide free, standardized cashew gum extract (Anacardium occidentale L.).

PubMed

da Silva, Daiany Priscilla Bueno; Florentino, Iziara Ferreira; da Silva Moreira, Lorrane Kelle; Brito, Adriane Ferreira; Carvalho, Verônica Vale; Rodrigues, Marcella Ferreira; Vasconcelos, Géssica Adriana; Vaz, Boniek Gontijo; Pereira-Junior, Marcus Antônio; Fernandes, Kátia Flávia; Costa, Elson Alves

2018-03-01

The cashew gum (Anacardium occidentale L.) is used in traditional Brazilian medicine in the treatment of inflammatory conditions, asthma, diabetes, and gastrointestinal disturbances. In the present study, we aimed at forming a chemical characterization and investigation of the antinociceptive and anti-inflammatory activities of the aqueous extract of cashew gum without the presence of polysaccharides in its composition (CGE). The CGE was obtained after the precipitation and removal of polysaccharides through the use of acetone. After, the acetone was removed by rotaevaporation, and the concentrated extract was lyophilized. The chemical characterization of CGE was performed by liquid chromatography mass spectrometry (LC-MS) and tandem mass spectrometry (MS/MS) analyses. Mice were used for the evaluation of the antinociceptive and anti-inflammatory activities. CGE was analyzed via the Irwin test, acetic acid-induced writhing test, formalin-induced pain test, and carrageenan-induced paw edema test. The motor activity or probable sedation was verified through the chimney, open-field, and sodium pentobarbital-induced sleep tests. We investigated if the analgesic and anti-inflammatory effects of CGE depend of reduction in PGE 2 levels, were performed the carrageenan or PGE 2 -induced hyperalgesia tests. The chemical characterization of CGE showed the presence of anacardic acids as the predominant phytoconstituents. The treatment with CGE (75, 150, and 300mg/kg, p.o.) inhibited the number of writhing in a dose-dependent manner. With an intermediate dose, CGE did not cause motor impairment with the chimney test or alterations in either the open-field or sodium pentobarbital-induced sleep. In the formalin-induced pain test, CGE (150mg/kg, p.o.) produced an antinociceptive effect only in the first phase of the test, suggesting anti-inflammatory activity. With the same dosage, CGE also reduced the carrageenan-induced paw edema at all hours of the test, confirming its anti-inflammatory effect. Furthermore, CGE (150mg/kg, p.o.) presented an antihyperalgic effect at all hours of the carrageenan-induced hyperalgesia test. However, this dose of CGE was not able to reduce the hyperalgesia induced by PGE 2 , suggesting that the anti-inflammatory effect of this extract depends on the reduction in the PGE 2 levels. The anacardic acids are the predominant phytoconstituents identified in the CGE. The action mechanisms of CGE suggest the reduction in the PGE 2 levels. These findings support the use of cashew gum in popular medicine and demonstrate that part of its antinociceptive and anti-inflammatory effects should also be attributed to the presence of anacardic acids in its composition, independent of the presence of polysaccharides. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of phytochemicals, antioxidant, and anti-inflammatory potential of Boerhavia procumbens Banks ex Roxb.

PubMed

Bokhari, Jasia; Khan, Muhammad Rashid; Haq, Ihsan Ul

2016-08-01

Boerhavia procumbens is traditionally used in the treatment of various disorders including jaundice and gonorrhea, is a refrigerant, and exhibits anti-inflammatory and antispasmodic activities. The purpose of this study was to determine the phytochemical classes, antioxidant and anti-inflammatory activities of methanol extract (BPME) and different fractions (n-hexane (BPHE), ethyl acetate (BPEE), n-butanol (BPBE), and residual aqueous fraction (BPAE)) of B. procumbens against carrageenan-induced paw edema in rats. To assess the anti-inflammatory effects of B. procumbens, 42 Sprague Dawley male rats (150-200 g) were randomly divided into seven groups. Group I received distilled water and group II was treated with diclofenac potassium (10 mg/kg) body weight (bw) orally. Groups III, IV, V, VI, and VII were administered BPME, BPHE, BPEE, BPBE, and BPAE (200 mg/kg bw) orally, 1 h before the treatment with carrageenan (10 mg/kg bw) in rats. Anti-inflammatory effects of B. procumbens were determined by estimating the inhibition of edema at 1st, 2nd, and 3rd hour after carrageenan injection. Qualitative analysis of methanol extract indicated the composition of diverse classes, namely, flavonoids, tannins, saponins, phlobatannins, cardiac glycosides, alkaloids, terpenoids, and anthraquinones. Quantitative determination illustrated that BPBE and BPEE possessed the highest concentration of total phenolic (60.45 ± 2.1 mg gallic acid equivalent per gram sample) and total flavonoid content (68.05 ± 2.3 mg rutin equivalent per gram sample), respectively. A dose-dependent response for antioxidant activity was exhibited by all the samples. The sample with the highest aptitude for antioxidant activity was the BPBE for 2,2-azobis,3-ethylbenzothiozoline-6-sulfonic acid radical scavenging and total antioxidant capacity. Carrageenan-induced paw edema was significantly (p < 0.05) inhibited by BPBE and BPME at the 1st, 2nd, and 3rd hour and was comparable to control drug diclofenac potassium. Results revealed that various fractions of B. procumbens manifested the antioxidant and anti-inflammatory potential and accredit the local use of B. procumbens in various disorders. © The Author(s) 2015.

Amelioration of FCA induced arthritis on topical application of curcumin in combination with emu oil.

PubMed

Jeengar, Manish Kumar; Shrivastava, Shweta; Mouli Veeravalli, S Chandra; Naidu, V G M; Sistla, Ramakrishna

2016-09-01

The aim of the present study was to investigate the skin penetration potential of emu oil and the possibility of enhancing the antiarthritic potential of lipophilic bioactive curcumin, which has poor permeability through biological membranes. Solubility and ex vivo skin permeation studies were performed with water, corn oil, and emu oil as a vehicle using curcumin as a model drug. Carrageenan induced inflammation and Freund's complete adjuvant-induced arthritic rat models were used to evaluate enhanced antiinflammatory and antiarthritic effect of curcumin in combination of emu oil via topical route. The skin permeation study resulted in the combination of emu oil with curcumin enhancing the flux 1.84 and 4.25 times through the rat skin compared to corn oil and water, respectively. Results of carrageenan induced rat paw edema model demonstrated that percentage of paw inhibition shown by curcumin-emu oil combination was 1.42-fold more compared to the total effect shown by both groups treated with curcumin aqueous suspension and emu oil per se. In Freund's complete adjuvant-induced arthritic model, the combined treatment was effective in bringing significant changes in the functional, biochemical, histopathologic, and radiologic parameters. Topical application of curcumin-emu oil combination resulted in significant reduced levels of proinflammatory mediators TNF-α, IL-1 β, and IL-6 (P < 0.05, 0.001, and 0.01, respectively) compared to arthritic animals. Topical delivery of curcumin with emu oil holds promise as a noninvasive and efficacious intervention for the treatment of inflammatory arthritis and it assists in further development of a topical formulation of curcumin using emu oil as a vehicle. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Saraca asoca (Asoka) on estradiol-induced keratinizing metaplasia in rat uterus.

PubMed

Shahid, Adangam Purath; Salini, Sasidharan; Sasidharan, Nanu; Padikkala, Jose; Raghavamenon, Achuthan Chathrattil; Babu, Thekkekara Devassy

2015-09-01

Estrogen-mediated uterus endometrium instability is considered as one of the etiological factors in dysfunctional uterine bleeding (DUB) and uterine cancer. Saraca asoca (Family: Fabaceae) and its fermented preparation, Asokarishta, are extensively used as uterine tonic to treat gynecological disorders in Ayurveda. The present study evaluated the effect of S. asoca (Asoka) on estrogen-induced endometrial thickening of rat uterus. Endometrial thickening was induced by intraperitoneal injection of estradiol (20 μg/kg b.wt) to 8-day-old immature rats for alternate 5 days. Methanolic extract (200 mg/kg b. wt) from S. asoca bark was given orally along with estradiol. Uterus endometrial thickening was analyzed histopathologically and serum estrogen level by radioimmunoassay (RIA). Cyclooxygenase (COX-2) expression in rat uterus was also estimated by Western blot. Anti-inflammatory activity of the extract was analyzed by formalin- and carrageenan-elicited paw edema models in mouse. Uterus endometrium proliferation and keratinized metaplasia with seven to eight stratified epithelial layers on day 16 was observed in rats administered with estradiol. Treatment with S. asoca reduced the thickening to two to four layers and the serum estrogen level diminished significantly to 82.9±12.87 pg/mL compared to rats administered with estrogen alone (111.2±10.68 pg/mL). A reduction of formalin- and carrageenan-induced paw edema in mouse by S. asoca extract was observed. Lower level of lipopolysaccharides (LPS)-induced COX-2 enzyme in rat uterus by the extract further confirms its anti-inflammatory activity. Present study reveals the antiproliferative and antikeratinizing effects of S. asoca in uterus endometrium possibly through its anti-estrogenic and anti-inflammatory properties.

Anti-inflammatory and antioxidant effect of Kerabala: a value-added ayurvedic formulation from virgin coconut oil inhibits pathogenesis in adjuvant-induced arthritis.

PubMed

Ratheesh, M; Sandya, S; Pramod, C; Asha, S; Svenia, Jose P; Premlal, S; GrishKumar, B

2017-02-01

Kerabala (CB) is a novel ayurvedic formulation used for treating various inflammatory diseases. This formulation was made from virgin coconut oil and it comprises extracts of Sida cordifolia, coconut milk and sesame oil. The current study was performed to evaluate the anti-inflammatory action of CB on carrageenan-induced acute and adjuvant-induced chronic experimental models. 5 mg/kg bwt was found to be potent dose from carrageenan model and evaluated its effect in adjuvant-induced chronic arthritic model. The antioxidant assays like SOD, catalase, glutathione peroxidase, lipid peroxidation product, nitrate level and GSH were measured in paw tissue. Hematological parameters like hemoglobin (HB) count, ESR, WBC count, plasma CRP levels were analyzed. By RT-PCR, the inflammatory markers like cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) expressions were evaluated. The extracellular matrix proteins like MMP-2 and MMP-9 were determined by zymography and its expression by western blotting. Histopathology and cytology of paw tissue and synovium were analyzed. The result indicated that there was a significant increment in the levels of antioxidant enzymes on CB administration. The hematological markers such as ESR, WBC and plasma CRP levels were reduced by CB treatment and it also increases the HB level. The upregulated gene level expressions of inflammatory markers like COX-2, iNOS, TNF-α and IL-6 were down regulated by administration of CB. MMP-2 and MMP-9 expression significantly reduced by CB administration. Massive influx of inflammatory cell infiltration, proliferative collagen in histological analysis of paw tissue of arthritic rat was decreased by CB administration. Synovial cytology of CB administrated group shows reduced number of reactive mesothelial cells and synovial inflammatory cells. This current study shows that ayurvedic drug CB has an antioxidant, anti-inflammatory and anti-arthritic activity in experimental arthritic model. CB as an anti-arthritic drug has beneficial effect for treating inflammation, tissue damage and pain associated with arthritis.

Antimicrobial, Anti-inflammatory and Antioxidant Activities of Jatropha multifida L. (Euphorbiaceae).

PubMed

Anani, Kokou; Adjrah, Yao; Améyapoh, Yaovi; Karou, Simplice Damintoti; Agbonon, Amegnona; de Souza, Comlan; Gbeassor, Messanvi

2016-01-01

Jatropha multifida is used in Togolease folk medicine for the healing of chronic wounds. This study aims to investigate antibacterial, anti-inflammatory and antioxidant activities of the leaves ethanolic extract. The antimicrobial activity was assayed by National Committee for Clinical Laboratory Standards broth microdilution method on strains of Staphylococcus aureus and Pseudomoas aeruginosa isolated from wounds, whereas the anti-inflammatory activity was performed by carrageenan and histamine induced paw edema method in rat modele. The 2, 2-diphenyl-1picrylhydrazyl (DPPH) free radical scavenging and ferric reducing antioxidant power (FRAP) were used for the antioxidant activity. The antibacterial assay showed an in vitro growth inhibition of P. aeruginosa and S. aureus in dose-dependent manner, with minimum inhibitory concentration values ranging from 2.5 to 3.12 mg/mL for S. aureus and from 6.25 to 12.5 mg/mL for P. aeruginosa. The maximum paw anti-inflammatory effect occurred after 3 and 5 h administration of histamine and carrageenan, respectively. The DPPH radical scavenging and the FRAP assays yielded weak antioxidant activity. J. multifida possesses antibacterial and anti-inflammatory activities that could justify the use of the plant for the treatment of wounds in the folk medicine. Antibacterial on germs isolated from wound, anti-inflammatory and antioxidant activities of Jatropha multifida were assayed by NCCLS broth method, carrageenan and histamine, DPPH and FRAP respectively. The results indicated that Jatropha multifida possesses antibacterial and anti-inflammatory and weak antioxidant activities that could justify its use for the treatment of wounds in the folk medicine.

Antimicrobial, Anti-inflammatory and Antioxidant Activities of Jatropha multifida L. (Euphorbiaceae)

PubMed Central

Anani, Kokou; Adjrah, Yao; Améyapoh, Yaovi; Karou, Simplice Damintoti; Agbonon, Amegnona; de Souza, Comlan; Gbeassor, Messanvi

2016-01-01

Background: Jatropha multifida is used in Togolease folk medicine for the healing of chronic wounds. Objective: This study aims to investigate antibacterial, anti-inflammatory and antioxidant activities of the leaves ethanolic extract. Materials and Methods: The antimicrobial activity was assayed by National Committee for Clinical Laboratory Standards broth microdilution method on strains of Staphylococcus aureus and Pseudomoas aeruginosa isolated from wounds, whereas the anti-inflammatory activity was performed by carrageenan and histamine induced paw edema method in rat modele. The 2, 2-diphenyl-1picrylhydrazyl (DPPH) free radical scavenging and ferric reducing antioxidant power (FRAP) were used for the antioxidant activity. Results: The antibacterial assay showed an in vitro growth inhibition of P. aeruginosa and S. aureus in dose-dependent manner, with minimum inhibitory concentration values ranging from 2.5 to 3.12 mg/mL for S. aureus and from 6.25 to 12.5 mg/mL for P. aeruginosa. The maximum paw anti-inflammatory effect occurred after 3 and 5 h administration of histamine and carrageenan, respectively. The DPPH radical scavenging and the FRAP assays yielded weak antioxidant activity. Conclusion: J. multifida possesses antibacterial and anti-inflammatory activities that could justify the use of the plant for the treatment of wounds in the folk medicine. SUMMARY Antibacterial on germs isolated from wound, anti-inflammatory and antioxidant activities of Jatropha multifida were assayed by NCCLS broth method, carrageenan and histamine, DPPH and FRAP respectively. The results indicated that Jatropha multifida possesses antibacterial and anti-inflammatory and weak antioxidant activities that could justify its use for the treatment of wounds in the folk medicine. PMID:27034606

In vivo anti-inflammatory activity of aqueous extract of Teucrium polium against carrageenan-induced inflammation in experimental models.

PubMed

Rahmouni, Fatma; Hamdaoui, Latifa; Rebai, Tarek

2017-12-01

The aim of this study was to evaluate the anti-inflammatory activity of Teucrium polium (TP). Rats were divided into four groups: group 1 controls received standard diet; group 2 inflamed by carrageenan (Carr) (1% Carr); group 3 as reference inflamed with Carr and treated with Indometacine (Ind) (150 mg/kg bw) and group 4 inflamed with Carr and pre0treated with TP (5 g/L). Oedema volume was measured 1 h to 5 h after injection. Administration of TP or Ind decreased the levels of hematology parameters relative to Carr and reduced the volume of rats induced by Carr. TP reduced levels of CRP, fibrinogen compared to treated, a decrease in oxidative stress (LP) and AOPP with an increase in the levels of SOD, CAT, GPx and Vit C in skin and erythrocytes. Carr increased the levels of lipid peroxidation and decreased levels of antioxidant enzymatic and Vit C. Our results were confirmed by histological sections of skin.

Antioxidant, analgesic and anti-inflammatory activities of the methanolic extract of Piper betle leaves

PubMed Central

Alam, Badrul; Akter, Fahima; Parvin, Nahida; Sharmin Pia, Rashna; Akter, Sharmin; Chowdhury, Jesmin; Sifath-E-Jahan, Kazi; Haque, Ekramul

2013-01-01

Objective: The present study was designed to evaluate the antioxidant, analgesic, and anti-inflammatory activities of the methanolic extract of Piper betle leaves (MPBL). Materials and Methods: MPBL was evaluated for anti-inflammatory activity using carrageenan-induced hind paw edema model. Analgesic activity of MPBL was evaluated by hot plate, writhing, and formalin tests. Total phenolic and flavonoids content, total antioxidant activity, scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, peroxynitrate (ONOO) as well as inhibition of total ROS generation, and assessment of reducing power were used to evaluate antioxidant potential of MPBL. Results: The extract of MPBL, at the dose of 100 and 200 mg/kg, produced a significant (p<0.05) increase in pain threshold in hot plate method whereas significantly (p<0.05) reduced the writhing caused by acetic acid and the number of licks induced by formalin in a dose-dependent manner. The same ranges of doses of MPBL caused significant (p<0.05) inhibition of carrageenan-induced paw edema after 4 h in a dose-dependent manner. In DPPH, ONOO-, and total ROS scavenging method, MPBL showed good antioxidant potentiality with the IC50 value of 16.33±1.02, 25.16±0.61 , and 41.72±0.48 µg/ml, respectively with a significant (p<0.05) good reducing power. Conclusion: The findings of the study suggested that MPBL has strong analgesic, anti-inflammatory, and antioxidant effects, conforming the traditional use of this plant for inflammatory pain alleviation to its antioxidant potentiality. PMID:25050265

Evaluation of the analgesic effect of low-power optical radiation in acute inflammatory process

NASA Astrophysics Data System (ADS)

Ferreira, Denise M.; Zangaro, Renato A.; Cury, Yara; Frigo, Lucio; Barbosa, Daniella G.; da Silva Melo, Milene; Munin, Egberto

2004-07-01

Many research works have explored the use of the low power laser as a tool for the control of inflammatory processes. The anti-inflammatory effect of low power optical radiation and its ability to induce analgesia has been reported for different experimental conditions. Many published works are very qualitative in nature. In this work the action of low power laser radiation on acute inflammatory process is evaluated. The time evolution of rat paw edema and pain induced by carrageenan was experimentally monitored. A 632.8 nm He-Ne laser was used for the treatment. The laser treatment, at a dosage of 2,5 J/cm2, was applied at the first, second and third hour after the induction of the inflammation. A hydroplethysmometer was used for the evaluation of the inflammation. The measurement of pain sensitivity was performed according to the method described by Randall and Selito, (1957). The laser treatment was capable of inhibiting the carrageenan-induced hyperalgesia by 49% (p<0,001) at the second hour after the induction, as compared to the non-treated group. At the fourth hour (peak of the carrageenan action on hyperalgesia) and at the sixth hour, the achieved inhibition was 49% (p<0,001) and 61% (p<0,001), respectively. In the treated groups, the edema evolution was inhibited by 38% (p<0,01), at the second hour after induction, as compared to the non-treated groups. At the fourth hour (peak of the carrageenan action on leakage) and at sixth hour the achieved inhibition was 35% (p<0,01) and 30% (p<0,05) respectively.

Borneol, a Bicyclic Monoterpene Alcohol, Reduces Nociceptive Behavior and Inflammatory Response in Mice

PubMed Central

Almeida, Jackson Roberto Guedes da Silva; Souza, Grasielly Rocha; Silva, Juliane Cabral; Saraiva, Sarah Raquel Gomes de Lima; Júnior, Raimundo Gonçalves de Oliveira; Quintans, Jullyana de Souza Siqueira; Barreto, Rosana de Souza Siqueira; Bonjardim, Leonardo Rigoldi; Cavalcanti, Sócrates Cabral de Holanda; Junior, Lucindo José Quintans

2013-01-01

Borneol, a bicyclic monoterpene, has been evaluated for antinociceptive and anti-inflammatory activities. Antinociceptive and anti-inflammatory activities were studied by measuring nociception by acetic acid, formalin, hot plate, and grip strength tests, while inflammation was prompted by carrageenan-induced peritonitis. The rotarod test was used to evaluate motor coordination. Borneol produced a significant (P < 0.01) reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice (formalin and writhing tests, resp.). When the hot plate test was conducted, borneol (in higher dose) produced an inhibition (P < 0.05) of the nociceptive behavior. Such results were unlikely to be provoked by motor abnormality. Additionally, borneol-treated mice reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. Together, our results suggest that borneol possess significant central and peripheral antinociceptive activity; it has also anti-inflammatory activity. In addition, borneol did not impair motor coordination. PMID:23710149

Anti-Inflammatory and Antibothropic Properties of Jatropha Elliptica, a Plant from Brazilian Cerrado Biome

PubMed Central

Ferreira-Rodrigues, Sára Cósta; Rodrigues, Cássio Milhomens; Dos Santos, Marcio Galdino; Gautuz, Jean Antonio Abraham; Silva, Magali Glauzer; Cogo, José Carlos; Batista-Silva, Camila; Dos Santos, Cleiton Pita; Groppo, Francisco Carlos; Cogo-Müller, Karina; Oshima-Franco, Yoko

2016-01-01

Purpose: The aim of this study was to evaluate the antibothropic and anti-inflammatory properties of J. elliptica. Methods: Phytochemical screening and thin-layer chromatography (TLC) assays were performed on J. elliptica hydroalcoholic extract (TE) in order to observe its main constituents. The antibothropic activity of TE was evaluated by the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu), in a mouse phrenic nerve-diaphragm model (PND). A quantitative histological study was carried out to observe a possible protection of TE against the venom myotoxicity. The anti-inflammatory activity was also evaluated in two models, Bjssu-induced paw edema, and carrageenan-induced neutrophils migration in the peritoneal cavity. Results: TLC analysis revealed several compounds in TE, such as saponins, alkaloids, and phenolic constituents. TE was able to neutralize the blockade and the myotoxicity induced by venom, when it was pre-incubated for 30 min with venom. In addition, it showed anti-inflammatory activity, inducing less neutrophils migration and reducing paw edema. Conclusion: J. elliptica showed both antibothropic and anti-inflammatory properties. PMID:28101464

Inflammatory process induced by carrageenan in adjacent tissue triggers the acute inflammation in deep digital flexor tendon of rats.

PubMed

Vieira, Cristiano Pedrozo; De Aro, Andrea Aparecida; Da Ré Guerra, Flávia; De Oliveira, Letícia Prado; De Almeida, Marcos Dos Santos; Pimentel, Edson Rosa

2013-08-01

Tendinopathy is a pathology found mainly in the rotator cuff, patellar, Achilles and flexor tendons. Tendinopathy is a significant impediment to performance in athletes and in workers in the labor market. Some studies have indicated that inflammation in adjacent tissues may affect the rotator cuff and Achilles tendon. In this study alterations were verified in the extracellular matrix (ECM) of the deep digital flexor tendon after two periods (12 and 24 hr) of induction inflammation in rat paw. Wistar rats were divided into three groups: those that received injection of 1% carrageenan; those that received 0.9% NaCl; and those that received no application. The tendon was divided into distal (d), proximal (p), and intermediate (i) regions. Biochemical analyses were performed and included non-collagenous proteins (NCP), glycosaminoglycans (GAGs), hydroxyproline (HoPro) and metalloproteinases 2 and 9. Tissue sections were stained with toluidine blue, hematoxylin-eosin, and Ponceau SS and observed under polarization microscopy. Remarkable results were detected that included the presence of MMP-9, degradation of NCP and GAG and the presence of cellular infiltrate closer to digits in d region. The different concentrations of HoPro, as well as alterations in the organization of the collagen fibers showed the collagenous matrix undergoing some alterations. The results indicated that the induced inflammation in rat paw exhibited characteristics similar to the typical acute inflammatory process observed in tendons. Copyright © 2013 Wiley Periodicals, Inc.

Anti-granuloma activity of Coriandrum sativum in experimental models

PubMed Central

Nair, Vinod; Singh, Surender; Gupta, Yogendra Kumar

2013-01-01

Background: Coriandrum sativum has been used in the traditional systems of medicine for management of arthritis and other inflammatory disorders. Objectives: In this study, we have evaluated the anti-inflammatory and anti-granuloma activities of Coriandrum sativum hydroalcoholic extract (CSHE) in experimental models. Materials and Methods: The anti-inflammatory activity of CSHE was evaluated using carrageenan-induced paw edema model and the anti-granuloma activity of CSHE was evaluated using the subcutaneous cotton pellet implantation-induced granuloma formation and stimulation of peritoneal macrophages with complete Freund's adjuvant. Serum tumor necrosis factor-α (TNF-α), IL-6, IL-1 β levels, and peritoneal macrophage expression of TNF-R1 were evaluated as markers of global inflammation. Results: CSHE at the highest dose tested (32 mg/kg) produced a significant reduction (P < 0.05) in paw edema after carrageenan administration. CSHE treatment also reduced dry granuloma weight in all treated animals. Serum IL-6 and IL-1 β levels were significantly (P < 0.05) lower in the CSHE (32 mg/kg)-treated group as compared to control. Although there was an increase in serum TNF-α level in the CSHE-treated group as compared to control, TNF-R1 expression on peritoneal macrophages was found to be reduced. Conclusion: Thus, the result of this study demonstrates the anti-inflammatory and anti-granuloma activities of CSHE in experimental models, and validates its traditional use for the management of arthritis and other inflammatory disorders. PMID:23741156

Evaluation of the antithrombotic effects of Crataegus monogyna and Crataegus davisii in the carrageenan-induced tail thrombosis model.

PubMed

Arslan, Rana; Bektas, Nurcan; Bor, Zeynep; Sener, Erol

2015-02-01

Crataegus species are widely used as herbal medicines for preventing cardiovascular diseases (CVDs). However, there are no studies on the effects of Crataegus monogyna Jacq. (Rosaceae) and C. davisii Browicz on thrombosis, which is an important mechanism in CVDs. The purpose of this study was to investigate the antithrombotic effects of ethanol extracts of Crataegus monogyna (CMEx) and C. davisii (CDEx) leaves by using the carrageenan-induced tail thrombosis model. The hind paw of each mouse was injected with 1% Type I carrageenan to induce thrombosis. CMEx was tested at the doses of 100, 200, and 300 mg/kg and CDEx at the dose of 50, 100, 200, and 300 mg/kg in comparison with heparin. The lengths of tail thrombosis were measured at the 24, 48, and 72 h. Does of 200 and 300 mg/kg CMEx showed significant effects (p < 0.01; p < 0.001) at 24 h when compared with the control group. The antithrombotic activity of 200 and 300 mg/kg CMEx showed a decrease at 48 and 72 h but the activity of 300 mg/kg dose of CMEx was still significant (p < 0.01). The activities of 50 and 100 mg/kg doses of CDEx were significant (p < 0.001; p < 0.01) between 24 and 72 h whereas 200 and 300 mg/kg CDEx did not show any significance. CMEx and CDEx significantly inhibited the carrageenan-induced mouse tail thrombosis. Based on these results, it was concluded that CDEx and CMEx may potentially be used as therapeutic agents or complementary treatments against thrombosis.

Anti-inflammatory and antinociceptive activities of Croton urucurana Baillon bark.

PubMed

Cordeiro, Kátia Wolff; Felipe, Josyelen Lousada; Malange, Kauê Franco; do Prado, Pâmela Rafaela; de Oliveira Figueiredo, Patrícia; Garcez, Fernanda Rodrigues; de Cássia Freitas, Karine; Garcez, Walmir Silva; Toffoli-Kadri, Mônica Cristina

2016-05-13

Croton urucurana (Euphorbiaceae) is popularly used in Brazil to treat inflammatory processes, pain, and gastric ulcers. To evaluate the anti-inflammatory and antinociceptive properties of the methanol extract from the bark of C. urucurana (MECu) in mice and identify its chemical constituents. The extract was characterized by UHPLC-DAD-ESI-Q-TOF-MS/MS. Extract doses of 25, 100, and 400mg/kg were employed in the biological assays. Evaluation of anti-inflammatory activity was based on paw edema and leukocyte recruitment into the peritoneal cavity of mice, both induced by carrageenan. Abdominal writhing caused by acetic acid and duration of formalin-induced paw-licking were the models employed to evaluate antinociceptive activity. Ten compounds were identified in the extract: (+)-gallocatechin (1), procyanidin B3 (2), (+)-catechin (3), (-)-epicatechin (4), tembetarine (5), magnoflorine (6), taspine (7), methyl-3-oxo-12-epi-barbascoate (8), methyl-12-epi-barbascoate (9), and hardwickiic acid (10). This is the first report of compounds 2, 4, 6, 7, and 10 in C. urucurana and compound 5 in the genus Croton. In addition to inhibiting paw edema and leukocyte recruitment (particularly of polymorphonuclear cells) into the peritoneal cavity of mice, MECu reduced the number of abdominal writhings induced by acetic acid and the duration of formalin-induced paw licking. The methanol extract of C. urucurana bark exhibited anti-inflammatory and antinociceptive properties, corroborating its use in folk medicine. These effects may be related to the presence of diterpenes, alkaloids, and flavonoids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anti-edematogenic and anti-inflammatory activity of the essential oil from Croton rhamnifolioides leaves and its major constituent 1,8-cineole (eucalyptol).

PubMed

Martins, Anita Oliveira Brito Pereira Bezerra; Rodrigues, Lindaiane Bezerra; Cesário, Francisco Rafael Alves Santana; de Oliveira, Maria Rayane Correia; Tintino, Cicera Datiane Morais; Castro, Fyama Ferreira E; Alcântara, Isabel Sousa; Fernandes, Maria Neyze Martins; de Albuquerque, Thaís Rodrigues; da Silva, Maria Sanadia Alexandre; de Sousa Araújo, Adriano Antunes; Júniur, Lucindo José Quintans; da Costa, José Galberto Martins; de Menezes, Irwin Rose Alencar; Wanderley, Almir Gonçalves

2017-12-01

The species Croton rhamnifolioides, belonging to the Croton genus, is known in ethnomedicine as "quebra faca" and is used in the treatment of stomach pain, vomiting and fever. This study aims to evaluate the anti-edematogenic and anti-inflammatory effect of Croton rhamnifolioides leaf essential oil (OEFC) and its major constituent: 1,8-cineole (eucalyptol). The essential oil was extracted from fresh leaves through a hydrodistillation system. The chemical analysis was determined by gas chromatography-mass spectrometry (GC-MS). The acute anti-inflammatory activity was determined from the models of: ear edema by the single application of croton oil, paw edema induced by: carrageenan, dextran, histamine and arachidonic acid, while vascular permeability was determined by Evans blue extravasation and chronic anti-inflammatory activity by granuloma induction using the implantation of cotton pellets. The GC-MS results identified and quantified 11 constituents, with the major component being 1,8-cineole (41.33%). The OEFC (20mg/mL) and 1,8-cineole (8.26mg/mL) significantly reduced the edema induced by croton oil by 42.1 and 34.9%, respectively. The OEFC (25, 50, 100 and 200mg/kg) and 1,8-cineole (10.33, 20.66, 41.33 and 82.66mg/kg) statistically reduced paw edema induced by carrageenan, dextran as well as vascular permeability (protein extravasation). The OEFC (25mg/kg) and 1,8-cineole (10.33mg/kg) demonstrated efficacy in reducing edema induced by histamine and arachidonic acid and granuloma. In conclusion, the OEFC and 1,8-cineole have anti-inflammatory activity in the acute and chronic phase, suggesting therapeutic potential as a source for the development of new anti-inflammatory agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Anti-inflammatory and analgesic activity of novel oral aspirin-loaded nanoemulsion and nano multiple emulsion formulations generated using ultrasound cavitation.

PubMed

Tang, Siah Ying; Sivakumar, Manickam; Ng, Angela Min-Hwei; Shridharan, Parthasarathy

2012-07-01

The present study investigated the anti-inflammatory and analgesic activities of novel aspirin oil-in-water (O/W) nanoemulsion and water-in-oil-in-water (W/O/W) nano multiple emulsion formulations generated using ultrasound cavitation techniques. The anti-inflammatory activities of nanoemulsion and nano multiple emulsion were determined using the λ-carrageenan-induced paw edema model. The analgesic activities of both nanoformulations were determined using acetic acid-induced writhing response and hot plate assay. For comparison, the effect of pretreatment with blank nanoemulsion and reference aspirin suspension were also studied for their anti-inflammatory and antinociceptive activities. The results showed that oral administration of nanoemulsion and nano multiple emulsion containing aspirin (60 mg/kg) significantly reduced paw edema induced by λ-carrageenan injection. Both nanoformulations decreased the number of abdominal constriction in acetic acid-induced writhing model. Pretreatment with nanoformulations led to a significant increase in reaction time in hot plate assay. Nanoemulsion demonstrated an enhanced anti-inflammatory and analgesic effects compared to reference suspension while nano multiple emulsion exhibited a mild inhibitory effects in the three experimental animal model tests. The results obtained for nano multiple emulsion were relatively lower than reference. However, administration of blank nanoemulsion did not alter the nociceptive response significantly though it showed slight anti-inflammatory effect. These experimental studies suggest that nanoemulsion and nano multiple emulsion produced a pronounced anti-inflammatory and analgesic effects in rats and may be candidates as new nanocarriers for pharmacological NSAIDs in the treatment of inflammatory disorders and alleviating pains. Copyright © 2012 Elsevier B.V. All rights reserved.

Vernonia cinerea L. scavenges free radicals and regulates nitric oxide and proinflammatory cytokines profile in carrageenan induced paw edema model.

PubMed

Kumar, P Pratheesh; Kuttan, Girija

2009-01-01

In this study, we evaluated the anti-oxidant and anti-inflammatory activities of the medicinal plant, Vernonia cinerea L (Asteraceae) using in vitro as well as in vivo models. Methanolic extract of Vernonia cinerea was found to scavenge the hydroxyl radical generated by Fenton reaction (IC(50)130 microg/ml), Superoxide generated by photo reduction of riboflavin (IC(50)190 microg/ml) and inhibited lipid peroxidation significantly (IC(50)130.5 microg/ml). The drug also scavenged nitric oxide (IC(50)210 microg/ml). Intraperitoneal administration of Vernonia cinerea was found to inhibit the PMA induced Superoxide generation in mice peritoneal macrophages. The administration of Vernonia cinerea to mice significantly increased the levels of catalase, superoxide dismutase, glutathione, glutathione peroxidase and glutathione-S transferase in blood and liver, whereas lipid peroxidation activity was significantly decreased. It was also found that Vernonia cinerea extract significantly inhibited carrageenan induced inflammation, compared with control models. Down regulation of pro-inflammatory cytokine level and gene expression were also support the above result.

Anti-Inflammatory Activity and Composition of Senecio salignus Kunth

PubMed Central

Pérez González, Cuauhtemoc; Serrano Vega, Roberto; González-Chávez, Marco; Zavala Sánchez, Miguel Angel; Pérez Gutiérrez, Salud

2013-01-01

We investigated the anti-inflammatory activity of Senecio salignus. This medicinal plant is often used in Mexico for the treatment of fever and rheumatism. Chloroform and methanol extracts of the plant were tested on 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced edema in mice ears. The methanol extract of the plant inhibited edema by 36 ± 4.4% compared with the control, while the chloroform extract exhibited an even greater level of inhibition (64.1%). The chloroform extract was then fractionated, and the composition of the active fraction was determined by GC-MS. The anti-inflammatory activity of this fraction was then tested on TPA-induced ear edema in mice, and we found that the active fraction could inhibit edema by 46.9%. The anti-inflammatory effect of the fraction was also tested on carrageenan-induced paw edema in rats at doses of 100 mg/kg; a 58.9 ± 2.8% reduction of the edema was observed 4 h after administration of carrageenan, and the effect was maintained for 5 h. PMID:23691512

Docking Studies, Synthesis and Biological Evaluation of β-aryl-β-hydroxy Propanoic Acids for Anti-inflammatory Activity.

PubMed

Savic, Jelena; Dilber, Sanda; Milenkovic, Marina; Kotur-Stevuljevic, Jelena; Markovic, Bojan; Vladimirov, Sote; Brboric, Jasmina

2017-01-01

Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs. The need is justified by the fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects. Eight β-hydroxy-β-arylpropanoic acids, which belong to the arylpropanoic acid class of compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Seven out of those eight acids were synthesized using already published modification of Reformatsky reaction additionally optimized by increasing temperature. Synthesized compounds were tested in vivo in order to elucidate anti-inflammatory activity, gastric tolerability and impact on liver function of rats. Results of docking studies have indicated that all compounds have potential to selectively inhibit COX-2 isoform, but that the compounds containing polar substituents on phenyl ring are better inhibitors. Results of carrageenan-induced rat paw oedema test have shown that all compounds exhibit dose dependence and good gastric tolerability and none of the tested compounds have shown negative effect on liver function compared to ibuprofen. The compound containing polar nitro group in para position has shown the best docking results, anti-inflammatory activity, low hepatotoxicity and good gastric tolerability. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Delivery system for mefenamic acid based on the nanocarrier layered double hydroxide: Physicochemical characterization and evaluation of anti-inflammatory and antinociceptive potential.

PubMed

Cunha, Vanessa R R; Guilherme, Viviane A; de Paula, Eneida; de Araujo, Daniele R; Silva, Renan O; Medeiros, Jand V R; Leite, José R S A; Petersen, Philippe A D; Foldvari, Marianna; Petrilli, Helena M; Constantino, Vera R L

2016-01-01

The anionic form of the drug mefenamic acid intercalated into the nanocarrier layered double hydroxide (LDH-Mef) was evaluated by anti-inflammatory and antinociceptive assays. The LDH-Mef material was characterized by a set of physicochemical techniques, which was supported by Density Functional Theory calculations. The pharmacological effects of LDH-Mef (40 wt% of drug) were evaluated by hemolytic, anti-inflammatory activity and antinociceptive assays. In vivo assays were conducted for the first time in order to assess the LDH-Mef potential. The hemolytic effects decreased for the intercalated Mef as demonstrated by the higher tolerated hemolytic concentration (1.83 mM) compared to mefenamic acid (MefH), 0.48 mM. Pretreatment of animals with MefH or LDH-Mef reduced carrageenan-, dextran sulfate- and PGE2-induced paw edema. MefH or LDH-Mef also decrease total leucocytes and neutrophil counts of the peritoneal cavity after inflammation induction with carrageenan. In the nociception model, oral pretreatment with LDH-Mef reduced mechanical hypernociception carrageenan-induced after 3-4h and also the number of writhings induced by acetic acid. This work shows the increase of the anti-inflammatory and antinociceptive potential of the drug confined into the LDH, as well as, its hemolytic effect. Copyright © 2015 Elsevier B.V. All rights reserved.

Esculin exhibited anti-inflammatory activities in vivo and regulated TNF-α and IL-6 production in LPS-stimulated mouse peritoneal macrophages in vitro through MAPK pathway.

PubMed

Niu, Xiaofeng; Wang, Yu; Li, Weifeng; Zhang, Hailin; Wang, Xiumei; Mu, Qingli; He, Zehong; Yao, Huan

2015-12-01

Esculin, a coumarinic derivative found in Aesculus hippocastanum L. (Horse-chestnut), has been reported to have potent anti-inflammatory properties. The present study is designed to investigate the protective effects of esculin on various inflammation models in vivo and in vitro and to clarify the possible mechanism. Induced-animal models of inflammation and lipopolysaccharide (LPS)-challenged mouse peritoneal macrophages were used to examine the anti-inflammatory activity of esculin. In present study, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, and carrageenan-induced mouse pleurisy were attenuated by esculin. In vitro, the pro-inflammatory cytokine levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in supernatant were reduced by esculin. Meanwhile, we found that esculin significantly inhibited LPS-induced activation of mitogen-activated protein kinase (MAPK) pathway in peritoneal macrophages. These results suggest that esculin has potent anti-inflammatory activities in vivo and in vitro, which may involve the inhibition of the MAPK pathway. Esculin may be a promising preventive agent for inflammatory diseases in human. Copyright © 2015 Elsevier B.V. All rights reserved.

Wound healing and anti-inflammatory activity of some Ononis taxons.

PubMed

Ergene Öz, Burçin; Saltan İşcan, Gülçin; Küpeli Akkol, Esra; Süntar, İpek; Keleş, Hikmet; Bahadır Acıkara, Özlem

2017-07-01

Ononis species are used for their laxative, diuretic, analgesic, anti-inflammatory, antiviral, cytotoxic and antifungal effects as well as against skin diseases for wound healing activity. In the light of this information n-hexane, ethylacetate and methanol extracts prepared from Ononis spinosa L. subsp. leiosperma (Boiss.) Sirj., Ononis variegata L., Ononis viscosa L. subsp. brevifolia (DC) Nym. and Ononis natrix L. subsp. natrix L. were tested for their wound healing, anti-inflammatory and antioxidant activities. Linear incision and circular excision wound models and hydroxypyroline estimation assay were used for the wound healing activity. For the assessment of chronic inflammation FCA-induced arthritis and for acute inflammation carrageenan-induced hind paw edema, TPA-induced ear edema and acetic acid-induced increase in capillary permeability tests were conducted. 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, 2,2-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) scavenging activity assay, reducing power assay and hydroxyl radical (OH - ) scavenging assay were used for determining antioxidant activities of the extracts. Results showed that O. spinosa subsp. leiosperma roots ethyl acetate extract exhibited remarkable wound healing activity with the 42.6% tensile strength value on the linear incision wound model and 60.1% reduction of the wound area at the day 12 on the circular excision wound model. Hydroxyproline content of the tissue treated by O. spinosa subsp. leiosperma roots ethyl acetate extract was found to be 41.3μg/mg. Acetic acid induced increase in capillary permeability test results revealed that O. spinosa subsp. leiosperma roots ethyl acetate extract and O. spinosa subsp. leiosperma roots methanol extract inhibited inflammation by 40.4% and 35.4% values respectively. O. spinosa subsp. leiosperma roots ethyl acetate extract showed 21.2-27.2% inhibition in carrageenan-induced hind paw edema test while did not posses activity on TPA-induced ear edema and FCA-induced arthritis models. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Improvement of bioavailability and anti-inflammatory potential of curcumin in combination with emu oil.

PubMed

Jeengar, Manish Kumar; Shrivastava, Shweta; Nair, Kala; Singareddy, Sreenivasa Reddy; Putcha, Uday Kumar; Talluri, M V N Kumar; Naidu, V G M; Sistla, Ramakrishna

2014-12-01

The purpose of the present study is to evaluate the effect of emu oil on bioavailability of curcumin when co-administered and to evaluate the property that enhances the anti-inflammatory potential of curcumin. Oral bioavailability of curcumin in combination with emu oil was determined by measuring the plasma concentration of curcumin by HPLC. The anti-inflammatory potential was evaluated in carrageenan-induced paw edema model (acute model) and in Freund's complete adjuvant (FCA)-induced arthritis model (chronic model) in male SD rats. The anti-inflammatory potential of curcumin in combination with emu oil has been significantly increased in both acute and chronic inflammatory models as evident from inhibition of increase in paw volume, arthritic score, and expression of pro-inflammatory cytokines. The increased anti-inflammatory activity in combination therapy is due to enhanced bioavailability (5.2-fold compared to aqueous suspension) of curcumin by emu oil. Finally, it is concluded that the combination of emu oil with curcumin will be a promising approach for the treatment of arthritis.

Investigation of the central and peripheral analgesic and anti-inflammatory activity of Draksharishta an Indian Ayurvedic formulation

PubMed Central

Kabir, Ashraf-ul; Samad, Mehdi Bin; D′Costa, Ninadh Malrina; Hannan, Juardar Mohammad

2012-01-01

Rationale: Draksharishta (DRK) is an Ayurvedic formulation approved by the “National formulary of Ayurvedic Medicine 2011”, of Bangladesh. It is widely available in the Bangladeshi market as an effective preparation to treat lumbago, sciatia and arthritic pain of joints. But there are very scientific evidences available to support their common uses. Objectives: Our present studies make an attempt toward identifying probable antinociceptive and anti-inflammatory effect and its mechanisms of DRK. Findings: DRK, at three doses, (10 mL/kg, 20 mL/kg, and 40 mL/kg) showed no involvement of the CNS in antinociceptive activity of the test drug. Both Carrageenan-induced paw edema and acetic acid writhing tests gave significant results (P < 0.05), indicating possible peripheral analgesic and anti-inflammatory action. Formalin-induced paw- licking test showed that DRK had significant effect in suppressing inflammatory pain (P < 0.05) but not neurogenic pain. Conclusions: Hence our study shows anti-inflammatory and peripheral analgesic action for DRK. PMID:24826047

A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome.

PubMed

Tékus, Valéria; Hajna, Zsófia; Borbély, Éva; Markovics, Adrienn; Bagoly, Teréz; Szolcsányi, János; Thompson, Victoria; Kemény, Ágnes; Helyes, Zsuzsanna; Goebel, Andreas

2014-02-01

The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Anti-arthritic activity of a lipophilic woad (Isatis tinctoria) extract.

PubMed

Recio, María-Carmen; Cerdá-Nicolás, Miguel; Hamburger, Matthias; Ríos, José-Luis

2006-06-01

A dichloromethane extract of Isatis tinctoria was tested in the adjuvant-induced arthritis model in rats. The extract (150 mg/kg p. o.) leads to a significant reduction of paw oedema. Radiographic, histological and clinical assessment confirmed reduced damage of cartilage and signs of inflammatory response in comparison to untreated control. No significant differences were observed in the tissular levels of cyclooxygenases 1 and -2, and of inducible nitric oxide synthase in Isatis treated and untreated animals. High dose treatment with Isatis extract for two weeks did not result in macroscopic lesions of the gastric mucosa.

Evaluation of cryogenine on rat paw thermal oedema and rat isolated uterus

PubMed Central

Malone, M. H.; Trottier, R. W.

1973-01-01

1. Significant inhibition of oedema formation caused by thermal injury was observed for calcium carbaspirin, phenylbutazone, hydrocortisone, cryogenine and indomethacin when given daily beginning 2 days prior to thermal exposure and afterwards. Several anti-inflammatory drugs, including cryogenine, failed to reduce thermal oedema significantly when given as single doses 1 h prior to the thermal injury. 2. Kinetic experiments on the rat isolated uterus demonstrated that cryogenine, chlorpromazine, and flufenamic acid were, in part, competitive inhibitors of synthetic bradykinin, while indomethacin and tetrabenazine showed only non-competitive antagonism. PMID:4733728

Anti-inflammatory effect of extract and fractions from the leaves of Byrsonima intermedia A. Juss. in rats.

PubMed

Moreira, Lucimara Q; Vilela, Fabiana C; Orlandi, Lidiane; Dias, Danielle F; Santos, Ana Laura A; da Silva, Marcelo A; Paiva, Renato; Alves-da-Silva, Geraldo; Giusti-Paiva, Alexandre

2011-11-18

Byrsonima intermedia is commonly used for its antiseptic, antimicrobial, and anti-inflammatory properties in the treatment of diarrhea and dysentery in Brazilian folk medicine. The purpose of this study was to examine the anti-inflammatory activity of the aqueous extract and fractions of Byrsonima intermedia leaves. Rats with carrageenan-induced paw edema and fibrovascular tissue growth, which was induced by subcutaneous implantation of a cotton pellet, were used as acute and chronic animal models of inflammation to investigate the anti-inflammatory effects of the aqueous extract and the individual ethyl acetate (EtOAc) and aqueous fractions of Byrsonima intermedia and catechin. High-performance liquid chromatography (HPLC) was used to determine the fingerprint chromatogram of the aqueous extract and fractions of Byrsonima intermedia. The crude aqueous extract at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reducing carrageenan-induced paw edema, as did the ethyl acetate (100mg/kg) and aqueous fractions (30-100mg/kg). In the chronic inflammation rat animal model with fibrovascular tissue growth, the aqueous extract of Byrsonima intermedia (BiAE) at doses of 30-300 mg/kg and the individual EtOAc and aqueous fractions at doses of 30-100mg/kg and catechin significantly reduced the formation of granulomatous tissue. The presence of catechin and phenolic compounds in the extract and fractions of Byrsonima intermedia was confirmed using HPLC. BiAE and the individual EtOAc and aqueous fractions of Byrsonima intermedia exhibited chronic and acute anti-inflammatory efficacy in rats, which supports previous claims of its use in traditional medicine. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Experimental evaluation of anti-inflammatory, antinociceptive and antipyretic activities of clove oil in mice

PubMed Central

Taher, Yousef A.; Samud, Awatef M.; El-Taher, Fathy E.; ben-Hussin, Ghazala; Elmezogi, Jamal S.; Al-Mehdawi, Badryia F.; Salem, Hanan A.

2015-01-01

Background Clove oil of Eugenia caryophyllata (Myrtaceae) is a light yellowish fluid obtained from dried flower buds. Clove oil is used traditionally to relieve toothache. Aim The aim of the present work was to study the anti-inflammatory, antinociceptive and antipyretic potential of clove oil in mice. Methods Analgesic activity was examined using acetic-acid-induced abdominal constrictions and the hot plate test. Carrageenan-induced paw edema and brewer's-yeast-induced pyrexia were used to investigate the anti-inflammatory activity and the antipyretic effects, respectively. The oil was administered intraperitoneally (i.p.) at a dose of 33 mg/kg body weight and the effects were compared with reference drugs. Results In the antinociceptive test, mice treated with clove oil exhibited significantly decreased acetic-acid-induced writhing movements by a maximum of 87.7% (p<0.01) compared with a decrease of 77.7% (p<0.01) in response to aspirin injection (100 mg/kg, intraperitoneal, i.p.). Similarly, in the hot plate test, clove oil significantly increased the reaction latency to pain after 60 min by 82.3% (p<0.05) compared with morphine value of 91.7% (p<0.01). In addition, clove oil and indomethacin produced anti-inflammatory effects, as demonstrated by respectively 50.6% (p<0.05) and 70.4% (p<0.01) inhibition of mouse paw edema induced by carrageenan. Furthermore, clove oil significantly attenuated the hyperthermia induced by yeast at ΔT-max by 2.7°C (p<0.001), and time of peak effects was 30–180 min compared with a paracetamol value ΔT-max of 3.2°C (p<0.001). The estimated i.p. LD50 of clove oil was 161.9 mg/kg. Phytochemical screening of the oil showed the presence of eugenol. Conclusion The present findings demonstrate the potential pharmacological properties of clove oil and provide further a support for its reported use in folk medicine. PMID:26333873

Effect of Lavender (Lavandula angustifolia) Essential Oil on Acute Inflammatory Response

PubMed Central

Cardia, Gabriel Fernando Esteves; Cavalcante, Heitor Augusto Otaviano; Cassarotti, Larissa Laila; Salvadego, Valter Eduardo Cocco; Spironello, Ricardo Alexandre; Bersani-Amado, Ciomar Aparecida

2018-01-01

Lavandula angustifolia is a plant of Lamiaceae family, with many therapeutic properties and biological activities, such as anticonvulsant, anxiolytic, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of this study was to evaluate the effect of Lavandula angustifolia Mill. essential oil (LEO) on acute inflammatory response. LEO was analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods and showed predominance of 1,8-cineole (39.83%), borneol (22.63%), and camphor (22.12%). LEO at concentrations of 0.5, 1, 3, and 10 μg/ml did not present in vitro cytotoxicity. Additionally, LEO did not stimulate the leukocyte chemotaxis in vitro. The LEO topical application at concentrations of 0.25, 0.5, and 1 mg/ear reduced edema formation, myeloperoxidase (MPO) activity, and nitric oxide (NO) production in croton oil-induced ear edema model. In carrageenan-induced paw edema model, LEO treatment at doses of 75, 100, and 250 mg/kg reduced edema formation, MPO activity, and NO production. In dextran-induced paw edema model, LEO at doses of 75 and 100 mg/kg reduced paw edema and MPO activity. In conclusion, LEO presented anti-inflammatory activity, and the mechanism proposed of LEO seems to be, at least in part, involving the participation of prostanoids, NO, proinflammatory cytokines, and histamine. PMID:29743918

Emu oil based nano-emulgel for topical delivery of curcumin.

PubMed

Jeengar, Manish Kumar; Rompicharla, Sri Vishnu Kiran; Shrivastava, Shweta; Chella, Naveen; Shastri, Nalini R; Naidu, V G M; Sistla, Ramakrishna

2016-06-15

Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis. Copyright © 2016 Elsevier B.V. All rights reserved.

Globularia alypum methanolic extract improves burn wound healing process and inflammation in rats and possesses antibacterial and antioxidant activities.

PubMed

Ghlissi, Zohra; Kallel, Rim; Sila, Assaad; Harrabi, Bahira; Atheymen, Rim; Zeghal, Khaled; Bougatef, Ali; Sahnoun, Zouheir

2016-12-01

Burns are known as one of the most common and destructive forms of injury with a vast spectrum of consequences. Despite the discovery of various antibacterial and antiseptic agents, burn wound healing still has remained a challenge to modern medicine. Plants have been considered as potential agents for prevention and treatment of disorders in recent years. Globularia alypum L. (GA) is widely used in folk medicine against skin diseases and abscesses, however there is no scientific evidence justifying its use. This study aimed to evaluate the wound healing and anti-inflammatory effect, the antibacterial and antioxidant activities, as well as the chemical compositions of GA methanolic extract (GAME). Chemical compounds of GAME were examined by GC-MS. Wound healing effect was assessed by second-degree burn wounds in rats, anti-inflammatory activity was studied by carrageenan-induced rat paw edema, antioxidant activity was estimated by the DPPH, reducing power and β-carotene tests and antimicrobial activity was tested against 6 bacteria. A total of 17 compounds were identified. GAME-treated rats showed an improvement in healing process and carrageenan-induced hind paws edema as assessed by histological and biochemical investigations, compared to the control. A significant antioxidant and antibacterial activities were also observed in GAME-treated rats. GAME revealed a burn wound healing activity probably due to the anti-inflammatory, antimicrobial and antioxidant activities of its phytochemical contents. Thus, this study confirms its traditional use, however further more precise studies are needed for future clinical application. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

In Vivo Evaluation of the Anti-Inflammatory Effect of Pistacia lentiscus Fruit Oil and Its Effects on Oxidative Stress

PubMed Central

Bardaa, Sana; Sahnoun, Zouheir; Rebai, Tarek

2016-01-01

In order to find new topical anti-inflammatory agents, we had recourse to a medicinal plant. This work was designed to determine the topical anti-inflammatory effect of Pistacia lentiscus fruit oil (PLFO), using carrageenan-induced paw edema rat model, and to evaluate its effects on oxidative stress. The topical anti-inflammatory activity of PLFO was compared to Inflocine® and estimated by measuring the diameter of paw edema, for 5 hours at a 1-hour interval. After that the rats were scarified and the inflamed paw tissue was removed for the exploration of some parameters of oxidative stress and histopathology. PLFO showed a significant anti-inflammatory activity in comparison with the Inflocine. The percentages of edema inhibition were 70% and % 51.5% (p < 0.01), respectively, after five hours. The treatment with PLFO and Inflocine led to significant increases (p ≤ 0.05) in the activities of CAT, SOD, and GPX and significant decreases in the MDA level and AOPP activity in the paw tissue after Carr injection, in comparison with the Carr group. Therefore, our findings demonstrate that PLFO might accelerate the development of new drugs which could be used scientifically as a source for natural health products in the treatment of topical inflammation. PMID:28070202

The Anti-Inflammatory and Antioxidant Potential of Pistachios (Pistacia vera L.) In Vitro and In Vivo.

PubMed

Paterniti, Irene; Impellizzeri, Daniela; Cordaro, Marika; Siracusa, Rosalba; Bisignano, Carlo; Gugliandolo, Enrico; Carughi, Arianna; Esposito, Emanuela; Mandalari, Giuseppina; Cuzzocrea, Salvatore

2017-08-22

Several reports have demonstrated the effectiveness of pistachio against oxidative stress and inflammation. In this study, we investigate if polyphenols extracts from natural raw shelled pistachios (NP) or roasted salted pistachio (RP) kernels have anti-inflammatory and antioxidant properties at lower doses than reported previously, in both in vitro and in vivo models. The monocyte/macrophage cell line J774 was used to assess the extent of protection by NP and RP pistachios against lipopolysaccharide (LPS)-induced inflammation. Moreover, antioxidant activity of NP and RP was assessed in an in vivo model of paw edema in rats induced by carrageenan (CAR) injection in the paw. Results from the in vitro study demonstrated that pre-treatment with NP (0.01, 0.1 and 0.5 mg/mL) and RP (0.01 and 0.1 mg/mL) exerted a significant protection against LPS induced inflammation. Western blot analysis showed NP reduced the degradation of IκB-α, although not significantly, whereas both NP and RP decreased the TNF-α and IL-1β production in a dose-dependent way. A significant reduction of CAR-induced histological paw damage, neutrophil infiltration and nitrotyrosine formation was observed in the rats treated with NP. These data demonstrated that, at lower doses, polyphenols present in pistachios possess antioxidant and anti-inflammatory properties. This may contribute toward a better understanding of the beneficial health effects associated with consumption of pistachios.

The Anti-Inflammatory and Antioxidant Potential of Pistachios (Pistacia vera L.) In Vitro and In Vivo

PubMed Central

Paterniti, Irene; Impellizzeri, Daniela; Cordaro, Marika; Bisignano, Carlo; Gugliandolo, Enrico; Carughi, Arianna; Esposito, Emanuela; Mandalari, Giuseppina

2017-01-01

Several reports have demonstrated the effectiveness of pistachio against oxidative stress and inflammation. In this study, we investigate if polyphenols extracts from natural raw shelled pistachios (NP) or roasted salted pistachio (RP) kernels have anti-inflammatory and antioxidant properties at lower doses than reported previously, in both in vitro and in vivo models. The monocyte/macrophage cell line J774 was used to assess the extent of protection by NP and RP pistachios against lipopolysaccharide (LPS)-induced inflammation. Moreover, antioxidant activity of NP and RP was assessed in an in vivo model of paw edema in rats induced by carrageenan (CAR) injection in the paw. Results from the in vitro study demonstrated that pre-treatment with NP (0.01, 0.1 and 0.5 mg/mL) and RP (0.01 and 0.1 mg/mL) exerted a significant protection against LPS induced inflammation. Western blot analysis showed NP reduced the degradation of IκB-α, although not significantly, whereas both NP and RP decreased the TNF-α and IL-1β production in a dose-dependent way. A significant reduction of CAR-induced histological paw damage, neutrophil infiltration and nitrotyrosine formation was observed in the rats treated with NP. These data demonstrated that, at lower doses, polyphenols present in pistachios possess antioxidant and anti-inflammatory properties. This may contribute toward a better understanding of the beneficial health effects associated with consumption of pistachios. PMID:28829406

Jobelyn® exhibited anti-inflammatory, antioxidant, and membrane-stabilizing activities in experimental models.

PubMed

Umukoro, Solomon; Oluwole, Oluwafemi Gabriel; Eduviere, Anthony T; Adrian, Omogbiya Itievere; Ajayi, Abayomi M

2015-09-01

Jobelyn® (JB) is an African sorghum-based food supplement claimed to be efficacious for the treatment of rheumatoid arthritis (RA). Although in vitro studies confirmed its anti-inflammatory property, no study had shown the effect of JB using in vivo animal models of inflammation. Thus, its effects on acute and chronic inflammation in rats were evaluated in this study. Its effect on rat red blood cell (RBC) lysis was also assessed. Acute inflammation was induced with intraplanter injection of carrageenan and increase in rat paw volume was measured using plethysmometer. The volume of fluid exudates, number of leukocytes, concentrations of malondialdehyde (MDA), and glutathione (GSH) in the fluid were measured on day 5 after induction of chronic inflammation with carrageenan in the granuloma air pouch model. RBC lysis induced by hypotonic medium as determined by release of hemoglobin was measured spectrophotometerically. JB (50-200 mg/kg) given orally produced a significant inhibition of acute inflammation induced by carrageenan in rats. It reduced the volume and number of leukocytes in inflammatory fluid in the granuloma air pouch model of chronic inflammation. It further decreased the levels of MDA in the fluid suggesting antioxidant property. JB elevated the concentrations of GSH in inflammatory exudates indicating free radical scavenging activity. It also significantly inhibited RBC lysis caused by hypotonic medium, suggesting membrane-stabilizing property. JB has in vivo anti-inflammatory activity, which may be related to its antioxidant and membrane-stabilizing properties, supporting its use for the treatment of arthritic disorder.

Silk sericin loaded alginate nanoparticles: Preparation and anti-inflammatory efficacy.

PubMed

Khampieng, Thitikan; Aramwit, Pornanong; Supaphol, Pitt

2015-09-01

In this study, silk sericin loaded alginate nanoparticles were prepared by the emulsification method followed by internal crosslinking. The effects of various silk sericin loading concentration on particle size, shape, thermal properties, and release characteristics were investigated. The initial silk sericin loadings of 20, 40, and 80% w/w to polymer were incorporated into these alginate nanoparticles. SEM images showed a spherical shape and small particles of about 71.30-89.50 nm. TGA analysis showed that thermal stability slightly increased with increasing silk sericin loadings. FTIR analysis suggested interactions between alginate and silk sericin in the nanoparticles. The release study was performed in acetate buffer at normal skin conditions (pH 5.5; 32 °C). The release profiles of silk sericin exhibited initial rapid release, consequently with sustained release. These silk sericin loaded alginate nanoparticles were further incorporated into topical hydrogel and their anti-inflammatory properties were studied using carrageenan-induced paw edema assay. The current study confirms the hypothesis that the application of silk sericin loaded alginate nanoparticle gel can inhibit inflammation induced by carrageenan. Copyright © 2015 Elsevier B.V. All rights reserved.

Anti-inflammatory activity of Albizia lebbeck Benth., an ethnomedicinal plant, in acute and chronic animal models of inflammation.

PubMed

Babu, N Prakash; Pandikumar, P; Ignacimuthu, S

2009-09-07

Albizia lebbeck Benth. is used both in Indian traditional system and folk medicine to treat several inflammatory pathologies such as asthma, arthritis and burns. The aim of the present study was to evaluate the scientific basis of anti-inflammatory activity of different organic solvent extracts of Albizia lebbeck. The anti-inflammatory activity of Albizia lebbeck was studied using the carrageenan, dextran, cotton pellet and Freund's complete adjuvant induced rat models. The extracts obtained using petroleum ether, chloroform and ethanol were administered at the concentrations of 100, 200 and 400mg/kg body weight. The petroleum ether and ethanol extracts at 400mg/kg, showed maximum inhibition of inflammation induced by carrageenan (petroleum ether-48.6%; ethanol-59.57%), dextran (petroleum ether-45.99%; ethanol-52.93%), cotton pellet (petroleum ether-34.46%; ethanol-53.57%) and Freund's adjuvant (petroleum ether-64.97%; ethanol-68.57%). The marked inhibitory effect on paw edema shows that Albizia lebbeck possesses remarkable anti-inflammatory activity, supporting the folkloric usage of the plant to treat various inflammatory diseases.

Anti-Inflammatory and Anti-Nociceptive Activities of Stem-Bark Extracts and Fractions of Carpolobia Lutea (Polygalaceae)

PubMed Central

Nwidu, Lucky Legbosi; Airhihen, Blessing; Ahmadu, Augustine

2016-01-01

Background: In Niger Delta, ethnomedicine hydroalcoholic extract of Carpolobia lutea (CL) (Polygalaceae) is used to relieve inflammatory pains. Objectives: The purpose of this study is to evaluate the anti-inflammatory and antinociceptive effects of ethanolic stem extract (ESE) and to fractionate the ESE for the elucidation of bioactive molecules. Materials and Methods: The antinociceptive effects for ESE were tested against two noxious stimuli; chemical (acetic acid-induced writhing and formalin-induced pain) and thermal (hot plate) stimuli. The effects of paracetamol (130 mg/kg), indomethacin (10 mg/kg), and morphine (5 mg/kg) pretreatment were investigated. To isolate the bioactive compounds with anti-inflammatory effect, two doses (86.6 and 173.2 mg/kg) of four fractions (methanol fraction MTF, ethyl acetate fraction EAF, chloroform fraction CHF, and n-hexane fraction n-HF) obtained from fractionating ESE were utilized. Carrageenan, egg albumin, and capsaicin-induced edema of the hind paw of the rats were the models adopted. Paw volume was measured by a digital vernier caliper from 0 to 6 h after injection. This was compared to standard drugs. The results were subjected to statistical analysis. Results: The ESE decreased significantly (P < 0.001) the writhing of acetic acid-induced abdominal contractions and licking of formalin-induced pains but does not have any effects on the hot plate test. Of the four fractions obtained, the EAFs demonstrated a significant (P < 0.001) inflammatory inhibition of 98.97% and 41.91% at 86.6 and 173.2 mg/kg, respectively, compared to 65.75% inhibition demonstrated by the reference drug, acetylsalicylic acid (100 mg/kg) on the carrageenan model while 36.36% and 29.87% inhibition of inflammation at 86.6 and 173.2 mg/kg, respectively, on the egg albumin models; there was no significant effect on the capsaicin model. Conclusion: The isolation of quercetin and kaemferol from CL gave credence to its anti-inflammatory and antinociceptive effects. PMID:28104971

Mechanisms of Analgesic and Anti-Inflammatory Properties of Annona muricata Linn. (Annonaceae) Fruit Extract in Rodents

PubMed Central

Ishola, Ismail O.; Olusayero, Abayomi Micheal; Ochieng, Charles O.

2014-01-01

Abstract Unripe fruit of Annona muricata Linn. (Annonaceae) (soursop) is used in traditional African medicine for the treatment of neuralgia, rheumatism, and arthritic pain. This study sought to investigate the analgesic and anti-inflammatory effects of lyophilized fruit extract of Annona muricata (AM) in rodents. The analgesic activity was evaluated using the mouse writhing, formalin, and hot-plate tests while the anti-inflammatory action was investigated using the carrageenan-induced rat paw edema and xylene-induced ear edema tests. Pretreatment with AM (50, 100, and 200 mg/kg, p.o.) produced dose-dependent (P<.001) inhibition of writhes and formalin-induced pain in the late phase. AM and morphine produced time-course increase in pain threshold in hot-plate test. However, the analgesic effect elicited by AM was reversed (P<.05) by naloxone pretreatment. Similarly, the time-dependent increase in paw circumference induced by carrageenan was inhibited by AM treatment with peak effect (0.23±0.10 cm; P<.001, 200 mg/kg; 6 h), which was comparatively similar to that of diclofenac treated. Further, the xylene-induced ear edema was significantly reduced by AM (50 or 100 mg/kg) pretreatment; however, the anti-inflammatory effect elicited by AM was prevented by pretreatment of mice with NG-nitro-l-arginine (20 mg/kg, i.p., nitric-oxide synthase inhibitor) 15 min before AM (200 mg/kg, p.o.). The in vitro cyclooxygenase assay also showed that AM produced concentration-dependent inhibition of both cyclooxygenase (COX)-1 and COX-2 activity by 39.44%±0.05% and 55.71%±0.12%, respectively, at 100 μg/mL. In conclusion, A. muricata possesses analgesic effect through interaction with opioidergic pathway and anti-inflammatory property through inhibition of chemical mediators of inflammation. PMID:25133801

Cyclo-oxygenase isozymes in mucosal ulcergenic and functional responses following barrier disruption in rat stomachs.

PubMed

Hirata, T; Ukawa, H; Yamakuni, H; Kato, S; Takeuchi, K

1997-10-01

1. We examined the effects of selective and nonselective cyclo-oxygenase (COX) inhibitors on various functional changes in the rat stomach induced by topical application of taurocholate (TC) and investigated the preferential role of COX isozymes in these responses. 2. Rat stomachs mounted in ex vivo chambers were perfused with 50 mM HCl and transmucosal potential difference (p.d.), mucosal blood flow (GMBF), luminal acid loss and luminal levels of prostaglandin E2 (PGE2) were measured before, during and after exposure to 20 mM TC. 3. Mucosal application of TC in control rats caused a reduction in p.d., followed by an increase of luminal acid loss and GMBF, and produced only minimal damage in the mucosa 2 h later. Pretreatment with indomethacin (10 mg kg[-1], s.c.), a nonselective COX-1 and COX-2 inhibitor, attenuated the gastric hyperaemic response caused by TC without affecting p.d. and acid loss, resulting in haemorrhagic lesions in the mucosa. In contrast, selective COX-2 inhibitors, such as NS-398 and nimesulide (10 mg kg[-1], s.c.), had no effect on any of the responses induced by TC and did not cause gross damage in the mucosa. 4. Luminal PGE2 levels were markedly increased during and after exposure to TC and this response was significantly inhibited by indomethacin but not by either NS-398 or nimesulide. The expression of COX-1-mRNA was consistently detected in the gastric mucosa before and after TC treatment, while a faint expression of COX-2-mRNA was detected only 2 h after TC treatment. 5. Both NS-398 and nimesulide significantly suppressed carrageenan-induced rat paw oedema, similar to indomethacin. 6. These results confirmed a mediator role for prostaglandins in the gastric hyperaemic response following TC-induced barrier disruption, and suggest that COX-1 but not COX-2 is a key enzyme in maintaining 'housekeeping' functions in the gastric mucosa under both normal and adverse conditions.

Label-free monitoring of inflammatory tissue conditions using a carrageenan-induced acute inflammation rat model.

PubMed

Lee, Seung Ho; Lee, Sang Hwa; Shin, Jae-Ho; Choi, Samjin

2018-06-01

Although the confirmation of inflammatory changes within tissues at the onset of various diseases is critical for the early detection of disease and selection of appropriate treatment, most therapies are based on complex and time-consuming diagnostic procedures. Raman spectroscopy has the ability to provide non-invasive, real-time, chemical bonding analysis through the inelastic scattering of photons. In this study, we evaluate the feasibility of Raman spectroscopy as a new, easy, fast, and accurate diagnostic method to support diagnostic decisions. The molecular changes in carrageenan-induced acute inflammation rat tissues were assessed by Raman spectroscopy. Volumes of 0 (control), 100, 150, and 200 µL of 1% carrageenan were administered to rat hind paws to control the degree of inflammation. The prominent peaks at [1,062, 1,131] cm -1 and [2,847, 2,881] cm -1 were selected as characteristic measurements corresponding to the C-C stretching vibrational modes and the symmetric and asymmetric C-H (CH 2 ) stretching vibrational modes, respectively. Principal component analysis of the inflammatory Raman spectra enabled graphical representation of the degree of inflammation through principal component loading profiles of inflammatory tissues on a two-dimensional plot. Therefore, Raman spectroscopy with multivariate statistical analysis represents a promising method for detecting biomolecular responses based on different types of inflammatory tissues. © 2018 Wiley Periodicals, Inc.

Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia.

PubMed

Huang, Chun-Ping; Chen, Hsiang-Ni; Su, Hong-Lin; Hsieh, Ching-Liang; Chen, Wei-Hsin; Lai, Zhen-Rung; Lin, Yi-Wen

2013-01-01

Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

Effects of Intrathecal SNC80, a Delta Receptor Ligand, on Nociceptive Threshold and Dorsal Horn Substance P Release

PubMed Central

Kouchek, Milad; Takasusuki, Toshifumi; Terashima, Tetsuji; Yaksh, Tony L.

2013-01-01

Delta-opioid receptors (DOR) are present in the superficial dorsal horn and are believed to regulate the release of small afferent transmitters as evidenced by the effects of spinally delivered delta-opioid preferring peptides. Here we examined the effects of intrathecal SNC80 [(+)-4-[α(R)-α-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-(methoxybenzyl)-N,N-diethylbenzamide], a selective nonpeptidic DOR agonist, in three preclinical pain models, acute thermal escape, intraplantar carrageenan-tactile allodynia, and intraplantar formalin flinches, and on the evoked release of substance P (SP) from small primary afferents. Rats with chronic intrathecal catheters received intrathecal vehicle or SNC80 (100 or 200 μg). Intrathecal SNC80 did not change acute thermal latencies or carrageenan-induced thermal hyperalgesia. However, SNC80 attenuated carrageenan-induced tactile allodynia and significantly reduced both phase 1 and phase 2 formalin-induced paw flinches, as assessed by an automatic flinch counting device. These effects were abolished by naltrindole (3 mg/kg i.p.), a selective DOR antagonist, but not CTOP (10 µg i.t.), a selective MOR antagonist. Furthermore, intrathecal SNC80 (200 μg) blocked formalin-induced substance P release otherwise evoked in the ispilateral superficial dorsal horn as measured by NK1 receptor internalization. In conclusion, intrathecal SNC80 alleviated pain hypersensitivity after peripheral inflammation in a fashion paralleling its ability to block peptide transmitter release from small peptidergic afferents, which by its pharmacology appears to represent an effect mediated by a spinal DOR. PMID:23978562

Antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom in experimental animal models.

PubMed

Ghosh, Susmita; Saha, Partha Pratim; Dasgupta, Subir C; Gomes, Antony

2016-09-01

Pain and inflammation are intimately associated with rheumatoid arthritis, a growing bone-joint related problem of the modern society. Though several therapeutic managements are available for arthritis, their side effects not only limit their use, but also advocate the quest for natural therapies. In this study, we explored the antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom (BFV) in experimental animal models. Rheumatoid arthritis was induced by Freund’s complete adjuvant (FCA) in male Wistar albino rats. Lyophilized BFV was diluted in 0.9% NaCl. Antiarthritic activity showed that BFV significantly reduced the paw and ankle diameters; urinary hydroxyproline, glucosamine levels and serum ACP/ALP/TNF-α/IL-1β/IL-17/Cathepsin-K/MMP-1 levels. These parameters were significantly increased in FCA induced arthritic animals. Joint histopathology study indicated the partial restoration of joint structure. Treatment with BFV significantly reduced the mean latency time of tail flick response, acetic acid induced writhing response and formalin induced licking response in male albino mice. BFV treatment also significantly reduced carrageenan induced paw edema and xylene induced ear edema in male albino mice. The results indicated that BFV possess antinociceptive, anti-inflammatory and antiarthritic properties and further studies are warranted to find the active constituents present in BFV.

Anti-inflammatory and antipyretic effects of Sonchus oleraceus in rats.

PubMed

Vilela, Fabiana C; Bitencourt, Andressa D; Cabral, Layla D M; Franqui, Lidiane S; Soncini, Roseli; Giusti-Paiva, Alexandre

2010-02-17

Sonchus oleraceus L. has been used to relieve headaches, general pain, hepatitis, infections, inflammation and rheumatism in Brazilian folk medicine. Nevertheless, scientific information regarding this species is scarce; there are no reports related to its possible anti-inflammatory effects. This study was aimed at evaluating the scientific basis for the traditional use of Sonchus oleraceus using in vivo inflammatory models. Carrageenan-induced paw edema, peritonitis and febrile response induced by lipopolysaccharide tests, as well as fibrovascular tissue growth induced by s.c. cotton pellet implantation were used to investigate the anti-inflammatory activity of Sonchus oleraceus hydroethanolic extract (SoHE) in rats. The SoHE at test doses of 100-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced paw edema induced by carragenan, inhibited leukocyte recruitment into the peritoneal cavity and reduced LPS-induced febrile response, and in the model of chronic inflammation using the cotton pellet-induced fibrovascular tissue growth in rats, the SoHE significantly inhibited the formation of granulomatous tissue. The extract administered at 300 mg/kg p.o. had a stronger anti-inflammatory effect than indomethacin (10mg/kg) or dexamethasone (1mg/kg). The hydroethanolic extract of Sonchus oleraceus markedly demonstrated anti-inflammatory action in rats, which supports previous claims of its traditional use. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Synthesis and antinociceptive evaluation of bioisosteres and hybrids of naproxen, ibuprofen and paracetamol.

PubMed

González-Trujano, María Eva; Uribe-Figueroa, Gerardo; Hidalgo-Figueroa, Sergio; Martínez, Ana Laura; Déciga-Campos, Myrna; Navarrete-Vazquez, Gabriel

2018-05-01

The aim of this work was to design, synthesize and characterize the potential anti-nociceptive and anti-inflammatory activities of a new series of bioisosteres and hybrids from known non-steroidal anti-inflammatory drugs (NSAIDs). The compounds 4-(acetylamino)phenyl (2S)-2-(6-methoxy-2-naphthyl)propanoate (GUF-1) and 4-(acetylamino)phenyl 2-(R,S)-(4-isobutylphenyl)propanoate (GUF-2) were synthesized as hybrids (also known as heterodimers); whereas those named 2-(R,S)-(4-isobutylphenyl)-N-1H-tetrazol-5-ylpropanamide (GUF-3), (2S)-2-(6-methoxy-2-naphthyl)-N-1H-tetrazol-5-ylpropanamide (GUF-4), [2-(R,S)-N-hydroxy-2-[4-(2-methylpropyl)phenyl]propanamide] (GUF-5), and (2S)-N-hydroxy-2-(6-methoxy-2-naphthyl)propanamide (GUF-6) were synthesized as bioisosteres of the NSAIDs paracetamol, ibuprofen, and naproxen, respectively. All these compounds were characterized by spectroscopic and spectrometric analysis. Antinociceptive activity of GUF-1 to GUF-6 was evaluated using the formalin test in rats. Pharmacological responses of GUF-1, GUF-2 (hybrids), and GUF-5 (bioisostere) demonstrated significant antinociceptive effects; thus these compounds were assayed in an inflammation test like carrageenan-induced paw oedema in rats. Complete molecular docking of cyclooxygenase and the GUF-1 and GUF-2 hybrids showed high docking scores, compared to the reference drugs. Our data demonstrate that compounds GUF-1, GUF-2, and GUF-5 possesses antinociceptive and antiinflammatory activities resembling and improving those known for the traditional NSAIDs, paracetamol, naproxen and ibuprofen. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Synergistic interaction between choline and aspirin against acute inflammation induced by carrageenan and lipopolysaccharide.

PubMed

Pan, Zhi-Yuan; Wang, Hai

2014-05-01

The simultaneous use of drugs with different mechanisms of anti-inflammatory action is a strategy for achieving effective control of inflammation while minimizing dose-related side effects. Choline was described to potentiate the antinociceptive action of aspirin at small doses in several inflammatory pain models. However, these findings are only limited to alleviating pain, more associated data are required to confirm the effectiveness of the combined choline and aspirin therapy against inflammatory disorders. Moreover, no report is available regarding the mechanism responsible for their synergism. Here, we first investigated the anti-inflammatory activity and pharmacological mechanisms of co-administration of choline and aspirin in 2 commonly studied inflammation models, carrageenan-induced paw edema and lipopolysaccharide (LPS)-induced sepsis in mice. Isobolographic analysis revealed that combined choline and aspirin administration exhibited a strong synergistic interaction in reducing carrageenan-mediated edema, and the estimated combination index values at 50%, 75%, and 90% effective dose (ED50, ED75, and ED90) were 0.25, 0.32, and 0.44. Drug co-administration also afforded synergistic protection against LPS-induced sepsis and mortality, since aspirin or choline alone was inadequate to improve survival. The effects of choline-aspirin co-administration were blocked by methyllycaconitine, suggesting that activation of alpha 7 nicotinic acetylcholine receptor participates in the interaction between choline and aspirin. Furthermore, co-administration of choline and aspirin was more likely to inhibit the production of pro-inflammatory mediators induced by LPS. Our results indicated that combined choline and aspirin therapy represented a significant synergistic interaction in attenuating acute inflammatory response. This preclinical relevant evidence provides a promising approach to treat inflammation-based diseases such as arthritis and sepsis. Copyright © 2014 Elsevier B.V. All rights reserved.

Ferulic acid ethyl ester diminished Complete Freund's Adjuvant-induced incapacitation through antioxidant and anti-inflammatory activity.

PubMed

Cunha, Francisco Valmor Macedo; Gomes, Bruno de Sousa; Neto, Benedito de Sousa; Ferreira, Alana Rodrigues; de Sousa, Damião Pergentino; de Carvalho e Martins, Maria do Carmo; Oliveira, Francisco de Assis

2016-01-01

Ferulic acid ethyl ester (FAEE) is a derivate from ferulic acid which reportedly has antioxidant effect; however, its role on inflammation was unknown. In this study, we investigated the orally administered FAEE anti-inflammatory activity on experimental inflammation models and Complete Freund's Adjuvant (CFA)-induced arthritis in rats. CFA-induced arthritis has been evaluated by incapacitation model and radiographic knee joint records at different observation time. FAEE (po) reduced carrageenan-induced paw edema (p < 0.001) within the 1st to 5th hours at 50 and 100 mg/kg doses. FAEE 50 and 100 mg/kg, po inhibited leukocyte migration into air pouch model (p < 0.001), and myeloperoxidase, superoxide dismutase, and catalase activities (p < 0.001) increased total thiol concentration and decreased the TNF-α and IL-1β concentrations, NO, and thiobarbituric acid reactive species. In the CFA-induced arthritis, FAEE 50 and 100 mg/kg significantly reduced the edema and the elevation paw time, a joint disability parameter, since second hour after arthritis induction (p < 0.001). FAEE presented rat joint protective activity in radiographic records (p < 0.001). The data suggest that the FAEE exerts anti-inflammatory activity by inhibiting leukocyte migration, oxidative stress reduction, and pro-inflammatory cytokines.

Methanolic extract of leaves of Jasminum grandiflorum Linn modulates oxidative stress and inflammatory mediators.

PubMed

Chaturvedi, Adya Prasad; Tripathi, Yamini Bhusan

2011-10-01

The leaves of Jasminum grandiflorum (JG) are in clinical use in Ayurveda for wound management. Since, oxidative stress and inflammation are the primary causes in delayed wound healing, so here its antioxidant and anti-inflammatory activities have been investigated using in vitro as well as in vivo models. The solvent-free methanolic extract of dried leaves of JG were tested for its trapping capacity toward pre-generated ABTS•+ radicals, instantly generated superoxide and hydroxyl radicals, along with metal chelation property, reducing power and total phenolic content. Further, it was tested on LPS-induced nitric oxide and cell viability, on primary culture of rat peritoneal macrophages. Its anti-inflammatory property was also tested on carrageenan-induced paw edema in rats. This extract significantly inhibited iron-induced lipid peroxidation and trapped ABTS•+, superoxide and OH radicals. It significantly inhibited nitric oxide (NO) release, without affecting the cell viability at 800 μg/ml concentration and reduced the formation of paw edema in rats. Thus, it could be suggested that the aforesaid anti-inflammatory properties of JG leaves are associated to its high phenolic content (2.25±0.105 mg/l of gallic acid equivalent), reducing power and its free radical-scavenging property.

Adelmidrol, a palmitoylethanolamide analogue, as a new pharmacological treatment for the management of acute and chronic inflammation.

PubMed

Impellizzeri, Daniela; Di Paola, Rosanna; Cordaro, Marika; Gugliandolo, Enrico; Casili, Giovanna; Morittu, Valeria Maria; Britti, Domenico; Esposito, Emanuela; Cuzzocrea, Salvatore

2016-11-01

The aim of study was to examine the anti-inflammatory and analgesic effects of adelmidrol, an analogue of palmitoylethanolamide (PEA), in animal models of acute and chronic inflammation [carrageenan-induced paw edema (CAR) and collagen-induced arthritis (CIA)]. In order to elucidate whether the action of adelmidrol is related to activation of peroxisome proliferator-activated receptors (PPAR-α or PPAR-γ), we investigated the effects of PPAR-γ antagonist, GW9662 on adelmidrol mechanism. CAR induced paw edema, hyperalgesia and the activation of pro-inflammatory NF-κB pathway were markedly reduced by treatment with adelmidrol. GW9662, (administered prior to adelmidrol treatment), antagonized the effect of adelmidrol abolishing its positive action. On the contrary, the genetic absence of PPAR-α receptor did not modify the beneficial results of adelmidrol treatment in the acute model of inflammation. In addition, for the first time, we demonstrated that adelmidrol was able to ameliorate both the clinical signs and the histopathology of the joint and the hind paw during chronic inflammation. In particular, the degree of oxidative damage and proinflammatory cytokines and chemokines production were significantly reduced in adelmidrol-treated mice. Moreover, in CIA model, the effect of GW9662 pre-treatment on adelmidrol mechanism was also confirmed. Thus, in this study, we report that adelmidrol reduces the development of acute and chronic inflammation and could represent a novel therapeutic approach for inflammation and pain. Copyright © 2016 Elsevier Inc. All rights reserved.

Enzymologic and pharmacologic profile of loxoprofen sodium and its metabolites.

PubMed

Noguchi, Masahiro; Kimoto, Aishi; Gierse, James Kevin; Walker, Mark Crossfield; Zweifel, Ben Scott; Nozaki, Kazutoshi; Sasamata, Masao

2005-11-01

We investigated the mechanism of inhibition of loxoprofen sodium, a non-steroidal anti-inflammatory drug (NSAID), and its active metabolite (loxoprofen-SRS) on cyclooxygenase (COX). In in vitro assays, loxoprofen sodium appeared inactive against recombinant human COX-1 and COX-2, whereas loxoprofen-SRS inhibited both. In the investigation of kinetic behavior, loxoprofen-SRS showed time-dependent inhibition for both isozymes. Human whole blood assay also showed that loxoprofen-SRS possesses the profile of a non-selective inhibitor for COX. In a rat air pouch model, oral administration of loxoprofen sodium lowered prostaglandin (PG) E2 in both fluid exudates of the inflammatory pouch and stomach tissue with ED50 values of 2.0 and 2.1 mg/kg, respectively. Additionally, platelet thromboxane B2 production was also inhibited by loxoprofen sodium (ED50 of 0.34 mg/kg). In a rat carrageenan-induced paw edema model, loxoprofen sodium dose-dependently reduced the paw edema, accompanied by a decrease in PGE2 content in inflamed paw exudates. These findings suggest that the COX inhibitory activity of loxoprofen sodium is attributable to its active metabolite, loxoprofen-SRS, and that loxoprofen-SRS shows non-selective inhibition for COX.

Evaluation of anti-inflammatory and gastric anti-ulcer activity of Phyllanthus niruri L. (Euphorbiaceae) leaves in experimental rats.

PubMed

Mostofa, Ronia; Ahmed, Shanta; Begum, Mst Marium; Sohanur Rahman, Md; Begum, Taslima; Ahmed, Siraj Uddin; Tuhin, Riazul Haque; Das, Munny; Hossain, Amir; Sharma, Manju; Begum, Rayhana

2017-05-16

The medicinal plants signify a massive basin of potential phytoconstituents that could be valuable as a substitute to allopathic drugs or considered as an analogue in drug development. Phyllanthus niruri L. (Euphorbiaceae) is generally used in traditional medicine to treat ulcer and inflammation. In this project we investigated the methanolic extract of leaves of Phyllanthus niruri for anti-inflammatory and anti-ulcer activity. The anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was evaluated at the doses of 100, 200 and 400 mg/kg, p.o. while using ibuprofen (20 mg/kg, p.o) as the standard drug. The animals used were Swiss albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. Paw tissues from the different groups were examined for inflammatory cell infiltration. On the other hand, antiulcer activity of methanolic extract of P. niruri leaves at the doses of 100, 200 and 400 mg/kg, p.o. were examined against ethanol-acid induced gastric mucosal injury in the Swiss albino rats - keeping omeprazole (20 mg/kg, p.o.) as reference. The rats were dissected and the stomachs were macroscopically examined to identify hemorrhagic lesions in the glandular mucosa. P. niruri significantly (p < 0.01) decreased carrageenan-induced paw edema; it exhibited a reduction of 46.80%, 55.32% and 69.14% at doses of 100, 200 and 400 mg/kg, respectively. These findings were further supported by the histological study. The methanolic extract also disclosed good protective effect against ethanol-acid induced gastric mucosal injury in the rats. Administration of the extract's doses (100, 200 and 400 mg/kg) demonstrated a significant (p < 0.01) reduction in the ethanol- acid induced gastric erosion in all the experimental groups when compared to the control. The methanolic extract at the higher dose (400 mg/kg) resulted in better inhibition of ethanol-acid induced gastric ulcer as compare to omeprazole (20 mg/kg). Histological studies of the gastric wall revealed that toxic control rats revealed mucosal degeneration, ulceration and migration of numerous inflammatory cells throughout the section. On the other hand, MEPN treatment groups showed significant regeneration of mucosal layer and significantly prevented the formation of hemorrhage and edema. The investigation suggests that methanolic extract of P. niruri leaf possess anti-inflammatory activity and promotes ulcer protection as ascertained by regeneration of mucosal layer and substantial prevention of the formation of hemorrhage and edema.

Synergistic interactions between paracetamol and oxcarbazepine in somatic and visceral pain models in rodents.

PubMed

Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

2010-04-01

Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of coadministered paracetamol, a widely used non-opioid analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic properties, in a rat model of paw inflammatory hyperalgesia and in a mice model of visceral pain and determined the type of interaction between components. The effects of paracetamol, oxcarbazepine, and their combinations were examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in rats and in an acetic acid-induced (10 mg/kg, 0.75%) writhing test in mice. In both models, drugs were coadministered in fixed-dose fractions of the 50% effective dose (ED(50)), and type of interaction was determined by isobolographic analysis. Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160 mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan-injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral), oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and 1/2 of a single drug ED(50)) significantly and dose dependently reduced the number of writhes. In both models, isobolographic analysis revealed a significant synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold reduction of doses of both drugs in combination, compared with single drugs ED(50). The synergistic interaction between paracetamol and oxcarbazepine provides new information about combination pain treatment and should be explored further in patients, especially with somatic and/or visceral pain.

Pharmacological Proprieties of the Ethanol Extract of Muehlenbeckia platyclada (F. Muell.) Meisn. Leaves

PubMed Central

Fagundes, Leopoldina Leonor; Vieira, Glauciemar Del-Vechio; de Pinho, José de Jesus R. G.; Yamamoto, Célia Hitomi; Alves, Maria Silvana; Stringheta, Paulo César; de Sousa, Orlando Vieira

2010-01-01

Antinociceptive and anti-inflammatory activities of the Muehlenbeckia platyclada leaves’ ethanol extract were investigated in animal models. The extract (p.o.) reduced the number of abdominal contortions induced by acetic acid by 21.57% (400 mg/kg). After intraplantar injection of formalin, a dose of 400 mg/kg (p.o.) inhibited the time spent paw licking in the first phase (26.43%), while the second phase was inhibited by 10.90 and 36.65% at the doses of 200 and 400 mg/kg, respectively. The extract (p.o.) increased the reaction time on a hot plate at a dose of 400 mg/kg (32.68 and 40.30%) after 60 and 90 minutes of treatment, respectively. The paw edema was reduced by extract (p.o.) at doses of 100 (15.46 and 16.67%), 200 (22.68 and 25.64%) and 400 mg/kg (29.50 and 37.33%) after 3 to 4 h of carrageenan application, respectively. Doses of 100, 200 and 400 mg/kg (p.o.), administered 4 h after the carrageenan injection, reduced the exudate volume (11.28, 21.54 and 45.13%), while leukocyte migration was reduced by 21.21 and 29.70% at the doses of 200 and 400 mg/kg, respectively. These results indicate that the ethanol extract from M. platyclada may constitute a potential target for the discovery of new molecules with antinociceptive and anti-inflammatory activities that can be explored for their therapeutic use. PMID:21152311

Spondias tuberosa (Anacardiaceae) leaves: profiling phenolic compounds by HPLC-DAD and LC-MS/MS and in vivo anti-inflammatory activity.

PubMed

da Silva Siqueira, Emerson Michell; Félix-Silva, Juliana; de Araújo, Lorena Maria Lima; Fernandes, Julia Morais; Cabral, Bárbara; Gomes, Jacyra Antunes Dos Santos; de Araújo Roque, Alan; Tomaz, José Carlos; Lopes, Norberto Peporine; de Freitas Fernandes-Pedrosa, Matheus; Giordani, Raquel Brandt; Zucolotto, Silvana Maria

2016-10-01

Spondias tuberosa is a medicinal plant used by several local communities in northeast Brazil to treat infections, digestive disorders and inflammatory conditions. The study aimed to identify and quantify the major phenolic in hydroethanolic extract of leaves from S. tuberosa and to evaluate its anti-inflammatory potential. The chemical profile of extract was analyzed by HPLC-DAD and HPLC-MS. The in vivo anti-inflammatory activity was investigated in carrageenan-induced hind paw edema and peritonitis models in mice. Identified and quantified through HPLC-DAD or HPLC-MS analyses of S. tuberosa extract were the following compounds: chlorogenic acid, caffeic acid, rutin and isoquercitrin. The inflammatory response to carrageenan was significantly reduced in both models by S. tuberosa extract. In hind paw edema, the edematogenic response was reduced by up to 63.6% and the myeloperoxidase activity was completely inhibited. In the peritonitis model, the total cell migration into the peritoneal cavity was reduced by up to 65%. The results obtained give evidence of the anti-inflammatory action of S. tuberosa and suggest the potential therapeutic benefit of this plant on inflammatory conditions. The chlorogenic acid, caffeic acid, rutin and isoquercitrin identified and quantified in S. tuberosa leaves enable us to suggest that these compounds could be used as chemical markers for quality control of derivative products from this species. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of the analgesic and anti-inflammatory effects of a Brazilian green propolis.

PubMed

Paulino, Niraldo; Teixeira, Cristiane; Martins, Regiane; Scremin, Amarilis; Dirsch, Verena M; Vollmar, Angelika M; Abreu, Sheila R; de Castro, Solange L; Marcucci, Maria Cristina

2006-08-01

Phamacological activities of a standard ethanol extract G1 from Brazilian green propolis, typified as BRP1, was evaluated in mouse models of pain and inflammation. Intraperitoneal injection ( I. P.) of G1 inhibited acetic acid-induced abdominal constrictions with an ID (50) = 0.75 +/- 0.05 mg/kg, and in the formalin test the ID (50) values were 0.85 +/- 0.07 mg/kg and 13.88 +/- 1.12 mg/kg, respectively, for the neurogenic and inflammatory phases. The extract was ineffective when assessed in the hot-plate assay. In serotonin-induced paw edema, G1 led to a maximal inhibition (MI) of 51.6 % after 120 min when administered I. P. and of 36 % after 15 min by the oral route ( O. R.). When the inflammatory agent was complete Freund's adjuvant, inhibition of paw edema was also observed after administration of the extract by both routes. In the capsaicin-induced ear edema the ID (50) values were 1.09 +/- 0.08 mg/kg ( I. P.) and 10.00 +/- 0.90 mg/kg ( O. R.). In the acute carrageenan-induced inflammatory reaction induced by carrageenan, G1 reduced the number of neutrophils in the peritoneal cavity with IC (50) values of 0.72 +/- 0.08 mg/kg and 4.17 +/- 0.50 mg/kg, by I. P. or O. R. administration, with a preferential migration of polymorphonuclear neutrophils. IN VITRO, G1 decreased nitric oxide production in LPS-stimulated RAW 264.7 cells (IC (50) = 41.60 microg/mL), and also the luciferase activity in TNF-alpha-stimulated HEK 293 cells transfected with NF-kappaB-luciferase reporter gene driven by the nuclear factor kappaB (NF-kappaB) (IC (50) = 200 microg/mL). This extract, which at low concentrations induces anti-inflammatory and analgesic effects in mouse models, presents a high content of flavonoids, known to inhibit inducible NOS (iNOS) activity. These data taken together led us to reinforce the hypothesis in the literature that the anti-inflammatory effect of propolis may be a due to inhibition of iNOS gene expression, through interference with NF-kappaB sites in the iNOS promoter.

Analgesic and anti-inflammatory effects of A-286501, a novel orally active adenosine kinase inhibitor.

PubMed

Jarvis, Michael F; Yu, Haixia; McGaraughty, Steve; Wismer, Carol T; Mikusa, Joe; Zhu, Chang; Chu, Katharine; Kohlhaas, Kathy; Cowart, Marlon; Lee, Chih Hung; Stewart, Andrew O; Cox, Bryan F; Polakowski, James; Kowaluk, Elizabeth A

2002-03-01

Adenosine (ADO) is an inhibitory neuromodulator that can increase nociceptive thresholds in response to noxious stimulation. Inhibition of the ADO-metabolizing enzyme, adenosine kinase (AK) increases extracellular ADO concentrations at sites of tissue trauma and AK inhibitors may have therapeutic potential as analgesic and anti-inflammatory agents. N7-((1'R,2'S,3'R,4'S)-2',3'-dihydroxy-4'-amino-cyclopentyl)-4-amino-5-bromo-pyrrolo[2,3-a]pyrimidine (A-286501) is a novel and potent (IC50=0.47 nM) carbocyclic nucleoside AK inhibitor that has no significant activity (IC50 >100 microM) at other sites of ADO interaction (A1, A2A, A3 receptors, ADO transporter, and ADO deaminase) or other (IC50 value >10 microM) neurotransmitter and peptide receptors, ion channel proteins, neurotransmitter reuptake sites and enzymes, including cyclooxygenases-1 and -2. A-286501 showed equivalent potency to inhibit AK from several mammalian species and kinetic studies revealed that A-286501 was a reversible and competitive inhibitor with respect to ADO and non-competitive with respect to MgATP2-. A-286501 was orally effective to reduce nociception in animal models of acute (thermal), inflammatory (formalin and carrageenan), and neuropathic (L5/L6 nerve ligation and streptozotocin-induced diabetic) pain. A-286501 was particularly potent (ED50=1 micromol/kg, p.o.) to reduce carrageenan-induced inflammatory thermal hyperalgesia as compared to its analgesic actions in other pain models (acute and neuropathic) and its ability to alter hemodynamic function and motor performance. A-286501 was also effective to reduce carrageenan-induced paw edema and myeloperoxidase activity, a measure of neutrophil influx (ED50=10 micromol/kg, p.o.), in the injured paw. The anti-nociceptive effects of A-286501 in the L5/L6 nerve injury model of neuropathic pain (ED50=20 micromol/kg, p.o.) were not blocked by the opioid antagonist naloxone, but were blocked by the ADO receptor antagonist, theophylline. Following repeated administration, A-286501 showed less potential to produce tolerance as compared to morphine. Thus, A-286501 is a structurally novel AK inhibitor that effectively attenuates nociception by a non-opioid, non-non-steroidal anti-inflammatory drug ADO, receptor mediated mechanism.

Studies on the pharmacological action of cactus: identification of its anti-inflammatory effect.

PubMed

Park, E H; Kahng, J H; Paek, E A

1998-02-01

The ethanol extracts of Opuntia ficus-indica fructus (EEOF) and Opuntia ficus-indica stem (EEOS) were prepared and used to evaluate the pharmacological effects of cactus. Both the extracts inhibited the writhing syndrome induced by acetic acid, indicating that they contains analgesic effect. The oral administrations of EEOF and EEOS suppressed carrageenan-induced rat paw edema and also showed potent inhibition in the leukocyte migration of CMC-pouch model in rats. Moreover, the extracts suppressed the release of beta-glucuronidase, a lysosomal enzyme in rat neutrophils. It was also noted that the extracts showed the protective effect on gastric mucosal layers. From the results it is suggested that the cactus extracts contain anti-inflammatory action having protective effect against gastric lesions.

Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism.

PubMed

de Garavilla, L; Vergnolle, N; Young, S H; Ennes, H; Steinhoff, M; Ossovskaya, V S; D'Andrea, M R; Mayer, E A; Wallace, J L; Hollenberg, M D; Andrade-Gordon, P; Bunnett, N W

2001-08-01

Thrombin, generated in the circulation during injury, cleaves proteinase-activated receptor 1 (PAR1) to stimulate plasma extravasation and granulocyte infiltration. However, the mechanism of thrombin-induced inflammation in intact tissues is unknown. We hypothesized that thrombin cleaves PAR1 on sensory nerves to release substance P (SP), which interacts with the neurokinin 1 receptor (NK1R) on endothelial cells to cause plasma extravasation. PAR1 was detected in small diameter neurons known to contain SP in rat dorsal root ganglia by immunohistochemistry and in situ hybridization. Thrombin and the PAR1 agonist TFLLR-NH(2) (TF-NH(2)) increased [Ca(2+)](i) >50% of cultured neurons (EC(50)s 24 mu ml(-1) and 1.9 microM, respectively), assessed using Fura-2 AM. The PAR1 agonist completely desensitized responses to thrombin, indicating that thrombin stimulates neurons through PAR1. Injection of TF-NH(2) into the rat paw stimulated a marked and sustained oedema. An NK1R antagonist and ablation of sensory nerves with capsaicin inhibited oedema by 44% at 1 h and completely by 5 h. In wild-type but not PAR1(-/-) mice, TF-NH(2) stimulated Evans blue extravasation in the bladder, oesophagus, stomach, intestine and pancreas by 2 - 8 fold. Extravasation in the bladder, oesophagus and stomach was abolished by an NK1R antagonist. Thus, thrombin cleaves PAR1 on primary spinal afferent neurons to release SP, which activates the NK1R on endothelial cells to stimulate gap formation, extravasation of plasma proteins, and oedema. In intact tissues, neurogenic mechanisms are predominantly responsible for PAR1-induced oedema.

Anti-inflammatory effect of Naravelia zeylanica DC via suppression of inflammatory mediators in carrageenan-induced abdominal oedema in zebrafish model.

PubMed

Ekambaram, Sanmuga Priya; Perumal, Senthamil Selvan; Pavadai, Selvaranjani

2017-02-01

The traditional herbal medicines are receiving great importance in the health care sector, especially in Indian system of medicine, i.e, Ayurveda. The present study focused on the standardization of Naravelia zeylanica (L.) DC in terms of its active phytochemicals and to evaluate the anti-inflammatory activity of ethanol extract of N. zeylanica (ENZ). An analytical method was developed by high-performance liquid chromatography for simultaneous determination of β-sitosterol, lupeol and oleanolic acid in ENZ. The cell viability of ENZ was investigated using MTT assay. IC 50 value of ENZ on cell viability was found to be 653.01 µg/mL. To determine the anti-inflammatory activity of ENZ by in vitro method, LPS was added to the macrophage cells to induce activation and ENZ was further added to observe the recovery of inflamed cells. These cells when treated with ENZ, the percentage of viable cells were considerably increased to 74.68%. Loss of mitochondrial membrane potential on treatment with LPS and its recovery by ENZ was studied and found that the number of cells that were damaged on treatment with ENZ + LPS was comparatively lesser than treatment with LPS only. An in vivo anti-inflammatory study was carried out in carrageenan-induced abdominal oedema method in adult zebrafish which revealed the percentage inhibition of inflammation at graded dose levels of ENZ as 23.5% at 100 mg/kg, 62.4% at 200 mg/kg and 87.05% at 350 mg/kg when compared with standard of diclofenac which showed 85% inhibition at 100 mg/kg. The PCR amplification of DNA extracted from adult zebrafish showed that increased concentration of ENZ considerably downregulates the expression of TNF-α and iNOS, the mediators of inflammation.

Polysaccharides from Arctium lappa L.: Chemical structure and biological activity.

PubMed

Carlotto, Juliane; de Souza, Lauro M; Baggio, Cristiane H; Werner, Maria Fernanda de P; Maria-Ferreira, Daniele; Sassaki, Guilherme L; Iacomini, Marcello; Cipriani, Thales R

2016-10-01

The plant Arctium lappa L. is popularly used to relieve symptoms of inflammatory disorders. A crude polysaccharide fraction (SAA) resulting of aqueous extraction of A. lappa leaves showed a dose dependent anti-edematogenic activity on carrageenan-induced paw edema, which persisted for up to 48h. Sequential fractionation by ultrafiltration at 50kDa and 30kDa cut-off membranes yielded three fractions, namely RF50, RF30, and EF30. All these maintained the anti-edematogenic effect, but RF30 showed a more potent action, inhibiting 57% of the paw edema at a dose of 4.9mg/kg. The polysaccharide RF30 contained galacturonic acid, galactose, arabinose, rhamnose, glucose, and mannose in a 7:4:2:1:2:1 ratio and had a Mw of 91,000g/mol. Methylation analysis and NMR spectroscopy indicated that RF30 is mainly constituted by a type I rhamnogalacturonan branched by side chains of types I and II arabinogalactans, and arabinan. Copyright © 2016 Elsevier B.V. All rights reserved.

Biological activity of cannabichromene, its homologs and isomers.

PubMed

Turner, C E; Elsohly, M A

1981-01-01

Cannabichromene (CBC) is one of four major cannabinoids in Cannabis sativa L. and is the second most abundant cannabinoid in drug-type cannabis. Cannabichromene and some of its homologs, analogs, and isomers were evaluated for antiinflammatory, antibacterial, and antifungal activity. Antiinflammatory activity was evaluated by the carrageenan-induced rat paw edema and the erythrocyte membrane stabilization method. In both tests, CBC was superior to phenylbutazone. Antibacterial activity of CBC and its isomers and homologs was evaluated using gram-positive, gram-negative, and acid-fast bacteria. Antifungal activity was evaluated using yeast-like and filamentous fungi and a dermatophyte. Antibacterial activity was strong, and the antifungal activity was mild to moderate.

Steroids block the anti-inflammatory effects of low level laser therapy

NASA Astrophysics Data System (ADS)

Lopes-Martins, Rodrigo Alvaro B.; Albertini, Regiane; Lopes-Martins, Patricia Sardinha L.; Iversen, Vegard V.; Bjordal, Jan M.

2006-02-01

Objective: Concomitant use of multiple therapies is common in musculoskeletal and airway disorders. Low level laser therapy (LLLT) is considered a promising therapy in arthritis, tendinopathies and rhinitis. We designed two animal studies to assess if the expected anti-inflammatory effect LLLT could be affected by resection of the adrenal gland or concomitant use of the cortisol antagonist mifepristone. Methods: Two studies were performed, with 40 male Wistar rats and with 40 Balb C male mice respectively.. In both studies, four groups received carrageenan and one control group received saline. At 1, 2, and 3 hours after injections, LLLT irradiation was performed with a dose of 7.5 J/cm2. In the rat study, two of the carrageenan groups had the adrenal gland dissected. In the mice study, two of the carrageenan-injected groups were in addition pre-treated with orally administered mifepristone. Results: In the rat paw study, LLLT reduced edema significantly compared to the carrageenan only group (1.5 vs 0.9 ml, p< 0.05), but LLLT failed to inhibit edema formation in the group which had the adrenal gland resected. In carrageenan-induced pleurisy, LLLT significantly reduced the number of leukocyte cells ( p<0.0001, Mean 34.5 [95%CI: 32.8 - 36.2] versus 87.7 [95%CI: 81.0 - 94.4]), and that the effect of LLLT could be totally blocked by adding the cortisol antagonist mifepristone ( p<0.0001, Mean 34.5 [95%CI: 32.1 - 36.9] versus 82.9 [95%CI: 70.5 - 95.3]). Conclusion: Steroid therapy should not be used concomitantly with LLLT, as the anti-inflammatory effect of LLLT is lost if cortisol receptors are downregulated.

Antinociceptive and anti-inflammatory effects of the methanolic stem bark extract of Antrocaryon klaineanum Pierre (Anacardiaceae) in mice and rat.

PubMed

Fongang, Annie Laure Magne; Laure Nguemfo, Edwige; Djouatsa Nangue, Yolande; Bogning Zangueu, Calvin; Fouokeng, Yannick; Azebaze, Anatole Guy Blaise; José Llorent-Martínez, Eulogio; Córdova, Maria Luisa Fernández-de; Bertrand Dongmo, Alain; Vierling, Wolfgang

2017-05-05

Antrocaryon klaineanum is used by traditional healers to treat many disorders including pain and inflammatory diseases. This study aimed to evaluate the analgesic and antiinflammatory activities of methanol extract of A. klaineanum in mice and rats. Reverse phase high-performance liquid chromatography (RP-HPLC) was performed to establish the chromatographic fingerprint and to identify various chemical components of the plant extract. The anti-nociceptive activity of methanol extract of A. klaineanum was assessed using the acetic acid-induced abdominal constriction model, formalin test, capsaicin and cinnamaldehyde induced-neurogenic pain and hot plate test. Anti-inflammatory activity was assessed on carrageenan-induced inflammation. Extract was administrated orally at 200, 400 and 600mg/kg. Phytochemical analysis indicated the presence of proanthocyanidins, phenolic acids and flavonoids. The results of anti-nociceptive and anti-inflammatory activities showed that methanol extract significantly (p<0.01) reduced the pain induced by acetic acid with an inhibition percentage of 45.49% (600mg/kg). In the formalin test, the extract also significantly (p<0.01) reduced linking time in both phase (neurogenic and inflammatory) of the test with inhibition percentage of 56.28% and 60.73% respectively at the dose of 600mg/kg. The methanol extract of A. klaineanum significantly (P<0.001) reduced neurogenic pain linking time induced by capsaicin and cinnamaldehyde by 82.54% and 75.94% at the highest dose (600mg/kg) respectively. More over the extract significantly increase the reaction time in hot plate test. In the inflammatory test, the plant extract significantly reduced the carrageen induced rat paw oedema from 30min to 6h with a maximum percentage inhibition of 89.88% (6h) at the dose of 600mg/kg. These results demonstrate that the methanol extract of A. klaineanum may possess analgesic and anti-inflammatory effects and provide support of the traditional use of this plant in the treatment of different pain and inflammatory conditions. Further investigation could reveal metabolites of the extract responsible for the observed effects. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Inhibitory Effects of Traditional Herbal Formula Pyungwi-San on Inflammatory Response In Vitro and In Vivo

PubMed Central

Cha, Ji Young; Jung, Ji Yun; Jung, Jae Yup; Lee, Jong Rok; Cho, Il Je; Ku, Sae Kwang; Byun, Sung Hui; Ahn, Yong-Tae; Lee, Chul Won; Kim, Sang Chan; An, Won G.

2013-01-01

Pyungwi-san (PWS) is a traditional basic herbal formula. We investigated the effects of PWS on induction of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)) and nuclear factor-kappa B (NF-κB) as well as mitogen-activated protein kinases (MAPKs) in lipopolysaccharide-(LPS-) induced Raw 264.7 cells and on paw edema in rats. Treatment with PWS (0.5, 0.75, and 1 mg/mL) resulted in inhibited levels of expression of LPS-induced COX-2, iNOS, NF-κB, and MAPKs as well as production of prostaglandin E2 (PGE2), nitric oxide (NO), IL-6, and TNF-α induced by LPS. Our results demonstrate that PWS possesses anti-inflammatory activities via decreasing production of pro-inflammatory mediators through suppression of the signaling pathways of NF-κB and MAPKs in LPS-induced macrophage cells. More importantly, results of the carrageenan-(CA-) induced paw edema demonstrate an anti-edema effect of PWS. In addition, it is considered that PWS also inhibits the acute edematous inflammations through suppression of mast cell degranulations and inflammatory mediators, including COX-2, iNOS and TNF-α. Thus, our findings may provide scientific evidence to explain the anti-inflammatory properties of PWS in vitro and in vivo. PMID:23533508

Investigations of anti-inflammatory and antinociceptive activities of Piper cubeba, Physalis angulata and Rosa hybrida.

PubMed

Choi, Eun-Mi; Hwang, Jae-Kwan

2003-11-01

The anti-inflammatory activities of Piper cubeba (fruit), Physalis angulata (flower) and Rosa hybrida (flower) were determined by carrageenan-induced paw edema, arachidonic acid-induced ear edema and formaldehyde-induced arthritis in mice. The anti-allergic and analgesic activities of these plants were also studied by using 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity reaction (type IV) and hot plate test in mice, respectively. These plant extracts clearly exhibited inhibitory effects against acute and subacute inflammation by oral administration (200 mg/kg). Also, administration (200 mg/kg, p.o.) of plant extracts for 1 week significantly inhibited type IV allergic reaction in mice (P<0.05). Rosa hybrida showed an analgesic effect against hot plate-induced thermal stimulation at a dose of 200 mg/kg. These results provide support for the use of Rosa hybrida in relieving inflammatory pain, and insight into the development of new agents for treating inflammatory diseases.

Anti-inflammatory effects of jojoba liquid wax in experimental models.

PubMed

Habashy, Ramy R; Abdel-Naim, Ashraf B; Khalifa, Amani E; Al-Azizi, Mohammed M

2005-02-01

Jojoba [Simmondsia chinensis (Link 1822) Schneider 1907] is an arid perennial shrub grown in several American and African countries. Jojoba seeds, which are rich in liquid wax, were used in folk medicine for diverse ailments. In the current study, the potential anti-inflammatory activity of jojoba liquid wax (JLW) was evaluated in a number of experimental models. Results showed that JLW caused reduction of carrageenin-induced rat paw oedema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In a test for anti-inflammatory potential utilizing the chick's embryo chroioallantoic membrane (CAM), JLW also caused significant lowering of granulation tissue formation. Topical application of JLW reduced ear oedema induced by croton oil in rats. In the same animal model, JLW also reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In addition, JLW ameliorated histopathological changes affected by croton oil application. In the lipopolysaccharide (LPS)-induced inflammation in air pouch in rats, JLW reduced nitric oxide (NO) level and tumor necrosis factor-alpha (TNF-alpha) release. In conclusion, this study demonstrates the effectiveness of JLW in combating inflammation in several experimental models. Further investigations are needed to identify the active constituents responsible for the anti-inflammatory property of JLW.

Analgesic and anti-inflammatory effects of the dry matter of culture broth of Termitomyces albuminosus and its extracts.

PubMed

Lu, Yi-Yu; Ao, Zong-Hua; Lu, Zhen-Ming; Xu, Hong-Yu; Zhang, Xiao-Mei; Dou, Wen-Fang; Xu, Zheng-Hong

2008-12-08

The objectives of this study were to investigate the analgesic and anti-inflammatory effects of the dry matter of culture broth (DMCB) of Termitomyces albuminosus in submerged culture and its crude saponin extract (CSE) and crude polysaccharide extract (CPE). The analgesic effects of DMCB, CSE and CPE were evaluated with models of acetic acid-induced writhing response and formalin test in mouse. The anti-inflammatory effects of DMCB, CSE and CPE were evaluated by using models of xylene-induced mouse ear swelling and carrageen-induced mouse paw edema. The DMCB, CSE and CPE significantly decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test. Treatment of DMCB (1000mg/kg), CSE (200mg/kg) or CPE (200mg/kg) inhibited the mouse ear swelling by 61.8%, 79.0% and 81.6%, respectively. In the carrageen-induced mouse paw edema test, the group treated with indomethacin showed the strongest inhibition of edema formation by 77.8% in the third hour after carrageenan administration, while DMCB (1000mg/kg), CSE (200mg/kg) and CPE (200mg/kg) showed 48.4%, 55.6% and 40.5%, respectively. The results suggested that DMCB of Termitomyces albuminosus possessed the analgesic and anti-inflammatory activities. Saponins and polysaccharides were proposed to be the major active constituents of Termitomyces albuminosus in submerged culture.

Applications of the hexanic fraction of Agave sisalana Perrine ex Engelm (Asparagaceae): control of inflammation and pain screening

PubMed Central

Dunder, Ricardo José; Luiz-Ferreira, Anderson; de Almeida, Ana Cristina Alves; de-Faria, Felipe Meira; Takayama, Christiane; Socca, Eduardo Augusto Rabelo; Salvador, Marcos José; Mello, Gláucia Coelho; dos Santos, Catarina; de Oliva-Neto, Pedro; Souza-Brito, Alba Regina Monteiro

2013-01-01

The present study evaluated the anti-inflammatory and analgesic properties of Agave sisalana Perrine in classic models of inflammation and pain. The hexanic fraction of A. sisalana (HFAS) was obtained by acid hydrolysis followed by hexanic reflux. Anti-inflammatory properties were examined in three acute mouse models (xylene ear oedema, hind paw oedema and pleurisy) and a chronic mouse model (granuloma cotton pellet). The antinociceptive potential was evaluated in chemical (acetic-acid) and thermal (tail-flick and hot-plate test) models of pain. When given orally, HFAS (5, 10, 25 and 50 mg/kg) reduced ear oedema (p < 0.0001; 52%, 71%, 62% and 42%, respectively). HFAS also reduced hind paw oedema at doses of 10 mg/kg and 25 mg/kg (p < 0.05; 42% and 58%, respectively) and pleurisy at doses of 10 mg/kg and 25 mg/kg (41% and 50%, respectively). In a chronic model, HFAS reduced inflammation by 46% and 58% at doses of 10 mg/kg and 25 mg/kg, respectively. Moreover, this fraction showed analgesic properties against the abdominal writhing in an acetic acid model (at doses of 5-25 mg/kg) with inhibitory rates of 24%, 54% and 48%. The HFAS also showed an increased latency time in the hot-plate (23% and 28%) and tail-flick tests (61% and 66%) for the 25 mg/kg and 50 mg/kg doses, respectively. These results suggest that HFAS has anti-inflammatory and analgesic properties. PMID:23778651

Antihyperalgesic Activity of Rhodiola rosea in a Diabetic Rat Model.

PubMed

Déciga-Campos, Myrna; González-Trujano, Maria Eva; Ventura-Martínez, Rosa; Montiel-Ruiz, Rosa Mariana; Ángeles-López, Guadalupe Esther; Brindis, Fernando

2016-02-01

Preclinical Research Rhodiola rosea L. (Crassulaceae) is used for enhancing physical and mental performance. Recent studies demonstrated that R. rosea had anti-inflammatory activity in animal models, for example, carrageenan- and nystatin-induced edema in rats, possibly by inhibiting phospholipase A2 and cyclooxygenases-1 and -2. In addition, R. rosea had antinociceptive activity in thermal and chemical pain tests as well as mechanical hyperalgesia. The purpose of the present study was to assess the antihyperalgesic effect of an ethanol extract of Rhodiola rosea (R. rosea) in a diabetic rat model. Rats were administered a single dose of streptozotocin (STZ; 50 mg/kg, i.p.) and hyperalgesia was evaluated four weeks later. Formalin-evoked (0.5%) flinching was increased in diabetic rats compared with nondiabetic controls Systemic (1-100 mg/kg, i.p.) and local (0.1-10 mg/paw into the dorsal surface of the right hind paw) administration of R. rosea ethanol extract dose-dependently reduced formalin-induced hyperalgesia in diabetic rats. The antihyperalgesic effect of R. rosea was compared with gabapentin. These results suggest that R. rosea ethanol extract may have potential as a treatment for diabetic hyperalgesia. © 2016 Wiley Periodicals, Inc.

Anticholinesterase, antioxidant, analgesic and anti-inflammatory activity assessment of Xeranthemum annuum L. and isolation of two cyanogenic compounds.

PubMed

Orhan, Ilkay Erdogan; Gulyurdu, Fulya; Kupeli Akkol, Esra; Senol, Fatma Sezer; Arabaci Anul, Serap; Tatli, Iffet Irem

2016-11-01

Xeranthemum annuum L. (Asteraceae) (XA) is an ornamental and medicinal species with limited bioactivity and phytochemical data. Identification of anticholinesterase, antioxidant, anti-inflammatory and analgesic effects of the flower and root-stem (R-S) extracts of XA. Anticholinesterase (at 100 μg mL -1 ) and antioxidant (at 1000 μg mL -1 ) effects of various extracts were evaluated via microtiter assays, while anti-inflammatory and analgesic effects of the R-S extracts were tested using carrageenan-induced hind paw oedema (100 and 200 mg kg -1 ) and p-benzoquinone (PBQ) writhing models (200 mg kg -1 ) in male Swiss albino mice. The R-S ethanol extract of XA was subjected to isolation studies using conventional chromatographic methods. Most of the extracts showed inhibition over 85% against butyrylcholinesterase and no inhibition towards acetylcholinesterase. The flower chloroform and the R-S ethyl acetate extracts were most effective (97.85 ± 0.94% and 96.89 ± 1.09%, respectively). The R-S ethanol extract displayed a remarkable scavenging activity against DPPH (77.33 ± 1.99%) and in FRAP assay, while the hexane extract of the R-S parts possessed the highest metal-chelating capacity (72.79 ± 0.33%). The chloroform extract of the R-S caused a significant analgesic effect (24.4%) in PBQ writhing model. No anti-inflammatory effect was observed. Isolation of zierin and zierin xyloside, which were inactive in anticholinesterase assays, was achieved from the R-S ethanol extract. This is the first report of anticholinesterase, antioxidant, analgesic and anti-inflammatory activities and isolation of zierin and zierin xyloside from XA. Therefore, XA seems to contain antioxidant and BChE-inhibiting compounds.

In vivo and in vitro anti-inflammatory effects of Sophora flavescens residues.

PubMed

Ma, Hongyan; Huang, Qi; Qu, Wenshan; Li, Linyuan; Wang, Min; Li, Shao; Chu, Fujiang

2018-06-15

The dried roots of Sophora flavescens Ait. (Leguminosae) is traditionally used as antipyretic medicine to reduce inflammation. It is well known that alkaloids and flavonoids are the main constituents of S. flavescens. However, the clinical researches and applications of S. flavescens is mainly based on its water-extracted alkaloids, its flavonoids may still remain in residues and have been underused. With development and manufacturing of S. flavescens in recent years, more herb residues are being produced. Since they are typically treated as waste and dumped openly in landfill sites, which can cause pollution, there is a great need to explore these wastes as recyclable resources and increase their added value. To date, whether other bioactive components would be found in the residues of S. flavescens is still unknown. If the extraction method of these active ingredients was established, the residues of S. flavescens could be turned from the harm to a benefit and make great sense of the comprehensive utilization of S. flavescens resources. This study aimed to establish an extraction method of the residues of S. flavescens and investigate the anti-inflammatory effect of it both in vivo and in vitro. Dried S. flavescens were decocted with distilled water firstly, then the residues were powdered and extracted with ethyl acetate by using ultrasonic wave. HPLC was utilized to analyze the chemical constituents of the water extracts of S. flavescens (WSF) and the ethyl acetate extracts of residues of S. flavescens (RSF). In vivo, the anti-inflammatory effect of WSF and RSF were evaluated using the xylene-induced auricle edema, acetic acid-induced peritoneal permeability and carrageenan-induced hind paw edema methods. In vitro, the inhibitory activities of WSF and RSF on NO, TNF-α, IL-6 and MCP-1 production of LPS-treated RAW264.7 cells were measured. The major ingredients of RSF were flavonoids, while WSF almost had no flavonoids. In vivo, WSF and RSF (200mg/kg) could significantly inhibit the edema in the xylene-induced mice auricle edema and carrageenan-induced hind paw edema as well as the peritoneal permeability increased by acetic acid. They can also lower production levels of PGE 2 in inflamed paw tissues. In vitro experimental results showed that RSF (25, 50, 100μg/mL) could significantly inhibit the release of pro-inflammatory cytokines NO, TNF-α, IL-6 and MCP-1 on LPS-induced RAW264.7 cells. The in vitro suppress effect of WSF had no dose-response relationship. The residues of S. flavescens had obvious flavonoids with anti-inflammatory activity. This study provided evidence for the reuse of residues from S. flavescens in the food additive, medicine and cosmetic industries. Copyright © 2018. Published by Elsevier B.V.

Physico-chemical characterization and pharmacological evaluation of sulfated polysaccharides from three species of Mediterranean brown algae of the genus Cystoseira.

PubMed

Hadj Ammar, Hiba; Lajili, Sirine; Ben Said, Rafik; Le Cerf, Didier; Bouraoui, Abderrahman; Majdoub, Hatem

2015-01-13

Seaweed polysaccharides are highly active natural substances having valuable applications. The present study was conducted to characterize the physico-chemical properties of sulphated polysaccharides from three Mediterranean brown seaweeds (Cystoseira sedoides, Cystoseira compressa and Cystoseira crinita) and to evaluate their anti-radical, anti-inflammatory and gastroprotective activities. The different rates of neutral sugars, uronic acids, L-fucose and sulphate content were determined by colorimetric techniques. The different macromolecular characteristics of isolated fucoidans were identified by size exclusion chromatography equipped with a triple detection: multiangle light scattering, viscometer and differential refractive index detectors, (SEC/MALS/VD/DRI). Anti-inflammatory activity was evaluated, using the carrageenan-induced rat paw edema test in comparison to the references drugs Acetylsalicylate of Lysine and Diclofenac. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats and to examine the antioxidant effect of fucoidans in the three species, the free radical scavenging activity was determined using 1,1-diphenyl-2-picrylhydrazyl. The pharmacological evaluation of the isolated fucoidans for their anti-inflammatory, and their gastroprotective effect established that these products from C. sedoides, C. compressa and C. crinita exhibited a significant anti-inflammatory activity at a dose of 50 mg/kg, i.p; the percentages of inhibition of the oedema were 51%, 57% and 58% respectively. And, at the same dose, these fucoidans from C. sedoides and C. compressa showed a significant decrease of the intensity of gastric mucosal damages compared to a control group by 68%, whereas, the fucoidan from C. crinita produced a less gastroprotective effect. Furthermore, the isolated fucoidans exhibited a radical scavenging activity. The comparative study of fucoidans isolated from three species of the genus Cystoseira showed that they have similar chemicals properties and relatives anti-radical, anti-inflammatory and gastroprotective activities which are found to be promising.

Amelioration of inflammatory responses by Socheongryong-Tang, a traditional herbal medicine, in RAW 264.7 cells and rats

PubMed Central

Kim, Youn Sook; Jung, Ji Yun; Park, Chung A.; Jegal, Kyung Hwan; Ku, Sae Kwang; Kim, Jae Kwang; Lee, Chul Won; Kim, Young Woo; Cho, Il Je; An, Won G.; Kim, Sang Chan

2018-01-01

Socheongryong-Tang (SCRT) is a natural medicine prescription that has been mainly used in East Asia for the treatment of inflammatory disorders, including asthma and allergic rhinitis. The present study evaluated the anti-inflammatory effects of SCRT on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in a rat model of carrageenan (CA)-induced paw edema. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E2 (PGE2) in the culture supernatant were quantified and nitric oxide (NO) production was monitored. In addition, the effect of SCRT on the protein expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was assessed by western blot analysis. Furthermore, the effects of SCRT on acute inflammation in vivo and changes in the histomorphometry and histopathology of paw skin were observed using CA-treated rats. SCRT (1 mg/ml) inhibited the LPS-induced changes in the protein expression of NF-κB, JNK, ERK1/2, iNOS and COX-2, as well as the production of NO, PGE2 and cytokines. In the rat paw edema assay, administration of 1 g/kg of lyophilized powder obtained from the aqueous extracts of SCRT for 3 consecutive days inhibited the CA-induced increases in skin thickness, mast cell degranulation, and infiltration of inflammatory cells in the ventral and dorsal pedis skin within 4 h. These results demonstrated that SCRT exerts its anti-inflammatory activities in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, including PGE2, NO and cytokines, via suppression of the NF-κB and JNK and ERK1/2 signaling pathways. In addition, the data of the CA-induced paw edema indicated an anti-edema effect of SCRT. SCRT (1 g/kg) reduced acute edematous inflammation through inhibition of mast cell degranulation and infiltration of inflammatory cells. Therefore, the present study provided scientific evidence for the anti-inflammatory activities of SCRT as well as the underlying mechanisms. PMID:29436586

Amelioration of inflammatory responses by Socheongryong-Tang, a traditional herbal medicine, in RAW 264.7 cells and rats.

PubMed

Park, Sang Mi; Lee, Tae Hoon; Zhao, Rongjie; Kim, Youn Sook; Jung, Ji Yun; Park, Chung A; Jegal, Kyung Hwan; Ku, Sae Kwang; Kim, Jae Kwang; Lee, Chul Won; Kim, Young Woo; Cho, Il Je; An, Won G; Kim, Sang Chan

2018-05-01

Socheongryong-Tang (SCRT) is a natural medicine prescription that has been mainly used in East Asia for the treatment of inflammatory disorders, including asthma and allergic rhinitis. The present study evaluated the anti-inflammatory effects of SCRT on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in a rat model of carrageenan (CA)-induced paw edema. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E2 (PGE2) in the culture supernatant were quantified and nitric oxide (NO) production was monitored. In addition, the effect of SCRT on the protein expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was assessed by western blot analysis. Furthermore, the effects of SCRT on acute inflammation in vivo and changes in the histomorphometry and histopathology of paw skin were observed using CA-treated rats. SCRT (1 mg/ml) inhibited the LPS-induced changes in the protein expression of NF-κB, JNK, ERK1/2, iNOS and COX-2, as well as the production of NO, PGE2 and cytokines. In the rat paw edema assay, administration of 1 g/kg of lyophilized powder obtained from the aqueous extracts of SCRT for 3 consecutive days inhibited the CA-induced increases in skin thickness, mast cell degranulation, and infiltration of inflammatory cells in the ventral and dorsal pedis skin within 4 h. These results demonstrated that SCRT exerts its anti-inflammatory activities in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, including PGE2, NO and cytokines, via suppression of the NF-κB and JNK and ERK1/2 signaling pathways. In addition, the data of the CA-induced paw edema indicated an anti-edema effect of SCRT. SCRT (1 g/kg) reduced acute edematous inflammation through inhibition of mast cell degranulation and infiltration of inflammatory cells. Therefore, the present study provided scientific evidence for the anti-inflammatory activities of SCRT as well as the underlying mechanisms.

Antioxidant and anti-inflammatory activities of aqueous extract of Centipeda minima.

PubMed

Huang, Shyh-Shyun; Chiu, Chuan-Sung; Lin, Tsung-Hui; Lee, Min-Min; Lee, Chao-Ying; Chang, Shu-Jen; Hou, Wen-Chi; Huang, Guan-Jhong; Deng, Jeng-Shyan

2013-05-20

Centipeda minima (L.) is traditionally used in Chinese folk medicine for the treatments of rhinitis, sinusitis, relieving pain, reducing swelling, and treating cancer for a long history in Taiwan. However, there is no scientific evidence which supports the use in the literature. The aim of this study was to evaluate the antioxidant and anti-inflammatory activities of the aqueous extract of Centipeda minima (ACM). The following activities were investigated: antioxidant activities [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), DPPH (1,1-diphenyl-2-picrylhydrazyl)], and anti-inflammatory [lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 macrophages and paw-edema induced by λ-carrageenan (Carr)]. We also investigated the anti-inflammatory mechanism of ACM via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the edema paw. Serum NO, tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were also measured in vivo. In HPLC analysis, the fingerprint chromatogram of ACM was established. ACM showed the highest TEAC and DPPH radical scavenging activities, respectively. ACM also had highest contents of polyphenol and flavonoid contents. We evaluated that ACM and the reference compound of protocatechualdehyde and caffeic acid decreased the LPS-induced NO production in RAW264.7 cells. Administration of ACM showed a concentration dependent inhibition on paw edema development after Carr treatment in mice. The anti-inflammatory effects of ACM could be via NO, TNF-α, and IL-1β suppressions and associated with the increase in the activities of antioxidant enzymes. Western blotting revealed that ACM decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. Anti-inflammatory mechanisms of ACM might be correlated to the decrease in the level of Malondialdehyde (MDA), iNOS, and COX-2 via increasing the activities of CAT, SOD, and GPx in the edema paw. Overall, the results showed that ACM demonstrated antioxidant and anti-inflammatory activity, which supports previous claims of the traditional use for inflammation and pain. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Identification of anti-inflammatory fractions of Geranium wilfordii using tumor necrosis factor-alpha as a drug target on Herbochip® - an array-based high throughput screening platform.

PubMed

Huang, Min; Yao, Pei-Wun; Chang, Margaret Dah-Tysr; Ng, Sim-Kun; Yu, Chien-Hui; Zhang, Yun-Feng; Wen, Meng-Liang; Yang, Xiao-Yuan; Lai, Yiu-Kay

2015-05-12

Geranium wilfordii is one of the major species used as Herba Geranii (lao-guan-cao) in China, it is commonly used solely or in polyherbal formulations for treatment of joint pain resulted from rheumatoid arthritis (RA) and gout. This herb is used to validate a target-based drug screening platform called Herbochip® and evaluate anti-inflammatory effects of Geranium wilfordii ethanolic extract (GWE) using tumor necrosis factor-alpha (TNF-α) as a drug target together with subsequent in vitro and in vivo assays. A microarray-based drug screening platform was constructed by arraying HPLC fractions of herbal extracts onto a surface-activated polystyrene slide (Herbochip®). Using TNF-α as a molecular probe, fractions of 82 selected herbal extracts, including GWE, were then screened to identify plant extracts containing TNF-α-binding agents. Cytotoxicity of GWE and modulatory effects of GWE on TNF-α expression were evaluated by cell-based assays using TNF-α sensitive murine fibrosarcoma L929 cells as an in vitro model. The in vivo anti-inflammatory effects of GWE were further assessed by animal models including carrageenan-induced hind paw edema in rats and xylene-induced ear edema in mice, in comparison with aspirin. The hybridization data obtained by Herbochip® analysis showed unambiguous signals which confirmed TNF-α binding activity in 46 herbal extracts including GWE. In L929 cells GWE showed significant inhibitory effect on TNF-α expression with negligible cytotoxicity. GWE also significantly inhibited formation of carrageenan-induced hind paw edema and xylene-induced ear edema in animal models, indicating that it indeed possessed anti-inflammatory activity. We have thus validated effectiveness of the Herbochip® drug screening platform using TNF-α as a molecular target. Subsequent experiments on GWE lead us to conclude that the anti-RA activity of GWE can be attributed to inhibitory effect of GWE on the key inflammatory factor, TNF-α. Our results contribute towards validation of the traditional use of GWE in the treatment of RA and other inflammatory joint disorders.

A comparative study on the antinociceptive and anti-inflammatory activities of five Juniperus taxa.

PubMed

Akkol, Esra Küpeli; Güvenç, Ayşegül; Yesilada, Erdem

2009-09-07

Juniperus L. (Cupressaceae) species have been used to various inflammatory and infectious diseases such as bronchitis, colds, cough, fungal infections, hemorrhoids, gynecological diseases, and wounds in Turkish folk medicine. To evaluate this traditional information, anti-inflammatory and antinociceptive activities of the methanolic and aqueous extracts prepared from different parts (stem, fruit and leaves) of the five Turkish taxa under Juniperus section of the gender; J. drupacea, J. communis var. communis, J. communis var. saxatilis, J. oxycedrus subsp. oxycedrus, and J. oxycedrus subsp. macrocarpa growing were investigated. For the anti-inflammatory activity, carrageenan-induced and PGE(2)-induced hind paw edema models, and for the antinociceptive activity p-benzoquinone-induced writhing and hot plate tests in mice were employed. The methanolic extracts of fruit and leaves from J. oxycedrus subsp. oxycedrus and J. communis var. saxatilis exhibited notable inhibition in carrageenan-induced edema model at a dose of 100mg/kg. The same extracts also displayed significant activity against PGE(2)-induced edema model. While, the remaining extracts were found inactive against these edema models. A similar activity pattern was observed against p-benzoquinone-induced abdominal constriction test without inducing any gastric damage or apparent acute toxicity, whereas all extracts were inactive in hot plate test. The experimental data demonstrated that J. oxycedrus subsp. oxycedrus and J. communis var. saxatilis displayed remarkable anti-inflammatory and antinociceptive activities; however, further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from these active species which may yield safe and effective agents to be used in the treatment of inflammatory disorders.

Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats.

PubMed

Richebé, Philippe; Rivalan, Bertrand; Rivat, Cyril; Laulin, Jean-Paul; Janvier, Gérard; Maurette, Pierre; Simonnet, Guy

2009-02-01

Opioids are widely used for anesthesia but paradoxically induce postoperative pain hypersensitivity via N-methyl-D: -aspartate (NMDA) receptor modulation. Sevoflurane effects on opioid-induced hyperalgesia have not been yet evaluated in vivo. Nevertheless, some experimental in vitro studies reported anti-NMDA receptor properties for sevoflurane. The aim of this study was to evaluate sevoflurane effects on fentanyl-induced hyperalgesia in opioid-naive rats and in rats with inflammatory pain. Sevoflurane effects on hyperalgesia were evaluated in Sprague-Dawley rats: opioid-naive rats, rats treated with fentanyl (4 x 60 microg kg(-1)) and rats with inflammatory pain (carrageenan) treated with fentanyl (4 x 60 microg kg(-1)). On day zero, subcutaneous fentanyl injections were administered and inflammatory pain was induced with one carrageenan injection in one hind paw. Rats were exposed to low concentrations of sevoflurane (1.0 or 1.5%) on day zero prior to fentanyl injections and inflammatory pain induction, and for the duration of the fentanyl analgesic effect. The nociceptive threshold (Randall-Selitto test) was evaluated daily for 7 days. On day seven, naloxone was injected and the nociceptive threshold was assessed 5 min later. In rats without inflammatory pain but treated with fentanyl on day zero, sevoflurane 1.0% reversed the early (day zero) and long-lasting (day zero to day three) hyperalgesia classically described after high-doses of fentanyl (P < 0.05). This sevoflurane concentration antagonized the hyperalgesia induced by naloxone on day seven (P = 0.33). In a second experiment in rats with inflammatory pain, exposure to low concentrations of sevoflurane (1.0 and 1.5%) did not reduce fentanyl-induced hyperalgesia (P > 0.05), but nevertheless antagonized the naloxone induced hyperalgesia on day seven (P = 0.061). Relatively low sevoflurane concentrations (1.0%) reverse fentanyl-induced hyperalgesia in rats without inflammatory pain. Nevertheless, the lack of effect of sevoflurane concentrations of 1.0% and 1.5% to oppose hyperalgesia following high-dose fentanyl and inflammatory pain suggests that sevoflurane anti-hyperalgesic properties are weak.

HPLC and anti-inflammatory studies of the flavonoid rich chloroform extract fraction of Orthosiphon stamineus leaves.

PubMed

Yam, Mun Fei; Lim, Vuanghao; Salman, Ibrahim Muhammad; Ameer, Omar Ziad; Ang, Lee Fung; Rosidah, Noersal; Abdulkarim, Muthanna Fawzy; Abdullah, Ghassan Zuhair; Basir, Rusliza; Sadikun, Amirin; Asmawi, Mohd Zaini

2010-06-21

The aim of the present study was to verify the anti-inflammatory activity of Orthosiphon stamineus leaf extracts and to identify the active compound(s) contributing to its anti-inflammatory activity using a developed HPLC method. Active chloroform extract of O. stamineus was fractionated into three fractions using a dry flash column chromatography method. These three fractions were investigated for anti-peritoneal capillary permeability, in vitro nitric oxide scavenging activity, anti-inflammatory and nitric oxide (NO) inhibition using carrageenan-induced hind paw edema method. The flavonoid rich chloroform extract fraction (CF2) [containing sinensetin (2.86% w/w), eupatorin (5.05% w/w) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (1.101% w/w)], significantly reduced rat hind paw edema, NO and decreased dye leakage to peritoneal cavity at p < 0.05. IC(50) of in vitro NO scavenging of CF2 was 0.3 mg/mL. These results suggest that the anti-inflammatory properties of these CF2 may possibly be due to the presence of flavonoid compounds capable of affecting the NO pathway.

Anti-Inflammatory Activities of Inotilone from Phellinus linteus through the Inhibition of MMP-9, NF-κB, and MAPK Activation In Vitro and In Vivo

PubMed Central

Huang, Guan-Jhong; Huang, Shyh-Shyun; Deng, Jeng-Shyan

2012-01-01

Inotilone was isolated from Phellinus linteus. The anti-inflammatory effects of inotilone were studied by using lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells and λ-carrageenan (Carr)-induced hind mouse paw edema model. Inotilone was tested for its ability to reduce nitric oxide (NO) production, and the inducible nitric oxide synthase (iNOS) expression. Inotilone was tested in the inhibitor of mitogen-activated protein kinase (MAPK) [extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase (JNK), p38], and nuclear factor-κB (NF-κB), matrix-metalloproteinase (MMP)-9 protein expressions in LPS-stimulated RAW264.7 cells. When RAW264.7 macrophages were treated with inotilone together with LPS, a significant concentration-dependent inhibition of NO production was detected. Western blotting revealed that inotilone blocked the protein expression of iNOS, NF-κB, and MMP-9 in LPS-stimulated RAW264.7 macrophages, significantly. Inotilone also inhibited LPS-induced ERK, JNK, and p38 phosphorylation. In in vivo tests, inotilone decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). We also demonstrated that inotilone significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5th h after Carr injection. Inotilone decreased the NO and tumor necrosis factor (TNF-α) levels on serum at the 5th h after Carr injection. Western blotting revealed that inotilone decreased Carr-induced iNOS, cyclooxygenase-2 (COX-2), NF-κB, and MMP-9 expressions at the 5th h in the edema paw. An intraperitoneal (i.p.) injection treatment with inotilone diminished neutrophil infiltration into sites of inflammation, as did indomethacin (Indo). The anti-inflammatory activities of inotilone might be related to decrease the levels of MDA, iNOS, COX-2, NF-κB, and MMP-9 and increase the activities of CAT, SOD, and GPx in the paw edema through the suppression of TNF-α and NO. This study presents the potential utilization of inotilone, as a lead for the development of anti-inflammatory drugs. PMID:22590514

Revealing anti-inflammation mechanism of water-extract and oil of forsythiae fructus on carrageenan-Induced edema rats by serum metabolomics.

PubMed

Yuan, An; Gong, Lihong; Luo, Lin; Dang, Jue; Gong, Xiaohong; Zhao, Mengjie; Li, Yan; Li, Yunxia; Peng, Cheng

2017-11-01

Forsythiae Fructus is an important Chinese medicine which shows a significant effect against inflammation. This study aimed to investigate the preventive anti-inflammation mechanism of Forsythiae Fructus by serum metabolomics strategy and compare the difference of the metabolism pathways between Forsythia extract and Forsythia oil in rat. Four groups (control group, model group, Forsythia extract group and Forsythia oil group) were orally administered 10mL/kg 0.5% Tween 80 solution, 10mL/kg 0.5% Tween 80 solution, 5g/kg Forsythia extract and 0.48mL/kg Forsythia oil respectively. 30min after drug administration, rat acute inflammation was induced by subcutaneous injection of carrageenan in the right paw in model group, Forsythia extract group and Forsythia oil group. After being administered Forsythia extract and Forsythia oil, the percentage of rat paw edema was significantly decreased (P<0.05) compared with model group. Metabolomics based on UPLC-Q-TOF-MS/MS was used to analyze the collected serum sample. Multivariate analysis was established for metabolomics analysis. According to Principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) results, four groups were clearly separated. And thirteen alterative biomarkers were identified in the serum, namely PC (19:0/0:0), LysoPC (20:0), LysoPC (20:1), LysoPC (17:0), Sphingosine, Linoleic acid, 3R-hydroxy-butanoic acid (3-HB), 2-hydroxyhexadecanoic acid, Lactic acid, L-Threonine, L-Leucine, Maleic acid, Adipic acid. The change of biomarkers suggested that Forsythia extract affected Linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, Sphingolipid metabolism and Glycerophospholipid metabolism. Forsythia oil affected Sphingolipid metabolism and Glycerophospholipid metabolism. It indicated that Forsythia extract and Forsythia oil both showed significant preventive anti-inflammatory effect through acting on different metabolism pathways. Moreover, efficacy mechanism of Forsythiae Fructus could recover metabolites disturb in the body through affecting particular drug targets associated with the inflammatory pathway. Copyright © 2017. Published by Elsevier Masson SAS.

Inhibition of lipoxygenases and cyclooxygenase-2 enzymes by extracts isolated from Bacopa monniera (L.) Wettst.

PubMed

Viji, V; Helen, A

2008-07-23

Bacopa monniera Linn is described in the Ayurvedic Materia Medica, as a therapeutically useful herb for the treatment of inflammation. In the current study, we investigated the anti-inflammatory activity of methanolic extract of Bacopa monniera (BME). For some experiments EtOAc and bacoside fractions were prepared from BME. The effect of these extracts in modulating key mediators of inflammation was evaluated. Carrageenan-induced rat paw edema, rat mononuclear cells and human whole blood assay were employed as in vivo and in vitro models. In carrageenan-induced rat paw edema, BME brought about 82% edema inhibition at a dose of 100mg/kg i.p. when compared to indomethacin (INDO) (3mg/kg) that showed 70% edema inhibition. BME also significantly inhibited 5-lipoxygenase (5-LOX), 15-LOX and cyclooxygenase-2 (COX-2) activities in rat monocytes in vivo. Among the fractions tested in vitro, EtOAc fraction possessed significant 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity with IC(50) value of 30 microg/ml compared to butylated hydroxyl toluene (IC(50) = 13 microg/ml). This fraction also exerted significant hydroxyl radical scavenging activity with IC(50) value of 25 microg/ml in comparison with quercetin (IC(50) = 5 microg/ml). Inhibitory effects of EtOAc and bacoside fractions on LOX and COX activities in Ca-A23187 stimulated rat mononuclear cells were also assessed. 5-LOX IC(50) values were 25 microg/ml for EtOAc, 68 microg/ml for bacosides and 2 microg/ml for nordihydroguaiaretic acid (NDGA) where as COX-2 IC(50) values were 1.32 microg/ml for EtOAc, 1.19 microg/ml for bacoside fraction and 0.23 microg/ml for indomethacin. EtOAc and bacoside fractions also brought about significant decrease in TNF-alpha release ex vivo. Bacopa monniera possesses anti-inflammatory activity through inhibition of COX and LOX and downregulation of TNF-alpha.

Effects of the selective EP4 antagonist, CJ-023,423 on chronic inflammation and bone destruction in rat adjuvant-induced arthritis.

PubMed

Okumura, Takako; Murata, Yoko; Taniguchi, Kana; Murase, Akio; Nii, Aisuke

2008-06-01

Prostaglandin E2 (PGE2) produced by cyclooxygenase (COX) is a potent pro-inflammatory mediator. We have recently discovered CJ-023,423, a highly selective antagonist of EP4 receptors, one of the PGE2 receptors. This agent is suitable for exploring the effects of blocking EP4 receptors following oral administration in rats. In this study, CJ-023,423 was used in rats with adjuvant-induced arthritis (AIA) to investigate the role of the EP4 receptor in chronic inflammation and bone destruction. These effects were compared with those of rofecoxib, a selective COX-2 inhibitor. CJ-023,423 had significant inhibitory effects on paw swelling, inflammatory biomarkers, synovial inflammation and bone destruction in AIA rats. In particular, the inhibitory effect on paw swelling in AIA rats was comparable to that of rofecoxib. These results suggest that PGE2 acting via the EP4 receptor is involved in the development of chronic inflammation and bone destruction, particularly with respect to oedema in AIA rats. This is the first study to confirm the in-vivo effects of EP4 receptor blockade on inflammation and bone destruction in AIA rats with a small-molecule compound.

The analgesic and anti-inflammatory activities of the extract of Albizia lebbeck in animal model.

PubMed

Saha, Achinto; Ahmed, Muniruddin

2009-01-01

The extract of the bark of Albizia lebbeck Benth. obtained by cold extraction of mixture of equal proportions of petroleum ether, ethyl acetate and methanol was chosen for pharmacological screening. In rat paw edema model induced by carrageenan, the extract at the 400 mg/kg dose level showed 36.68% (p<0.001) inhibition of edema volume at the end of 4h. In the acetic acid-induced writhing test, the extract at the 200 and 400 mg/kg dose level showed 39.9% and 52.4 % inhibition of writhing, respectively. In radiant heat tail-flick method the crude extract produced 40.74% (p<0.001) and 61.48% (p<0.001) elongation of tail flicking time 30 minutes after oral administration at the 200 and 400 mg/kg dose level, respectively.

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models.

PubMed

Woode, Eric; Ameyaw, Elvis O; Boakye-Gyasi, Eric; Abotsi, Wonder K M

2012-10-01

Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE) and xylopic acid (XA), in murine models. XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (Tail-flick and Hargreaves thermal hyperalgesia tests), and mechanical (Randall-Selitto paw pressure test) pain models. XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg(-1), p.o.) and XA (10-100 mg kg(-1), p.o.) inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg(-1), i.p.) and diclofenac (1-10 mg kg(-1), i.p.), used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.

Involvement of NO-cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia.

PubMed

Otari, K V; Upasani, C D

2015-08-01

The association of elevated level of cyclic guanosine monophosphate (cGMP) with inhibition of hyperalgesia and involvement of nitric oxide (NO)-cGMP pathway in the modulation of pain perception was previously reported. Phosphodiesterases 5 (PDE5) inhibitors, sildenafil and tadalafil (TAD) used in erectile dysfunction, are known to act via the NO-cGMP pathway. TAD exerts its action by increasing the levels of intracellular cGMP. Hence, the present study investigated the effect of TAD 5, 10, or 20 mg/kg, per os (p.o.) or L-NAME 20 mg/kg, intraperitoneally (i.p.) and TAD (20 mg/kg, p.o.) in carrageenan- and diabetes-induced hyperalgesia in rats using hot plate test at 55 ± 2 °C. In carrageenan- and diabetes-induced hyperalgesia, TAD (10 and 20 mg/kg, p.o.) significantly increased paw withdrawal latencies (PWLs) as compared to the control group. L-NAME significantly decreased PWLs as compared to the normal group and aggravated the hyperalgesia. Moreover, significant difference in PWLs of L-NAME and TAD 20 was evident. Co-administration of L-NAME (20 mg/kg) with TAD (20 mg/kg) showed significant difference in PWLs as compared to the TAD (20 mg/kg), indicating L-NAME reversed and antagonized TAD-induced anti-hyperalgesia. This suggested an important role of NO-cGMP pathway in TAD-induced anti-hyperalgesic effect.

Gas chromatographic mass analysis and further pharmacological actions of Cymbopogon proximus essential oil.

PubMed

Al-Taweel, A M; Fawzy, G A; Perveen, S; El Tahir, K E H

2013-09-01

The present study reports Gas chromatographic mass analysis (GC-MS) as well as important biological activities of Cymbopogon proximus essential oil. The chemical composition of the essential oil of Cymbopogon proximus was investigated by GC-MS. Furthermore, the effects of Cymbopogon proximus essential oil on the cardiac parasympathetic ganglia in rats, the intra-tracheal pressure in guinea-pigs and on carrageenan-induced inflammation in the rats paw, were studied. The GC-MS study led to the identification of 22 components with Piperitone representing (73.81%), Elemol (9.32%), alpha-Eudesmol (5.21%) and alpha-Terpineol (3.01%) of the oils composition. The percentage protective effect of the oil on the vagus-induced bradycardia in rats was 90.1±3.1%, which represents a significant protection. As for the effect of Cymbopogon oil on bronchoconstrictors-induced increase in intra-tracheal pressure in guinea-pigs, the oil antagonized the actions of 5-HT and histamine by 80±3.7 and 93±8.3%, respectively. Pharmacological investigations using Cymbopogon oil revealed its inherent ability to possess a bronchodilator activity mediated via blockade of both histamine and serotonin receptors. It possessed a significant ganglionic blocking action and a limited anti-inflammatory activity that seemed to involve blockade of histamine and serotonin receptors in the rats' paws. © Georg Thieme Verlag KG Stuttgart · New York.

Rose geranium essential oil as a source of new and safe anti-inflammatory drugs

PubMed Central

Boukhatem, Mohamed Nadjib; Kameli, Abdelkrim; Ferhat, Mohamed Amine; Saidi, Fairouz; Mekarnia, Maamar

2013-01-01

Background Since the available anti-inflammatory drugs exert an extensive variety of side effects, the search for new anti-inflammatory agents has been a priority of pharmaceutical industries. Aims The aim of the present study was to assess the anti-inflammatory activities of the essential oil of rose geranium (RGEO). Methods The chemical composition of the RGEO was investigated by gas chromatography. The major components were citronellol (29.13%), geraniol (12.62%), and citronellyl formate (8.06%). In the carrageenan-induced paw edema, five different groups were established and RGEO was administered orally in three different doses. Results RGEO (100 mg/kg) was able to significantly reduce the paw edema with a comparable effect to that observed with diclofenac, the positive control. In addition, RGEO showed a potent anti-inflammatory activity by topical treatment in the method of croton oil-induced ear edema. When the dose was 5 or 10 µl of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively. This is the first report to demonstrate a significant anti-inflammatory activity of Algerian RGEO. In addition, histological analysis confirmed that RGEO inhibited the inflammatory responses in the skin. Conclusion Our results indicate that RGEO may have significant potential for the development of novel anti-inflammatory drugs with improved safety profile. PMID:24103319

Anti-inflammatory and antipyretic properties of Corchorus olitorius aqueous root extract in Wistar rats.

PubMed

Owoyele, Bamidele V; Oyewole, Aboyeji L; Alimi, Modupe L; Sanni, Shukurat A; Oyeleke, Sabitiu A

2015-07-01

This study was designed to provide information about the antipyretic and anti-inflammatory effects of Corchorus olitorius root. Thirty male Wistar rats were divided into six groups of five animals each; the control and reference groups were administered normal saline (10 mL/kg) and indomethacin (5 mg/kg), respectively, whereas the remaining four groups were administered aqueous extract of C. olitorius at doses of 25, 50, 100, or 200 mg/kg, respectively. Pyrexia was induced by injecting 10 mL/kg of 20% (w/v) brewer's yeast suspension into the dorsum of rats, whereas inflammation was induced through an injection of 0.1% carrageenan into the right hind paw of each rat and through a subcutaneous implantation of a 30-g sterilized cotton pellet into the groin of each rat. The results showed that C. olitorius root extract (p<0.05) decreased the elevated temperature after brewer's yeast injection compared with the 17 h (pre-drug) temperature. In the inflammatory tests, the paw sizes and granuloma weights in the test groups were significantly (p<0.05) decreased compared with the control group. Corchorus olitorius root is another good source of phytomedicine that can be used effectively to treat inflammation and pyrexia that accompany some diseases.

5-phosphonato-3,4-dihydropyrimidin-2(1H)-ones: Zinc triflate-catalyzed one-pot multi-component synthesis, X-ray crystal structure and anti-inflammatory activity

NASA Astrophysics Data System (ADS)

Essid, Idris; Lahbib, Karima; Kaminsky, Werner; Ben Nasr, Cherif; Touil, Soufiane

2017-08-01

Herein we report a simple and efficient one-pot three-component synthesis of 5-phosphonato-3,4-dihydropyrimidin-2(1H)-ones, through the zinc triflate-catalyzed Biginelli-type reaction of β-ketophosphonates, aldehydes and urea. The compounds obtained were characterized by various spectroscopic tools including IR, NMR (1H, 31P, 13C) spectroscopy, mass spectrometry and single crystal X-ray diffraction. All the synthesized compounds were screened, for the first time, for anti-inflammatory activity by carrageenan-induced hind paw edema method, using female Wister rats and they showed significant anti-inflammatory activity in some cases higher than the standard indomethacin.

Synthesis, Characterization, and Anti-Inflammatory Activities of Methyl Salicylate Derivatives Bearing Piperazine Moiety.

PubMed

Li, Jingfen; Yin, Yong; Wang, Lisheng; Liang, Pengyun; Li, Menghua; Liu, Xu; Wu, Lichuan; Yang, Hua

2016-11-23

In this study, a new series of 16 methyl salicylate derivatives bearing a piperazine moiety were synthesized and characterized. The in vivo anti-inflammatory activities of target compounds were investigated against xylol-induced ear edema and carrageenan-induced paw edema in mice. The results showed that all synthesized compounds exhibited potent anti-inflammatory activities. Especially, the anti-inflammatory activities of compounds M15 and M16 were higher than that of aspirin and even equal to that of indomethacin at the same dose. In addition, the in vitro cytotoxicity activities and anti-inflammatory activities of four target compounds were performed in RAW264.7 macrophages, and compound M16 was found to significantly inhibit the release of lipopolysaccharide (LPS)-induced interleukin (IL)-6 and tumor necrosis factor (TNF)-α in a dose-dependent manner. In addition, compound M16 was found to attenuate LPS induced cyclooxygenase (COX)-2 up-regulation. The current preliminary study may provide information for the development of new and safe anti-inflammatory agents.

Anti-inflammatory and analgesic effects of Bi-yuan-ling granules.

PubMed

Chen, Xiao-Bing; Su, Han-Wen; Liu, Huan-Xiang; Yin, Xian; He, Feng; Ren, Yong-Shen; Dai, Kang; Xiang, Mei-Xian

2016-06-01

Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD50), median effective dose (ED50) and half maximal inhibitory concentration (IC50) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti-inflammatory and analgesic effects and it may help reduce the damage of ALI.

Effect of intraarticular tramadol administration in the rat model of knee joint inflammation.

PubMed

Garlicki, Jarosław; Dorazil-Dudzik, Magdalena; Wordliczek, Jerzy; Przewłocka, Barbara

2006-01-01

Local administration of exogenous opioids may cause effective analgesia without adverse symptoms from the central nervous system. Experiments show that peripheral antinociceptive effect of opioids is observed especially in inflammatory pain. The aim of the research was to estimate the effect of tramadol on nociceptive process at the level of peripheral nervous system, after its local administration in the model of knee joint inflammation. Tramadol was administered intraarticulary into the rat knee joint, before the inflammation as a preemptive analgesia and, for comparison, after the intraarticular injection of carrageenan. The research determined the influence of tramadol injection on pain threshold for thermal stimuli, development of inflammatory processes using the measurement of joint edema and motor function following the induction of knee joint inflammation in the rat. Functional assessment of knee joint with inflammation, in terms of rats' mobility and body position as well as joint loading and mobility were studied. The results of the experiments show that local administration of tramadol induces antinociceptive effect. The effect of tramadol, which elicits also a decrease in inflammatory edema, appears not only after its administration after carrageenan when inflammation was already present, but also in the case of its injection prior to carrageenan in the scheme of preemptive analgesia. The results of the described research show that not only morphine but also another opioid, tramadol, widely used in clinical practice, inhibits nociception, edema and functional impairment of the paw after its local application directly to the inflamed knee joint.

Synthesis and biological evaluation of pyrazolylthiazole carboxylic acids as potent anti-inflammatory-antimicrobial agents.

PubMed

Khloya, Poonam; Kumar, Satish; Kaushik, Pawan; Surain, Parveen; Kaushik, Dhirender; Sharma, Pawan K

2015-03-15

Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole carboxylates 1a-1p and corresponding acid derivatives 2a-2p. All 32 novel compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for in vitro antimicrobial activity. All the tested compounds exhibited excellent AI activity profile. Three compounds 1p (R=Cl, R(1)=Cl), 2c (R=H, R(1)=F) and 2n (R=Cl, R(1)=OCH3) were identified as potent anti-inflammatory agents exhibiting edema inhibition of 93.06-89.59% which is comparable to the reference drug indomethacin (91.32%) after 3h of carrageenan injection while most of the other compounds displayed inhibition ⩾80%. In addition, pyrazolylthiazole carboxylic acids (2a-2p) also showed good antimicrobial profile. Compound 2h (R=OCH3, R(1)=Cl) showed excellent antimicrobial activity (MIC 6.25μg/mL) against both Gram positive bacteria comparable with the reference drug ciprofloxacin (MIC 6.25μg/mL). Copyright © 2015 Elsevier Ltd. All rights reserved.

Piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine as orally-active adhesion molecule inhibitors.

PubMed

Kaneko, Toshihiko; Clark, Richard S J; Ohi, Norihito; Ozaki, Fumihiro; Kawahara, Tetsuya; Kamada, Atsushi; Okano, Kazuo; Yokohama, Hiromitsu; Ohkuro, Masayoshi; Muramoto, Kenzo; Takenaka, Osamu; Kobayashi, Seiichi

2004-06-01

Novel piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine were prepared and evaluated for their inhibitory activity on the upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Replacement of the methanesulfonyl group on the piperidine ring of previously prepared derivatives with a carboxylic acid-containing moiety resulted in a number of potent adhesion molecule inhibitors. Of these, (anti) [3-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)methyl-3-azabicyclo[3.3.1]non-9-yl]acetic acid 2q (ER-49890), showed the most potent oral inhibitory activities against neutrophil migration in an interleukin-1 (IL-1) induced paw inflammation model using mice, and leukocyte accumulation in a carrageenan pleurisy model in the rat, and therapeutic effect on collagen-induced arthritis in rats.

Virgin coconut oil supplementation ameliorates cyclophosphamide-induced systemic toxicity in mice.

PubMed

Nair, S S; Manalil, J J; Ramavarma, S K; Suseela, I M; Thekkepatt, A; Raghavamenon, A C

2016-02-01

Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties. © The Author(s) 2015.

A report of a galactan from marine alga Gelidium crinale with in vivo anti-inflammatory and antinociceptive effects.

PubMed

de Sousa, Albertina A S; Benevides, Norma M B; de Freitas Pires, Alana; Fiúza, Felipe P; Queiroz, Maria G R; Morais, Thamires M F; Pereira, Maria G; Assreuy, Ana M S

2013-04-01

The sulfated galactan of the red marine alga Gelidium crinale (SG-Gc) was purified by ion exchange chromatography and tested by intravenous (i.v.) route in rodent experimental models of inflammation and nociception. The anti-inflammatory activity of SG-Gc (0.01, 0.1 and 1 mg/kg) was evaluated in the model of rat paw edema induced by different inflammatory stimuli, while SG-Gc (0.1, 1 and 10 mg/kg) antinociceptive effect was assessed in models of nociception/hyperalgesia elicited by chemical (formalin test), thermal (hot plate), and mechanical (von Frey) stimuli in mice. In addition, the toxicity was evaluated after rat treatment with SG-Gc (1 mg/kg; i.v.) during 10 days, followed by analysis of the wet weight of animal's body/organs and hematological/biochemical parameters. Sulfated galactan of G. crinale inhibited the time course of dextran-induced paw edema, at all doses, showing maximal effect at 1 mg/kg (42%) and that induced by carrageenan at 0.01 (18%) and 1 mg/kg (20%), but was ineffective on the edema elicited by zymosan. At the highest dose, SG-Gc also inhibited the paw edema induced by histamine (49%), compound 48/80 (32%), and phospholipase A(2) (44%). Sulfated galactan of G. crinale inhibited both neurogenic and inflammatory phases of the formalin test, at all doses, and at 10 mg/kg, the animals flinch reaction in the von Frey test in the 1st and 3rd h by 19 and 26%, respectively. Additionally, SG-Gc treatment was well tolerated by animals. In conclusion, SG-Gc presents anti-inflammatory effect involving the inhibition of histamine and arachidonic acid metabolites and also antinociceptive activity, especially the inflammatory pain with participation of the opioid system. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Toxicological analysis and anti-inflammatory effects of essential oil from Piper vicosanum leaves.

PubMed

Hoff Brait, Débora Regina; Mattos Vaz, Márcia Soares; da Silva Arrigo, Jucicléia; Borges de Carvalho, Luciana Noia; Souza de Araújo, Flávio Henrique; Vani, Juliana Miron; da Silva Mota, Jonas; Cardoso, Claudia Andrea Lima; Oliveira, Rodrigo Juliano; Negrão, Fábio Juliano; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2015-12-01

This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models

PubMed Central

Woode, Eric; Ameyaw, Elvis O.; Boakye-Gyasi, Eric; Abotsi, Wonder K. M.

2012-01-01

Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE) and xylopic acid (XA), in murine models. Materials and Methods: XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (Tail-flick and Hargreaves thermal hyperalgesia tests), and mechanical (Randall-Selitto paw pressure test) pain models. Results: XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg-1, p.o.) and XA (10-100 mg kg-1, p.o.) inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg-1, i.p.) and diclofenac (1-10 mg kg-1, i.p.), used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. Conclusions: These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid. PMID:23248562

Anti-inflammatory and analgesic activities of Chaenomeles speciosa fractions in laboratory animals.

PubMed

Li, X; Yang, Y-B; Yang, Q; Sun, L-N; Chen, W-S

2009-10-01

The prescription of current existing anti-inflammatory drugs is hampered by their adverse effects over time. Botanical extracts are thought to be a potential source of a natural anti-inflammatory property with fewer adverse effects. Chaenomeles speciosa has long been used as an herbal medicine for treatment of various diseases such as rheumatoid arthritis, prosopalgia, and hepatitis. Until now there have been no reports on the specific anti-inflammatory fractions of extract of C. speciosa (ECS). In the present study the anti-inflammatory activities of different fractions of ECS were evaluated using carrageenan-induced paw edema in rats. The 10% ethanol fraction (C3) was found to have stronger anti-inflammatory effects compared with other fractions at the same dose. We also found that chlorogenic acid was one of the active constituents responsible for the anti-inflammatory effect using bioassay-guided fractionation by means of high-performance liquid chromatography. Compared with controls, fraction C3 demonstrated significant anti-inflammatory activity in the xylene-induced ear edema test (P < .01), acetic acid-induced peritoneal capillary permeability test, and the cotton pellet granuloma test in mice or rats (P < .01); it also showed marked analgesic activity in the acetic acid-induced abdominal contraction test and formalin-induced paw licking test in mice and rats (P < .05 or .01). However, fraction C3 showed no significant effect in the hot plate test in mice. These findings justify the use of the C. speciosa for treating pain and inflammation. These results support the proposal of C. speciosa fraction C3 as a potential anti-inflammatory agent.

Widespread pain reliever profile of a flower extract of Tanacetum parthenium.

PubMed

Di Cesare Mannelli, Lorenzo; Tenci, Barbara; Zanardelli, Matteo; Maidecchi, Anna; Lugli, Andrea; Mattoli, Luisa; Ghelardini, Carla

2015-07-15

Tanacetum parthenium L., commonly called Feverfew, is known for anti-inflammatory and anti-migraine properties. Aimed to individuate new therapeutical strategies to control acute and persistent pain induced by different origins we tested two hydroalcoholic extracts obtained from Feverfew flowers and leaves, respectively. Extracts were characterized according to the European Pharmacopoeia monograph. Both the extracts were tested after acute per os administration in the dose range 30-1000 mg kg(-1). The anti-nociceptive properties were evaluated by the Writhing test in mice. The number of abdominal contractions was dose dependently reduced by the flower extract. It reduced mechanical hypersensitivity (Paw pressure test) related to the acute inflammatory phase induced by carrageenan similarly to diclofenac and ibuprofen. In the osteoarthritis model induced by intra articular injection of monoiodoacetate (MIA) the flower extract significantly increased the pain threshold peaking 30 min after treatment. Moreover, it was effective in the chronic constriction injury model of neuropathic pain showing activity similar to the anti-epileptic drug gabapentin. The flower extract activity was confirmed in rat models of chemotherapy-induced neuropathic pain. The mechanical hypersensitivity induced by repeated treatments with the anticancer drug oxaliplatin and with the antiviral dideoxycytidine was significantly reduced after a single injection of Feverfew flower extract. The leaf extract showed lesser efficacy and potency and it was devoid of any effect in carrageenan-, MIA- and chemotherapy-induced pain. The present Feverfew flower extract behaves as a potent pain reliever in acute, inflammatory, articular and neuropathic pain. It appears as a natural strategy potentially suitable for the treatment of different kinds of pain. Copyright © 2015 Elsevier GmbH. All rights reserved.

A study of the anti-inflammatory effect of the leaves of Psidium guajava Linn. on experimental animal models

PubMed Central

Dutta, Sarmistha; Das, Swarnamoni

2010-01-01

Introduction: The aim is to study the anti-inflammatory effect of the ethanolic extract of the leaves of Psidium guajava(PGE) on experimental animal models. Materials and Methods: Fresh leaves were collected, air-dried, powdered, and percolated in 95% ethanol. Acute toxicity test was done according to OECD guidelines. Four groups of animals of either sex, weighing 150–200g of the species Rattus norvegicus were taken for the study (n = 6). Group A was taken as control (3% gum acacia in 10 mL/kg body weight), Group B as test group (PGE 250 mg/kg body weight), Group C as test group (PGE 500 mg/kg body weight), and Group D as standard (Aspirin 100 mg/kg body weight). The animals were studied for acute inflammation by Carrageenan-induced rat paw edema, subacute inflammation by Granuloma pouch method, and chronic inflammation by Freund’s adjuvant-induced arthritis method. Statistical analysis was done by one-way analysis of variance followed by multiple comparison tests. Results: In acute inflammation, there was significant inhibition of paw edema in Groups B, C, and D in comparison with Group A (P < 0.05). In subacute inflammation, there was significant inhibition of exudate formation in Groups B, C, and D in comparison to Group A (P < 0.05). In chronic inflammation, there was significant inhibition of paw edema and inhibition of weight reduction in Groups B, C, and D compared with Group A. Downregulation of arthritis index was also significant in Groups B, C, and D in comparison with Group A (P < 0.05). Conclusion: The ethanolic extract of PGE has significant anti-inflammatory activity. PMID:21589759

Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum essential oil and its main compound estragole: In vivo mouse models.

PubMed

Rodrigues, Lindaiane Bezerra; Oliveira Brito Pereira Bezerra Martins, Anita; Cesário, Francisco Rafael Alves Santana; Ferreira E Castro, Fyama; de Albuquerque, Thaís Rodrigues; Martins Fernandes, Maria Neyze; Fernandes da Silva, Bruno Anderson; Quintans Júnior, Lucindo José; da Costa, José Galberto Martins; Melo Coutinho, Henrique Douglas; Barbosa, Roseli; Alencar de Menezes, Irwin Rose

2016-09-25

The genus Ocimum are used in cooking, however, their essential oils are utilized in traditional medicine as aromatherapy. The present study was carried out to investigate the chemical composition and systemic anti-inflammatory activity of the Ocimum basilicum essential oil (EOOB) and its major component estragole, as well as its possible mechanisms of action. The Ocimum basilicum essential oil was obtained by hydrodistillation and analyzed by GC-MS. The anti-inflammatory action was verified using acute and chronic in vivo tests as paw edema, peritonitis, and vascular permeability and granulomatous inflammation model. The anti-inflammatory mechanism of action was analyzed by the participation of histamine and arachidonic acid pathways. The chemical profile analysis identified fourteen components present in the essential oil, within them: estragole (60.96%). The in vivo test results show that treatment with EOOB (100 and 50 mg/kg) and estragole (60 and 30 mg/kg) significantly reduced paw edema induced by carrageenan and dextran. The smallest doses of EOOB (50 mg/kg) and estragole (30 mg/kg) showed efficacy in the reduction of paw edema induced by histamine and arachidonic acid, vascular permeability inhibition and leukocyte emigration in the peritoneal fluid. Theses doses were capable of reducing the chronic inflammatory process. The results observed between the EOOB and estragole demonstrate efficacy in anti-inflammatory activity, however, the essential oil is more efficacious in the acute and chronic anti-inflammatory action. This study confirms the therapeutic potential of this plant and reinforces the validity of its use in popular medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of α7 Nicotinic Acetylcholine Receptors in Mice

PubMed Central

Bagdas, Deniz; Targowska-Duda, Katarzyna M.; López, Jhon J.; Perez, Edwin G.; Arias, Hugo R.; Damaj, M. Imad

2016-01-01

BACKGROUND Positive allosteric modulators (PAMs) facilitate endogenous neurotransmission and/or enhance the efficacy of agonists without directly acting on the orthosteric binding sites. In this regard, selective α7 nicotinic acetylcholine receptor type II PAMs display antinociceptive activity in rodent chronic inflammatory and neuropathic pain models. This study investigates whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a new putative α7-selective type II PAM, attenuates experimental inflammatory and neuropathic pains in mice. METHODS We tested the activity of PAM-2 after intraperitoneal administration in 3 pain assays: the carrageenan-induced inflammatory pain, the complete Freund adjuvant induced inflammatory pain, and the chronic constriction injury–induced neuropathic pain in mice. We also tested whether PAM-2 enhanced the effects of the selective α7 agonist choline in the mouse carrageenan test given intrathecally. Because the experience of pain has both sensory and affective dimensions, we also evaluated the effects of PAM-2 on acetic acid–induced aversion by using the conditioned place aversion test. RESULTS We observed that systemic administration of PAM-2 significantly reversed mechanical allodynia and thermal hyperalgesia in inflammatory and neuropathic pain models in a dose- and time-dependent manner without motor impairment. In addition, by attenuating the paw edema in inflammatory models, PAM-2 showed antiinflammatory properties. The antinociceptive effect of PAM-2 was inhibited by the selective competitive antagonist methyllycaconitine, indicating that the effect is mediated by α7 nicotinic acetylcholine receptors. Furthermore, PAM-2 enhanced the antiallodynic and antiinflammatory effects of choline, a selective α7 agonist, in the mouse carrageenan test. PAM-2 was also effective in reducing acetic acid induced aversion in the conditioned place aversion assay. CONCLUSIONS These findings suggest that the administration of PAM-2, a new α7-selective type II PAM, reduces the neuropathic and inflammatory pain sensory and affective behaviors in the mouse. Thus, this drug may have therapeutic applications in the treatment and management of chronic pain. PMID:26280585

A RG-II Type Polysaccharide Purified from Aconitum coreanum Alleviates Lipopolysaccharide-Induced Inflammation by Inhibiting the NF-κB Signal Pathway

PubMed Central

Li, Xiaojun; Jiang, Jiaye; Shi, Songshan; Bligh, S. W. Annie; Li, Yuan; Jiang, Yongbo; Huang, Dan; Ke, Yan; Wang, Shunchun

2014-01-01

Korean mondshood root polysaccharides (KMPS) isolated from the root of Aconitum coreanum (Lévl.) Rapaics have shown anti-inflammatory activity, which is strongly influenced by their chemical structures and chain conformations. However, the mechanisms of the anti-inflammatory effect by these polysaccharides have yet to be elucidated. A RG-II polysaccharide (KMPS-2E, Mw 84.8 kDa) was isolated from KMPS and its chemical structure was characterized by FT-IR and NMR spectroscopy, gas chromatography–mass spectrometry and high-performance liquid chromatography. The backbone of KMPS-2E consisted of units of [→6) -β-D-Galp (1→3)-β-L-Rhap-(1→4)-β-D-GalpA-(1→3)-β-D-Galp-(1→] with the side chain →5)-β-D-Arap (1→3, 5)-β-D-Arap (1→ attached to the backbone through O-4 of (1→3,4)-L-Rhap. T-β-D-Galp is attached to the backbone through O-6 of (1→3,6)-β-D-Galp residues and T-β-D-Ara is connected to the end group of each chain. The anti-inflammatory effects of KMPS-2E and the underlying mechanisms using lipopolysaccharide (LPS) - stimulated RAW 264.7 macrophages and carrageenan-induced hind paw edema were investigated. KMPS-2E (50, 100 and 200 µg/mL) inhibits iNOS, TLR4, phospho-NF-κB–p65 expression, phosphor-IKK, phosphor-IκB-α expression as well as the degradation of IκB-α and the gene expression of inflammatory cytokines (TNF-α, IL-1β, iNOS and IL-6) mediated by the NF-κB signal pathways in macrophages. KMPS-2E also inhibited LPS-induced activation of NF-κB as assayed by electrophorectic mobility shift assay (EMSA) in a dose-dependent manner and it reduced NF-κB DNA binding affinity by 62.1% at 200µg/mL. In rats, KMPS-2E (200 mg/kg) can significantly inhibit carrageenan-induced paw edema as ibuprofen (200 mg/kg) within 3 h after a single oral dose. The results indicate that KMPS-2E is a promising herb-derived drug against acute inflammation. PMID:24927178

Protective Effect of Crocodile Hemoglobin and Whole Blood Against Hydrogen Peroxide-Induced Oxidative Damage in Human Lung Fibroblasts (MRC-5) and Inflammation in Mice.

PubMed

Phosri, Santi; Jangpromma, Nisachon; Patramanon, Rina; Kongyingyoes, Bunkerd; Mahakunakorn, Pramote; Klaynongsruang, Sompong

2017-02-01

A putative protective effect of cHb and cWb against H 2 O 2 -induced oxidative damage was evaluated in detail using MRC-5 cells. In addition, the carrageenan (Carr)-induced mouse paw edema model and the cotton pellet-induced granuloma model were employed to examine the in vivo anti-inflammatory activity of cHb and cWb in mice. It was demonstrated that both cHb and cWb treatments significantly increased cell viability and inhibited morphology alterations in MRC-5 cells exposed to H 2 O 2 . Orally administered cHb and cWb significantly reduced Carr-induced paw edema volume and cotton pellet-induced granuloma formation. Moreover, cHb and cWb decreased the expression levels of important pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), while only cWb was found to increase the expression of the anti-inflammatory cytokine IL-10 significantly. Finally, the activity of antioxidant enzymes (SOD, CAT, and GPx) in the liver improved after cHb and cWb treatment under acute and chronic inflammation. Taken collectively, the results of this study suggest that both cHb and cWb protect against hydrogen peroxide-induced damage in fibroblast cells. Moreover, cHb and cWb were found to exhibit anti-inflammatory activity in both the acute and chronic stages of inflammation and appear to enhance antioxidant enzyme activity and decrease lipid peroxidation in the livers of mice. Therefore, this study indicates that cHb and cWb have great potential to be used in the development of dietary supplements for the prevention of oxidative stress related to inflammatory disorders.

Anti-inflammatory effects of seeds of the tropical fruit camu-camu (Myrciaria dubia).

PubMed

Yazawa, Kazunaga; Suga, Katsumi; Honma, Atsushi; Shirosaki, Miyuki; Koyama, Tomoyuki

2011-01-01

The methanolic extract of seeds of the tropical fruit camu-camu was screened for its anti-inflammatory activity in carrageenan-induced paw edema model mice. The extract significantly suppressed both the formation of edema in mice by oral administration and the release of nitric oxide from macrophage-derived RAW 264.7 cells in vitro. Based on the results of a spectroscopic analysis, the active compound was identified by in vivo bioassay-guided fractionation to be 3β-hydroxy-lup-20(29)-en-28-oic acid, betulinic acid, known as an anti-inflammatory triterpenoid. These findings suggest that camu-camu seed extract is a potentially useful material as a source of betulinic acid and as a functional food for prevention of immune-related diseases.

Anti-inflammatory activities of cucurbitacin E isolated from Citrullus lanatus var. citroides: role of reactive nitrogen species and cyclooxygenase enzyme inhibition.

PubMed

Abdelwahab, Siddig Ibrahim; Hassan, Loiy Elsir Ahmed; Sirat, Hasnah Mohd; Yagi, Sakina M Ahmed; Koko, Waleed S; Mohan, Syam; Taha, Manal Mohamed Elhassan; Ahmad, Syahida; Chuen, Cheah Shiau; Narrima, Putri; Rais, Mohd Mustafa; Hadi, A Hamid A

2011-12-01

The in vivo and in vitro mechanistic anti-inflammatory actions of cucurbitacin E (CE) (Citrullus lanatus var. citroides) were examined. The results showed that LPS/INF-γ increased NO production in RAW264.7 macrophages, whereas L-NAME and CE curtailed it. CE did not reveal any cytotoxicity on RAW264.7 and WRL-68 cells. CE inhibited both COX enzymes with more selectivity toward COX-2. Intraperitoneal injection of CE significantly suppressed carrageenan-induced rat's paw edema. ORAC and FRAP assays showed that CE is not a potent ROS scavenger. It could be concluded that CE is potentially useful in treating inflammation through the inhibition of COX and RNS but not ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

Houttuynia cordata Thunb. volatile oil exhibited anti-inflammatory effects in vivo and inhibited nitric oxide and tumor necrosis factor-α production in LPS-stimulated mouse peritoneal macrophages in vitro.

PubMed

Li, Weifeng; Fan, Ting; Zhang, Yanmin; Fan, Te; Zhou, Ping; Niu, Xiaofeng; He, Langchong

2013-11-01

Houttuynia cordata Thunb. (HC) is a medicinal herb that generally used in traditional Chinese medicine for treating allergic inflammation. The present study investigated the inhibitory effect of the volatile oil from HC Thunb. on animal models of inflammation and the production of inflammatory mediators in vivo and in vitro. In vivo, xylene-induced mouse ear edema, formaldehyde-induced paw edema and carrageenan-induced mice paw edema were significantly decreased by HC volatile oil. HC volatile oil showed pronounced inhibition of prostaglandin (PG) E2 and malondialdehyde production in the edematous exudates. In vitro exposure of mouse resident peritoneal macrophages to 1, 10, 100 and 1000 µg/mL of HC volatile oil significantly suppressed lipopolysaccharide (LPS)-stimulated production of NO and tumor necrosis factor-α (TNF-α) in a dose-dependent manner. Exposure to HC volatile oil had no effect on cell viability and systemic toxicity. Furthermore, HC volatile oil inhibited the production of NO and TNF-α by down-regulating LPS-stimulated iNOS and TNF-α mRNA expression. Western blot analysis showed that HC volatile oil attenuated LPS-stimulated synthesis of iNOS and TNF-α protein in the macrophages, in parallel. These findings add a novel aspect to the biological profile of HC and clarify its anti-inflammatory mechanism. Copyright © 2012 John Wiley & Sons, Ltd.

n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels.

PubMed

Fakhrudin, Nanang; Dwi Astuti, Eny; Sulistyawati, Rini; Santosa, Djoko; Susandarini, Ratna; Nurrochmad, Arief; Wahyuono, Subagus

2017-03-13

Inflammation is involved in the progression of many disorders, such as tumors, arthritis, gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still challenging. Medicinal plants have been used traditionally to treat various diseases including inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo anti-inflammatory activities of a n -hexane insoluble fraction of P. lanceolata leaves dichloromethane extract (HIFPL). We first evaluated its potency to reduce paw edema induced by carrageenan, and the expression of the proinflammatory enzyme, cyclooxygenase (COX)-2, in mice. The efficacy of HIFPL to inhibit COX-2 was also evaluated in an in vitro enzymatic assay. We further studied the effect of HIFPL on leukocytes migration in mice induced by thioglycollate. The level of chemokines facilitating the migration of leukocytes was also measured. We found that HIFPL (40, 80, 160 mg/kg) demonstrated anti-inflammatory activities in mice. The HIFPL reduced the volume of paw edema and COX-2 expression. However, HIFPL acts as an unselective COX-2 inhibitor as it inhibited COX-1 with a slightly higher potency. Interestingly, HIFPL strongly inhibited leukocyte migration by reducing the level of chemokines, Interleukine-8 (IL-8) and Monocyte chemoattractant protein-1 (MCP-1).

Anti-inflammatory, Antipyretic, and Antinociceptive Effects of a Cressa cretica Aqueous Extract.

PubMed

Abdallah, Heba Mohammed Ibrahim; Elshamy, Abdelsamed Ibrahim; El Gendy, Abd El-Nasser Gaber; Abd El-Gawad, Ahmed Mohamed; Omer, Elsayed Abouelfotowh; De Leo, Marinella; Pistelli, Luisa

2017-11-01

Cressa cretica is a widely grown halophytic plant traditionally used for the treatment of different ailments. Previous investigations reported its biological activity on a wide spectrum of diseases. In this study, in vivo antinociceptive, anti-inflammatory, and antipyretic activities of C. cretica aqueous extract whole plant were evaluated. In addition, the total polyphenol content, the total flavonoid content, and the chemical characterization of the extract were performed. C. cretica showed writhing inhibition in acetic acid-induced peripheral nociception of 43 and 48 % at doses of 50 and 100 mg/kg, respectively. The same doses increased latency time in a hot plate model of central analgesia by 66 and 78 % compared to the control group, respectively. The acute anti-inflammatory effect of the extract was explored in the carrageenan-induced rat hind paw test. The inhibition of paw volume was better than that of the standard drug indomethacin. C. cretica significantly decreased rectal temperature in the rats injected with Brewer's yeast. C. cretica aqueous extract showed both central and peripheral antinociceptive activities and was effective as an anti-inflammatory and antipyretic. Phenolic compounds, including chlorogenic acids and flavonol glycosides, were identified by HPLC-PDA-ESI-MS techniques. These findings indicate the medicinal importance of this traditionally used plant as a therapeutic remedy for different ailments. Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of Anti-inflammatory and Antimicrobial Activity of AHPL/AYCAP/0413 Capsule.

PubMed

Nipanikar, Sanjay; Chitlange, Sohan; Nagore, Dheeraj

2017-01-01

Conventional therapeutic agents used for treatment of Acne are associated with various adverse effects necessitating development of safe and effective alternative therapeutic agents. In this context, a polyherbal formulation AHPL/AYCAP/0413 was developed for treatment of Acne. To evaluate Anti-inflammatory and antimicrobial activity of AHPL/AYCAP/0413. 1) Anti-inflammatory activity: Anti-inflammatory activity of AHPL/AYCAP/0413 in comparison with Diclofenac was assessed in carrageenan induced rat Paw edema model. 2) Anti-microbial activity for P. acne : Propionibacterium acnes were incubated under anaerobic conditions. Aliquots of molten BHI with glucose agar were used as the agar base. Formulation and clindamycin (10 μg/ml) were introduced in to the Agar wells randomly. 3) Anti-microbial activity for Staphylococcus epidermidis and Staphylococcus aureus : Staphylococcus epidermidis and Staphylococcus aureus were incubated under aerobic conditions at 37°C. TSB with glucose agar was used as the agar base. 0.5ml of formulation and clindamycin (10 μg/ml) were introduced in to the wells randomly. The antibacterial activity was evaluated by measuring zones of inhibition (in mm). Significant reduction in rat paw edema (51% inhibition) was observed with formulation AHPL/AYCAP/0413 which was also comparable to that of Diclofenac (58% inhibition). Zone of inhibition for formulation was 18.33 mm, 19.20 mm and 26.30 mm for P. acnes , S. epidermidis and S. aureus respectively. This activity was also comparable to that of Clindamycin. AHPL/AYCAP/0413 capsule possesses significant Anti-inflammatory and Anti-microbial activities which further justifies its role in the management of Acne vulgaris. Anti-inflammatory and antimicrobial activities of polyherbal formulation AHPL/AYCAP/0413 were evaluatedAHPL/AYCAP/0413 contains Guduchi extract ( Tinospora cordifolia ), Manjishtha extract ( Rubia cordifolia ), Sariva extract ( Hemidesmus indicus ), Nimba extract ( Azardirachta indica ), Khadira extract ( Acacia catechu ) and Kakmachi extract ( Solanum nigrum )Anti-inflammatory activity of AHPL/AYCAP/0413 in comparison with Diclofenac was assessed in carrageenan induced rat Paw edema model. Significant reduction in rat paw edema (51% inhibition) was observed with formulation AHPL/AYCAP/0413 which was also comparable to that of Diclofenac (58% inhibition)Anti-microbial activity of AHPL/AYCAP/0413 was assessed against Propionibacterium acnes , Staphylococcus epidermidis and Staphylococcus aureus . Zone of inhibition for formulation was 18.33 mm, 19.20 mm and 26.30 mm for P. acnes , S. epidermidis and S. aureus respectively indicating 68.42%, 85.71% and 81.17% activity. This activity was also comparable to that of ClindamycinTherefore it is evident that, AHPL/AYCAP/0413 capsule possesses significant Anti-inflammatory and Anti-microbial activities which further justifies its role in the management of Acne vulgaris. Abbreviations Used : mg: Milligram, kg: Kilogram, w/v: Weight by volume, ml: Milliliters, h: Hour, BHI: Brain Heart Infusion, CFU: Colony forming units, μg: Microgram, A.I.: Activity index, P.I.: Percent inhibition, TSB: Trypticsoy Broth, mm: millimeters, P. acnes : Propionibacterium acnes , S. epidermidis : Staphylococcus epidermidis, S. aureus : Staphylococcus aureus.

Biological effects of 2,4-pentadiene-1-ol.

PubMed

Benesová, O; Sprincl, L; Ulbrich, K; Obereigner, B; Drobník, J; Kálal, J; Kopecek

1977-07-01

The biological effects of 2,4-pentadiene-1-ol (CH2 = CH--CH = CH--CH2--OH) the starting monomer in the preparation of a biocompatible polymer were studied. The experiments in rats revealed both a high local (oedema, necrosis) and systemic toxicity. Within 5-10 min after dermal application of 0.2 ml the compound evoked intensive hyperaemia of acral parts (ears, snout, paws) and induced severe breathing difficulties which led to death in half of the animals after a single administration. The most evident macroscopic and microscopic pathologic changes were found in the place of application and in the lungs (haemorrhage in alveolae). Both clinical and histological findings indicated that the toxicity is due to an increased permeability of capillaries.

Carrageenan-induced colitis is associated with decreased population of anti-inflammatory bacterium, Akkermansia muciniphila, in the gut microbiota of C57BL/6J mice.

PubMed

Shang, Qingsen; Sun, Weixia; Shan, Xindi; Jiang, Hao; Cai, Chao; Hao, Jiejie; Li, Guoyun; Yu, Guangli

2017-09-05

Carrageenan as a food additive has been used for years. However, controversy exists regarding to the safety of carrageenan and accumulating evidence indicates that it could induce colitis in experimental models. Here, to provide more information on this issue and solve the debate, we studied and compared in detail the toxic effects of different isomers of carrageenan (κ-, ι-, and λ-) on the colon of C57BL/6J mice. Interestingly, all isomers of carrageenan were found to induce colitis with a comparable activity. Given that carrageenan is unabsorbed after oral administration, and also in light of the fact that gut microbiota plays a pivotal role in the pathogenesis of colitis, we further investigated the effect of carrageenan on gut microbiota using high-throughput sequencing. Intriguingly, carrageenan-induced colitis was observed to be robustly correlated with changes in the composition of gut microbiota. Specifically, all carrageenans significantly decreased the abundance of a potent anti-inflammatory bacterium, Akkermansia muciniphila, in the gut, which is highly relevant for understanding the toxic effect of carrageenan. Altogether, our results corroborate previous studies demonstrating harmful gastrointestinal effect of carrageenan and, from a gut microbiota perspective, shed new light into the mechanism by which carrageenan induces colitis in experimental animals. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the wound healing property of Boesenbergia longiflora rhizomes.

PubMed

Sudsai, Teeratad; Wattanapiromsakul, Chatchai; Nakpheng, Titpawan; Tewtrakul, Supinya

2013-10-28

The rhizomes of Boesenbergia longiflora (Wall.) Kuntze (Zingiberaceae) have been traditionally used for treatment of inflammatory bowel disease, ulcerative colitis, aphthous ulcer and abscess by decoction with alcohol. The rhizomes of Boesenbergia longiflora were carried out to investigate for anti-inflammatory and wound healing activities in order to support the traditional use. The ethanolic extract of Boesenbergia longiflora and its fractions were tested using relevant in vitro anti-inflammatory and wound healing assays. For the in vitro studies, murine macrophage RAW264.7 cells and mouse fibroblast L929 cells were assessed for anti-inflammatory and fibroblast stimulatory activities, respectively. In vivo anti-inflammatory activity was determined by carrageenan-induced rat paw edema model as well as acute toxicity estimated by the up-and-down method in mice. The present study has demonstrated that the ethanolic extract of Boesenbergia longiflora rhizomes possesses a potent anti-inflammatory and wound healing activities. Among the isolated fractions, the CHCl3 fraction showed potent anti-inflammatory effect through nitric oxide inhibitory activity (IC50=5.5 μg/ml) and reduction of carrageenan-induced rat paw edema (ED50=222.7 mg/kg), whereas this fraction exhibited wound healing property via fibroblast migration on both day 1 (77.3%) and day 2 (100%) as well as enhanced collagen production (187.5 μg/ml) at concentration of 3 μg/ml, compared to that of the controls, 39.4% for fibroblast and 60.8 μg/ml for collagen, respectively. The anti-inflammatory mechanism of the CHCl3 fraction is found to suppress the iNOS and COX-2 mRNA expression. The scientific investigation of wound healing activity of Boesenbergia longiflora rhizomes support the Thai traditional uses for treatment of inflammatory bowel disease, ulcerative colitis, aphthous ulcer and abscess. The EtOH extract and CHCl3 fraction exert potential wound healing property through NO inhibition, anti-oxidant effect and stimulation of fibroblast migration and collagen production. The phytochemical screening revealed that the CHCl3 fraction of Boesenbergia longiflora rhizomes contains diarylheptanoids, flavonoids and terpenes. The isolation of the compounds responsible for the wound healing effect is now in progress. © 2013 Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory, analgesic and anti-pyretic activities of standardized root extract of Jasminum sambac.

PubMed

Sengar, Nidhi; Joshi, Apurva; Prasad, Satyendra K; Hemalatha, S

2015-02-03

The plant Jasminum sambac L. (Oleaceae) is cultivated throughout India. The leaves and roots of the plant are used traditionally in the treatment of inflammation, fever and pain. The leaves of the plant have been reported to posses significant anti-inflammatory and analgesic activities. To scientifically validate anti-inflammatory, analgesic and anti-pyretic activities of roots from Jasminum sambac. Ethanol root extract of Jasminum sambac (EJS) was standardized using HPTLC and was subjected to acute oral toxicity study. Further, analgesic activity of EJS at 100, 200 and 400mg/kg, p.o. was evaluated using writhing test on Swiss albino mice and tail-flick test on Charles Foster albino rats. Anti-inflammatory activity of EJS was assessed by carrageenan-induced rat paw edema, cotton pellet-induced granuloma and Freund׳s adjuvant-induced arthritis models, while antipyretic activity was evaluated using Brewer׳s yeast induced pyrexia. In addition, biochemical parameters such as alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) in blood serum and edematous tissue of rats exposed to acute (carrageenan) and granulomatous tissue in sub-chronic (cotton pellet granuloma) inflammation models were also evaluated. Phytochemical analysis of EJS revealed the presence of flavonoids, phenols, saponins, tannins and carbohydrates in major quantities, while the quantity of hesperidin in EJS (using HPTLC) was found to be 4.25%w/w. EJS at 400mg/kg, p.o. reduced writhing count up to 49.21%, whereas in tail-flick test, EJS in a dose dependent manner increased latency in flicking tail. EJS at 400mg/kg, p.o. showed significant anti-inflammatory activity after 2nd, 3rd, 4th and 6thh of treatment in carrageenan-induced edema, while a 33.58% inhibition in cotton pellet induced granuloma formation was observed at same dose level. EJS significantly (p<0.001) inhibited adjuvant-induced arthritis and also showed significant antipyretic activity. Further, a significant reversal in alterations of all the biochemical parameters (except ALP) in tissues was also observed. The study confirms the anti-inflammatory, analgesic and antipyretic activity of EJS which may be attributed to the presence of various phytoconstituents quantified especially hesperidin which have already been reported for its significant role in the treatment of inflammation and associated problems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of intraplantar botulinum toxin-B on carrageenan-induced changes in nociception and spinal phosphorylation of GluA1 and Akt.

PubMed

Sikandar, Shafaq; Gustavsson, Ynette; Marino, Marc J; Dickenson, Anthony H; Yaksh, Tony L; Sorkin, Linda S; Ramachandran, Roshni

2016-07-01

Increasing evidence suggests that botulinum neurotoxins (BoNTs) delivered into the skin and muscle in certain human and animal pain states may exert antinociceptive efficacy though their uptake and transport to central afferent terminals. Cleavage of soluble N-methylaleimide-sensitive attachment protein receptor by BoNTs can impede vesicular mediated neurotransmitter release as well as transport/insertion of channel/receptor subunits into plasma membranes, an effect that can reduce activity-evoked facilitation. Here, we explored the effects of intraplantar botulinum toxin- B (BoNT-B) on peripheral inflammation and spinal nociceptive processing in an inflammatory model of pain. C57BL/6 mice (male) received unilateral intraplantar BoNT (1 U, 30 μL) or saline prior to intraplantar carrageenan (20 μL, 2%) or intrathecal N-methyl-D-aspartate (NMDA), substance P or saline (5 μL). Intraplantar carrageenan resulted in edema and mechanical allodynia in the injected paw and increased phosphorylation of a glutamate subunit (pGluA1ser845) and a serine/threonine-specific protein kinase (pAktser473) in spinal dorsal horn along with an increased incidence of spinal c-Fos positive cells. Pre-treatment with intraplantar BoNT-B reduced carrageenan evoked: (i) allodynia, but not edema; (ii) pGluA1 and pAkt and (iii) c-Fos expression. Further, intrathecal NMDA and substance P each increased dorsal horn levels of pGluA1 and pAkt. Intraplantar BoNT-B inhibited NMDA, but not substance P evoked phosphorylation of GluA1 and Akt. These results suggest that intraplantar toxin is transported centrally to block spinal activation and prevent phosphorylation of a glutamate receptor subunit and a kinase, which otherwise contribute to facilitated states. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation

PubMed Central

Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

2017-01-01

Introduction The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. Aim This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Materials and Methods Albino rats of either sex were divided into five groups of six rats each (Group I – Control, Group II –Gel base, Group III –P. santalinus paste, Group IV –P. santalinus gel, Group V– Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund’s Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey’s test was used for comparison among groups. Results Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Conclusion Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation. PMID:28892928

Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation.

PubMed

Dhande, Priti Pravin; Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

2017-07-01

The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Albino rats of either sex were divided into five groups of six rats each (Group I - Control, Group II -Gel base, Group III - P. santalinus paste, Group IV - P. santalinus gel, Group V- Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund's Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey's test was used for comparison among groups. Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation.

Endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization Via a NMDA-dependent process.

PubMed

Le Roy, Chloé; Laboureyras, Emilie; Gavello-Baudy, Stéphanie; Chateauraynaud, Jérémy; Laulin, Jean-Paul; Simonnet, Guy

2011-10-01

Although stress induces analgesia, there is evidence that stressful events may exacerbate pain syndromes. Here, we studied the effects of 1 to 3 prestressful events (days 0, 2, and 7), such as non-nociceptive environmental stress, on inflammatory hyperalgesia induced by a carrageenan injection (day 14) in 1 rat hind paw. Changes in nociceptive threshold were evaluated by the paw pressure vocalization test. The higher the number of stress sessions presented to the rats, the greater was the inflammatory hyperalgesia. Blockade of opioid receptors by naltrexone before each stress inhibited stress-induced analgesia and suppressed the exaggerated inflammatory hyperalgesia. Stressed versus nonstressed animals could be discriminated by their response to a fentanyl ultra-low dose (fULD), that produced hyperalgesia or analgesia, respectively. This pharmacological test permitted the prediction of the pain vulnerability level of prestressed rats because fULD analgesic or hyperalgesic indices were positively correlated with inflammatory hyperalgesic indices (r(2) = .84). In prestressed rats, fULD-induced hyperalgesia and the exaggerated inflammatory hyperalgesia were prevented NMDA receptor antagonists. This study provides some preclinical evidence that pain intensity is not only the result of nociceptive input level but is also dependent on the individual history, especially prior life stress events associated with endogenous opioid release. Based on these preclinical data, it would be of clinical interest to evaluate whether prior stressful events may also affect further pain sensation in humans. Moreover, this preclinical model could be a good tool for evaluating new therapeutic strategies for relieving pain hypersensitivity. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Pharmacological activities of the organic extracts and fatty acid composition of the petroleum ether extract from Haplophyllum tuberculatum leaves.

PubMed

Hamdi, Assia; Majouli, Kaouther; Abdelhamid, Amal; Marzouk, Belsem; Belghith, Hèla; Chraief, Imed; Bouraoui, Abderrahman; Marzouk, Zohra; Heyden, Yvan Vander

2018-04-24

Haplophyllum tuberculatum is used in traditional medicine to treat many disorders including inflammation and pain. The aim of this study is to investigate the organic extracts from H. tuberculatum leaves against inflammation, gastric ulcer and pain. Acute toxicity was studied in vivo to determine the toxic doses of the organic extracts. Anti-inflammatory activity was also evaluated in vivo using carrageenan-induced paw edema in Wistar rats. Gastroprotective activity was tested using the HCl/ethanol-induced gastric ulcer test in rats. Peripheral and central analgesic activities were assessed using the acetic acid-induced writhing test and the hot-plate method, respectively. The chemical composition of the fatty acids in the petroleum ether (PE) extract was determined with GC-MS. At 25, 50 and 100mg/kg PE extract was the most active against inflammation. Percentages inhibition 5h after carrageenan-injection were 51.12; 86.71% and 96.92%, respectively. The same extract at 100mg/kg showed good analgesic activities using the acetic acid-induced writhing test and the hot-plate method. The chloroform, ethyl acetate (EtOAc) and butanolic (n-BuOH) extracts exhibited strong anti-inflammatory, gastroprotective and analgesic activities at 100mg/kg. The GC-FID analysis revealed that the PE extract was rich in γ-linolenic acid (45.50%) followed by palmitic acid (18.48%), linoleic acid (10.73%), erucic acid (4.72), stearic acid (3.96%) and oleic acid (2.57%). The results of the present study support the traditional use of the leaves of H. tuberculatum and may possibly serve as prospective material for further development of safe new phytochemical anti-inflammatory, gastroprotective and/or analgesic agents. Copyright © 2018 Elsevier B.V. All rights reserved.

New carboxamide derivatives bearing benzenesulphonamide as a selective COX-II inhibitor: Design, synthesis and structure-activity relationship

PubMed Central

Okoro, Uchechukwu Chris; Ahmad, Hilal

2017-01-01

Sixteen new carboxamide derivatives bearing substituted benzenesulphonamide moiety (7a-p) were synthesized by boric acid mediated amidation of appropriate benzenesulphonamide with 2-amino-4-picoline and tested for anti-inflammatory activity. One compound 7c showed more potent anti-inflammatory activity than celecoxib at 3 h in carrageenan-induced rat paw edema bioassay. Compounds 7g and 7k also showed good anti-inflammatory activity comparable to celecoxib. Compound 7c appeared selectivity index (COX-2/COX-1) better than celecoxib. Compound 7k appeared selectivity index (COX-2/COX-1) a little higher than the half of celecoxib while compound 7g is non-selective for COX-2. The LD50 of compounds 7c, 7g and 7k were comparable to celecoxib. PMID:28922386

Anti-arthritic activity of 11-O-(4'-O-methyl galloyl)-bergenin and Crassula capitella extract in rats.

PubMed

El-Hawary, Seham S; Mohammed, Rabab; Abouzid, Sameh; Ali, Zeinab Y; Elwekeel, Ahlam

2016-06-01

Isolation and identification of phytochemicals of Crassula capitella (Thunberg), evaluation of the anti-arthritic potential of the extract and the major isolated compound; 11-O-(4'-O-methyl galloyl)-bergenin and underlying their mechanism on rat model of rheumatoid arthritis (RA). Different fractions were subjected to column chromatography giving fourteen compound identified by mass and NMR spectroscopic techniques. RA was induced by intraplantar injection of complete Freund's adjuvant into the right hind paw of rats. Influence of tested samples in comparable to methotrexate on paw oedema, body weight gain, serum diagnostic markers, cartilage and bone degeneration enzymes, pro-inflammatory mediators and oxidative stress biomarkers in arthritic rats. Fourteen phenolic compounds were isolated and identified for the first time from C. capitella. The major compound identified as 11-O-(4'-O-methyl galloyl)-bergenin. Treatment of arthritic rats with extract or 11-O-(4'-O-methyl galloyl)-bergenin with the tested doses can reduce the progression and severity of RA. Crassula capitella is a new natural and abundant source for 11-O-(4'-O-methyl galloyl)-bergenin for resolving chronic inflammatory diseases as RA through antioxidant, anti-inflammatory and membrane stabilizing mechanism. © 2016 Royal Pharmaceutical Society.

Assessment of anti-inflammatory, antinociceptive, immunomodulatory, and antioxidant activities of Cajanus cajan L. seeds cultivated in Egypt and its phytochemical composition.

PubMed

Hassan, Emad M; Matloub, Azza A; Aboutabl, Mona E; Ibrahim, Nabaweya A; Mohamed, Samy M

2016-08-01

Cajanus cajan L. (Fabaceae), a food crop, is widely used in traditional medicine. The phytochemical composition of C. cajan seeds and evaluation of the anti-inflammatory, immunomodulatory, antinociceptive, and antioxidant activities were studied. Unsaponifiable matter and fatty acids were analyzed by GC and GC/MS. The n-butanol fraction was chromatographed on polyamide column. The anti-inflammatory activity of hexane extract (200 and 400 mg/kg, p.o.) was evaluated using the carrageenan-induced rat paw edema at 1, 2, and 3 h. The serum tumor necrosis factor-α, interleukin-6, and immunoglobulin G levels were detected by ELISA. The hexane extract antinociceptive activity was determined by adopting the writhing test in mice. DPPH radical scavenging, total reduction capability, and inhibition of lipid peroxidation of butanol fraction were evaluated. Twenty-one unsaponifiable compounds (mainly phytol, 2,6-di-(t-butyl)-4-hydroxy-4-methyl-2,5-cyclohexadiene-1-one, β-sitosterol, stigmasterol, and campesterol), as well as 12 fatty acids (primarily 9,12-octadecadienoic and palmitic acids) were identified in hexane extract of C. cajan seeds. n-BuOH fraction contains quercetin-3-O-β-d-glucopyranoside, orientin, vitexin, quercetin, luteolin, apigenin, and isorhamnetin. For the first time, quercetin-3-O-β-d-glucopyranoside is isolated from C. cajan plant. The hexane extract (200 and 400 mg/kg) inhibited carrageenan-induced inflammation by 85 and 95%, respectively, 3 h post-carrageenan challenge. This was accompanied by an 11 and 20%, 8 and 13%, respectively, decrease of TNF-α and IL-6, as well as significant decrease in IgG serum levels. Moreover, hexane extract (200 and 400 mg/kg) decreased the number of writhings by 61 and 83%, respectively. The butanol fraction showed DPPH radical scavenging (inhibitory concentration (IC50) value: 9.07 μg/ml).

Toxicological evaluation and anti-inflammatory potential of an ethanolic extract from Bromelia balansae (Bromeliaceae) fruit.

PubMed

da Silva Balin, Paola; Zanatta, Flavia Carina; Jorge, Bárbara Campos; Leitão, Maicon; Kassuya, Roberto Mikio; Cardoso, Claudia Andrea Lima; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2018-05-03

Bromelia balansae is a relatively unexplored medicinal species that is used for nutritional purposes and in folk medicine to treat cough or wounds. This study assessed the anti-inflammatory activity of the ethanolic extract obtained from Bromelia balansae fruit (EEBB) as well as the toxicological potential of this extract after single and repeated exposure. Male rats (Wistar) were gavaged with 2000 mg/kg of extract from the fruit of B. balansae for the acute toxicity test and with 25, 100, or 400 mg/kg of EEBB for the subacute toxicity test. The anti-inflammatory effect of EEBB was evaluated in vivo (30, 100, or 300 mg/kg) by carrageenan (Cg) induced-oedema and pleurisy in Swiss mice. A single oral dose of EEBB did not result in toxicity, demonstrating that the LD 50 of this extract was greater than 2000 mg/kg. In the subacute toxicity test, the tested doses produced no significant changes in the haematological, biochemical or histopathological parameters of treated animals. Similarly, there were no statistically significant differences in the sperm parameters. A dose of 300 mg/kg of EEBB significantly reduced oedema formation, Cg-induced mechanical hypersensitivity and cold sensitivity, as well as leukocyte migration in the pleurisy model. These results show that EEBB has an anti-inflammatory potential without causing acute or subacute toxicity. These data may contribute to the advancement of biopharmaceutical applications for this species. Copyright © 2018 Elsevier B.V. All rights reserved.

Inflammatory Process Modulation by Homeopathic Arnica montana 6CH: The Role of Individual Variation

PubMed Central

Kawakami, Ana Paula; Sato, Cesar; Cardoso, Thayna Neves; Bonamin, Leoni Villano

2011-01-01

The effects of Arnica montana 6cH on the individual modulation of acute inflammation kinetics in rats were evaluated. Adult male Wistar rats were inoculated with 1% carrageenan into the footpad and treated with Arnica montana 6cH, dexamethasone (4.0 mg/kg; positive control) or 5% hydroalcoholic solution (negative control), per os, each 15 minutes, between 30 and 180 minutes after the irritant inoculation. Histopathological and immunohistochemistry procedures were done in order to get a panel of inflammatory positive cells for CD3 (T lymphocytes), CD45RA (B lymphocytes), CD18 (beta 2 integrin), CD163 (ED2 protein), CD54 (ICAM-1), and MAC 387 (monocytes and macrophages). The statistical treatment of data included a posteriori classification of animals from each group (N = 20) in two subgroups presenting spontaneous precocious or late oedema. Animals that presented precocious oedema were less responsible to Arnica montana 6cH in relation to hemodynamic changes. Instead, rats that exhibited late oedema presented less intense oedema (P = .01), lower percentage of mast cell degranulation (P = .0001), and increase in lymphatic vessels diameter (P = .05). The data suggest an individually qualitative adjustment of inflammatory vascular events by Arnica montana 6cH. PMID:21318109

Antinociceptive, anti-inflammatory and antipyretic properties of Melastoma malabathricum leaves aqueous extract in experimental animals.

PubMed

Zakaria, Z A; Raden Mohd Nor, R N S; Hanan Kumar, G; Abdul Ghani, Z D F; Sulaiman, M R; Rathna Devi, G; Mat Jais, A M; Somchit, M N; Fatimah, C A

2006-12-01

The present study was carried out to establish the antinociceptive, anti-inflammatory, and antipyretic properties of the aqueous extract of Melastoma malabathricum leaves in experimental animals. The antinociceptive activity was measured using abdominal constriction, hot-plate, and formalin tests, whereas the anti-inflammatory and antipyretic activities were measured using carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. The extract, which was obtained after soaking the air-dried leaves in distilled water for 72 h and then preparing in concentrations of 10%, 50%, and 100% (v/v), was administered subcutaneously 30 min prior to subjection to the above mentioned assays. At all concentrations tested, the extract was found to exhibit significant (P < 0.05) antinociceptive, anti-inflammatory, and antipyretic activities in a concentration-independent manner. Our findings that the aqueous extract of M. malabathricum possesses antinociceptive, anti-inflammatory, and antipyretic activities supports previous claims on its traditional uses to treat various ailments.

Assembled nanomedicines as efficient and safe therapeutics for articular inflammation.

PubMed

Che, Ling; Zhou, Jianzhi; Li, Shuhui; He, Hongmei; Zhu, Yuxuan; Zhou, Xing; Jia, Yi; Liu, Yao; Zhang, Jianxiang; Li, Xiaohui

2012-12-15

Highly efficient nanomedicines were successfully fabricated by the indomethacin (IND) directed self-assembly of β-cyclodextrin (β-CD)-conjugated polyethyleneimine (PEI-CD), taking advantage of the multiple interactions between drug and polymer. These nanoscaled assemblies exhibited spherical shape and positively charged surface. Compared with the commercial tablet, the relative oral bioavailability of IND-nanomedicines was significantly enhanced. Evaluation based on either carrageenan-induced paw edema or complete Freund's adjuvant (CFA)-induced arthritis suggested the newly developed nanomedicines were more effective than raw IND or IND tablet in terms of prophylactic effect and therapeutic activity. Even the low dose of nanomedicines offered the comparable results to those of control groups at the high dosage in most cases. Moreover, the nanoformulation exhibited ameliorated gastrointestinal stimulation. All these positive results indicated that this type of nanomedicines might serve as a highly efficient and effective delivery nanoplatform for the oral delivery of water-insoluble therapeutics. Copyright © 2012 Elsevier B.V. All rights reserved.

Modulation between high- and low-frequency transcutaneous electric nerve stimulation delays the development of analgesic tolerance in arthritic rats.

PubMed

Desantana, Josimari M; Santana-Filho, Valter J; Sluka, Kathleen A

2008-04-01

To investigate whether repeated administration of modulating frequency transcutaneous electric nerve stimulation (TENS) prevents development of analgesic tolerance. Knee joint inflammation (3% carrageenan and kaolin) was induced in rats. Either mixed or alternating frequency was administered daily (20min) for 2 weeks to the inflamed knee under light halothane anesthesia (1%-2%). Laboratory. Adult male Sprague-Dawley rats (N=36). Mixed- (4Hz and 100Hz) or alternating- (4Hz on 1 day; 100Hz on the next day) frequency TENS at sensory intensity and 100micros pulse duration. Paw and joint withdrawal thresholds to mechanical stimuli were assessed before induction of inflammation, and before and after daily application of TENS. The reduced paw and joint withdrawal thresholds that occur 24 hours after the induction of inflammation were significantly reversed by the first administration of TENS when compared with sham treatment or to the condition before TENS treatment, which was observed through day 9. By the tenth day, repeated daily administration of either mixed- or alternating-frequency TENS did not reverse the decreased paw and joint withdrawal thresholds. These data suggest that repeated administration of modulating frequency TENS leads to a development of opioid tolerance. However, this tolerance effect is delayed by approximately 5 days compared with administration of low- or high-frequency TENS independently. Clinically, we can infer that a treatment schedule of repeated daily TENS administration will result in a tolerance effect. Moreover, modulating low and high frequency TENS seems to produce a better analgesic effect and tolerance is slower to develop.

[Biologically active compounds from the aqueous extract of Urtica dioica].

PubMed

Wagner, H; Willer, F; Kreher, B

1989-10-01

From the water extract of the roots of Urtica dioica (stinging nettle) a polysaccharide fraction was isolated which revealed activity in the carrageenan rat paw edema model and lymphocyte transformation test. Ion exchange chromatography and gel filtration of this fraction afforded 4 different polysaccharides, one of which reduced dose dependent hemolysis in the classical pathway of the complement test. The Urtica dioica lectin (UDA) was reisolated and found to stimulate the proliferation of human lymphocytes.

The anti-inflammatory activity of dillapiole and some semisynthetic analogues.

PubMed

Parise-Filho, Roberto; Pastrello, Michelli; Pereira Camerlingo, Carla Emygdio; Silva, Gisele Juni; Agostinho, Leonardo Aguiar; de Souza, Thaís; Motter Magri, Fátima Maria; Ribeiro, Roberto Rodrigues; Brandt, Carlos Alberto; Polli, Michelle Carneiro

2011-11-01

Piper aduncum L. (Piperaceae) produces an essential oil (dillapiole) with great exploitative potential and it has proven effects against traditional cultures of phytopathogens, such as fungi, bacteria and mollusks, as well as analgesic action with low levels of toxicity. This study investigated the in vivo anti-inflammatory activity of dillapiole. Furthermore, in order to elucidate its structure-anti-inflammatory activity relationship (SAR), semisynthetic analogues were proposed by using the molecular simplification strategy. Dillapiole and safrole were isolated and purified using column chromatography. The semisynthetic analogues were obtained by using simple organic reactions, such as catalytic reduction and isomerization. All the analogues were purified by column chromatography and characterized by (1)H and (13)C NMR. The anti-inflammatory activities of dillapiole and its analogues were studied in carrageenan-induced rat paw edema model. Dillapiole and di-hydrodillapiole significantly (p<0.05) inhibited rat paw edema. All the other substances tested, including safrole, were less powerful inhibitors with activities inferior to that of indomethacin. These findings showed that dillapiole and di-hydrodillapiole have moderate anti-phlogistic properties, indicating that they can be used as prototypes for newer anti-inflammatory compounds. Structure-activity relationship studies revealed that the benzodioxole ring is important for biological activity as well as the alkyl groups in the side chain and the methoxy groups in the aromatic ring.

Beneficial Effects of Trillium govanianum Rhizomes in Pain and Inflammation.

PubMed

Ur Rahman, Shafiq; Adhikari, Achyut; Ismail, Muhammad; Raza Shah, Muhammad; Khurram, Muhammad; Shahid, Muhammad; Ali, Farman; Haseeb, Abdul; Akbar, Fazal; Iriti, Marcello

2016-08-20

Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity of extract and fractions was investigated in the carrageenan induced paw edema assay. The in vitro suppression of oxidative burst of extract, fractions and isolated compounds was assessed through luminol-enhanced chemiluminescence assay. The in vivo analgesic activity was assayed in chemical and thermal induced nociceptive pain models. The crude methanol extract and its solvent fractions showed anti-inflammatory and analgesic responses, exhibited by significant amelioration of paw edema and relieve of the tonic visceral chemical and acute phasic thermal nociception. In the oxidative burst assay, based on IC50, the crude methanol extract and n-butanol soluble fraction produced a significant inhibition, followed by chloroform and hexane soluble fractions as compared to ibuprofen. Similarly, the isolated compounds pennogenin and borassoside E exhibited significant level of oxidative burst suppressive activity. The in vivo anti-inflammatory and analgesic activities as well as the in vitro inhibition of oxidative burst validated the traditional use of T. govanianum rhizomes as a phytotherapeutic remedy for both inflammatory conditions and pain. The observed activities might be attributed to the presence of steroids and steroid-based compounds. Therefore, the rhizomes of this plant species could serve as potential novel source of compounds effective for alleviating pain and inflammation.

Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) root extract exhibits anti-nociceptive and antipyretic activities in murine models.

PubMed

Abotsi, Wonder Kofi Mensah; Lamptey, Stanley Benjamin; Boakye-Gyasi, Eric; Woode, Eric

2017-03-06

The root extract of Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) is traditionally used in the management of pain and fever. However, little scientific data exists in literature to support its use. The present study evaluated the anti-nociceptive and antipyretic properties of the hydroethanolic extract of the roots of Albizia zygia in animal models. The analgesic effects were investigated in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (tail-immersion test) and mechanical (carrageenan-induced hyperalgesia) pain models. Possible mechanisms of anti-nociception were also assessed with antagonists in the formalin test. The anti-pyretic effect was evaluated using the baker yeast-induced pyrexia model in young rats. The extract (30-300mg/kg, p.o.) and positive controls, diclofenac (3-30mg/kg, i.p.) and morphine (1-10mg/kg, i.p.), significantly (at least P<0.01) attenuated acetic acid-induced visceral pain, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical hyperalgesia in animals. The anti-nociceptive effect of the extract was reversed (at least P<0.05) by the pre-emptive administration of naloxone and atropine; the administration of theophylline, however, exhibited no significant (P>0.05) inhibition of anti-nociception. The extract (30-300mg/kg, p.o) and paracetamol (15-150mg/kg, p.o.) both reversed yeast-induced pyrexia in rats with ED 50 values of 48.59±2.59 and 26.19±1.33mg/kg respectively. The findings indicate that the extract possesses significant anti-nociceptive and antipyretic effects which justify its traditional use in the management of pain and fever. Also, anti-nociceptive effect of the extract involves opioidergic and muscarinic cholinergic mechanisms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

[Exercise-induced oedema due to hormone-containing intrauterine device].

PubMed

Franssen, Laurens E; Bos, Willem-Jan W

2012-01-01

Oedema is a known adverse effect of the levonorgestrel-containing intrauterine device (Mirena IUD). However, exercise-induced oedema has not been described before. A 38-year-old woman presented with symptoms of diffuse, exercise-induced oedema and dyspnoea. Tests for heart failure and other causes of oedema showed no abnormalities. All symptoms resolved spontaneously after the patient initiated removal of the IUD. The pathophysiology of exercise-induced oedema is still poorly understood. When confronted with a patient with oedema (induced by exercise or other cause), the most common causes must first be excluded. If no explanation can be found, then the effects of medication must not be overlooked.

Beneficial effects of raxofelast (IRFI 016), a new hydrophilic vitamin E-like antioxidant, in carrageenan-induced pleurisy

PubMed Central

Cuzzocrea, Salvatore; Costantino, Giuseppina; Mazzon, Emanuela; Caputi, Achille P

1999-01-01

Peroxynitrite is a strong oxidant that results from reaction between NO and superoxide. It has been recently proposed that peroxynitrite plays a pathogenetic role in inflammatory processes. Here we have investigated the therapeutic efficacy of raxofelast, a new hydrophilic vitamin E-like antioxidant agent, in rats subjected to carrageenan-induced pleurisy. In vivo treatment with raxofelast (5, 10, 20 mg kg−1 intraperitoneally 5 min before carrageenan) prevented in a dose dependent manner carrageenan-induced pleural exudation and polymorphonuclear migration in rats subjected to carrageenan-induced pleurisy. Lung myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels, as well as histological organ injury were significantly reduced by raxofelast. Immunohistochemical analysis for nitrotyrosine, a footprint of peroxynitrite, revealed a positive staining in lungs from carrageenan-treated rats. No positive nitrotyrosine staining was found in the lungs of the carrageenan-treated rats, which received raxofelast (20 mg kg−1) treatment. Furthermore, in vivo raxofelast (5, 10, 20 mg kg−1) treatment significantly reduced peroxynitrite formation as measured by the oxidation of the fluorescent dihydrorhodamine 123, prevented the appearance of DNA damage, the decrease in mitochondrial respiration and partially restored the cellular level of NAD+ in ex vivo macrophages harvested from the pleural cavity of rats subjected to carrageenan-induced pleurisy. In conclusion, our study demonstrates that raxofelast, a new hydrophilic vitamin E-like antioxidant agent, exerts multiple protective effects in carrageenan-induced acute inflammation. PMID:10077232

Antinociceptive interactions between anandamide and endomorphin-1 at the spinal level.

PubMed

Tuboly, Gabor; Mecs, Laszlo; Benedek, György; Horvath, Gyöngyi

2009-04-01

1. Although it is well known that the combined administration of synthetic or plant-originated opioids with cannabinoids (CB) results in synergistic antinociception, the effects of combined administration of endogenous ligands acting at micro-opioid and CB receptors are not known. The aim of the present study was to determine the interaction between anandamide (AEA; a CB(1) receptor agonist) and endomorphin-1 (EM-1; a micro-opioid receptor agonist) after intrathecal administration. 2. Nociception was assessed by the paw-withdrawal test after carrageenan-induced inflammation in male Wistar rats. 3. Endomorphin-1 (16.4 pmol to 16.4 nmol) and AEA (4.3-288 nmol) alone dose-dependently decreased carrageenan-induced thermal hyperalgesia, although the highest dose of AEA also exhibited pain-inducing potential. The potency of AEA was approximately 59-fold lower than that of EM-1 (35% effective dose (ED(35)) 194.4 vs 3.3 nmol, respectively). Coadministration of these ligands revealed that combinations of 16.4 pmol EM-1 plus 28.8 or 86.5 nmol AEA were more effective than either drug alone, but other combinations were no more effective than the administration of EM-1 itself. Therefore, coadministration of AEA did not significantly shift the dose-response curve to EM-1. 4. The results of the present study indicate that the coadministration of AEA and EM-1 results in potentiated antihyperalgesia only for a combination of specific doses. Because AEA activates other receptor types (e.g. TRPV1) in addition to CB(1) receptors, the results of the present suggest that, after the coadministration of EM-1 and AEA, complex interactions ensue that may lead to different outcomes compared with those seen following the injection of exogenous ligands.

Anti-inflammatory and analgesic activities of solvent fractions of the leaves of Moringa stenopetala Bak. (Moringaceae) in mice models.

PubMed

Tamrat, Yohannes; Nedi, Teshome; Assefa, Solomon; Teklehaymanot, Tilahun; Shibeshi, Workineh

2017-09-29

Many people still experience pain and inflammation regardless of the available drugs for treatments. In addition, the available drugs have many side effects, which necessitated a quest for new drugs from several sources in which medicinal plants are the major one. This study evaluated the analgesic and anti- inflammatory activity of the solvent fractions of Moringa stenopetala in rodent models of pain and inflammation. Successive soxhlet and maceration were used as methods of extractions using solvents of increasing polarity; chloroform, methanol and water. Swiss albino mice models were used in radiant tail flick latency, acetic acid induced writhing and carrageenan induced paw edema to assess the analgesic and anti-inflammatory activities. The test groups received different doses (100 mg/kg, 200 mg/kg and 400 mg/kg) of the three fractions (chloroform, methanol and aqueous). The positive control groups received morphine (20 mg/kg) or aspirin (100 mg/kg or 150 mg/kg) based on the respective models. The negative control groups received the 10 ml/kg of vehicles (distilled water or 2% Tween 80). In all models, the chloroform fraction had protections only at a dose of 400 mg/kg. However, the methanol and aqueous fraction at all doses have shown significant central and peripheral analgesic activities with a comparable result to the standards. The aqueous and methanol fractions significantly reduced carrageenan induced inflammation in a dose dependent manner, in which the highest reduction of inflammation was observed in aqueous fraction at 400 mg/kg. This study provided evidence on the traditionally claimed uses of the plant in pain and inflammatory diseases, and Moringa stenopetala could be potential source for development of new analgesic and anti-inflammatory drugs.

Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling

PubMed Central

Ashraf, Zaman; Alamgeer; Kanwal, Munazza; Hassan, Mubashir; Abdullah, Sahar; Waheed, Mamuna; Ahsan, Haseeb; Kim, Song Ja

2016-01-01

Flurbiprofen–antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (–COOH) was temporarily masked by esterification with phenolic –OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (4b) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer’s yeast-induced pyrexia model, and significant (P<0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug. PMID:27555750

Flurbiprofen-antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling.

PubMed

Ashraf, Zaman; Alamgeer; Kanwal, Munazza; Hassan, Mubashir; Abdullah, Sahar; Waheed, Mamuna; Ahsan, Haseeb; Kim, Song Ja

2016-01-01

Flurbiprofen-antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (-COOH) was temporarily masked by esterification with phenolic -OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (4b) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer's yeast-induced pyrexia model, and significant (P<0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug.

Anti-inflammatory activity of Shirishavaleha: An Ayurvedic compound formulation.

PubMed

Yadav, Shyamlal Singh; Galib; Ravishankar, B; Prajapati, P K; Ashok, B K; Varun, B

2010-10-01

The purpose of the present study was to evaluate the anti-inflammatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth.), viz. the bark (Twak) and the heartwood (Sara). The activity was screened in the carrageenan-induced rat paw edema model in albino rats. The raw materials were collected and authenticated in the university and the trial formulations were prepared by following standard classical guidelines. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 1.8 g/kg for 5 days. Phenylbutazone was used as the standard anti-inflammatory drug for comparison. Between the two different test samples studied, the formulation made from heartwood showed a weak anti-inflammatory activity in this model while that made from the bark produced a considerable suppression of edema after 6 h. It appears that the bark sample would be preferable for clinical use.

Two new triterpene saponins from the anti-inflammatory saponin fraction of Ilex pubescens root.

PubMed

Wang, Jing-Rong; Zhou, Hua; Jiang, Zhi-Hong; Liu, Liang

2008-07-01

The saponin fraction from the ethanolic extracts of the root of Ilex pubescens Hook. et Arn. (Ilexaceae) was found to exhibit potent anti-inflammatory effects on carrageenan-induced paw edema in rats. Two novel triterpene saponins, pubescenosides C and D (1 and 2, resp.), together with five known saponins were isolated from this saponin fraction. The structures of 1 and 2 were elucidated as (20beta)-3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl]ursa-12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester, and (20beta)-3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl]ursa- 12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester, respectively, on the basis of chemical and spectroscopic data. Five known saponins isolated from the saponin fraction were identified as ilexsaponin B(1), B(2), B(3), A(1), and chikusetsusaponin IV(a).

Pain Reduces Sexual Motivation in Female But Not Male Mice

PubMed Central

Farmer, Melissa A.; Leja, Alison; Foxen-Craft, Emily; Chan, Lindsey; MacIntyre, Leigh C.; Niaki, Tina; Chen, Mengsha; Mapplebeck, Josiane C.S.; Tabry, Vanessa; Topham, Lucas; Sukosd, Melissa; Binik, Yitzchak M.; Pfaus, James G.

2014-01-01

Chronic pain is often associated with sexual dysfunction, suggesting that pain can reduce libido. We find that inflammatory pain reduces sexual motivation, measured via mounting behavior and/or proximity in a paced mating paradigm, in female but not male laboratory mice. Pain was produced by injection of inflammogens zymosan A (0.5 mg/ml) or λ-carrageenan (2%) into genital or nongenital (hind paw, tail, cheek) regions. Sexual behavior was significantly reduced in female mice experiencing pain (in all combinations); male mice similarly treated displayed unimpeded sexual motivation. Pain-induced reductions in female sexual behavior were observed in the absence of sex differences in pain-related behavior, and could be rescued by the analgesic, pregabalin, and the libido-enhancing drugs, apomorphine and melanotan-II. These findings suggest that the well known context sensitivity of the human female libido can be explained by evolutionary rather than sociocultural factors, as female mice can be similarly affected. PMID:24760835

Synthesis and anti-inflammatory activity of some benzofuran and benzopyran-4-one derivatives.

PubMed

Ragab, Fatma Abd El-Fattah; Eid, Nahed Mahmoud; Hassan, Ghaneya Sayed; Nissan, Yassin Mohammed

2012-01-01

New series of furosalicylic acids 3a-c, furosalicylanilides 6a-n, furobenzoxazines 8a-f, 1-benzofuran-3-arylprop-2-en-1-ones 12a,b, 6-(aryl-3-oxoprop-1-enyl)-4H-chromen-4-ones 16a-c and 6-[6-aryl-2-thioxo-2,5-dihydropyrimidin-4-yl]-4H-chromen-4-ones 17a-c were synthesized. Anti-inflammatory activity evaluation was performed using carrageenan-induced paw edema model in rats and prostaglandin E(2) (PGE(2)) synthesis inhibition activity. Some of the tested compounds revealed comparable activity with less ulcerogenic effect than Diclofenac at a dose 100 mg/kg. All the synthesized compounds were docked on the active site of cyclooxygenase-2 (COX-2) enzyme and most of them showed good interactions with the amino acids of the active site comparable to the interactions exhibited by Diclofenac.

Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes

PubMed Central

Das, Hiranmoy; Kumar, Ajay; Lin, Zhiyong; Patino, Willmar D.; Hwang, Paul M.; Feinberg, Mark W.; Majumder, Pradip K.; Jain, Mukesh K.

2006-01-01

The mechanisms regulating activation of monocytes remain incompletely understood. Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes. In vitro, KLF2 expression in monocytes is reduced by cytokine activation or differentiation. Consistent with this observation, KLF2 expression in circulating monocytes is reduced in patients with chronic inflammatory conditions such as coronary artery disease. Adenoviral overexpression of KLF2 inhibits the LPS-mediated induction of proinflammatory factors, cytokines, and chemokines and reduces phagocytosis. Conversely, short interfering RNA-mediated reduction in KLF2 increased inflammatory gene expression. Reconstitution of immunodeficient mice with KLF2-overexpressing monocytes significantly reduced carrageenan-induced acute paw edema formation. Mechanistically, KLF2 inhibits the transcriptional activity of both NF-κB and activator protein 1, in part by means of recruitment of transcriptional coactivator p300/CBP-associated factor. These observations identify KLF2 as a novel negative regulator of monocytic activation. PMID:16617118

Synthesis, anti-inflammatory evaluation in vivo and docking studies of some new 5-(benzo[b]furan-2-ylmethyl)-6-methyl-pyridazin-3(2H)-one derivatives

NASA Astrophysics Data System (ADS)

Boukharsa, Youness; Lakhlili, Wiame; El harti, Jaouad; Meddah, Bouchra; Tiendrebeogo, Ramata Yvette; Taoufik, Jamal; El Abbes Faouzi, My; Ibrahimi, Azeddine; Ansar, M'hammed

2018-02-01

Seven novel 5-(benzo[b]furan-2-ylmethyl)-6-methyl-pyridazin-3(2H)-one derivatives (6a to 6g) have been synthesized by the condensation of appropriate 3-(benzofuran-2-ylmethylene)-4-oxopentanoic acid and hydrazine hydrate in ethanol. Structures of all compounds were elucidated by elemental analysis, IR, 1H NMR and 13C NMR. These compounds were tested for their anti-inflammatory activity in carrageenan-induced rat paw edema model. In silico molecular docking study has been executed to study the binding interactions of the synthesized compounds with COX-2 protein. Compounds 6a, 6b, 6e and 6g showed a good anti-inflammatory activity at 50 mg/kg compared with the indometacin at 10 mg/kg and the aspirin at 150 mg/kg and good binding affinity with COX-2.

Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB, JNK and p38 MAPK inactivation.

PubMed

Zhou, Hong Yu; Shin, Eun Myoung; Guo, Lian Yu; Youn, Ui Joung; Bae, KiHwan; Kang, Sam Sik; Zou, Li Bo; Kim, Yeong Shik

2008-05-31

The extracts or constituents from the bark of Magnolia (M.) obovata are known to have many pharmacological activities. 4-Methoxyhonokiol, a neolignan compound isolated from the stem bark of M. obovata, was found to exhibit a potent anti-inflammatory effect in different experimental models. Pretreatment with 4-methoxyhonokiol (i.p.) dose-dependently inhibited the dye leakage and paw swelling in an acetic-acid-induced vascular permeability assay and a carrageenan-induced paw edema assay in mice, respectively. In the lipopolysaccharide (LPS)-induced systemic inflammation model, 4-methoxyhonokiol significantly inhibited plasma nitric oxide (NO) release in mice. To identify the mechanisms underlying this anti-inflammatory action, we investigated the effect of 4-methoxyhonokiol on LPS-induced responses in a murine macrophage cell line, RAW 264.7. The results demonstrated that 4-methoxyhonokiol significantly inhibited LPS-induced NO production as well as the protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, 4-methoxyhonokiol inhibited LPS-mediated nuclear factor-kappaB (NF-kappaB) activation via the prevention of inhibitor kappaB (IkappaB) phosphorylation and degradation. 4-Methoxyhonokiol had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), whereas it attenuated the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH2-terminal kinase (JNK) in a concentration-dependent manner. Taken together, our data suggest that 4-methoxyhonokiol is an active anti-inflammatory constituent of the bark of M. obovata, and that its anti-inflammatory property might be a function of the inhibition of iNOS and COX-2 expression via down-regulation of the JNK and p38 MAP kinase signal pathways and inhibition of NF-kappaB activation in RAW 264.7 macrophages.

Sucrose esters from Physalis peruviana calyces with anti-inflammatory activity.

PubMed

Franco, Luis A; Ocampo, Yanet C; Gómez, Harold A; De la Puerta, Rocío; Espartero, José L; Ospina, Luis F

2014-11-01

Physalis peruviana is a native plant from the South American Andes and is widely used in traditional Colombian medicine of as an anti-inflammatory medicinal plant, specifically the leaves, calyces, and small stems in poultice form. Previous studies performed by our group on P. peruviana calyces showed potent anti-inflammatory activity in an enriched fraction obtained from an ether total extract. The objective of the present study was to obtain and elucidate the active compounds from this fraction and evaluate their anti-inflammatory activity in vivo and in vitro. The enriched fraction of P. peruviana was purified by several chromatographic methods to obtain an inseparable mixture of two new sucrose esters named peruviose A (1) and peruviose B (2). Structures of the new compounds were elucidated using spectroscopic methods and chemical transformations. The anti-inflammatory activity of the peruvioses mixture was evaluated using λ-carrageenan-induced paw edema in rats and lipopolysaccharide-activated peritoneal macrophages. Results showed that the peruvioses did not produce side effects on the liver and kidneys and significantly attenuated the inflammation induced by λ-carrageenan in a dosage-dependent manner, probably due to an inhibition of nitric oxide and prostaglandin E2, which was demonstrated in vitro. To our knowledge, this is the first report of the presence of sucrose esters in P. peruviana that showed a potent anti-inflammatory effect. These results suggest the potential of sucrose esters from the Physalis genus as a novel natural alternative to treat inflammatory diseases. Georg Thieme Verlag KG Stuttgart · New York.

Anti-inflammatory and wound healing activities of Aloe littoralis in rats

PubMed Central

Hajhashemi, V.; Ghannadi, A.; Heidari, A.H.

2012-01-01

Aloe littoralis Baker (Asphodelaceae family) is a well known plant in southern parts of Iran. Because of its use in Iranian folk medicine as a wound-healing agent, the present study was carried out to investigate anti-inflammatory and wound healing activities of this plant in Wistar rats. A. littoralis raw mucilaginous gel (ALRMG) and also two gel formulations prepared from the raw mucilaginous gel were used in this study. Gel formulations (12.5% and 100% v/w Aloe mucilage in a carbomer base) were applied topically (500 mg once daily) for 24 days in the thermal wound model. Also Aloe gel formulation (100%) and ALRMG (500 mg daily) were evaluated in incisional wound model. Carrageenan-induced paw edema was used to assess the anti-inflammatory effect of intraperitoneal injection of ALRMG. In burn wound, ALRMG and Aloe formulated gel (100%) showed significant (P<0.05) healing effect. Topical application of ALMRG and Aloe formulated gel (100%) promoted healing rate of incisional wound. In carrageenan test, ALRMG (2.5 and 5 ml/Kg) revealed significant (P<0.05) anti-inflammatory activity. Results showed that A. littoralis is a potential wound-healing and anti-inflammatory agent in rats. Further studies are needed to find out the mechanism of these biological effects and also the active constituents responsible for the effects. PMID:23181083

Chemical composition, antinociceptive and anti-inflammatory effects in rodents of the essential oil of Peperomia serpens (Sw.) Loud.

PubMed

Pinheiro, B G; Silva, A S B; Souza, G E P; Figueiredo, J G; Cunha, F Q; Lahlou, S; da Silva, J K R; Maia, J G S; Sousa, P J C

2011-11-18

Peperomia serpens (Piperaceae), popularly known as "carrapatinho", is an epiphyte herbaceous liana grown wild on different host trees in the Amazon rainforest. Its leaves are largely used in Brazilian folk medicine to treat inflammation, pain and asthma. This study investigated the effects of essential oil of Peperomia serpens (EOPs) in standard rodent models of pain and inflammation. The antinociceptive activity was evaluated using chemical (acetic acid and formalin) and thermal (hot plate) models of nociception in mice whereas the anti-inflammatory activity was evaluated by carrageenan- and dextran-induced paw edema tests in rats croton oil-induced ear edema, as well as cell migration, rolling and adhesion induced by carrageenan in mice. Additionally, phytochemical analysis of the EOPs has been also performed. Chemical composition of the EOPs was analyzed by gas chromatography and mass spectrometry (GC/MS). Twenty-four compounds, representing 89.6% of total oil, were identified. (E)-Nerolidol (38.0%), ledol (27.1%), α-humulene (11.5%), (E)-caryophyllene (4.0%) and α-eudesmol (2.7%) were found to be the major constituents of the oil. Oral pretreatment with EOPs (62.5-500 mg/kg) significantly reduced the writhing number evoked by acetic acid injection, with an ED(50) value of 188.8 mg/kg that was used thereafter in all tests. EOPs had no significant effect on hot plate test but reduced the licking time in both phases of the formalin test, an effect that was not significantly altered by naloxone (0.4 mg/kg, s.c.). EOPs inhibited the edema formation induced by carrageenan and dextran in rats. In mice, EOPs inhibited the edema formation by croton oil as well as the leukocyte and neutrophil migration, the rolling and the adhesion of leukocytes. These data show for the first time that EOPs has a significant and peripheral antinociceptive effect that seems unrelated to interaction with the opioid system. EOPs also displays a significant anti-inflammatory effect in acute inflammation models. This effect seems to be related to components which inhibit the production of several inflammatory mediators. These results support the widespread use of Peperomia serpens in popular medicine to treat inflammation and pain. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Free and nanoencapsulated vitamin D3 : effects on E-NTPDase and E-ADA activities in an animal model with induced arthritis.

PubMed

da Silveira, Karine Lanes; da Silveira, Leonardo Lanes; Thorstenberg, Maria Luiza Prates; Cabral, Fernanda Licker; Castilhos, Livia Gelain; Rezer, João Felipe Peres; de Andrade, Diego Fontana; Beck, Ruy Carlos Ruver; Einloft Palma, Heloísa; de Andrade, Cinthia Melazzo; Pereira, Renata da Silva; Martins, Nara Maria Beck; Bertonchel Dos Santos, Claudia de Mello; Leal, Daniela Bitencourt Rosa

2016-06-01

The effect of vitamin D3 in oral solution (VD3 ) and vitamin D3 -loaded nanocapsules (NC-VD3 ) was analysed in animals with complete Freund's adjuvant (CFA) induced arthritis (AR). For this purpose, we evaluated scores for arthritis, thermal hyperalgesia and paw oedema, as well as histological analyses and measurements of the activity of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase (E-ADA) enzymes in rat lymphocytes. Haematological and biochemical parameters were also determined. The doses administered were 120 UI/day of VD3 and 15.84 UI/day of NC-VD3 . Fifteen days after the induction of AR, the groups were treated for 15 days with vitamin D3 . The results demonstrated that VD3 was able to reduce arthritis scores, thermal hyperalgesia and paw oedema in rats with CFA-induced arthritis. However, treatment with NC-VD3 did not reduce arthritis scores. The histological analyses showed that both formulations were able to reduce the inflammatory changes induced by CFA. The activity of E-NTPDase in rat lymphocytes was higher in the AR compared with the control group, while the activity of E-ADA was lower. This effect was reversed after the 15-day treatment. Data from this study indicates that both forms of vitamin D3 seem to contribute to decreasing the inflammatory process induced by CFA, possibly altering the activities of ectoenzymes. Copyright © 2016 John Wiley & Sons, Ltd. The effects promoted by both formulations of vitamin D3 , either in oral solution or nanoencapsulated form, strongly suggests the softening of the inflammatory process induced by complete Freund's adjuvant (CFA), possibly altering the E-NTPDase and E-ADA activities. However, it is known that vitamin D has a beneficial effect on the modulation of the immune system components responsible for the inflammatory process. Moreover, the establishment of responses to treatment with vitamin D3 may provide an alternative for inhibiting the proinflammatory response, assisting in our understanding of the immunopathology of this disease and possibly improving the signs and symptoms that hinder the quality of life of patients with rheumatoid arthritis. Evaluation of the effects on the E-NTPDase and E-ADA activities in an animal model of induced arthritis. Two formulations of vitamin D3 were used: form oral solution and nanoencapsulated. Vitamin D3 seems to contribute to the inflammatory process induced by CFA. Vitamin D3 possibly alters the E-NTPDase and E-ADA activities. Vitamin D3 may be an alternative supplementary treatment for chronic arthritis. Copyright © 2016 John Wiley & Sons, Ltd.

Modulation Between High- and Low-Frequency Transcutaneous Electric Nerve Stimulation Delays the Development of Analgesic Tolerance in Arthritic Rats

PubMed Central

DeSantana, Josimari M.; Santana-Filho, Valter J.; Sluka, Kathleen A.

2009-01-01

Objective To investigate whether repeated administration of modulating frequency transcutaneous electric nerve stimulation (TENS) prevents development of analgesic tolerance. Design Knee joint inflammation (3% carrageenan and kaolin) was induced in rats. Either mixed or alternating frequency was administered daily (20min) for 2 weeks to the inflamed knee under light halothane anesthesia (1%–2%). Setting Laboratory. Animals Adult male Sprague-Dawley rats (N=36). Intervention Mixed- (4Hz and 100Hz) or alternating- (4Hz on 1 day; 100Hz on the next day) frequency TENS at sensory intensity and 100μs pulse duration. Main Outcome Measures Paw and joint withdrawal thresholds to mechanical stimuli were assessed before induction of inflammation, and before and after daily application of TENS. Results The reduced paw and joint withdrawal thresholds that occur 24 hours after the induction of inflammation were significantly reversed by the first administration of TENS when compared with sham treatment or to the condition before TENS treatment, which was observed through day 9. By the tenth day, repeated daily administration of either mixed- or alternating-frequency TENS did not reverse the decreased paw and joint withdrawal thresholds. Conclusions These data suggest that repeated administration of modulating frequency TENS leads to a development of opioid tolerance. However, this tolerance effect is delayed by approximately 5 days compared with administration of low- or high-frequency TENS independently. Clinically, we can infer that a treatment schedule of repeated daily TENS administration will result in a tolerance effect. Moreover, modulating low and high frequency TENS seems to produce a better analgesic effect and tolerance is slower to develop. PMID:18374009

NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

PubMed Central

Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A.; Kashfi, Khosrow

2015-01-01

Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. PMID:26394025

Anti-hypernociceptive properties of agmatine in persistent inflammatory and neuropathic models of pain in mice.

PubMed

Paszcuk, Ana Flávia; Gadotti, Vinicius M; Tibola, Daiane; Quintão, Nara L M; Rodrigues, Ana Lúcia S; Calixto, João B; Santos, Adair R S

2007-07-23

The present study examined the anti-hypernociceptive effects of agmatine (AGM) in acute and chronic models of behavioural pain in mice. Agmatine (30 mg/kg, i.p. 30 min early), produced time-dependent inhibition of mechanical hypernociception induced by Complete Freund's Adjuvant (CFA) injected in the mice paw (inhibition of 52+/-7%) after 4 h. Given chronically (twice a day) during 10 days, AGM significantly reversed the mechanical hypernociception caused by CFA (inhibition of 43+/-6% to 67+/-5%). Moreover, AGM also significantly reduced the mechanical hypernociception caused by partial sciatic nerve ligation (PSNL) during 6 h, with inhibition of 81+/-8%. In thermal hypernociception (cold stimuli) caused by PSNL the antinociceptive effect of AGM was prolonged by 4 h with inhibition of 97+/-3% observed 1 h after the treatment. Nevertheless, AGM failed to inhibit the paw oedema caused by CFA and the myeloperoxidase enzyme activity. Of note, AGM (10-100 mg/kg, i.p., 30 min before) also elicited a pronounced inhibition of the biting response induced by TNF-alpha and IL-1beta in mice, with mean ID(50) values of 61.3 mg/kg (47.7-78.6 mg/kg) and 30.4 mg/kg (18.6-49.8 mg/kg) and inhibitions of 75+/-5% and 66+/-6%, respectively. Together, present and previous findings show that AGM given systemically is effective in inhibiting mechanical and thermal hypernociception present in chronic inflammatory processes caused by CFA and also the neuropathic pain caused by PSNL.

A multi-target therapeutic potential of Prunus domestica gum stabilized nanoparticles exhibited prospective anticancer, antibacterial, urease-inhibition, anti-inflammatory and analgesic properties.

PubMed

Islam, Nazar Ul; Amin, Raza; Shahid, Muhammad; Amin, Muhammad; Zaib, Sumera; Iqbal, Jamshed

2017-05-23

Phytotherapeutics exhibit diverse pharmacological effects that are based on the combined action of a mixture of phytoconstituents. In this study, Prunus domestica gum-loaded, stabilized gold and silver nanoparticles (Au/Ag-NPs) were evaluated for their prospective anticancer, antibacterial, urease-inhibition, anti-inflammatory, and analgesic properties. Au/Ag-NPs were biosynthesized and characterized with UV-Vis, FTIR, SEM, EDX, and XRD techniques. The effect of gum and metal ion concentration, reaction temperature, and time on the synthetic stability of nanoparticles was studied along with their post-synthetic stability against varying pH and salt concentrations, long-term storage and extremes of temperature. Nanoparticles were tested for anticancer (HeLa cervical cancer cells), antibacterial (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa), urease inhibition (jack-bean urease), anti-inflammatory (carrageenan-induced paw edema), and antinociceptive (abdominal constriction response) activities. The nanoparticles were mostly spherical with an average particle size between 7 and 30 nm (Au-NPs) and 5-30 nm (Ag-NPs). Au/Ag-NPs maintained their colloidal stability and nanoscale characteristics against variations in physicochemical factors. Au/Ag-NPs have potent anticancer potential (IC 50  = 2.14 ± 0.15 μg/mL and 3.45 ± 0.23 μg/mL). Au/Ag-NPs selectively suppressed the growth of S. aureus (10.5 ± 0.6 mm, 19.7 ± 0.4 mm), E. coli (10 ± 0.4 mm, 14.4 ± 0.7 mm), and P. aeruginosa (8.2 ± 0.3 mm, 13.1 ± 0.2 mm), as well as showed preferential inhibition against jack-bean urease (19.2 ± 0.86%, 21.5 ± 1.17%). At doses of 40 and 80 mg/kg, Au-NPs significantly ameliorated the increase in paw edema during the 1st h (P < 0.05, P < 0.01) and 2-5 h (P < 0.001) of carrageenan-induced inflammation compared to the 200 and 400 mg/kg doses of P. domestica gum (P < 0.05, P < 0.001). At similar doses, Au-NPs also significantly abolished (P < 0.01) the tonic visceral, chemically-induced nociception, which was comparable to that of P. domestica gum (200 mg/kg; P < 0.05, 400 mg/kg; P < 0.01).

Formulation and Characterization of Aceclofenac -Aloe vera Transemulgel.

PubMed

Raju, Y Prasanna; Haritha, K; Satyanarayana, Rao P; Vandana, K R; Bindu, D Thushara; Vinesha, V; Chowdary, V Harini

2015-01-01

The present research was aimed to formulate aceclofenac transemulgel using Aloe vera as gel base. The prepared formulations were subjected to physical characterization, in-vitro and in-vivo assessment. Aceclofenac, a hydrophobic potential non steroidal anti inflammatory drug, causes ulceration upon chronic oral administration, could be formulated into transemulgel to enhance therapeutic efficacy and to lower the unwanted side effects. The transemulgel was prepared from aqueous Aloe vera gel and aceclofenac emulsion. The prepared transemulgel was evaluated for its pH, viscosity, drug content, skin irritation, in-vitro diffusion and accelerated stability studies. The prepared aceclofenac-Aloe vera tranemulgel and commercial aceclofenac gel were subjected to pharmacodynamic studies in albino rats of Wistar strain employing carrageenan induced left hind paw edema method to assess the anti-inflammatory effect. The transemulgel showed a pH of 6.78 and viscosity of 18 cps. In-vitro diffusion data revealed better permeation characteristics. Topical application of formulation found no skin irritation. Stability study has proved the integrity of the formulation. The prepared aceclofenac Aloe vera transemulgel showed better in-vitro drug release when compared with the commercial aceclofenac gel formulation. Anti-inflammatory activity in treated rats showed the significant paw volume reduction at p<0.05 compared with that of control. Thus, it is concluded that aceclofenac, a potential non steroidal anti inflammatory drug, showed high therapeutic efficiency when formulated into transemulgel using aqueous Aloe vera as gel base.

Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors.

PubMed

de Oliveira Lopes, Raquel; Romeiro, Nelilma Correia; de Lima, Cleverton Kleiton F; Louback da Silva, Leandro; de Miranda, Ana Luisa Palhares; Nascimento, Paulo Gustavo B D; Cunha, Fernando Q; Barreiro, Eliezer J; Lima, Lídia Moreira

2012-08-01

p38 mitogen-activated protein kinase (p38 MAPK) is an important signal transducing enzyme involved in many cellular regulations, including signaling pathways, pain and inflammation. Several p38 MAPK inhibitors have been developed as drug candidates to treatment of autoimmune disorders, such as rheumatoid arthritis. In this paper we reported the docking, synthesis and pharmacological activity of novel urea-derivatives (4a-e) designed as p38 MAPK inhibitors. These derivatives presented good theoretical affinity to the target p38 MAPK, standing out compound 4e (LASSBio-998), which showed a better score value compared to the prototype GK-00687. This compound was able to reduce in vitro TNF-α production and was orally active in a hypernociceptive murine model sensible to p38 MAPK inhibitors. Otherwise, compound 4e presented a dose-dependent analgesic effect in a model of antigen (mBSA)-induced arthritis and anti-inflammatory profile in carrageenan induced paw edema, indicating its potential as a new antiarthritis prototype. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Garcinia morella fruit, a promising source of antioxidant and anti-inflammatory agents induces breast cancer cell death via triggering apoptotic pathway.

PubMed

Choudhury, Bhaswati; Kandimalla, Raghuram; Elancheran, R; Bharali, Rupjyoti; Kotoky, Jibon

2018-04-17

A rapid rise in cancer cases worldwide, especially breast cancer in females, instigates the need for more effective and less side effect causing drugs from natural origin. Thereby, in the present study, Garcinia morella fruit was investigated for antioxidant, anti-inflammatory and anti-breast cancer activity. Preliminary antioxidant and anticancer evaluation of different fractions and crude methanol extract of G. morella fruit suggested chloroform fraction as the bioactive fraction. Time course analysis (by 24 h, 48 h and 72 h) of the bioactive fraction (1.56-25) μg/ml treatment on breast cancer cell lines (MCF7, MDAMB231 and SKBR3) showed dose and time dependent antiproliferative responses. Further, mechanistic studies involving morphological observation and western blotting analysis, revealed its apoptosis inducing effect on breast cancer. P53 dependent up-regulation of Bax and down-regulation of Bcl X L is suggested as the possible pathway of apoptosis followed by MCF7 cells on exposure to the bioactive fraction. The anti-inflammatory assays revealed that it significantly lowered the release of nitrite and TNF-α level of LPS induced RAW 264.7 cells (p < 0.05). Moreover, pre treatment of Carrageenan induced paw edema animals with 20 mg/kg of the bioactive fraction significantly (p < 0.05) inhibited paw inflammation and controlled the cytokine and nitrite levels of the edema induced rat. Its main bioactive component was identified to be Garcinol by UHPLC and ESI-MS/MS. Thereby, this study clearly reflects that G. morella fruit is a valuable antioxidant and anti-inflammatory gift of nature with the potential to be used against breast cancer. This is also the first report of isolation of bioactive compound Garcinol from G. morella fruit. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

In vivo and in vitro anti-inflammatory properties of Achyrocline alata (Kunth) DC.

PubMed

Toffoli-Kadri, Mônica Cristina; Carollo, Carlos Alexandre; Lourenço, Letícia Dias; Felipe, Josyelen Lousada; Néspoli, José Henrique Brandini; Wollf, Luis Guilherme Campos; Resende, Glenda Mara Sousa; de Lima, Jaqueline Rodrigues; Franco, Vanessa Natachi Penteado; Vieira, Maria do Carmo; de Siqueira, João Máximo

2014-04-28

Achyrocline alata is a locally marketed (Mato Grosso do Sul/ Brazil) herb used in folk medicine as an anti-inflammatory and a sedative. Evaluate the anti-inflammatory properties of Achyrocline alata in both in vivo and in vitro models. A hydroethanolic extract from inflorescences of Achyrocline alata (HEAa) was characterized by HPLC-DAD and compared to standards (chlorogenic acid; isoquercetrin; quercetin; 4,2',4'-trihydroxy-6'-methoxychalcone; gnaphalin; 3-O-methyl-quercetin; 3,5-dicaffeoyl-quinic acid and 4,5-dicaffeoyl-quinic acid). The in vivo anti-inflammatory properties of the HEAa (4, 20 and 100 mg/kg, per os) were evaluated using the following animal models: carrageenan-induced paw edema in rats, carrageenan-induced vascular permeability and peritonitis in mice and an acetic acid-induced writhing model to test antihyperalgesic activity in mice. In vitro assays were performed to study the effects of the HEAa (0.16, 0.8 and 4 mg/ml) on the cell viability, cell spreading and production of NO and H2O2 in stimulated macrophages. The A. alata extract inhibited the development of edema and vascular permeability, reduced polymorphonuclear cell recruitment in the acute peritonitis assay and decreased the amount of writhing induced by acetic acid. The HEAa did not increase NO/H2O2 production, while it did inhibit production when the macrophages were stimulated by LPS or PMA at all tested concentrations. In the presence of HEAa, macrophage spreading did not increase even after stimulation with LPS. Additionally, the HEAa was nontoxic to macrophages at all tested concentrations. The HEAa displayed anti-inflammatory and antihyperalgesic effects, which supports the use of this plant in folk medicine. These effects might be due to the flavonoids and phenylpropanoids derivatives present in the HEAa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Bioassay-guided evaluation of anti-inflammatory and antinociceptive activities of pistachio, Pistacia vera L.

PubMed

Orhan, I; Küpeli, E; Aslan, M; Kartal, M; Yesilada, E

2006-04-21

The ethanolic and aqueous extracts prepared from different parts of Pistacia vera L. (Anacardiaceae) as well as its oleoresin were evaluated for their in vivo anti-inflammatory and antinociceptive activities. Among the extracts screened, only the oleoresin was shown to possess a marked anti-inflammatory activity against carrageenan-induced hind paw edema model in mice without inducing any gastric damage at both 250 and 500 mg/kg doses whereas the rest of the extracts were totally inactive. While the oleoresin was found to display significant antinociceptive activity at 500 mg/kg dose, the ethanolic and aqueous extracts belonging to fruit, leaf, branch and peduncle of Pistacia vera did not exhibit any noticeable antinociception in p-benzoquinone-induced abdominal contractions in mice. Fractionation of the oleoresin indicated the n-hexane fraction to be active, which further led to recognition of some monoterpenes, mainly alpha-pinene (77.5%) by capillary gas chromatography-mass spectrometry (GC-MS) as well as the oleoresin itself. alpha-Pinene was also assessed for its antinociceptive and anti-inflammatory activities in the same manner and exerted a moderate anti-inflammatory effect at 500 mg/kg dose.

Subacute arsenic exposure through drinking water reduces the pharmacodynamic effects of ketoprofen in male rats.

PubMed

Ahmad, Wasif; Prawez, Shahid; Chanderashekara, H H; Tandan, Surendra Kumar; Sankar, Palanisamy; Sarkar, Souvendra Nath

2012-03-01

We evaluated the modulatory role of the groundwater contaminant arsenic on the pharmacodynamic responses of the nonsteroidal analgesic-antipyretic drug ketoprofen and the major pro-inflammatory mediators linked to the mechanism of ketoprofen's therapeutic effects. Rats were pre-exposed to sodium arsenite (0.4, 4 and 40 ppm) through drinking water for 28 days. The pharmacological effects of orally administered ketoprofen (5 mg/kg) were evaluated the following day. Pain, inflammation and pyretic responses were, respectively, assessed through formalin-induced nociception, carrageenan-induced inflammation and lipopolysaccharide-induced pyrexia. Arsenic inhibited ketoprofen's analgesic, anti-inflammatory and antipyretic effects. Further, arsenic enhanced cyclooxygenase-1 and cyclooxygenase-2 activities and tumor necrosis factor-α, interleukin-1β and prostaglandin-E(2) production in hind paw muscle. These results suggest a functional antagonism of ketoprofen by arsenic. This may relate to arsenic-mediated local release of tumor necrosis factor-α and interleukin-1β, which causes cyclooxygenase induction and consequent prostaglandin-E(2) release. In conclusion, subacute exposure to environmentally relevant concentrations of arsenic through drinking water may aggravate pain, inflammation and pyrexia and thereby, may reduce the therapeutic efficacy of ketoprofen. Copyright © 2011 Elsevier B.V. All rights reserved.

Evaluation of Antioxidant, Anti-cholinesterase, and Anti-inflammatory Effects of Culinary Mushroom Pleurotus pulmonarius.

PubMed

Nguyen, Trung Kien; Im, Kyung Hoan; Choi, Jaehyuk; Shin, Pyung Gyun; Lee, Tae Soo

2016-12-01

Culinary mushroom Pleurotus pulmonarius has been popular in Asian countries. In this study, the anti-oxidant, cholinesterase, and inflammation inhibitory activities of methanol extract (ME) of fruiting bodies of P. pulmonarius were evaluted. The 1,1-diphenyl-2-picryl-hydrazy free radical scavenging activity of ME at 2.0 mg/mL was comparable to that of butylated hydroxytoluene, the standard reference. The ME exhibited significantly higher hydroxyl radical scavenging activity than butylated hydroxytoluene. ME showed slightly lower but moderate inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase than galantamine, a standard AChE inhibitor. It also exhibited protective effect against cytotoxicity to PC-12 cells induced by glutamate (10~100 µg/mL), inhibitory effect on nitric oxide (NO) production and inducible nitric oxide synthase protein expression in lipopolysaccharide-stimulated RAW 264.7 macrophages, and carrageenan-induced paw edema in a rat model. High-performance liquid chromatography analysis revealed the ME of P. pulmonarius contained at least 10 phenolic compounds and some of them were identified by the comparison with known standard phenolics. Taken together, our results demonstrate that fruiting bodies of P. pulmonarius possess antioxidant, anti-cholinesterase, and inflammation inhibitory activities.

Evaluation of Antioxidant, Anti-cholinesterase, and Anti-inflammatory Effects of Culinary Mushroom Pleurotus pulmonarius

PubMed Central

Nguyen, Trung Kien; Im, Kyung Hoan; Choi, Jaehyuk; Shin, Pyung Gyun

2016-01-01

Culinary mushroom Pleurotus pulmonarius has been popular in Asian countries. In this study, the anti-oxidant, cholinesterase, and inflammation inhibitory activities of methanol extract (ME) of fruiting bodies of P. pulmonarius were evaluted. The 1,1-diphenyl-2-picryl-hydrazy free radical scavenging activity of ME at 2.0 mg/mL was comparable to that of butylated hydroxytoluene, the standard reference. The ME exhibited significantly higher hydroxyl radical scavenging activity than butylated hydroxytoluene. ME showed slightly lower but moderate inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase than galantamine, a standard AChE inhibitor. It also exhibited protective effect against cytotoxicity to PC-12 cells induced by glutamate (10~100 µg/mL), inhibitory effect on nitric oxide (NO) production and inducible nitric oxide synthase protein expression in lipopolysaccharide-stimulated RAW 264.7 macrophages, and carrageenan-induced paw edema in a rat model. High-performance liquid chromatography analysis revealed the ME of P. pulmonarius contained at least 10 phenolic compounds and some of them were identified by the comparison with known standard phenolics. Taken together, our results demonstrate that fruiting bodies of P. pulmonarius possess antioxidant, anti-cholinesterase, and inflammation inhibitory activities. PMID:28154487

Diethylcarbamazine Attenuates the Development of Carrageenan-Induced Lung Injury in Mice

PubMed Central

Ribeiro, Edlene Lima; Barbosa, Karla Patricia de Souza; Fragoso, Ingrid Tavares; Donato, Mariana Aragão Matos; Oliveira dos Santos Gomes, Fabiana; da Silva, Bruna Santos; Silva, Amanda Karolina Soares e; Rocha, Sura Wanessa Santos; Amaro da Silva Junior, Valdemiro; Peixoto, Christina Alves

2014-01-01

Diethylcarbamazine (DEC) is an antifilarial drug with potent anti-inflammatory properties as a result of its interference with the metabolism of arachidonic acid. The aim of the present study was to evaluate the anti-inflammatory activity of DEC in a mouse model of acute inflammation (carrageenan-induced pleurisy). The injection of carrageenan into the pleural cavity induced the accumulation of fluid containing a large number of polymorphonuclear cells (PMNs) as well as infiltration of PMNs in lung tissues and increased production of nitrite and tumor necrosis factor-α and increased expression of interleukin-1β, cyclooxygenase (COX-2), and inducible nitric oxide synthase. Carrageenan also induced the expression of nuclear factor-κB. The oral administration of DEC (50 mg/Kg) three days prior to the carrageenan challenge led to a significant reduction in all inflammation markers. The present findings demonstrate that DEC is a potential drug for the treatment of acute lung inflammation. PMID:24550603

Hyperforin, an Anti-Inflammatory Constituent from St. John's Wort, Inhibits Microsomal Prostaglandin E2 Synthase-1 and Suppresses Prostaglandin E2 Formation in vivo

PubMed Central

Koeberle, Andreas; Rossi, Antonietta; Bauer, Julia; Dehm, Friederike; Verotta, Luisella; Northoff, Hinnak; Sautebin, Lidia; Werz, Oliver

2010-01-01

The acylphloroglucinol hyperforin (Hyp) from St. John's wort possesses anti-inflammatory and anti-carcinogenic properties which were ascribed among others to the inhibition of 5-lipoxygenase. Here, we investigated whether Hyp also interferes with prostanoid generation in biological systems, particularly with key enzymes participating in prostaglandin (PG)E2 biosynthesis, i.e., cyclooxygenases (COX)-1/2 and microsomal PGE2 synthase (mPGES)-1 which play key roles in inflammation and tumorigenesis. Similar to the mPGES-1 inhibitors MK-886 and MD-52, Hyp significantly suppressed PGE2 formation in whole blood assays starting at 0.03–1 μM, whereas the concomitant generation of COX-derived 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid, thromboxane B2, and 6-keto PGF1α was not significantly suppressed up to 30 μM. In cell-free assays, Hyp efficiently blocked the conversion of PGH2 to PGE2 mediated by mPGES-1 (IC50 = 1 μM), and isolated COX enzymes were not (COX-2) or hardly (COX-1) suppressed. Intraperitoneal (i.p.) administration of Hyp (4 mg kg−1) to rats impaired exudate volume and leukocyte numbers in carrageenan-induced pleurisy associated with reduced PGE2 levels, and Hyp (given i.p.) inhibited carrageenan-induced mouse paw edema formation (ED50 = 1 mg kg−1) being superior over indomethacin (ED50 = 5 mg kg−1). We conclude that the suppression of PGE2 biosynthesis in vitro and in vivo by acting on mPGES-1 critically contributes to the anti-inflammatory efficiency of Hyp. PMID:21687502

Anti-inflammatory evaluation and characterization of leaf extract of Ananas comosus.

PubMed

Kargutkar, Samira; Brijesh, S

2018-04-01

Ananas comosus (L.) Merr (Pineapple) is a tropical plant with an edible fruit. In the present study, the potential anti-inflammatory activity of A. comosus leaf extract (ALE) was studied. ALE prepared using soxhlet apparatus was subjected to preliminary qualitative phytochemical analysis and quantitative estimations of flavonoids and tannins. The components present in ALE were identified using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Inhibitory effects of ALE on protein denaturation, and proteinase activity were assessed. Its effect on secretion of pro-inflammatory cytokines and inflammatory mediators by lipopolysaccharide-stimulated macrophages was also analyzed. Further, its anti-inflammatory activity in carrageenan-induced inflammatory rat model was examined. The preliminary qualitative phytochemical analysis revealed presence of flavonoids, phenols, tannins, carbohydrates, glycosides, and proteins in the extract. Total flavonoids and total tannins were 0.17 ± 0.006 mg equivalent of quercetin/g of ALE and 4.04 ± 0.56 mg equivalent of gallic acid/g of ALE. LC-MS analysis identified the presence of 4-hydroxy pelargonic acid, 3,4,5-trimethoxycinnamic and 4-methoxycinnamic acid, whereas GC-MS analysis identified the presence of campesterol and ethyl isoallocholate that have been previously reported for anti-inflammatory activity. ALE showed significant inhibition of protein denaturation and proteinase activity and also controlled secretion of tumour necrosis factor-α, interleukin-1β and prostaglandins, as well as the generation of reactive oxygen species by activated macrophages. ALE also significantly decreased carrageenan-induced acute paw edema. The study, therefore, identified the components present in ALE that may be responsible for its anti-inflammatory activity and thus demonstrated its potential use against acute inflammatory diseases.

Some Novel Mannich Bases of 5-(3,4-Dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one and Their Anti-Inflammatory Activity.

PubMed

Koksal, Meric; Ozkan-Dagliyan, Irem; Ozyazici, Tugce; Kadioglu, Beril; Sipahi, Hande; Bozkurt, Ayhan; Bilge, Suleyman S

2017-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for the treatment of rheumatic arthritis, pain, and many different types of inflammatory disorders, cause serious gastrointestinal (GI) side effects. The free carboxylic acid group existing on their chemical structure is correlated with GI toxicity related with all routine NSAIDs. Replacing this functional group with the 1,3,4-oxadiazole bioisostere is a generally used strategy to obtain an anti-inflammatory agent devoid of GI side effects. In the present work, a novel group of 5-(3,4-dichlorophenyl)-1,3,4-oxadiazole-2(3H)-one Mannich bases were synthesized and characterized on the basis of IR, 1 H NMR, and elemental analysis results. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for anti-inflammatory screening. Anti-inflammatory effects of the compounds were evaluated by in vitro lipopolysaccharide (LPS)-induced NO production and in vivo carrageenan footpad edema with ulcerogenic profile. In LPS-induced RAW 264.7 macrophages, most of the compounds showed inhibitory activity on nitrite production while compounds 5a, 5h, and 5j exhibited the best profiles by suppressing the NO production. To evaluate the in vivo anti-inflammatory potency of the compounds, the inflammatory response was quantified by increment in paw size in the carrageenan footpad edema assay. The anti-inflammatory data scoring showed that compounds 5a-d, 5g, and 5j, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5g was comparable to that of the reference drug indomethacin with 53.9% and 55.5% inhibition in 60 and 120 min, respectively. © 2017 Deutsche Pharmazeutische Gesellschaft.

Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain.

PubMed

Drinovac Vlah, V; Bach-Rojecky, L; Lacković, Z

2016-12-01

"Mirror pain" or mirror-image pain (MP) is pain opposite to the side of injury. Mechanism and frequency in humans are not known. There is no consent on therapy. Here we report that unilaterally injected botulinum toxin type A (BT-A) has bilateral effect in experimental MP, thus deserves to be investigated as therapy for this condition. We examined the localization of BT-A's bilateral antinociceptive action in MP induced by 3 % carrageenan intramuscular injection in Wistar rats. BT-A was applied peripherally (5 U/kg), into ipsilateral or contralateral hind paw pad (i.pl.) and centrally (1 U/kg), at spinal (intrathecally, i.t.) or supraspinal (intracisternally, i.c.) level. Additionally, we examined the involvement of central opioid and GABAergic systems, as well as the contribution of peripheral capsaicin-sensitive neurons to BT-A's bilateral antinociceptive effect. Ipsilateral i.pl. and i.t. BT-A reduced the bilateral mechanical sensitivity to von Frey filaments, while contralateral i.pl. and i.c. treatments had no effect on either tested side. Bilateral antinociceptive effect of ipsilateral i.pl. BT-A was prevented by μ-opioid antagonist naloxonazine (1.5 μg/10 μl) and GABA A antagonist bicuculline (1 μg/10 μl) if applied at the spinal level, in contrast to supraspinal application of the same doses. Local treatment of sciatic nerve with 2 % capsaicin 5 days following BT-A i.pl. injection caused desensitization of sciatic capsaicin-sensitive fibers, but did not affect bilateral antinociceptive effect of BT-A and the presence of cleaved SNAP-25 at the spinal cord slices. Present experiments suggest segmental actions of peripheral BT-A at spinal level, which are probably not solely dependent on capsaicin-sensitive neurons.

Inhibitory effects of aspirin-triggered resolvin D1 on spinal nociceptive processing in rat pain models.

PubMed

Meesawatsom, Pongsatorn; Burston, James; Hathway, Gareth; Bennett, Andrew; Chapman, Victoria

2016-09-02

Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects. Pain behaviour was assessed in rats with established carrageenan-induced inflammatory or monosodium iodoacetate (MIA)-induced OA pain, and changes in spinal gene expression of resolvin receptors and relevant enzymatic pathways were examined. At timepoints of established pain behaviour, responses of deep dorsal horn wide dynamic range (WDR) neurones to transcutaneous electrical stimulation of the hind paw were recorded pre- and post direct spinal administration of AT-RvD1 (15 and 150 ng/50 μl). AT-RvD1 (15 ng/50 μl) significantly inhibited WDR neurone responses to electrical stimuli at C- (29 % inhibition) and Aδ-fibre (27 % inhibition) intensities. Both wind-up (53 %) and post-discharge (46 %) responses of WDR neurones in carrageenan-treated animals were significantly inhibited by AT-RvD1, compared to pre-drug response (p < 0.05). These effects were abolished by spinal pre-administration of a formyl peptide receptor 2 (FPR2/ALX) antagonist, butoxy carbonyl-Phe-Leu-Phe-Leu-Phe (BOC-2) (50 μg/50 μl). AT-RvD1 did not alter evoked WDR neurone responses in non-inflamed or MIA-treated rats. Electrophysiological effects in carrageenan-inflamed rats were accompanied by a significant increase in messenger RNA (mRNA) for chemerin (ChemR23) receptor and 5-lipoxygenase-activating protein (FLAP) and a decrease in 15-lipoxygenase (15-LOX) mRNA in the ipsilateral spinal cord of the carrageenan group, compared to controls. Our data suggest that peripheral inflammation-mediated changes in spinal FLAP expression may contribute to the novel inhibitory effects of spinal AT-RvD1 on WDR neuronal excitability, which are mediated by FPR2/ALX receptors. Inflammatory-driven changes in this pathway may offer novel targets for inflammatory pain treatment.

Oxazolo[4,5-b]pyridine-Based Piperazinamides as GSK-3β Inhibitors with Potential for Attenuating Inflammation and Suppression of Pro-Inflammatory Mediators.

PubMed

Tantray, Mushtaq A; Khan, Imran; Hamid, Hinna; Alam, Mohammad Sarwar; Dhulap, Abhijeet; Ganai, Ajaz Ahmad

2017-08-01

Recent studies reveal that glycogen synthase kinase-3β (GSK-3β) acts as a pro-inflammatory enzyme, and by inhibiting this kinase, inflammation can be controlled. In this regard, a series of 17 piperazine-linked oxazolo[4,5-b]pyridine-based derivatives was synthesized and evaluated for in vitro GSK-3β inhibitory and in vivo anti-inflammatory activity. The compounds 7d, 7e, 7g, and 7c displayed the best GSK-3β inhibitory activity among all the synthesized compounds, with corresponding IC 50 values of 0.34, 0.39, 0.47, and 0.53 µM. Among the compounds 7d, 7e, 7g, and 7c examined for in vivo anti-inflammatory activity in the rat paw edema model, compound 7d exhibited maximum inhibition, reducing the paw volume by 62.79 and 65.91% at 3 and 5 h post-carrageenan administration, respectively, in comparison to indomethacin (76.74% at 3 h and 79.54% at 5 h after carrageenan administration). Furthermore, these compounds (7d, 7e, 7g, and 7c) were also found to substantially inhibit pro-inflammatory mediators, i.e., TNF-α, IL-1β, and IL-6, ex vivo in comparison to indomethacin and did not pose any gastric ulceration risk, indicating the potential of this oxazolopyridine scaffold for the development of GSK-3β inhibitors and their application as anti-inflammatory agents. © 2017 Deutsche Pharmazeutische Gesellschaft.

Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat

PubMed Central

Asante, Curtis O.; Dickenson, Anthony H.

2010-01-01

We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. We also investigated the effects of spinally administered cell cycle inhibitor (CCI)-779 (a rapamycin ester analogue) on deep dorsal horn neurons from rats with carrageenan-induced inflammation of the hind paw. Unlike some other models of persistent pain, this model does not involve an altered 5-HT3R-mediated descending serotonergic drive. We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states. PMID:20709148

PHYTOCHEMICAL SCREENING, ANTI-INFLAMMATORY AND ANALGESIC PROPERTIES OF PENTANISIA PRUNELLOIDES FROM THE EASTERN CAPE PROVINCE, SOUTH AFRICA.

PubMed

Mathews, Miya Gugulethu; Ajayi, Oyemitan Idris; Opeoluwa, Oyedeji Oyehan; Oluwatobi, Oluwafemi Samuel; Benedicta N, Nkeh-Chungag; Phindile, Songca Sandile; Oyedeji; Omowumi, Adebola

2016-01-01

Pentanisia prunelloides is a medicinal plant widely used to remedy various ailments including infections, fever and rheumatism in Eastern Cape Province of South Africa. There is scanty report on the phytochemical and biological properties of the plant; hence various solvent extracts of the dried plant materials were phytochemically screened, and its aqueous extract evaluated for acute toxicity effect, analgesic and antiinflammatory properties in rodents. Different extracts of both leaf and rhizome were obtained separately with ethanol, methanol and water. Portions of the filtrate were used for qualitative screening of secondary metabolites and remaining portions were concentrated and dried. Dried grounded leaf and rhizome of the plant were also used for quantitative screening for some major components. The aqueous extract of the leaf and rhizome were used for acute toxicity (LD 50 ) test, antiinflammatory and analgesic activities in rodents. The qualitative phytochemical screening showed the presence of several phytoconstituents with saponins, flavonoids and alkaloids constituting highest constituents in the leaf and rhizome. The LD50: of the aqueous extracts (from leaf or rhizome) was found to be ≥5000 mg/kg orally. The leaf and rhizome aqueous extract (250-500 mg/kg) significantly (p<0.01) reduced egg albumin-induced paw oedema and paw licking in mice induced by formalin, signifying antinociceptive and antiinflammatory activities respectively. It is concluded that the leaf and rhizome of P. prunelloides are rich in various phytochemicals which could be associated with their medicinal uses. The aqueous leaf and rhizome extracts are similarly non-toxic orally, showed antiinflammatory and analgesic potentials thus rationalizing its use in folkloric medicine.

Insulin-induced oedema in a patient with diabetes mellitus complicated by ketoacidosis.

PubMed

Onyiriuka, Alphonsus N; Ehirim, Frances A

2014-10-01

In this article we reported a recent case of a 15-year-old grossly underweight (29 kg) Nigerian girl diagnosed of type 1 diabetes mellitus four years ago and who defaulted from follow up but presented with diabetic ketoacidosis. Glycaemic control was poor because of poor compliance. On the 5th day on admission, a non tender pitting oedema without skin discolouration developed over the ankles. The natural history of insulin-induced oedema was observed in this patient since the oedema resolved seven days later without any specific therapy, such as administration of diuretics. The major causes of generalized oedema in childhood and adolescence, such as kwashiorkor, nephrotic syndrome, liver cirrhosis, congestive heart failure and acute glumerulonephritis were excluded by findings from the history, physical examination and relevant laboratory investigations. Having excluded these major causes of oedema, the obvious conclusion was that the insulin therapy was the cause of the oedema observed in our patient. The aim of this article is to review existing medical literature on the subject of insulin-induced oedema and raise the awareness of clinicians on the subject. In conclusion, insulin-induced oedema should be considered in the differential diagnosis of oedema in children and adolescents with type 1 diabetes mellitus complicated by ketoacidosis, particularly if they are underweight.

Anti-inflammatory activity of Shirishavaleha: An Ayurvedic compound formulation

PubMed Central

Yadav, Shyamlal Singh; Galib; Ravishankar, B.; Prajapati, P.K.; Ashok, B.K.; Varun, B.

2010-01-01

The purpose of the present study was to evaluate the anti-inflammatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth.), viz. the bark (Twak) and the heartwood (Sara). The activity was screened in the carrageenan-induced rat paw edema model in albino rats. The raw materials were collected and authenticated in the university and the trial formulations were prepared by following standard classical guidelines. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 1.8 g/kg for 5 days. Phenylbutazone was used as the standard anti-inflammatory drug for comparison. Between the two different test samples studied, the formulation made from heartwood showed a weak anti-inflammatory activity in this model while that made from the bark produced a considerable suppression of edema after 6 h. It appears that the bark sample would be preferable for clinical use. PMID:21455445

Evaluation of Anti-Inflammatory Activity and In-vitro Antioxidant Activity of Indian Mistletoe, the Hemiparasite Dendrophthoe falcate L. F. (Loranthaceae)

PubMed Central

Patil, Satish; Anarthe, Sneha; Jadhav, Ram; Surana, Sanjay

2011-01-01

Methanolic and aqueous extracts of Dendrophthoe falcata Linn. leaves which belongs to the Loranthaceae family, were evaluated through DPPH (1, 1-diphenyl -2-picryl-hydrazyl), antilipid peroxidation and nitric oxide scavenging methods to assess the antioxidant activity. Methanolic and aqueous extracts of Dendrophthoe falcata leaves were also evaluated for their anti-inflammatory activity by carrageenan and cotton pellet induced granuloma tests for their effect on the acute and chronic phase inflammation models in rats. It was found that the methanolic extract of Dendrophthoe falcata leaves demonstrates potent antioxidant activity as compared to aqueous extraction of Dendrophthoe falcata leaves for DPPH (1, 1-diphenyl-2-picryl-hydrazyl) radical scavenging, anti-lipid peroxidation and nitric oxide scavenging activity respectively (having IC50 value 77.8, 79.36 and 86.2, 144, 87, 104). The maximum inhibition for aqueous extract of Dendrophthoe falcata leaves (30.95%) and methanolic extract of Dendrophthoe falcata leaves (23.41%) were obtained at a dose of 300 mg/Kg after 4h of drug treatment in carrageenan induced paw edema, whereas diclofenac sodium (standard drug) produced 42.85% inhibition. In the chronic model (cotton pellet induced granuloma), aqueous extracts of Dendrophthoe falcata leaves and methanolic extracts of Dendrophthoe falcata leaves (at doses of 300 mg/Kg), phenylbutazone as standard drug showed decreased formation of granuloma tissue by 51%, 48%, 53% respectively. In addition, the total phenolic and flavonoid content of aqueous extracts of Dendrophthoe falcata leaves and methanolic extracts of Dendrophthoe falcata leaves were found to be 2.12 % w/w, 4.39 % w/w, 0.31 mg/g and 0.85 mg/g respectively. Thus the results indicate that methanolic and aqueous extracts of Dendrophthoe falcataleaves on animal models have potent anti-inflammatory and in-vitro antioxidant effects. PMID:24250351

Local administration of mangiferin prevents experimental inflammatory mechanical hyperalgesia through CINC-1/epinephrine/PKA pathway and TNF-α inhibition.

PubMed

Rocha, Lilian Wünsch; Bonet, Ivan José Magayewski; Tambeli, Claudia Herrera; de-Faria, Felipe Meira; Parada, Carlos Amilcar

2018-07-05

Steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to control inflammatory pain, but there is a risk of gastrointestinal bleeding and increased heart failure risk. The search for new drugs remains ongoing, and natural products are a source for potential new compounds. Mangiferin, a natural xanthone C-glucoside, has demonstrated biological activity, including anti-inflammatory and analgesic properties, but it's mechanisms are poorly understood. In this study, we investigated the mechanisms underlying the anti-inflammatory and analgesic effects of local administration of mangiferin. We employed an electronic von Frey apparatus to evaluate mechanical hyperalgesia induced by carrageenan in rats. Mangiferin (150-1200 µg/paw), administered locally into the hindpaw, prevented hyperalgesia in a dose-dependent - 150 µg (- 9%), 300 µg (- 27%, P < 0.01), 600 µg (- 77%, P < 0.001) and 1000 µg (- 93%, P < 0.001) - and local manner. Mangiferin showed decreased levels of TNF-α (P < 0.001) and CINC-1 (P < 0.001), but not IL-1β; it also prevented neutrophil migration (P < 0.01), but not the increased COX-2 expression in peripheral tissue challenged with carrageenan. To further explore the mechanisms of mangiferin actions, rats were injected with modulators of inflammation and nociception; mangiferin prevented hyperalgesia induced by IL-1β (P < 0.01), CINC-1 (P < 0.01), epinephrine (P < 0.01), 8-Br-cAMP (P < 0.01) or capsaicin (P < 0.01), but not that induced by PGE 2 or α,β-MeATP. Our study shows that mangiferin has anti-inflammatory and analgesic properties when locally administrated. The control of the inflammatory response and mechanical hyperalgesia by mangiferin depends on the inhibition of TNF-α production/release and the CINC1/epinephrine/PKA pathway, supporting its marked inhibition of inflammatory mechanical hyperalgesia. Copyright © 2018 Elsevier B.V. All rights reserved.

Nickel(II) Complex of Polyhydroxybenzaldehyde N4-Thiosemicarbazone Exhibits Anti-Inflammatory Activity by Inhibiting NF-κB Transactivation

PubMed Central

Loh, Sheng Wei; Looi, Chung Yeng; Hassandarvish, Pouya; Phan, Alicia Yi Ling; Wong, Won Fen; Wang, Hao; Paterson, Ian C.; Ea, Chee Kwee; Mustafa, Mohd Rais; Maah, Mohd Jamil

2014-01-01

Background The biological properties of thiosemicarbazone have been widely reported. The incorporation of some transition metals such as Fe, Ni and Cu to thiosemicarbazone complexes is known to enhance its biological effects. In this study, we incorporated nickel(II) ions into thiosemicarbazone with N4-substitution groups H3L (H; H3L1, CH3; H3L2, C6H5; H3L3 and C2H5; H3L4) and examined its potential anti-inflammatory activity. Methodology/Principal Findings Four ligands (1–4) and their respective nickel-containing complexes (5–8) were synthesized and characterized. The compounds synthesized were tested for their effects on NF-κB nuclear translocation, pro-inflammatory cytokines secretion and NF-κB transactivation activity. The active compound was further evaluated on its ability to suppress carrageenan-induced acute inflammation in vivo. A potential binding target of the active compound was also predicted by molecular docking analysis. Conclusions/Significance Among all synthesized compounds tested, we found that complex [Ni(H2L1)(PPh3)]Cl (5) (complex 5), potently inhibited IκBα degradation and NF-κB p65 nuclear translocation in LPS-stimulated RAW264.7 cells as well as TNFα-stimulated HeLa S3 cells. In addition, complex 5 significantly down-regulated LPS- or TNFα-induced transcription of NF-κB target genes, including genes that encode the pro-inflammatory cytokines TNFα, IFNβ and IL6. Luciferase reporter assays confirmed that complex 5 inhibited the transactivation activity of NF-κB. Furthermore, the anti-inflammatory effect of complex 5 was also supported by its suppressive effect on carrageenan-induced paw edema formation in wild type C57BL/6 mice. Interestingly, molecular docking study showed that complex 5 potentially interact with the active site of IKKβ. Taken together, we suggest complex 5 as a novel NF-κB inhibitor with potent anti-inflammatory effects. PMID:24977407

Polymethoxyflavones from Nicotiana plumbaginifolia (Solanaceae) Exert Antinociceptive and Neuropharmacological Effects in Mice

PubMed Central

Shajib, Md. Shafiullah; Rashid, Ridwan B.; Ming, Long C.; Islam, Shanta; Sarker, Md. Moklesur R.; Nahar, Lutfun; Sarker, Satyajit D.; Datta, Bidyut K.; Rashid, Mohammad A.

2018-01-01

Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties. Nicotiana plumbaginifolia, an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3′,5,6,7,8-hexamethoxy-4′,5′-methylenedioxyflavone (1), 3,3′,4′,5′,5,6,7,8-octamethoxyflavone (exoticin) (2), 6,7,4′,5′-dimethylenedioxy-3,5,3′-trimethoxyflavone (3), and 3,3′,4′,5,5′,8-hexamethoxy-6,7-methylenedioxyflavone (4), isolated and identified from N. plumbaginifolia. Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds 1, 3, and 4 (12.5–25 mg/kg b.w.) exhibited dose-dependent and significant (p < 0.01) antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate)-induced pain models. The association of ATP-sensitive K+ channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound 1, 3, and 4 (12.5 mg/kg b.w.) demonstrated significant (p < 0.05) anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABAA receptor in the action of compound 3 and 4 was evident from the reversal effects of flumazenil. In addition, compounds 1 and 4 (12.5–25 mg/kg b.w) exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones (1–4) from N. Plumbaginifolia could be considered as suitable candidates for the development of analgesic and anxiolytic agents. PMID:29515437

Polymethoxyflavones from Nicotiana plumbaginifolia (Solanaceae) Exert Antinociceptive and Neuropharmacological Effects in Mice.

PubMed

Shajib, Md Shafiullah; Rashid, Ridwan B; Ming, Long C; Islam, Shanta; Sarker, Md Moklesur R; Nahar, Lutfun; Sarker, Satyajit D; Datta, Bidyut K; Rashid, Mohammad A

2018-01-01

Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties. Nicotiana plumbaginifolia , an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3',5,6,7,8-hexamethoxy-4',5'-methylenedioxyflavone ( 1 ), 3,3',4',5',5,6,7,8-octamethoxyflavone (exoticin) ( 2 ), 6,7,4',5'-dimethylenedioxy-3,5,3'-trimethoxyflavone ( 3 ), and 3,3',4',5,5',8-hexamethoxy-6,7-methylenedioxyflavone ( 4 ), isolated and identified from N. plumbaginifolia . Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds 1 , 3 , and 4 (12.5-25 mg/kg b.w.) exhibited dose-dependent and significant ( p < 0.01) antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate)-induced pain models. The association of ATP-sensitive K + channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound 1 , 3 , and 4 (12.5 mg/kg b.w.) demonstrated significant ( p < 0.05) anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABA A receptor in the action of compound 3 and 4 was evident from the reversal effects of flumazenil. In addition, compounds 1 and 4 (12.5-25 mg/kg b.w) exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones ( 1-4 ) from N. Plumbaginifolia could be considered as suitable candidates for the development of analgesic and anxiolytic agents.

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats

PubMed Central

2013-01-01

Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund’s Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Methods Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. Results CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. Conclusions TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway. PMID:23768044

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

PubMed

Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

2013-06-15

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1/2 and COX-2, and over-production of PGE2 induced by CFA, were suppressed by TENS administration. TENS may be an effective therapy in controlling inflammatory pain induced by CFA. Its analgesic effect may be associated with the inhibition of activation of the spinal ERK1/2-COX-2 pathway.

Rat models of acute inflammation: a randomized controlled study on the effects of homeopathic remedies

PubMed Central

Conforti, Anita; Bellavite, Paolo; Bertani, Simone; Chiarotti, Flavia; Menniti-Ippolito, Francesca; Raschetti, Roberto

2007-01-01

Background One of the cardinal principles of homeopathy is the "law of similarities", according to which patients can be treated by administering substances which, when tested in healthy subjects, cause symptoms that are similar to those presented by the patients themselves. Over the last few years, there has been an increase in the number of pre-clinical (in vitro and animal) studies aimed at evaluating the pharmacological activity or efficacy of some homeopathic remedies under potentially reproducible conditions. However, in addition to some contradictory results, these studies have also highlighted a series of methodological difficulties. The present study was designed to explore the possibility to test in a controlled way the effects of homeopathic remedies on two known experimental models of acute inflammation in the rat. To this aim, the study considered six different remedies indicated by homeopathic practice for this type of symptom in two experimental edema models (carrageenan- and autologous blood-induced edema), using two treatment administration routes (sub-plantar injection and oral administration). Methods In a first phase, the different remedies were tested in the four experimental conditions, following a single-blind (measurement) procedure. In a second phase, some of the remedies (in the same and in different dilutions) were tested by oral administration in the carrageenan-induced edema, under double-blind (treatment administration and measurement) and fully randomized conditions. Seven-hundred-twenty male Sprague Dawley rats weighing 170–180 g were used. Six homeopathic remedies (Arnica montana D4, Apis mellifica D4, D30, Atropa belladonna D4, Hamamelis virginiana D4, Lachesis D6, D30, Phosphorus D6, D30), saline and indomethacin were tested. Edema was measured using a water-based plethysmometer, before and at different times after edema induction. Data were analyzed by ANOVA and Student t test. Results In the first phase of experiments, some statistically significant effects of homeopathic remedies (Apis, Lachesis and Phosporus) were observed (the reduction in paw volume increase ranging from 10% to 28% at different times since edema induction). In the second phase of experiments, the effects of homeopathic remedies were not confirmed. On the contrary, the unblinded standard allopathic drug indomethacin exhibited its anti-inflammatory effect in both experimental phases (the reduction in paw volume increase ranging from 14% to 40% in the first phase, and from 18% to 38% in the second phase of experiments). Conclusion The discrepancies between single-blind and double-blind methods in animal pharmacological research are noteworthy and should be better investigated, also in non-homeopathic research. PMID:17233886

Rat models of acute inflammation: a randomized controlled study on the effects of homeopathic remedies.

PubMed

Conforti, Anita; Bellavite, Paolo; Bertani, Simone; Chiarotti, Flavia; Menniti-Ippolito, Francesca; Raschetti, Roberto

2007-01-17

One of the cardinal principles of homeopathy is the "law of similarities", according to which patients can be treated by administering substances which, when tested in healthy subjects, cause symptoms that are similar to those presented by the patients themselves. Over the last few years, there has been an increase in the number of pre-clinical (in vitro and animal) studies aimed at evaluating the pharmacological activity or efficacy of some homeopathic remedies under potentially reproducible conditions. However, in addition to some contradictory results, these studies have also highlighted a series of methodological difficulties.The present study was designed to explore the possibility to test in a controlled way the effects of homeopathic remedies on two known experimental models of acute inflammation in the rat. To this aim, the study considered six different remedies indicated by homeopathic practice for this type of symptom in two experimental edema models (carrageenan- and autologous blood-induced edema), using two treatment administration routes (sub-plantar injection and oral administration). In a first phase, the different remedies were tested in the four experimental conditions, following a single-blind (measurement) procedure. In a second phase, some of the remedies (in the same and in different dilutions) were tested by oral administration in the carrageenan-induced edema, under double-blind (treatment administration and measurement) and fully randomized conditions. Seven-hundred-twenty male Sprague Dawley rats weighing 170-180 g were used. Six homeopathic remedies (Arnica montana D4, Apis mellifica D4, D30, Atropa belladonna D4, Hamamelis virginiana D4, Lachesis D6, D30, Phosphorus D6, D30), saline and indomethacin were tested. Edema was measured using a water-based plethysmometer, before and at different times after edema induction. Data were analyzed by ANOVA and Student t test. In the first phase of experiments, some statistically significant effects of homeopathic remedies (Apis, Lachesis and Phosporus) were observed (the reduction in paw volume increase ranging from 10% to 28% at different times since edema induction). In the second phase of experiments, the effects of homeopathic remedies were not confirmed. On the contrary, the unblinded standard allopathic drug indomethacin exhibited its anti-inflammatory effect in both experimental phases (the reduction in paw volume increase ranging from 14% to 40% in the first phase, and from 18% to 38% in the second phase of experiments). The discrepancies between single-blind and double-blind methods in animal pharmacological research are noteworthy and should be better investigated, also in non-homeopathic research.

Effect of carrageenans alone and in combination with casein or lipopolysaccharide on human epithelial intestinal HT-29 cells.

PubMed

Sokolova, E V; Kuz'mich, A S; Byankina, A O; Yermak, I M

2017-10-01

The research described here was focused on the effect on human intestinal epithelial cell monolayers of sulfated red algal polysaccharides (κ-, λ-, and κ/β-carrageenans) alone and in combination with casein or lipopolysaccharide (LPS). HT-29 cells were investigated under normal and stress conditions; stress was induced by exposure to ethanol. Cell viability was monitored with a real-time system. The change in binding properties of negatively sulfated red algal polysaccharides assessed by the measurement of free carrageenans in mixtures with casein or McCoy's 5 A culture medium by means of toluidine blue O. Low sulfate content and the presence of 3,6-anhydogalactose are prerequisites for the recovery of ethanol-exposed HT-29 cells by carrageenans. Analysis of carrageenan binding ability confirmed that casein and LPS should affect carrageenan activity. Whether the combined action of the mucin-containing layer and carrageenans or the action of carrageenans alone was responsible for enhanced cell viability under stress conditions induced by ethanol is a subject for further research. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2843-2850, 2017. © 2017 Wiley Periodicals, Inc.

Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System.

PubMed

Ferreira, Renata Cristina Mendes; Almeida-Santos, Ana Flávia; Duarte, Igor Dimitri Gama; Aguiar, Daniele C; Moreira, Fabricio A; Romero, Thiago Roberto Lima

2017-01-01

Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect. Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E 2 (PGE 2 , 2  μ g). Aripiprazole was injected 10 min before the measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and bestatin were given 30 min before aripiprazole. Nociceptive thresholds were measured in the 3rd hour after PGE 2 injection. Aripiprazole (100  μ g/paw) injected locally into the right hind paw induced an antinociceptive effect that was blocked by naloxone (50  μ g/paw), a nonselective opioid receptor antagonist. The role of μ -, δ -, and κ -opioid receptors was investigated using the selective antagonists, clocinnamox (40  μ g/paw), naltrindole (15, 30, and 60  μ g/paw), and nor-binaltorphimine (200  μ g/paw), respectively. The data indicated that only the δ -opioid receptor antagonist inhibited the peripheral antinociception induced by aripiprazole. Bestatin (400  μ g), an aminopeptidase-N inhibitor, significantly enhanced low-dose (25  μ g/paw) aripiprazole-induced peripheral antinociception. The results suggest the participation of the opioid system via δ -opioid receptor in the peripheral antinociceptive effect induced by aripiprazole.

Proniosomal formulation of curcumin having anti-inflammatory and anti-arthritic activity in different experimental animal models.

PubMed

Kumar, K; Rai, A K

2012-10-01

Curcumin, the active ingredient of the spice turmeric, has a long history as an herbal remedy for a variety of diseases. Transdermal drug delivery has been recognized as an alternative route to oral delivery. Proniosomes offer a versatile vesicle delivery concept with the potential for drug delivery via the transdermal route. In this study, different proniosomal gel bases were prepared by the ether injection method, using Span 60 and Span 80, Tween 20, cholesterol, and formulation PA2. They were characterized by scanning electron microscopy, revealing vesicular structures, and assessed for stability and effect on in vitro skin permeation using rat skin. Anti-inflammatory and anti-arthritic effects of formulation PA2 and PB1 were compared with a standard market product containing indomethacin. The effect of formulation PA2 and PB1 was evaluated for acute inflammation in carrageenan induced rat paw edema and for chronic inflammation in complete Freud's adjuvant (CFA) induced arthritis in rats. Further histopathological and radiographic evaluation was performed. The investigated curcumin loaded proniosomal formula proved to be non-irritant, non-toxic, but had lower anti-inflammatory and anti-arthritic effects than the marketed indomethacin products.

Antioxidant, Anti-Inflammatory, and Antitumor Activities of Cultured Mycelia and Fruiting Bodies of the Elm Oyster Mushroom, Hypsizygus ulmarius (Agaricomycetes).

PubMed

Greeshma, Panavalappil; Ravikumar, Korattuvalappil S; Neethu, Mangalathmelathil N; Pandey, Meera; Zuhara, Karattuthodi Fathimathu; Janardhanan, Kainoor K

2016-01-01

Ethanoic extracts from the fruiting bodies and mycelia of the elm oyster mushroom, Hypsizygus ulmarius, were evaluated for their antioxidant, anti-inflammatory, and antitumor properties. Ethnolic extracts of fruiting body and mycelia showed 88%, 85%, 71%, and 85%, 65%, 70% 2,2-diphenyl-1-picrylhydrazyl, hydroxyl (DPPH) and 2,2'-azinobis (3-ethyl benzothiazolin-6-sulfonic acid) (ABTS) radical-scavenging activities, respectively, at a concentration of 1000 µg/mL. The anti-inflammatory activity was determined using carrageenan- and formalin- induced paw edema models. Diclofenac was used as the standard drug. In both models, the mycelia extract showed higher activity than the fruiting body extract. The antitumor effect of the extracts against Dalton's Lymphoma Ascites cell-line-induced tumors showed significant antitumor activity. Mycochemical analysis confirmed the presence of many pharmacologically active compounds such as phenol, alkaloids, proteins, tannins, and polysaccharides. Among these, polysaccharides and phenolic compounds were present at a higher concentration in both extracts. These compounds might be largely responsible for the mushroom's medicinal properties. The results of this study indicate that H. ulmarius possesses significant antioxidant, anti-inflammatory, and antitumor properties.

Moringa oleifera, a species with potential analgesic and anti-inflammatory activities.

PubMed

Martínez-González, Claudia Lizbeth; Martínez, Laura; Martínez-Ortiz, Efraín J; González-Trujano, María Eva; Déciga-Campos, Myrna; Ventura-Martínez, Rosa; Díaz-Reval, Irene

2017-03-01

Moringa oleifera has long been used in large demand in folk medicine to treat pain. The present study was undertaken to examine the antinociceptive and anti-inflammatory spectrum of M. oleifera leaf extracts discriminating the constituents' nature by using different kind of experimental models in rats. Pharmacological evaluation of a non-polar and/or polar extracts at several doses (30-300mg/kg, p.o.) was explored through experimental nociception using formalin test, carrageenan-induced paw edema and arthritis with subcutaneous injection of collagen in rats. Basic morphology characterization was done by scanning electronic microscopy and laser scanning confocal microscopy. Not only polar (from 30 or 100mg/kg, p.o.) but also non-polar extract produced significant inhibition of the nociceptive behavior with major efficacy in the inflammatory response in different assessed experimental models. This antinociceptive activity involved constituents of different nature and depended on the intensity of the induced painful stimulus. Phytochemical analysis showed the presence of kaempferol-3-glucoside in the polar extract and fatty acids like chlorogenic acid, among others, in the non-polar extract. Data obtained with M. oleifera leaf extracts give evidence of its potential for pain treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Anti-inflammatory and analgesic activities of Tunisian Citrullus colocynthis Schrad. immature fruit and seed organic extracts.

PubMed

Marzouk, B; Marzouk, Z; Fenina, N; Bouraoui, A; Aouni, M

2011-06-01

Inflammations and immune-related diseases including rheumatoid arthritis are widespread in the entire globe. The treatment of these illnesses is mainly based on the use of synthetic and biotechnological drugs, in recent years. Tunisian traditional medicine is a potential source of new remedies namely Citrullus colocynthis Schrad. (Cucurbitaceae): endemic in southern Tunisia and used in folk medicine to treat many inflammation disorders. Our goal was to assess the in vivo analgesic and anti-inflammatory activities of Tunisian Citrullus colocynthis immature fruit and seed organic extracts (petroleum ether, chloroform, ethyl acetate, acetone and finely methanol extract). Yields of prepared organic extracts are gravimetrically determined. For the analgesic and anti-inflammatory activities, we have used respectively, the acetic acid writhing test in mice and the carrageenan-induced paw edema assay in rats. All extracts displayed an important analgesic and anti-inflammatory activities at different doses without inducing any side effects. This study has demonstrated the analgesic and anti-inflammatory activities of Citrullus colocynthis immature fruit and seed extracts. Experiment results provide scientific insight into the ancient practice of utilizing Citrullus colocynthis Schrad. as analgesic and as anti-inflammatory agents.

Multi-constituent synergism is responsible for anti-inflammatory effect of Azadirachta indica leaf extract.

PubMed

Umar, Muhammad Ihtisham; Asmawi, Mohd Zaini; Sadikun, Amirin; Abdul Majid, A M S; Atangwho, Item Justin; Khadeer Ahamed, Mohamed B; Altaf, Rabia; Ahmad, Ashfaq

2014-11-01

Azadirachta indica A. Juss. (Meliaceaes) leaves have been used traditionally to treat swelling and rheumatism in Indian cultures. To fractionate A. indica leaf extracts using bioactivity guided manner for identification of the active anti-inflammatory principles. Polarity-gradient sequential extracts (petroleum ether, chloroform, methanol, and water) of A. indica leaves were screened for their anti-inflammatory potential using the carrageenan-induced rat paw edema model (1 g/kg). The chloroform extract was sequentially fractionated to obtain n-hexane (F-1), n-hexane-chloroform (F-2), and chloroform (F-3) fractions and their inhibitory effect on rat paw edema was evaluated (500 mg/kg). Inhibitory effect of F-2 on granuloma formation, plasma interleukin (IL-1), and tumor necrosis factor (TNF-α) was assessed at the doses of 100, 200, and 400 mg/kg using the cotton pellet assay in rats. Three sub-fractions (SF-1, SF-2, and SF-3) were obtained upon chromatography of F-2, and their inhibitory effect on cyclooxygenase was assessed at 200 µg/mL concentration. The sub-fractions were subjected to gas chromatography-mass spectrometry (GC-MS). All the extracts showed significant anti-inflammatory effect; however, chloroform extract was the most effective against paw edema (53.25% inhibition). The three fractions of chloroform extract showed significant effect, while F-2 being the most potent (51.02%). F-2 demonstrated dose-dependent inhibition of granuloma and cytokines. Interestingly, all the sub-fractions of F-2 inhibited COX-1 and COX-2 with almost equal potential. GC-MS revealed that chemically the sub-fractions were totally different from each other. Anti-inflammatory effect of A. indica is a result of cumulative and synergistic effects of diversified constituents with varying polarities that collectively exert the effect via suppression of cyclo-oxygenases and cytokines (IL-1 and TNF-α).

Noradrenaline activates the NO/cGMP/ATP-sensitive K(+) channels pathway to induce peripheral antinociception in rats.

PubMed

Romero, Thiago R L; Guzzo, Luciana S; Perez, Andrea C; Klein, André; Duarte, Igor D G

2012-03-31

Despite the classical peripheral pronociceptive effect of noradrenaline (NA), recently studies showed the involvement of NA in antinociceptive effect under immune system interaction. In addition, the participation of the NO/cGMP/KATP pathway in the peripheral antinociception has been established by our group as the molecular mechanism of another adrenoceptor agonist xylazine. Thus the aim of this study was to obtain pharmacological evidences for the involvement of the NO/cGMP/KATP pathway in the peripheral antinociceptive effect induced by exogenous noradrenaline. The rat paw pressure test was used, with hyperalgesia induced by intraplantar injection of prostaglandin E(2) (2μg/paw). All drugs were locally administered into the right hind paw of male Wistar rats. NA (5, 20 and 80ng/paw) elicited a local inhibition of hyperalgesia. The non-selective NO synthase inhibitor l-NOarg (12, 18 and 24μg/paw) antagonized the antinociception effect induced by the highest dose of NA. The soluble guanylyl cyclase inhibitor ODQ (25, 50 and 100μg/paw) antagonized the NA-induced effect; and cGMP-phosphodiesterase inhibitor zaprinast (50μg/paw) potentiated the antinociceptive effect of NA low dose (5ng/paw). In addition, the local effect of NA was antagonized by a selective blocker of an ATP-sensitive K(+) channel, glibenclamide (20, 40 and 80μg/paw). On the other hand, the specifically voltage-dependent K(+) channel blocker, tetraethylammonium (30μg/paw), Ca(2+)-activated K(+) channel blockers of small and large conductance types dequalinium (50μg/paw) and paxilline (20μg/paw), respectively, were not able to block local antinociceptive effect of NA. The results provide evidences that NA probably induces peripheral antinociceptive effects by activation of the NO/cGMP/KATP pathway. Copyright © 2012 Elsevier Inc. All rights reserved.

TRPA1, NMDA receptors and nitric oxide mediate mechanical hyperalgesia induced by local injection of magnesium sulfate into the rat hind paw.

PubMed

Srebro, Dragana P; Vučković, Sonja M; Savić Vujović, Katarina R; Prostran, Milica Š

2015-02-01

Previous studies have shown that while magnesium, an antagonist of the glutamate subtype of N-methyl-D-aspartate receptors, possesses analgesic properties, it can induce writhing in rodents. The aim of this study was to determine the effect and mechanism of action of local (intraplantar) administration of magnesium sulfate (MS) on the paw withdrawal threshold (PWT) to mechanical stimuli. The PWT was evaluated by the electronic von Frey test in male Wistar rats. Tested drugs were either co-administered intraplantarly (i.pl.) with MS or given into the contralateral paw to exclude systemic effects. MS at doses of 0.5, 1.5, 3 and 6.2 mg/paw (i.pl.) induced a statistically significant (as compared to 0.9% NaCl) and dose-dependent mechanical hyperalgesia. Only isotonic MS (250 mmol/l or 6.2% or 6.2 mg/paw) induced mechanical hyperalgesia that lasted at least six hours. Isotonic MS-induced mechanical hyperalgesia was reduced in a dose-dependent manner by co-injection of camphor, a non-selective TRPA1 antagonist (0.3, 1 and 2.5 μg/paw), MK-801, a NMDA receptor antagonist (0.001, 0.025 and 0.1 μg/paw), L-NAME, a non-selective nitric oxide (NO) synthase inhibitor (20, 50 and 100 μg/paw), ARL 17477, a selective neuronal NOS inhibitor (5.7 and 17 μg/paw), SMT, a selective inducible NOS inhibitor (1 and 2.78 μg/paw), and methylene blue, a guanylate cyclase inhibitor (5, 20 and 125 μg/paw). Drugs injected into the contralateral hind paw did not produce significant effects. These results suggest that an i.pl. injection of MS produces local peripheral mechanical hyperalgesia via activation of peripheral TRPA1 and NMDA receptors and peripheral production of NO. Copyright © 2014 Elsevier Inc. All rights reserved.

Proteomic Analysis Reveals Inflammation Modulation of κ/ι-Carrageenan Hexaoses in Lipopolysaccharide-Induced RAW264.7 Macrophages.

PubMed

Guo, Juanjuan; Chen, Jinghao; Lu, Xu; Guo, Zebin; Huang, Zhiwei; Zeng, Shaoxiao; Zhang, Yi; Zheng, Baodong

2018-05-09

κ/ι-Carrageenan hexaoses (κ/ι-neocarrahexaoses, KCO-4) are a type of carrageenan oligosaccharide that have a broad spectrum of bioactivities due to the presence of sulfate groups. However, the anti-inflammatory capacity of purified carrageenan oligosaccharides and the underlying mechanism has not been completely elucidated. The present study aimed to investigate inflammatory signaling modulation of KCO-4 in LPS-induced macrophages using a quantitative proteomic strategy. KCO-4 inhibited the oversecretion of inflammatory mediators (i.e., NO, TNF-α, IL-1β, IL-8, iNOS, and COX-2). KCO-4 treatment altered proteome profile, and metabolic processes in mitochondria were significantly disrupted. The IPA network analysis proposed that KCO-4 triggered the NF-κB signaling pathway-dependent anti-inflammation process through the inhibition of CD14/Rel@p50 in LPS-induced RAW264.7 macrophages. These data improve our understanding of the anti-inflammatory mechanism and contribute to exposure biomarker screening of κ-carrageenan oligosaccharides.

In vivo antinociceptive and anti-inflammatory activities of dried and fermented processed virgin coconut oil.

PubMed

Zakaria, Z A; Somchit, M N; Mat Jais, A M; Teh, L K; Salleh, M Z; Long, K

2011-01-01

The present study was carried out to investigate the antinociceptive and anti-inflammatory activities of virgin coconut oil (VCO) produced by the Malaysian Agriculture Research and Development Institute (MARDI) using various in vivo models. Two types of VCOs, produced via standard drying (VCOA) and fermentation (VCOB) processes were used in this study. Both VCOA and VCOB were serially diluted using 1% Tween 80 to concentrations (v/v) of 10, 50 and 100%. Antinociceptive and anti- inflammatory activities of both VCOs were examined using various in vivo model systems. The antinociceptive activity of the VCOs were compared to those of 1% Tween 80 (used as a negative control), morphine (5 mg/kg) and/or acetylsalicylic acid (100 mg/kg). Both VCOA and VCOB exhibited significant (p < 0.05) dose-dependent antinociceptive activity in the acetic acid-induced writhing test. Both VCOs also exerted significant (p < 0.05) antinociceptive activity in both phases of the formalin and hot-plate tests. Interestingly, the VCOs exhibited anti-inflammatory activity in an acute (carrageenan-induced paw edema test), but not in a chronic (cotton-pellet-induced granuloma test) model of inflammation. The MARDI-produced VCOs possessed antinociceptive and anti-inflammatory activities. Further studies are needed to confirm these observations. Copyright © 2011 S. Karger AG, Basel.

Interactions of different carrageenan isoforms and flour components in breadmaking.

PubMed

León, A E; Ribotta, P D; Ausar, S F; Fernández, C; Lanada, C A; Beltramo, D M

2000-07-01

The aim of this study was to compare the effects of carrageenans with different sulfate contents on bread volume and dough rheological properties. Results showed that only lambda carrageenan, the most sulfated isoform, produced a significant increase in bread volume. In contrast, the different carrageenans induced a negative effect on the cookie factor. Alveographic and farinographic analyses indicated that dough rheological properties were differentially modified depending on whether lambda carrageenan was added to flour and then hydrated or vice versa. Analysis of the interaction between lambda carrageenan and flour components by infrared spectroscopy and SDS-PAGE indicated that a pool of low molecular weight hydrophobic gluten proteins interact with carrageenan. This interaction drastically changes their physicochemical properties since carrageenan-gluten protein complexes show a hydrophilic behavior. In addition, the results indicate that carrageenan sulfate groups and probably the amino groups of glutamines present in the primary structure of gluten proteins are involved in the interaction.

Antinociceptive and anti-inflammatory effects of Brazilian red propolis extract and formononetin in rodents.

PubMed

Lima Cavendish, Rodrigo; de Souza Santos, Jandson; Belo Neto, Reinaldo; Oliveira Paixão, Ailma; Valéria Oliveira, Juciele; Divino de Araujo, Edilson; Berretta E Silva, Andresa Aparecida; Maria Thomazzi, Sara; Cordeiro Cardoso, Juliana; Zanardo Gomes, Margarete

2015-09-15

Propolis has been used as a folk medicine for centuries around the world due to its wide spectrum of biological activities. The red propolis, a new Brazilian variety of this apimaterial, has presented an unusual chemical composition, including isoflavones such as formononetin and biochanin A. Since both the green and red varieties of propolis are traditionally used as medicine and commercialized with no label differentiation, the study of the activities of red propolis extract has become important in order to clarify whether this product has the same activities as commercial ones. In this work, we demonstrated the potential action of the hydroalcoholic extract of red propolis (HERP) and its biomarker, formononetin, as antinociceptive and anti-inflammatory drugs on experimental models. The HERP was chemically characterised by HPLC/DAD analyses. The biological activities of the HERP (3, 10, and 30mg/kg) and formononetin (10mg/kg) were evaluated using the antinociceptive (acetic acid, formalin, and glutamate injections) and anti-inflammatory (carrageenan-induced hindpaw oedema and peritonitis) models in mice after oral administration. The open field test was also performed. Formononetin, one of the main biomarker of red propolis, was identified in the HERP (21.62mg/g). Pretreatment with the HERP (10 and 30mg/kg) and formononetin (10mg/kg) produced reduction (P<0.001) in the number of abdominal writhes, but the HERP was more effective (P<0.001) than formononetin. In the formalin test, all HERP doses (3, 10, and 30mg/kg, P<0.001) inhibited the late phase (inflammatory pain) of formalin-induced licking, but the inhibition of neurogenic pain was observed only when the higher doses (10 and 30mg/kg; P<0.05) were used. Formononetin caused inhibition (P<0.001) only in the second phase of formalin-induced nociception similarly at all HERP doses in the same phase of the test. The responses in glutamate-induced model presented crescent inhibition (P<0.05) with 10 and 30mg/kg of HERP. Also, formononetin inhibited (P<0.001) the nociception induced by glutamate similarly to 30mg/kg of HERP. There were no significant differences in the open field test after HERP administration, but formononetin decrease the spontaneous motor behaviour. Regarding the anti-inflammatory assessment, the HERP (10 and 30mg/kg, P<0.05) and formononetin (P<0.001) treatments caused a significant inhibition of the oedema response. All doses of HERP (3, 10, and 30mg/kg, P<0.05) and formononetin (P<0.001) also inhibited the carrageenan-induced leukocyte migration. In both cases, the results for the HERP at 30mg/kg and formononetin were similar. The HERP and formononetin presented significant anti-inflammatory activity. Moreover, the HERP presented antinociceptive action on inflammatory and neurogenic pain without motor side effects, possibly due to the action of other constituents present in the extract. These results, together, support the popular usage of this natural product. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Binding of (-)-epigallocatechin-3-gallate with thermally-induced bovine serum albumin/ι-carrageenan particles.

PubMed

Li, Jinbing; Wang, Xiaoyong

2015-02-01

Novel thermally-induced BSA/ι-carrageenan particles are used as a protective carrier for (-)-epigallocatechin-3-gallate (EGCG). The addition of EGCG to BSA/ι-carrageenan particles can highly quench the intrinsic fluorescence of BSA, which is explained in terms of the binding of EGCG to the hydrophobic pockets of BSA mainly through the hydrophobic force. According to the double logarithm equation, the binding constant is determined as 1.1×10(8)M(-1) for the binding of EGCG with BSA/ι-carrageenan particles. The high binding affinity is ascribed to both the molecular structure of EGCG and the partial unfolding state of BSA in BSA/ι-carrageenan particles. The circular dichroism spectra and calculated α-helix of BSA suggest that the bound EGCG leads to a more random secondary structure of BSA. Furthermore, BSA/ι-carrageenan particles are found to be superior to native BSA and pure BSA particles for improving the stability and radical scavenging activity of EGCG. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antinociceptive and Anti-Inflammatory Effects of Ethanol Extract from Vernonia polyanthes Leaves in Rodents

PubMed Central

Temponi, Vanessa dos Santos; da Silva, Jucélia Barbosa; Alves, Maria Silvana; Ribeiro, Antônia; de Jesus Ribeiro Gomes de Pinho, José; Yamamoto, Célia Hitomi; Pinto, Miriam Aparecida Oliveira; Del-Vechio-Vieira, Glauciemar; de Sousa, Orlando Vieira

2012-01-01

The ethanol extract from Vernonia polyanthes leaves (EEVP) was investigated for antinociceptive and anti-inflammatory effects at the doses (p.o.) of 100, 200 and 400 mg/kg in animal models. The extract reduced the number of abdominal contortions by 16.75% and 31.44% at a dose of 200 and 400 mg/kg, respectively. The results obtained showed that EEVP exerted a significant antinociceptive effect in the two phases of formalin. The EEVP increased the reaction time on a hot plate at the doses of 100, 200 and 400 mg/kg after 90 min of treatment. The paw edema was reduced by EEVP at the doses of 100, 200 and 400 mg/kg after 4 h of application of carrageenan. Doses of 200 and 400 mg/kg, administered 4 h before the carrageenan injection, significantly reduced the exudate volume (29.25 and 45.74%, respectively) and leukocyte migration (18.19 and 27.95%, respectively). These results suggest that V. polyanthes can be an active source of substances with antinociceptive and anti-inflammatory activities. PMID:22489187

Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System

PubMed Central

Ferreira, Renata Cristina Mendes; Almeida-Santos, Ana Flávia; Aguiar, Daniele C.; Moreira, Fabricio A.

2017-01-01

Background Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect. Methods Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2, 2 μg). Aripiprazole was injected 10 min before the measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and bestatin were given 30 min before aripiprazole. Nociceptive thresholds were measured in the 3rd hour after PGE2 injection. Results Aripiprazole (100 μg/paw) injected locally into the right hind paw induced an antinociceptive effect that was blocked by naloxone (50 μg/paw), a nonselective opioid receptor antagonist. The role of μ-, δ-, and κ-opioid receptors was investigated using the selective antagonists, clocinnamox (40 μg/paw), naltrindole (15, 30, and 60 μg/paw), and nor-binaltorphimine (200 μg/paw), respectively. The data indicated that only the δ-opioid receptor antagonist inhibited the peripheral antinociception induced by aripiprazole. Bestatin (400 μg), an aminopeptidase-N inhibitor, significantly enhanced low-dose (25 μg/paw) aripiprazole-induced peripheral antinociception. Conclusion The results suggest the participation of the opioid system via δ-opioid receptor in the peripheral antinociceptive effect induced by aripiprazole. PMID:28758123

PHYTOCHEMICAL SCREENING, ANTI-INFLAMMATORY AND ANALGESIC PROPERTIES OF PENTANISIA PRUNELLOIDES FROM THE EASTERN CAPE PROVINCE, SOUTH AFRICA

PubMed Central

Mathews, Miya Gugulethu; Ajayi, Oyemitan Idris; Opeoluwa, Oyedeji Oyehan; Oluwatobi, Oluwafemi Samuel; Benedicta N, Nkeh-Chungag; Phindile, Songca Sandile; Oyedeji; Omowumi, Adebola

2016-01-01

Background: Pentanisia prunelloides is a medicinal plant widely used to remedy various ailments including infections, fever and rheumatism in Eastern Cape Province of South Africa. There is scanty report on the phytochemical and biological properties of the plant; hence various solvent extracts of the dried plant materials were phytochemically screened, and its aqueous extract evaluated for acute toxicity effect, analgesic and antiinflammatory properties in rodents. Methods and Materials: Different extracts of both leaf and rhizome were obtained separately with ethanol, methanol and water. Portions of the filtrate were used for qualitative screening of secondary metabolites and remaining portions were concentrated and dried. Dried grounded leaf and rhizome of the plant were also used for quantitative screening for some major components. The aqueous extract of the leaf and rhizome were used for acute toxicity (LD50) test, antiinflammatory and analgesic activities in rodents. Results: The qualitative phytochemical screening showed the presence of several phytoconstituents with saponins, flavonoids and alkaloids constituting highest constituents in the leaf and rhizome. The LD50: of the aqueous extracts (from leaf or rhizome) was found to be ≥5000 mg/kg orally. The leaf and rhizome aqueous extract (250-500 mg/kg) significantly (p<0.01) reduced egg albumin-induced paw oedema and paw licking in mice induced by formalin, signifying antinociceptive and antiinflammatory activities respectively. Conclusion: It is concluded that the leaf and rhizome of P. prunelloides are rich in various phytochemicals which could be associated with their medicinal uses. The aqueous leaf and rhizome extracts are similarly non-toxic orally, showed antiinflammatory and analgesic potentials thus rationalizing its use in folkloric medicine. PMID:28480377

The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity.

PubMed

Ezzat, Shahira M; Ezzat, Marwa I; Okba, Mona M; Menze, Esther T; Abdel-Naim, Ashraf B

2018-03-25

Ginger (Zingiber officinale Roscoe) is a well known anti-inflammatory drug in the Egyptian, Indian and Chinese folk medicines, yet its mechanism of action is unclear. To explore its mechanism of action and to correlate it to its biophytochemicals. Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated using protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated using carrageenan-induced rat paw edema in rats at doses 25, 50, 100 and 200mg/kg b.wt. All the tested extracts showed significant (p< 0.1) in vitro anti-inflammatory activities. The strongest anti-lipoxygenase activity was observed for AE that was more significant than that of diclofenac (58% and 52%, respectively) at the same concentration (125μg/ml). Purification of AE led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G1, G2 and G8 exhibited potent activity in all the studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw edema in a dose-dependent manner. AE (at 200mg/kg) showed significant reduction in production of PGE2, TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated upon activation, normal T-cell expressed and secreted (RANTES), myeloperoxidase (MPO) activity by 60%, 57%, 60%, 41%, 32% and 67%, respectively. AE at 100 and 200mg/kg was equipotent to indomethacin in reduction of NO x level and in increasing the total antioxidant capacity (TAC). Histopathological examination revealed very few inflammatory cells infiltration and edema after administration of AE (200mg/kg) prior to carrageenan. Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. This was evidenced by the dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenishment the total antioxidant capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation, characterization and antibacterial activity of oxidized κ-carrageenan.

PubMed

Zhu, Mingjin; Ge, Liming; Lyu, Yongbo; Zi, Yaxin; Li, Xinying; Li, Defu; Mu, Changdao

2017-10-15

The oxidized κ-carrageenans with different oxidation levels were prepared through the hydrogen peroxide and copper sulfate redox system. The oxidation level of oxidized κ-carrageenan was successfully controlled by adjusting the dosage of hydrogen peroxide. The results showed that the microtopography of oxidized κ-carrageenan changed from rough granules to smooth flakes, mainly resulting from the easily melting property of oxidized κ-carrageenan induced by introduced carboxyl and aldehyde groups. Especially, the antibacterial activity of oxidized κ-carrageenans against Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) was systematically investigated. The results showed that the oxidized κ-carrageenan could damage the bacterial cell wall and cytoplasmic membrane and suppress the growth of both Gram-positive and Gram-negative bacteria. The oxidized κ-carrageenan possessed broad-spectrum antibacterial activity, which may be used as a new antibacterial agent. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cafestol, a coffee-specific diterpene, induces peripheral antinociception mediated by endogenous opioid peptides.

PubMed

Guzzo, Luciana S; Perez, Andrea C; Romero, Thiago Rl; Azevedo, Adolfo O; Duarte, Igor Dg

2012-05-01

The opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, including non-steroidal anti-inflammatory drugs and α(2) -adrenoceptor agonists. The aims of the present study were to investigate the possible peripheral antinociceptive effect of cafestol, a diterpene present in the oil derived from coffee beans, and to evaluate the involvement of opioid peptides in its effect. The rat paw pressure test was used to assess antinocipeptive effects. Hyperalgesia was induced by intraplantar injection of prostaglandin E(2) (2 μg/paw). All drugs were locally administered into the hind-paws of male Wistar rats. Intraplantar injection of cafestol (20, 40 and 80 μg) induced peripheral antinociception. The antinociceptive effect of cafestol was due to a local action because the higher dose (80 μg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (25, 50 and 100 μg/paw) prevented the action of cafestol (80 μg/paw), whereas the aminopeptidase inhibitor bestatin (400 μg/paw) potentiated the antinociceptive effect of cafestol (40 μg/paw). The results of the present study provide evidence that cafestol treatment has a peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.

Green tea polyphenol extract attenuates lung injury in experimental model of carrageenan-induced pleurisy in mice

PubMed Central

Di Paola, Rosanna; Mazzon, Emanuela; Muià, Carmelo; Genovese, Tiziana; Menegazzi, Marta; Zaffini, Raffaela; Suzuki, Hisanory; Cuzzocrea, Salvatore

2005-01-01

Here we investigate the effects of the green tea extract in an animal model of acute inflammation, carrageenan-induced pleurisy. We report here that green tea extract (given at 25 mg/kg i.p. bolus 1 h prior to carrageenan), exerts potent anti-inflammatory effects in an animal model of acute inflammation in vivo. Injection of carrageenan (2%) into the pleural cavity of mice elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity that contained many neutrophils (PMNs), an infiltration of PMNs in lung tissues and increased production of nitrite/nitrate, tumour necrosis factor alpha. All parameters of inflammation were attenuated by green tea extract treatment. Furthermore, carrageenan induced an up-regulation of the adhesion molecule ICAM-1, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) formation, as determined by immunohistochemical analysis of lung tissues. Staining for the ICAM-1, nitrotyrosine, and PARS was reduced by green tea extract. Our results clearly demonstrate that treatment with green tea extract exerts a protective effect and offers a novel therapeutic approach for the management of lung injury. PMID:15987519

Osthole attenuates the development of carrageenan-induced lung inflammation in rats.

PubMed

Li, Zhipeng; Ji, Haijie; Song, Xiuyun; Hu, Jinfeng; Han, Ning; Chen, Naihong

2014-05-01

Osthole has been reported to possess a variety of pharmacological activities, such as antiinflammatory effect. In the present study, we have investigated the effect of osthole on lung inflammation associated with carrageenan-induced pleurisy in rats. The result showed that osthole could inhibit significantly pleural exudates formation and PMNs infiltration. Histological examination revealed osthole could reduce lung inflammation in rats treated with carrageenan. The myeloperoxidase (MPO) level was examined in pleural exudates. The result showed that osthole could attenuate MPO level in pleural exudates. Further studies showed osthole could decrease tumor necrosis factor alpha (TNF-α) and interleukin 1beta (IL-1β) levels in the lungs. Taken together, the present results suggested that osthole could inhibit lung inflammation on carrageenan-induced pleurisy in rats and that could be related to a reduction of PMNs infiltration and release of inflammatory factors. Copyright © 2014 Elsevier B.V. All rights reserved.

A novel nano-carrier transdermal gel against inflammation.

PubMed

Chaudhary, Hema; Kohli, Kanchan; Kumar, Vikash

2014-04-25

The objective was to develop a stable, reproducible and patient non-infringing novel transdermal drug delivery system "nano-carrier transdermal gel" (NCTG) in combination of partial dose replacement of diclofenac diethylamine (DDEA) by curcumin (CRM). The drug content of gel was 99.30 and 97.57% for DDEA and CRM. Plasma samples were analyzed by liquid chromatography with triple-quadrupole tandem mass spectrometer (LC-MS/MS). Data were integrated with Analyst™ and analyzed by WinNonlin; stability parameters were analyzed using Tukey-Kramer multiple comparison test. Its average skin irritation scored 0.49 concluded to be non-irritant, safe for human use and in vivo studies revealed significantly greater extent of absorption and highly significant inhibition (%) of carrageenan induced paw edema. The results also demonstrated that encapsulation of drugs in nano-carrier increases its biological activity due to superior skin penetration potential. Hence, a novel once day transdermal gel of nano-carrier (nano-transfersomes; deformable vesicular) is achieved, to increase systemic availability, subsequent reduction in dose and toxicity of DDEA was developed for the treatment of inflammation. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of analgesic and anti-inflammatory activity of a combination of tramadol-ibuprofen in experimental animals.

PubMed

Suthakaran, Chidambarann; Kayalvizhi, Muniyagounder K; Nithya, Karnam; Raja, Thozhudalangudy Ar

2017-01-01

Pain is the major concern of patients attending dental clinics, and satisfactory pain relief has always been difficult to achieve. Since the pathophysiology of pain is a complex, central and peripheral nervous system process, combined analgesic regimens with different mechanisms of action as a multimodal approach are becoming popular among the clinicians and dentists. The aim of the present study was to evaluate the analgesic and anti-inflammatory activity of ibuprofen and tramadol when used alone or in combination in animal models of pain and inflammation. The animals were divided into six groups with six animals in each group. Analgesic activity was assessed by hot plate method in rats and by acetic acid-induced writhing test in mice. Paw edema model in rats after induction with 0.1 mL of 1% carrageenan was used to assess the anti-inflammatory activity. Analysis of variance followed by Tukey's honestly significant difference post hoc test was used for statistical analysis. Combined use of tramadol and ibuprofen provided enhanced analgesic and anti-inflammatory effects in animal models of pain and inflammation.

1,4-Naphthoquinones potently inhibiting P2X7 receptor activity.

PubMed

Faria, R X; Oliveira, F H; Salles, J P; Oliveira, A S; von Ranke, N L; Bello, M L; Rodrigues, C R; Castro, H C; Louvis, A R; Martins, D L; Ferreira, V F

2018-01-01

P2X7 receptor (P2X7R) is an ATP-gated ion-channel with potential therapeutic applications. In this study, we prepared and searched a series of 1,4-naphthoquinones derivatives to evaluate their antagonistic effect on both human and murine P2X7 receptors. We explored the structure-activity relationship and binding mode of the most active compounds using a molecular modeling approach. Biological analysis of this series (eight analogues and two compounds) revealed significant in vitro inhibition against both human and murine P2X7R. Further characterization revealed that AN-03 and AN-04 had greater potency than BBG and A740003 in inhibiting dye uptake, IL-1β release, and carrageenan-induced paw edema in vivo. Moreover, we used electrophysiology and molecular docking analysis for characterizing AN-03 and AN-04 action mechanism. These results suggest 1,4-napthoquinones, mainly AN-04, as potential leads to design new P2X7R blockers and anti-inflammatory drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dual effects of Rho-kinase inhibitors on a rat model of inflammatory pain.

PubMed

Paiva-Lima, Patricia; Bakhle, Y S; Francischi, Janetti Nogueira

2014-01-01

Rho-kinases (ROCKs), a family of small GTP-dependent enzymes, are involved in a range of pain models, and their inhibition typically leads to antinociceptive effects. To study the effects of inhibiting ROCKs using two known inhibitors, Y27632 and HA1077 (fasudil), administered locally, on nociception and paw edema in rats. A range of doses of Y27632 or HA1077 (2.5 μg to 1000 μg) were injected locally into rat paws alone or in combination with carrageenan, a known proinflammatory stimulus. Nociceptive responses to mechanical stimuli and increased paw volume, reflecting edema formation, were measured at 2 h and 3 h, using a Randall-Selitto apparatus and a hydroplethysmometer, respectively. Animals treated with either ROCK inhibitor showed biphasic nociceptive effects, with lower doses being associated with pronociceptive, and higher doses with antinociceptive responses. In contrast, a monophasic dose-dependent increase in edema was observed in the same animals. Local injection of 8-bromo-cyclic (c)GMP, an activator of the nitric oxide⁄cGMP⁄protein kinase G pathway, also produced biphasic effects on nociceptive responses in rat paws; however, low doses were antinociceptive and high doses were pronociceptive. Local administration of cytochalasin B, an inhibitor of actin polymerization and a downstream mediator of ROCK activity, reversed the antinociceptive effect of Y27632. The results of the present study suggest that ROCKs participate in the local mechanisms associated with nociception⁄antinociception and inflammation, with a possible involvement of the nitric oxide⁄cGMP⁄protein kinase G pathway. Also, drug effects following local administration may differ markedly from the effects following systemic administration. Finally, separate treatment of pain and edema may be needed to maximize clinical benefit in inflammatory pain.

Pharmacological interaction between oxcarbazepine and two COX inhibitors in a rat model of inflammatory hyperalgesia.

PubMed

Stepanović-Petrović, Radica M; Tomić, Maja A; Vučković, Sonja M; Poznanović, Goran; Ugrešić, Nenad D; Prostran, Milica Š; Bošković, Bogdan

2011-01-01

Oxcarbazepine, ibuprofen and etodolac have efficacy in inflammatory pain. The combination of different drugs activates both central and peripheral pain inhibitory pathways to induce additive or synergistic antinociception, and this interaction may allow lower doses of each drug combined and improve the safety profile, with lower side-effects. This study aimed to examine the effects of oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations, in a rat model of inflammatory hyperalgesia, and determine the type of interaction between drugs. Rats were intraplantarly injected with carrageenan (0.1 ml, 1%) and the hyperalgesia was assessed by modified paw pressure test. The anti-hyperalgesic effects of oxcarbazepine, ibuprofen and etodolac and oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations were examined. Drugs were co-administered in a fixed-dose fractions of the ED₅₀ and the type of interaction was determined by isobolographic analysis. Oxcarbazepine (40-160 mg/kg; p.o.), ibuprofen (10-120 mg/kg; p.o.) and etodolac (5-20 mg/kg; p.o.) produced a significant, dose-dependent anti-hyperalgesia in carrageenan-injected rats. ED₅₀ values (mean±SEM) for oxcarbazepine, ibuprofen and etodolac were 88.17±3.65, 47.07±10.27 and 13.05±1.42 mg/kg, respectively. Oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations induced significant and dose-dependent anti-hyperalgesia. Isobolographic analysis revealed that oxcarbazepine exerts a synergistic interaction with ibuprofen, with almost 4-fold reduction of doses of both drugs in combination. In contrast, there was an additive interaction with etodolac. Synergistic interaction of oxcarbazepine with ibuprofen and its additive interaction with etodolac provide new information about the combination pain treatment and could be explored further in patients with inflammatory pain. Adverse effect analysis of the combinations is necessary to verify possible clinical use of the mixtures. Copyright © 2010 Elsevier Inc. All rights reserved.

Inhibition of NF-κB pathway in fibroblast-like synoviocytes by α-mangostin implicated in protective effects on joints in rats suffering from adjuvant-induced arthritis.

PubMed

Zuo, Jian; Yin, Qin; Wang, Yu-Wei; Li, Yan; Lu, Lin-Ming; Xiao, Zhan-Gang; Wang, Guo-Dong; Luan, Jia-Jie

2018-03-01

α-Mangostin (MG) is a bioactive compound isolated from mangosteen. This study was aimed to investigate effects of MG on adjuvant-induced arthritis (AA) in rats and decipher the underlying mechanisms. Clinical severity of AA was evaluated by paw oedema, arthritis score, and hematological parameters. Digital radiography (DR) and histological examinations were employed to assess joints destructions. Immune functions were evaluated by T cell subsets distribution. Effects on NF-κB pathway were investigated by immunohistochemical, western-blot and immunofluorescence methods both in vivo and vitro. It was found MG possessed superior anti-inflammatory effects in vivo, suggested by attenuated paw swelling, reduced inflammatory cells infiltration and decreased the secretion of TNF-α and IL-1β in serum. Meanwhile MG inhibited fibrous hyperplasia, synovial angiogenesis, cartilage and bone degradation in AA rats. Although MG exerted little effects on CD4 + population, it greatly decreased IFN-γ positive cells and promoted expression of FOXP3 in immune organs, indicating restoration of Th1/Treg cells ratio and recovery of immune homeostasis in vivo. Inhibition of NF-κB induced by MG was indicated by reduced the expression of p-p65 and VEGF in synovium. In vitro experiments found MG at 10 μg/ml significantly suppressed the expression and phosphorylation of key proteins implicated in NF-κB pathway and inhibited nucleus translocation of p65. These changes led to increased apoptosis and proliferation inhibition of HFLS-RA cells. The results demonstrated regulation of immune functions was deeply involved in the therapeutic actions of MG on AA, and it's inhibition on NF-κB in fibroblast-like synoviocytes was associated to the protective effects on joints. Copyright © 2018 Elsevier B.V. All rights reserved.

Dietary Blue Pigments Derived from Genipin, Attenuate Inflammation by Inhibiting LPS-Induced iNOS and COX-2 Expression via the NF-κB Inactivation

PubMed Central

Wang, Qiang-Song; Xiang, Yaozu; Cui, Yuan-Lu; Lin, Ke-Ming; Zhang, Xin-Fang

2012-01-01

Background and Purpose The edible blue pigments produced by gardenia fruits have been used as value-added colorants for foods in East Asia for 20 years. However, the biological activity of the blue pigments derived from genipin has not been reported. Methodology/Principal Findings The anti-inflammatory effect of blue pigments was studied in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage in vitro. The secretions of nitric oxide (NO) and prostaglandin E2 (PGE2) were inhibited in concentration-dependent manner by blue pigments. Real-time reverse-transcription polymerase chain reaction (Real-time RT-PCR) analyses demonstrated that the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) was inhibited, moreover, ELISA results showed that the productions of IL-6 and TNF-α were inhibited. Cell-based ELISA revealed the COX-2 protein expression was inhibited. The proteome profiler array showed that 12 cytokines and chemokines involved in the inflammatory process were down-regulated by blue pigments. Blue pigments inhibited the nuclear transcription factor kappa-B (NF-κB) activation induced by LPS, and this was associated with decreasing the DNA-binding activity of p65 and p50. Furthermore, blue pigments suppressed the degradation of inhibitor of κB (IκB) α, Inhibitor of NF-κB Kinase (IKK) α, IKK-β, and phosphorylation of IκB-α. The anti-inflammatory effect of blue pigments in vivo was studied in carrageenan-induced paw edema and LPS-injecting ICR mice. Finally, blue pigments significantly inhibited paw swelling and reduced plasma TNF-α and IL-6 production in vivo. Conclusions and Implications These results suggest that the anti-inflammatory properties of blue pigments might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1β, and TNF-α expression through the down-regulation of NF-κB activation, which will provide strong scientific evidence for the edible blue pigments to be developed as a new health-enhancing nutritional food for the prevention and treatment of inflammatory diseases. PMID:22479539

Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice.

PubMed

Marabese, I; de Novellis, V; Palazzo, E; Scafuro, M A; Vita, D; Rossi, F; Maione, S

2007-02-01

In this study, the effect of (S)-3,4-dicarboxyphenylglycine (DCPG), a selective mGlu8 receptor agonist, has been investigated in inflammatory and neuropathic pain models in order to elucidate the role of mGlu8 receptor in modulating pain perception. Inflammatory pain was induced by the peripheral injection of formalin or carrageenan in awake mice. Systemic administration of (S)-3,4-DCPG, performed 15 min before formalin, decreased both early and delayed nociceptive responses of the formalin test. When this treatment was carried out 15 min after the peripheral injection of formalin it still reduced the late hyperalgesic phase. Similarly, systemic (S)-3,4-DCPG reduced carrageenan-induced thermal hyperalgesia and mechanical allodynia when administered 15 min before carrageenan, but no effect on pain behaviour was observed when (S)-3,4-DCPG was given after the development of carrageenan-induced inflammatory pain. When microinjected into the lateral PAG (RS)-alpha-methylserine-O-phoshate (MSOP), a group III receptor antagonist, antagonised the analgesic effect induced by systemic administration of (S)-3,4-DCPG in both of the inflammatory pain models. Intra-lateral PAG (S)-3,4-DCPG reduced pain behaviour when administered 10 min before formalin or carrageenan; both the effects were blocked by intra-lateral PAG MSOP. (S)-3,4-DCPG was ineffective in alleviating thermal hyperalgesia and mechanical allodynia 7 days after the chronic constriction injury of the sciatic nerve, whereas it proved effective 3 days after surgery. Taken together these results suggest that stimulation of mGlu8 receptors relieve formalin and carrageenan-induced hyperalgesia in inflammatory pain, whereas it would seem less effective in established inflammatory or neuropathic pain.

Evaluation of amentoflavone isolated from Cnestis ferruginea Vahl ex DC (Connaraceae) on production of inflammatory mediators in LPS stimulated rat astrocytoma cell line (C6) and THP-1 cells.

PubMed

Ishola, I O; Chaturvedi, J P; Rai, S; Rajasekar, N; Adeyemi, O O; Shukla, R; Narender, T

2013-03-27

Cnestisferruginea (CF) Vahl ex DC (Connaraceae) is a shrub widely used in traditional African medicine for the treatment of various psychiatric illness and inflammatory conditions. This study was carried out to investigate the effect of amentoflavone isolated from methanolic root extract of CF on lipopolysaccharide (LPS)-induced neuroinflammatory cascade of events associated to the oxidative and nitrative stress, and TNF-α production in rat astrocytoma cell line (C6) and human monocytic leukemia cell line (THP-1), respectively. Rat astrocytoma cells (C6) were stimulated with LPS (10μg/ml) alone and in the presence of different concentrations of amentoflavone (0.1-3μg/ml) for 24h incubation period. Nitrite release, reactive oxygen species (ROS), malondialdehyde (MDA) and reduced-glutathione (GSH) in C6 cells were estimated; while the TNF-α level was estimated in THP-1 cell lysate. In vivo analgesic activity was evaluated using mouse writhing and hot plate tests while the anti-inflammatory effect was investigated using carrageenan-induced oedema test. LPS (10μg/ml) significantly (P<0.05) stimulated C6 cells to release nitrite, ROS, MDA, and TNF-α generation while GSH was down regulated in comparison to control. However, amentoflavone significantly (P<0.05) attenuated nitrite, ROS, MDA and TNF-α generation and also up regulated the level of GSH. Amentoflavone per se did not have any significant effect on C6 and THP-1 cells. Amentoflavone (6.25-50mg/kg) significantly (P<0.05) reduced number of writhes and also increase pain threshold in hot plate test. It produced time course significant (P<0.05) decrease in oedema formation in rodents. Findings in this study demonstrate the anti-neuroinflammatory and antinoceptive effects of amentoflavone which may suggest its beneficial roles in neuroinflammation associated disorders. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Insulin oedema and treatment-induced neuropathy occurring in a 20-year-old patient with Type 1 diabetes commenced on an insulin pump.

PubMed

Rothacker, K M; Kaye, J

2014-01-01

Oedema may occur following initiation or intensification of insulin therapy in patients with Type 1 and Type 2 diabetes. Mild oedema is thought to be not uncommon, but under-reported, whilst generalized oedema with involvement of serous cavities has rarely been described. Multiple pathogenic mechanisms have been proposed, including insulin-induced sodium and water retention. Patients at greater risk for insulin oedema include those with poor glycaemic control. Dramatic improvement in glycaemic control is also associated with sensory and autonomic neuropathy. We describe a case of generalized oedema occurring in a 20-year-old, low body weight patient with Type 1 diabetes with poor glycaemic control 3 days following commencement of an insulin pump; blood sugars had dramatically improved with this treatment. Alternative causes for oedema were excluded. Oedema slowly improved with insulin dose reduction with higher blood sugar targets plus frusemide treatment. Subsequent to oedema resolution, the patient unfortunately developed generalized neuropathic pain, thought to be another manifestation of rapid improvement in glycaemic control. Caution should be taken when a patient with diabetes that is poorly controlled has an escalation in therapy that may dramatically improve their blood sugar levels; this includes the initiation of an insulin pump. Clinicians and patients should be aware of the potential risk of insulin oedema, treatment-induced neuropathy and worsening of diabetic retinopathy in the setting of rapid improvement in glycaemic control. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear oedema.

PubMed Central

Inoue, H.; Mori, T.; Shibata, S.; Koshihara, Y.

1989-01-01

1. The anti-inflammatory effects of glycyrrhetinic acid and its derivatives on TPA (12-O-tetradecanoylphorbol-13-acetate)-induced mouse ear oedema were studied. The mechanisms of TPA-induced ear oedema were first investigated with respect to the chemical mediators. 2. The formation of ear oedema reached a maximum 5 h after TPA application (2 micrograms per ear) and the prostaglandin E2 (PGE2) production of mouse ear increased with the oedema formation. 3. TPA-induced ear oedema was prevented by actinomycin D and cycloheximide (0.1 mg per ear, respectively) when applied during 60 min after TPA treatment. 4. Of glycyrrhetinic acid derivatives examined, dihemiphthalate derivatives (IIe, IIe', IIIa, IIIa', IVa, IVa') most strongly inhibited ear oedema on both topical (ID50, 1.6 mg per ear for IIe, 2.0 mg per ear for IIIa and 1.6 mg per ear for IVa) and oral (ID50, 88 mg kg-1 for IIe', 130 mg kg-1 for IIIa' and 92 mg kg-1 for IVa') administration. 5. Glycyrrhetinic acid (Ia) and its derivatives applied 30 min before TPA treatment were much more effective in inhibiting oedema than when applied 30 min after TPA. A dihemiphthalate of triterpenoid compound IVa completely inhibited oedema, even when applied 3 h before TPA treatment. 6. Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the parent compounds, produced little inhibition by oral administration at less than 200 mg kg-1. 7. These results suggest that the dihemiphthalate derivatives of triterpenes derived from glycyrrhetinic acid by chemical modification are useful for the treatment of skin inflammation by both topical and oral application. PMID:2924072

In vitro and in vivo assessment of meadowsweet (Filipendula ulmaria) as anti-inflammatory agent.

PubMed

Katanić, Jelena; Boroja, Tatjana; Mihailović, Vladimir; Nikles, Stefanie; Pan, San-Po; Rosić, Gvozden; Selaković, Dragica; Joksimović, Jovana; Mitrović, Slobodanka; Bauer, Rudolf

2016-12-04

Meadowsweet (Filipendula ulmaria (L.) Maxim, Rosaceae) has been traditionally used in most European countries for the treatment of inflammatory diseases due to its antipyretic, analgesic, astringent, and anti-rheumatic properties. However, there is little scientific evidence on F. ulmaria anti-inflammatory effects regarding its impact on cyclooxygenases enzymatic activity and in vivo assessment of anti-inflammatory potential. This study aims to reveal the anti-inflammatory activity of methanolic extracts from the aerial parts (FUA) and roots (FUR) of F. ulmaria, both in in vitro and in vivo conditions. The characteristic phenolic compounds in F. ulmaria extracts were monitored via high performance thin layer chromatography (HPTLC). The in vitro anti-inflammatory activity of F. ulmaria extracts was evaluated using cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays, and an assay for determining COX-2 gene expression. The in vivo anti-inflammatory effect of F. ulmaria extracts was determined in two doses (100 and 200 mg/kg b.w.) with hot plate test and carrageenan-induced paw edema test in rats. Inflammation was also evaluated by histopathological and immunohistochemical analysis. FUA extract showed the presence of rutoside, spiraeoside, and isoquercitrin. Both F. ulmaria extracts at a concentration of 50μg/mL were able to inhibit COX-1 and -2 enzyme activities, whereby FUA extract (62.84% and 46.43% inhibition, respectively) was double as effective as the root extract (32.11% and 20.20%, respectively). Extracts hardly inhibited the level of COX-2 gene expression in THP-1 cells at a concentration of 25μg/mL (10.19% inhibition by FUA and 8.54% by FUR). In the hot plate test, both extracts in two doses (100 and 200mg/kg b.w.), exhibited an increase in latency time when compared with the control group (p<0.05). In the carrageenan-induced acute inflammation test, FUA at doses of 100 and 200mg/kg b.w., and FUR at 200mg/kg, were able to significantly reduce the mean maximal swelling of rat paw until 6h of treatment. Indomethacin, FUA, and FUR extracts significantly decreased inflammation score and this effect was more pronounced after 24h, compared to the control group (p<0.05). The observed results of in vitro and, for the first time, in vivo anti-inflammatory activity of meadowsweet extracts, provide support of the traditional use of this plant in the treatment of different inflammatory conditions. Further investigation of the anti-inflammatory compounds could reveal the mechanism of anti-inflammatory action of these extracts. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Automated assessment of pain in rats using a voluntarily accessed static weight-bearing test.

PubMed

Kim, Hung Tae; Uchimoto, Kazuhiro; Duellman, Tyler; Yang, Jay

2015-11-01

The weight-bearing test is one method to assess pain in rodent animal models; however, the acceptance of this convenient method is limited by the low throughput data acquisition and necessity of confining the rodents to a small chamber. We developed novel data acquisition hardware and software, data analysis software, and a conditioning protocol for an automated high throughput static weight-bearing assessment of pain. With this device, the rats voluntarily enter the weighing chamber, precluding the necessity to restrain the animals and thereby removing the potential stress-induced confounds as well as operator selection bias during data collection. We name this device the Voluntarily Accessed Static Incapacitance Chamber (VASIC). Control rats subjected to the VASIC device provided hundreds of weight-bearing data points in a single behavioral assay. Chronic constriction injury (CCI) surgery and paw pad injection of complete Freund's adjuvant (CFA) or carrageenan in rats generated hundreds of weight-bearing data during a 30 minute recording session. Rats subjected to CCI, CFA, or carrageenan demonstrated the expected bias in weight distribution favoring the un-operated leg, and the analgesic effect of i.p. morphine was demonstrated. In comparison with existing methods, brief water restriction encouraged the rats to enter the weighing chamber to access water, and an infrared detector confirmed the rat position with feet properly positioned on the footplates, triggering data collection. This allowed hands-off measurement of weight distribution data reducing operator selection bias. The VASIC device should enhance the hands-free parallel collection of unbiased weight-bearing data in a high throughput manner, allowing further testing of this behavioral measure as an effective assessment of pain in rodents. Copyright © 2015. Published by Elsevier Inc.

Automated assessment of pain in rats using a voluntarily accessed static weight-bearing test

PubMed Central

Kim, Hung Tae; Uchimoto, Kazuhiro; Duellman, Tyler; Yang, Jay

2015-01-01

The weight-bearing test is one method to assess pain in rodent animal models; however, the acceptance of this convenient method is limited by the low throughput data acquisition and necessity of confining the rodents to a small chamber. New methods We developed novel data acquisition hardware and software, data analysis software, and a conditioning protocol for an automated high throughput static weight-bearing assessment of pain. With this device, the rats voluntarily enter the weighing chamber, precluding the necessity to restrain the animals and thereby removing the potential stress-induced confounds as well as operator selection bias during data collection. We name this device the Voluntarily Accessed Static Incapacitance Chamber (VASIC). Results Control rats subjected to the VASIC device provided hundreds of weight-bearing data points in a single behavioral assay. Chronic constriction injury (CCI) surgery and paw pad injection of complete Freund's adjuvant (CFA) or carrageenan in rats generated hundreds of weight-bearing data during a 30 minute recording session. Rats subjected to CCI, CFA, or carrageenan demonstrated the expected bias in weight distribution favoring the un-operated leg, and the analgesic effect of i.p. morphine was demonstrated. In comparison with existing methods, brief water restriction encouraged the rats to enter the weighing chamber to access water, and an infrared detector confirmed the rat position with feet properly positioned on the footplates, triggering data collection. This allowed hands-off measurement of weight distribution data reducing operator selection bias. Conclusion The VASIC device should enhance the hands-free parallel collection of unbiased weight-bearing data in a high throughput manner, allowing further testing of this behavioral measure as an effective assessment of pain in rodents. PMID:26143745

Vitamin D Inhibits COX-2 Expression and Inflammatory Response by Targeting Thioesterase Superfamily Member 4*

PubMed Central

Wang, Qingsong; He, Yuhu; Shen, Yujun; Zhang, Qianqian; Chen, Di; Zuo, Caojian; Qin, Jing; Wang, Hui; Wang, Junwen; Yu, Ying

2014-01-01

Inadequate vitamin D status has been linked to increased risk of type 2 diabetes and cardiovascular disease. Inducible cyclooxygenase (COX) isoform COX-2 has been involved in the pathogenesis of such chronic inflammatory diseases. We found that the active form of vitamin D, 1,25(OH)2D produces dose-dependent inhibition of COX-2 expression in murine macrophages under both basal and LPS-stimulated conditions and suppresses proinflammatory mediators induced by LPS. Administration of 1,25(OH)2D significantly alleviated local inflammation in a carrageenan-induced paw edema mouse model. Strikingly, the phosphorylation of both Akt and its downstream target IκBα in macrophages were markedly suppressed by 1,25(OH)2D in the presence and absence of LPS stimulation through up-regulation of THEM4 (thioesterase superfamily member 4), an Akt modulator protein. Knockdown of both vitamin D receptor and THEM4 attenuated the inhibitory effect of 1,25(OH)2D on COX-2 expression in macrophages. A functional vitamin D-responsive element in the THEM4 promoter was identified by chromatin immunoprecipitation and luciferase reporter assay. Our results indicate that vitamin D restrains macrophage-mediated inflammatory processes by suppressing the Akt/NF-κB/COX-2 pathway, suggesting that vitamin D supplementation might be utilized for adjunctive therapy for inflammatory disease. PMID:24619416

Enhanced therapeutic anti-inflammatory effect of betamethasone on topical administration with low-frequency, low-intensity (20 kHz, 100 mW/cm(2)) ultrasound exposure on carrageenan-induced arthritis in a mouse model.

PubMed

Cohen, Gadi; Natsheh, Hiba; Sunny, Youhan; Bawiec, Christopher R; Touitou, Elka; Lerman, Melissa A; Lazarovici, Philip; Lewin, Peter A

2015-09-01

The purpose of this work was to investigate whether low-frequency, low-intensity (20 kHz, <100 mW/cm(2), spatial-peak, temporal-peak intensity) ultrasound, delivered with a lightweight (<100 g), tether-free, fully wearable, battery-powered applicator, is capable of reducing inflammation in a mouse model of rheumatoid arthritis. The therapeutic, acute, anti-inflammatory effect was estimated from the relative swelling induced in mice hindlimb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near-infrared labeled 2-deoxyglucose. The outcome of the experiments indicated that the combination of ultrasound exposure and topical application of 0.1% (w/w) betamethasone gel resulted in statistically significantly (p < 0.05) enhanced anti-inflammatory activity in comparison with drug or ultrasound treatment alone. The present study underscores the potential benefits of low-frequency, low-intensity ultrasound-assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, tolerable low-frequency, low-intensity ultrasound-promoted non-invasive drug delivery. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Pinosylvin and monomethylpinosylvin, constituents of an extract from the knot of Pinus sylvestris, reduce inflammatory gene expression and inflammatory responses in vivo.

PubMed

Laavola, Mirka; Nieminen, Riina; Leppänen, Tiina; Eckerman, Christer; Holmbom, Bjarne; Moilanen, Eeva

2015-04-08

Scots pine (Pinus sylvestris) is known to be rich in phenolic compounds, which may have anti-inflammatory properties. The present study investigated the anti-inflammatory effects of a knot extract from P. sylvestris and two stilbenes, pinosylvin and monomethylpinosylvin, isolated from the extract. Inflammation is characterized by increased release of pro-inflammatory and regulatory mediators including nitric oxide (NO) produced by the inducible nitric oxide synthase (iNOS) pathway. The knot extract (EC50 values of 3 and 3 μg/mL) as well as two of its constituents, pinosylvin (EC50 values of 13 and 15 μM) and monomethylpinosylvin (EC50 values of 8 and 12 μM), reduced NO production and iNOS expression in activated macrophages. They also inhibited the production of inflammatory cytokines IL-6 and MCP-1. More importantly, pinosylvin and monomethylpinosylvin exerted a clear anti-inflammatory effect (80% inhibition at the dose of 100 mg/kg) in the standard in vivo model, carrageenan-induced paw inflammation in the mouse, with the effect being comparable to that of a known iNOS inhibitor L-NIL. The results reveal that the Scots pine stilbenes pinosylvin and monomethylpinosylvin are potential anti-inflammatory compounds.

Effect of prostanoid EP4 receptor antagonist, CJ-042,794, in rat models of pain and inflammation.

PubMed

Murase, Akio; Okumura, Takako; Sakakibara, Ayano; Tonai-Kachi, Hiroko; Nakao, Kazunari; Takada, Junji

2008-02-02

Recent study suggests that the proinflammatory and nociceptive effects of prostaglandin E(2) are mediated by prostanoid receptor subtype EP(4) and prostanoid EP(4) receptor may be a potential target for the treatment of inflammatory pain. Here we describe pharmacological characterization of a novel prostanoid EP(4) receptor antagonist, CJ-042,794 (4-{(1S)-1-[({5-chloro-2-[(4-fluorophenyl) oxy] phenyl} carbonyl) amino] ethyl} benzoic acid) in comparison with piroxicam (non-steroidal anti-inflammatory drug) or rofecoxib (cyclooxygenase-2 inhibitor). CJ-042,794 competitively antagonized cAMP accumulation with a pA(2) value of 8.7 in HEK293 cells overexpressing rat prostanoid EP(4) receptors. Orally administered CJ-042,794 dose-dependently inhibited carrageenan-induced mechanical hyperalgesia with an ED(50) value of 4.7 mg/kg (11 micromol/kg) and its maximal activity was somewhat less effective than that of 10 mg/kg piroxicam (30 micromol/kg p.o.). When CJ-042,794 and rofecoxib were administered to adjuvant-induced arthritis rats on Days 12-22 twice daily, both compounds reversed paw swelling to normal levels. These results suggest that a pharmacological blockade of the prostanoid EP(4) receptor may represent a new therapeutic strategy in signs and symptomatic relief of osteoarthritis and/or rheumatoid arthritis.

Enhanced therapeutic anti-inflammatory effect of betamethasone upon topical administration with low frequency, low intensity (20 kHz, 100 mW/cm2) ultrasound exposure on carrageenan-induced arthritis in mice model

PubMed Central

Cohen, Gadi; Natsheh, Hiba; Sunny, Youhan; Bawiec, Christopher R.; Touitou, Elka; Lerman, Melissa A.; Lazarovici, Philip; Lewin, Peter A.

2015-01-01

The purpose of this work was to investigate whether low frequency, low intensity (LFLI, 20 kHz, <100 mW/cm2, spatial-peak, temporal-peak) ultrasound (US), delivered by a light-weight (<100g), tether-free, fully wearable, battery powered applicator is capable of reducing inflammation in a mouse model of Rheumatoid Arthritis (RA). The therapeutic, acute, anti-inflammatory effect was estimated by the relative swelling induced in mice hind limb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near infrared labeled 2-deoxy-glucose (2DG). The outcome of the experiments indicated that the combination of US exposure with topical application of 0.1% w/w betamethasone gel, exhibited statistically significant (p<0.05) enhanced anti-inflammatory properties in comparison with the drug or US treatment alone. The present study underscores the potential benefits of LFLI US assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, safe, LFLI ultrasound promoted non-invasive drug delivery. PMID:26003010

Balanophora spicata and Lupeol Acetate Possess Antinociceptive and Anti-Inflammatory Activities In Vivo and In Vitro

PubMed Central

Chen, Yuh-Fung; Ching, Chien; Wu, Tian-Shung; Wu, Chi-Rei; Hsieh, Wen-Tsong; Tsai, Huei-Yann

2012-01-01

Aims of the present study were to investigate effects of Balanophora spicata (BS) on antinociception and anti-inflammation both in vivo and in vitro. Crude extract of BS inhibited vascular permeability induced by histamine, serotonin, bradykinin, and PGE2, but not by PAF. Furthermore, BS crude extract, different layers (n-hexane, ethyl acetate, n-butanol, and water layer), and lupeol acetate had significant antinociceptive and anti-inflammatory effects on acetic acid-induced abdominal writhing response, formalin-induced licking behavior, carrageenan-, and serotonin-induced paw edema. The n-hexane layer had the most effective potency among all layers (IC50: 67.33 mg/kg on writhing response; IC50s: 34.2 mg/kg and 21.29 mg/kg on the early phase and late phase of formalin test, resp.). Additionally, lupeol acetate which was isolated from the n-hexane layer of BS effectively inhibited the acetic acid-induced writhing response (IC50: 28.32 mg/kg), formalin-induced licking behavior (IC50: 20.95 mg/kg), NO production (IC50: 4.102 μM), iNOS expression (IC50: 5.35 μM), and COX2 expression (IC50: 5.13 μM) in LPS-stimulated RAW 264.7 cells. In conclusion, BS has antinociceptive and anti-inflammatory effects which may be partially due to the inhibition of changes in vascular permeability induced by histamine, serotonin, bradykinin, and PGE2 and the attenuation of iNOS and COX-2 expression. PMID:23243439

Antihyperalgesic/antinociceptive effects of ceftriaxone and its synergistic interactions with different analgesics in inflammatory pain in rodents.

PubMed

Stepanovic-Petrovic, Radica M; Micov, Ana M; Tomic, Maja A; Kovacevic, Jovana M; Boškovic, Bogdan D

2014-03-01

The β-lactam antibiotic ceftriaxone stimulates glutamate transporter GLT-1 expression and is effective in neuropathic and visceral pain models. This study examined the effects of ceftriaxone and its interactions with different analgesics (ibuprofen, celecoxib, paracetamol, and levetiracetam) in somatic and visceral pain models in rodents. The effects of ceftriaxone (intraperitoneally/intraplantarly), analgesics (orally), and their combinations were examined in the carrageenan-induced paw inflammatory hyperalgesia model in rats (n = 6-12) and in the acetic acid-induced writhing test in mice (n = 6-10). The type of interaction between ceftriaxone and analgesics was determined by isobolographic analysis. Pretreatment with intraperitoneally administered ceftriaxone (10-200 mg/kg per day) for 7 days produced a significant dose-dependent antihyperalgesia in the somatic inflammatory model. Acute administration of ceftriaxone, via either intraperitoneal (10-200 mg/kg) or intraplantar (0.05-0.2 mg per paw) routes, produced a significant and dose-dependent but less efficacious antihyperalgesia. In the visceral pain model, significant dose-dependent antinociception of ceftriaxone (25-200 mg/kg per day) was observed only after the 7-day pretreatment. Isobolographic analysis in the inflammatory hyperalgesia model revealed approximately 10-fold reduction of doses of both drugs in all examined combinations. In the visceral nociception model, more than 7- and 17-fold reduction of doses of both drugs was observed in combinations of ceftriaxone with ibuprofen/paracetamol and celecoxib/levetiracetam, respectively. Ceftriaxone exerts antihyperalgesia/antinociception in both somatic and visceral inflammatory pain. Its efficacy is higher after a 7-day pretreatment than after acute administration. The two-drug combinations of ceftriaxone and the nonsteroidal analgesics/levetiracetam have synergistic interactions in both pain models. These results suggest that ceftriaxone, particularly in combinations with ibuprofen, celecoxib, paracetamol, or levetiracetam, may provide useful approach to the clinical treatment of inflammation-related pain.

Procyanidin B2 ameliorates carrageenan-induced chronic nonbacterial prostatitis in rats via anti-inflammatory and activation of the Nrf2 pathway.

PubMed

Wang, Wei; Chen, Renzong; Wang, Jiye

2017-11-04

Prostatitis is one of the most prevalent problems in andriatry and urinary surgery. In the present study, we evaluated the effect of procyanidin B2 (PB) on carrageenan-induced chronic nonbacterial prostatitis in rats. Results showed that PB significantly decreased the prostatic index and enhanced the body weight inhibited by carrageenan. Biochemical results revealed that PB significantly lowered the prostatic specific antigen (PSA) and alleviated oxidative stress in serum. The levels of TNF-α, IL-6, and IL-10 in prostatic homogenate were also significantly decreased after PB treatment. We also found evidence that PB treatment reversed the suppression of Nrf2 nuclear translocation, and increased the expressions of NQO1 and HO-1 in the prostate glands. In conclusion, treatment with PB attenuates carrageenan-induced chronic nonbacterial prostatitis via anti-inflammatory and activation of the Nrf2 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum pinnatum (Crassulaceae) leaf aqueous extract.

PubMed

Ojewole, John A O

2005-05-13

In order to scientifically appraise some of the ethnomedical uses of Bryophyllum pinnatum leaves, the present study was undertaken to investigate the antinociceptive, anti-inflammatory and antidiabetic properties of the plant's leaf aqueous extract in experimental animal models. The antinociceptive effect of the herb's leaf extract was evaluated by the 'hot-plate' and 'acetic acid' test models of pain in mice. The anti-inflammatory and antidiabetic effects of the plant's extract were investigated in rats, using fresh egg albumin-induced pedal (paw) oedema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used respectively as reference drugs for comparison. Bryophyllum pinnatum leaf aqueous extract (BPE, 25-800 mg/kg i.p.) produced significant (P<0.05-0.001) antinociceptive effects against thermally- and chemically-induced nociceptive pain stimuli in mice. The plant extract (BPE, 25-800 mg/kg p.o. or i.p.) also significantly (P<0.05-0.001) inhibited fresh egg albumin-induced acute inflammation and caused significant (P<0.05-0.001) hypoglycaemia in rats. The results of this experimental animal study suggest that Bryophyllum pinnatum leaf aqueous extract possesses antinociceptive, anti-inflammatory and hypoglycaemic properties. The different flavonoids, polyphenols, triterpenoids and other chemical constituents of the herb are speculated to account for the observed antinociceptive, anti-inflammatory and antidiabetic properties of the plant.

Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation

PubMed Central

Kataoka, Takahiro

2013-01-01

Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation. PMID:23420683

Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation.

PubMed

Kataoka, Takahiro

2013-07-01

Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation.

A novel approach to arthritis treatment based on resveratrol and curcumin co-encapsulated in lipid-core nanocapsules: In vivo studies.

PubMed

Coradini, Karine; Friedrich, Rossana B; Fonseca, Francisco N; Vencato, Marina S; Andrade, Diego F; Oliveira, Cláudia M; Battistel, Ana Paula; Guterres, Silvia S; da Rocha, Maria Izabel U M; Pohlmann, Adriana R; Beck, Ruy C R

2015-10-12

Resveratrol and curcumin are two natural polyphenols extensively used due to their remarkable anti-inflammatory activity. The present work presents an inedited study of the in vivo antioedematogenic activity of these polyphenols co-encapsulated in lipid-core nanocapsules on Complete Freund's adjuvant (CFA)-induced arthritis in rats. Lipid-core nanocapsules were prepared by interfacial deposition of preformed polymer. Animals received a single subplantar injection of CFA in the right paw. Fourteen days after arthritis induction, they were treated with resveratrol, curcumin, or both in solution or loaded in lipid-core nanocapsules (1.75 mg/kg/twice daily, i.p.), for 8 days. At the doses used, the polyphenols in solution were not able to decrease paw oedema. However, nanoencapsulation improved the antioedematogenic activity of polyphenols at the same doses. In addition, the treatment with co-encapsulated polyphenols showed the most pronounced effects, where an inhibition of 37-55% was observed between day 16 and 22 after arthritis induction. This treatment minimized most of the histological changes observed, like fibrosis in synovial tissue, cartilage and bone loss. In addition, unlike conventionally arthritis treatment, resveratrol and curcumin co-encapsulated in lipid-core nanocapsules did not alter important hepatic biochemical markers (ALP, AST, and ALT). In conclusion, the strategy of co-encapsulating resveratrol and curcumin in lipid-core nanocapsules improves their efficacy as oedematogenic agents, with no evidence of hepatotoxic effects. This is a promising strategy for the development of new schemes for treatment of chronic inflammation diseases, like arthritis. Copyright © 2015 Elsevier B.V. All rights reserved.

Indolyl-isoxazolidines attenuate LPS-stimulated pro-inflammatory cytokines and increase survival in a mouse model of sepsis: Identification of potent lead.

PubMed

Singh, Gagandeep; Singh, Gurjit; Bhatti, Rajbir; Gupta, Mehak; Kumar, Ajay; Sharma, Ankita; Singh Ishar, Mohan Paul

2018-06-10

A library of indolyl-isoxazolidines (6-9) has been synthesized by regio- and stereoselective microwave irradiated 1,3-dipolar cycloadditions of C-(3-indolyl)-N-phenylnitrone (2') with variedly substituted dipolarophiles (3'-5') and screened for their anti-inflammatory activities through inhibition of pro-inflammatory cytokines such as TNF-α and IL-6. Amongst the evaluated compounds (6-9), bicyclic isoxazolidine (9a) was found to exhibit significant inhibitory potential against LPS induced human IL-6 and TNF-α in THP-1 cells. Compound 9a was further assessed for in vivo analgesic and anti-inflammatory activities via acetic acid induced writhing and carrageenan induced paw edema models in mice, respectively. The results showed that compound possesses potent anti-inflammatory-analgesic activity comparable to indomethacin and did not show toxicity up to a 2000 mg kg -1 dose as evidenced by histopathological studies. Consequently, the most active compound 9a was also evaluated against LPS-induced septic death and exhibited a significant protection in in vivo mouse model. Taken all together, the results suggest that the compound 9a is able to attenuate pro-inflammatory cytokines such as IL-6 and TNF-α; accelerate resolution of inflammation, and also increased survival rate of septic mice. Therefore, these "lead" isoxazolidines can be used as promising candidate for further analgesic/anti-inflammatory drug design and development. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea-pig.

PubMed Central

Marcus, S. N.; Marcus, A. J.; Marcus, R.; Ewen, S. W.; Watt, J.

1992-01-01

The pre-ulcerative phase of carrageenan-induced colonic ulceration was investigated in guinea-pigs supplied 3% degraded carrageenan as an aqueous solution as drinking fluid for 2 or 3 days during which no ulceration of the bowel was observed with the naked eye or dissecting microscope. Mucosal microscopic changes, from caecum to rectum, were multifocal and included cellular infiltrates, dilatation of glands, crypt abscesses, micro-ulcers and sulphated polysaccharide in the lamina propria. Sulphated polysaccharide was also demonstrated histologically for the first time within the surface epithelium and showed ultrastructural features similar to carrageenan. The results indicate that colonic epithelium in the guinea-pig is capable of macromolecular absorption. Carrageenan, a highly active polyanionic electrolyte, within the surface epithelial cells is most likely a primary factor in the breakdown of mucosal integrity. Macromolecular absorption causing enteropathy of the large bowel is a new pathophysiological concept which may have implications in man, particularly in the pathology of large bowel disease. Images Fig. 7 Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1356411

Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via 1H2O MRI: implications for boron neutron capture therapy of malignant brain tumours

NASA Astrophysics Data System (ADS)

Medina, Daniel C.; Li, Xin; Springer, Charles S., Jr.

2005-05-01

In addition to its common usage as a tracer in metabolic and physiological studies, deuterium possesses anti-tumoural activity and confers protection against γ-irradiation. A more recent interest in deuterium emanates from the search for alternatives capable of improving neutron penetrance whilst reducing healthy tissue radiation dose deposition in boron neutron capture therapy of malignant brain tumours. Despite this potential clinical application, deuterium induces brain oedema, which is detrimental to neutron capture therapy. In this study, five adult male rats were titrated with deuterated drinking water while brain oedema was monitored via water proton magnetic resonance imaging. This report concludes that deuterium, as well as deuterium-induced brain oedema, possesses a uniform brain bio-distribution. At a steady-state blood fluid deuteration value of 16%, when the deuterium isotope fraction in drinking water was 25%, a mean oedematous volume change of 9 ± 2% (p-value <0.001) was observed in the rat brain—this may account for neurological and behavioural abnormalities found in mammals drinking highly deuterated water. In addition to characterizing the pharmaco-thermodynamics of deuterium-induced oedema, this report also estimates the impact of oedema on thermal neutron enhancement and effective dose reduction factors using simple linear transport calculations. While body fluid deuteration enhances thermal neutron flux penetrance and reduces dose deposition, oedema has the opposite effect because it increases the volume of interest, e.g., the brain volume. Thermal neutron enhancement and effective dose reduction factors could be reduced by as much as ~10% in the presence of a 9% water volume increase (oedema). All three authors have contributed equally to this work.

Catecholamine plasma levels, IFN-γ serum levels and antibodies production induced by rabies vaccine in dogs selected for their paw preference.

PubMed

Siniscalchi, Marcello; Cirone, Francesco; Guaricci, Antonio Ciro; Quaranta, Angelo

2014-01-01

To explore the possible role of the sympathetic nervous activity in the asymmetrical crosstalk between the brain and immune system, catecholamine (E, NE) plasma levels, Interferon-γ (IFN-γ) serum levels and production of antibodies induced by rabies vaccine in dogs selected for their paw preference were measured. The results showed that the direction of behavioural lateralization influenced both epinephrine levels and immune response in dogs. A different kinetic of epinephrine levels after immunization was observed in left-pawed dogs compared to both right-pawed and ambidextrous dogs. The titers of antirabies antibodies were lower in left-pawed dogs than in right-pawed and ambidextrous dogs. Similarly, the IFN-γ serum levels were lower in left-pawed dogs than in the other two groups. Taken together, these findings showed that the left-pawed group appeared to be consistently the different group stressing the fundamental role played by the sympathetic nervous system as a mechanistic basis for the crosstalk between the brain and the immune system.

Differential Action between Schisandrin A and Schisandrin B in Eliciting an Anti-Inflammatory Action: The Depletion of Reduced Glutathione and the Induction of an Antioxidant Response

PubMed Central

Leong, Pou Kuan; Wong, Hoi Shan; Chen, Jihang; Chan, Wing Man; Leung, Hoi Yan; Ko, Kam Ming

2016-01-01

Schisandrin A (Sch A) and schisandrin B (Sch B) are active components of Schisandrae Fructus. We compared the biochemical mechanism underlying the anti-inflammatory action of Sch A and Sch B, using cultured lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and concanavalin (ConA)-stimulated mouse splenocytes. Pre-incubation with Sch A or Sch B produced an anti-inflammatory action in LPS-stimulated RAW264.7 cells, as evidenced by the inhibition of the pro-inflammatory c-Jun N-terminal kinases/p38 kinase/nuclear factor-κB signaling pathway as well as the suppression of various pro-inflammatory cytokines and effectors, with the extent of inhibition by Sch A being more pronounced. The greater activity of Sch A in anti-inflammatory response was associated with a greater decrease in cellular reduced glutathione (GSH) level and a greater increase in glutathione S-transferase activity than corresponding changes produced by Sch B. However, upon incubation, only Sch B resulted in the activation of the nuclear factor (erythroid-derived 2)-like factor 2 and the induction of a significant increase in the expression of thioredoxin (TRX) in RAW264.7 cells. The Sch B-induced increase in TRX expression was associated with the suppression of pro-inflammatory cytokines and effectors in LPS-stimulated macrophages. Studies in a mouse model of inflammation (carrageenan-induced paw edema) indicated that while long-term treatment with either Sch A or Sch B suppressed the extent of paw edema, only acute treatment with Sch A produced a significant degree of inhibition on the inflammatory response. Although only Sch A decreased the cellular GSH level and suppressed the release of pro-inflammatory cytokines and cell proliferation in ConA-simulated splenocytes in vitro, both Sch A and Sch B treatments, while not altering cellular GSH levels, suppressed ConA-stimulated splenocyte proliferation ex vivo. These results suggest that Sch A and Sch B may act differentially on activating GST/ depleting cellular GSH and inducing an antioxidant response involved in their anti-inflammatory actions. PMID:27195753

Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression.

PubMed Central

Gerritsen, M. E.; Carley, W. W.; Ranges, G. E.; Shen, C. P.; Phan, S. A.; Ligon, G. F.; Perry, C. A.

1995-01-01

Treatment of human endothelial cells with cytokines such as interleukin-1, tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma induces the expression of specific leukocyte adhesion molecules on the endothelial cell surface. Interfering with either leukocyte adhesion or adhesion protein upregulation is an important therapeutic target as evidenced by the potent anti-inflammatory actions of neutralizing antibodies to these ligands in various animal models and in patients. In the present study we report that cotreatment of human endothelial cells with certain hydroxyflavones and flavanols blocks cytokine-induced ICAM-1, VCAM-1, and E-selectin expression on human endothelial cells. One of the most potent flavones, apigenin, exhibited a dose- and time-dependent, reversible effect on adhesion protein expression as well as inhibiting adhesion protein upregulation at the transcriptional level. Apigenin also inhibited IL-1 alpha-induced prostaglandin synthesis and TNF-alpha-induced IL-6 and IL-8 production, suggesting that the hydroxyflavones may act as general inhibitors of cytokine-induced gene expression. Although apigenin did not inhibit TNF-alpha-induced nuclear translocation of NF-kappa B(p50(NFKB1)/p65(RelA)) we found this flavonoid did inhibit TNF-alpha induced beta-galactosidase activity in SW480 cells stably transfected with a beta-galactosidase reporter construct driven by four NF-kappa B elements, suggesting an action on NF-kappa B transcriptional activation. Adhesion of leukocytes to cytokine-treated endothelial cells was blocked in endothelial cells cotreated with apigenin. Finally, apigenin demonstrated potent anti-inflammatory activity in carrageenan induced rat paw edema and delayed type hypersensitivity in the mouse. We conclude that flavonoids offer important therapeutic potential for the treatment of a variety of inflammatory diseases involving an increase in leukocyte adhesion and trafficking. Images Figure 7 Figure 8 Figure 11 PMID:7543732

Mechanisms underlying the antinociceptive effect of mangiferin in the formalin test.

PubMed

Izquierdo, Teresa; Espinosa de los Monteros-Zuñiga, Antonio; Cervantes-Durán, Claudia; Lozada, María Concepción; Godínez-Chaparro, Beatriz

2013-10-15

The purpose of this study was to investigate the possible antinociceptive effect of mangiferin, a glucosylxanthone present in Mangifera indica L., in inflammatory pain. Furthermore, we sought to investigate the possible mechanisms action that contributes to these effects. The ipsilateral local peripheral (1-30 µg/paw), intrathecal (1-30 µg/rat) and oral (1-30 mg/kg) administration of mangiferin produced a dose-dependent reduction in formalin-induced nociception. The antinociceptive effect of this drug was similar to that induced by diclofenac after oral and local peripheral administration. Furthermore, mangiferin was also able to reduce 0.1% capsaicin- and serotonin-induced nociceptive behavior. The local peripheral antinociceptive effect of mangiferin in the formalin test was blocked by naloxone (50 μg/paw), naltrindole (1 μg/paw), 5-guanidinonaltrindole (5-GNTI, 1 μg/paw), N(G)-L-nitro-arginine methyl ester (L-NAME, 100 µg/paw), 1H-(1,2,4)-oxadiazolo [4,2-a]quinoxalin-1-one (ODQ, 50 µg/paw) and glibenclamide (50 μg/paw), but not by methiothepin (30 μg/paw). These results suggest that the antinociceptive effects induced by mangiferin are mediated by the peripheral opioidergic system involving the activation of δ, κ, and probably µ, receptors, but not serotonergic receptors. Data also suggests that mangiferin activates the NO-cyclic GMP-ATP-sensitive K(+) channels pathway in order to produce its local peripheral antinociceptive effect in the formalin test. Mangiferin may prove to be effective in treating inflammatory pain in humans. © 2013 Elsevier B.V. All rights reserved.

The Role of Carrageenan and Carboxymethylcellulose in the Development of Intestinal Inflammation

PubMed Central

Martino, John Vincent; Van Limbergen, Johan; Cahill, Leah E.

2017-01-01

Although the exact pathophysiology remains unknown, the development of inflammatory bowel disease (IBD) is influenced by the interplay between genetics, the immune system, and environmental factors such as diet. The commonly used food additives, carrageenan and carboxymethylcellulose (CMC), are used to develop intestinal inflammation in animal models. These food additives are excluded from current dietary approaches to induce disease remission in Crohn’s disease such as exclusive enteral nutrition (EEN) using a polymeric formula. By reviewing the existing scientific literature, this review aims to discuss the role that carrageenan and CMC may play in the development of IBD. Animal studies consistently report that carrageenan and CMC induce histopathological features that are typical of IBD while altering the microbiome, disrupting the intestinal epithelial barrier, inhibiting proteins that provide protection against microorganisms, and stimulating the elaboration of pro-inflammatory cytokines. Similar trials directly assessing the influence of carrageenan and CMC in humans are of course unethical to conduct, but recent studies of human epithelial cells and the human microbiome support the findings from animal studies. Carrageenan and CMC may trigger or magnify an inflammatory response in the human intestine but are unlikely to be identified as the sole environmental factor involved in the development of IBD or in disease recurrence after treatment. However, the widespread use of carrageenan and CMC in foods consumed by the pediatric population in a “Western” diet is on the rise alongside a corresponding increase in IBD incidence, and questions are being raised about the safety of frequent usage of these food additives. Therefore, further research is warranted to elucidate the role of carrageenan and CMC in intestinal inflammation, which may help identify novel nutritional strategies that hinder the development of the disease or prevent disease relapse post-EEN treatment. PMID:28507982

Evaluation of the efficacy of Hylotelephium purpureum gel in the treatment of experimental periodontitis

PubMed Central

Wang, Xiaofeng; Wang, Wei; Li, Wei; Niu, Zhiduo; Wang, Qing; Zhang, Dianwen; Li, Hui; Wang, Jincheng

2018-01-01

Local drug delivery systems have been proposed for the treatment of periodontitis, and Hylotelephium purpureum may be a suitable agent for use in such a system. The present study aimed to formulate a Hylotelephium purpureum gel (HPG) and evaluate the anti-inflammatory activity and antinociceptive effects of Hylotelephium purpureum and to assess the duration of action and efficacy of HPG in the treatment of experimental periodontitis in a KM mouse model. First, an acute toxicity study was performed, and secondly, xylene-induced mouse-ear edema, acetic acid-induced mouse peritoneal capillary permeability and carrageenan-induced hind-paw edema tests were used to investigate the anti-inflammatory activity of the gel. The acetic acid-induced writhing response and hot-plate tests were used to evaluate the antinociceptive activity. The therapeutic effects of HPG in experimental periodontitis were evaluated and minimum inhibitory concentration of the gel was determined. The results showed that intragastrically administration of 80 ml/kg of HPG produced no toxic effects. There were statistically significant changes in gingival indexes and sulcus bleeding indexes in the high-dose HPG-treated group. The serum levels of superoxide dismutase and glutathione peroxidase were significantly heightened, while the level of malondialdehyde was decreased. HPG exhibited 32.7% inhibition of edema, and altered the peritoneal capillary permeability in mice. The gel had relatively good bacteriostatic and bactericidal effects. It also exhibited antinociceptive activity, as demonstrated by the acetic acid-induced writhing response test and hot-plate test. In summary, the present study demonstrates that HPG is effective in the treatment of experimental periodontitis. PMID:29541459

Formulation and evaluation of flurbiprofen microemulsion.

PubMed

Ambade, K W; Jadhav, S L; Gambhire, M N; Kurmi, S D; Kadam, V J; Jadhav, K R

2008-01-01

The purpose of the present study was to investigate the microemulsion formulations for topical delivery of Flurbiprofen (FP) in order to by pass its gastrointestinal adverse effects. The pseudoternary phase diagrams were developed and various microemulsion formulations were prepared using Isopropyl Myristate (IPM), Ethyl Oleate (EO) as oils, Aerosol OT as surfactant and Sorbitan Monooleate as cosurfactant. The transdermal permeability of flurbiprofen from microemulsions containing IPM and EO as two different oil phases was analyzed using Keshary-Chien diffusion cell through excised rat skin. Flurbiprofen showed higher in vitro permeation from IPM as compared to that of from EO microemulsion. Thus microemulsion containing IPM as oil phase were selected for optimization. The optimization was carried out using 2(3) factorial design. The optimized formula was then subjected to in vivo anti-inflammatory study and the performance of flurbiprofen from optimized formulation was compared with that of gel cream. Flurbiprofen from optimized microemulsion formulation was found to be more effective as compared to gel cream in inhibiting the carrageenan induced rat paw edema at all time intervals. Histopathological investigation of rat skin revealed the safety of microemulsion formulation for topical use. Thus the present study indicates that, microemulsion can be a promising vehicle for the topical delivery of flurbiprofen.

Biosynthesis, characterization, and evaluation of bioactivities of leaf extract-mediated biocompatible silver nanoparticles from an early tracheophyte, Pteris tripartita Sw.

PubMed Central

Baskaran, Xavierravi; Geo Vigila, Antony Varuvel; Parimelazhagan, Thangaraj; Muralidhara-Rao, Doulathabad; Zhang, Shouzhou

2016-01-01

The objective of the study was to characterize silver nanoparticles (Ag-NPs) and their bioactivities in early tracheophytes (Pteridophyta). Aqueous leaf extract of a critically endangered fern, Pteris tripartita Sw., was used for one-step green synthesis of Ag-NPs. The biosynthesized Ag-NPs were characterized using ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and high-resolution transmission electron microscopy. Morphologically, the Ag-NPs showed hexagonal, spherical, and rod-shaped structures. Size distributions of Ag-NPs, calculated using Scherrer’s formula, showed an average size of 32 nm. Ag-NPs were studied for in vitro antioxidant, antimicrobial, and in vivo anti-inflammatory activities. Ag-NPs exhibited significant anti-inflammatory activity in carrageenan-induced paw volume tests performed in female Wistar albino rats. Furthermore, Ag-NPs showed significant antimicrobial activity against 12 different microorganisms in three different assays (disk diffusion, time course growth, and minimum inhibitory concentration). This study reports that colloidal Ag-NPs can be synthesized by simple, nonhazardous methods, and that biosynthesized Ag-NPs have significant therapeutic properties. PMID:27895478

New Coumarin Derivatives as Potent Selective COX-2 Inhibitors: Synthesis, Anti-Inflammatory, QSAR, and Molecular Modeling Studies.

PubMed

Dawood, Dina H; Batran, Rasha Z; Farghaly, Thoraya A; Khedr, Mohammed A; Abdulla, Mohamed M

2015-12-01

Two new series of coumarin derivatives incorporating thiazoline and thiazolidinone moieties were designed, synthesized, and investigated in vivo for their anti-inflammatory activities using the carrageenan-induced rat paw edema model and in vitro for their inhibitory activities against the human cyclooxygenase (COX)-1 and COX-2 isoforms. Most of the synthesized compounds demonstrated exceptionally high in vivo anti-inflammatory activity and displayed superior GI safety profiles (0-7% ulceration) as compared to indomethacin. All the bioactive compounds showed in vitro high affinity and selectivity toward the COX-2 isoenzyme, compared to the reference celecoxib with IC50 values ranging from 0.31 to 0.78 μM. The ethyl thiosemicarbazone 2b, thiazoline derivatives 3a, 3b, 5b, 6a, and 7f, and the thiazolidinone compounds 8b and 9a showed the highest in vivo and in vitro anti-inflammatory activities with remarkable COX-2 selectivity. Quantitative structure-activity relationship study (QSAR) was done and resulted in a highly predictive power R(2) (0.908). A molecular docking study revealed a relationship between the docking affinity and the biological results. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The involvement of peripheral alpha 2-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain.

PubMed

Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Paranos, Sonja Lj; Prostran, Milica S; Bosković, Bogdan

2007-11-01

We studied whether peripheral alpha2-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha2-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)-adrenoceptor antagonist), MK-912 (selective alpha2C-adrenoceptor antagonist), and clonidine (alpha2-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia. Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.pl.), BRL 44408 (100 and 200 nmol/paw; i.pl.) and MK-912 (10 and 20 nmol/paw; i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/paw; i.pl.) in a dose-dependent manner. The effects of antagonists were due to local effects since they were not observed after administration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED(50) (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. Isobolographic analysis revealed an additive antihyperalgesic effect. Our results indicate that the peripheral alpha2A and alpha2C adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia.

Potential of carrageenans to protect drugs from polymorphic transformation.

PubMed

Schmidt, Andrea G; Wartewig, Siegfried; Picker, Katharina M

2003-07-01

Carrageenans were analysed in mixture with polymorphic drugs to test their potential for minimising polymorphic or pseudopolymorphic transitions, which are induced by the tableting process. The kappa-carrageenans Gelcarin GP-812 NF and Gelcarin GP-911 NF and the iota-carrageenan Gelcarin GP-379 NF were tested in comparison to the well-known tableting excipients microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), and dicalcium phosphate dihydrate (DCPD). Amorphous indomethacin was chosen as model drug since its well-known recrystallisation behaviour can be mechanically stimulated. Further on, theophylline monohydrate was used. Its dehydration is induced by tableting. Pure materials and mixtures containing 20% (w/w) drug were compressed up to different maximum relative densities. The data obtained during tableting were analysed by three-dimensional (3D) modelling. Afterwards tablets were broken and examined by Fourier transform Raman spectroscopy in order to determine the degree of transformation inside the tablet. For quantitative interpretation, the intensities of representative bands were used. Thermal analysis was used additionally. Using 3D modelling a decrease of plastic deformation can be noticed in the order HPMC>MCC>carrageenans, whereas DCPD represents an exception because of brittle fracture. Best hindrance of polymorphic transformation showed the carrageenans, the hindrance was slightly worse for HPMC. MCC and DCPD could not hinder transformation. A complete protection of the amorphous form could not be achieved. For theophylline monohydrate, the results were similar.

Analgesic and anti-inflammatory activities of 80% methanol root extract of Jasminum abyssinicum Hochst. ex. Dc. (Oleaceae) in mice.

PubMed

Tadiwos, Yohannes; Nedi, Teshome; Engidawork, Ephrem

2017-04-18

Pain and inflammation are associated with the pathophysiology of various clinical conditions. Most analgesic and anti-inflammatory drugs available in the market present a wide range of problems. The current study was aimed at investigating the analgesic and anti-inflammatory activity of 80% methanol extract of J. abyssinicum root. The analgesic activity was determined using tail-flick test and acetic acid induced writhing, whereas anti-inflammatory activity was determined by carrageenan induced paw edema and formalin induced pedal edema, carried out in vivo. The test group received three different doses of the extract (50mg/kg, 100mg/kg and 200mg/kg) orally. The positive control group received diclofenac (10mg/kg), aspirin (100mg/kg or 150mg/kg) or morphine (20mg/kg) orally. The negative control group received vehicle (2% Tween 80, 10ml/kg) orally. Furthermore, preliminary phytochemical screening was carried out. Oral administration of J. abbysinicum 80% methanol extract (at all doses) significantly (p<0.001) inhibit pain sensation in the pain models. Similarly, the extract demonstrated anti-inflammatory effect in the inflammation models in mice. Preliminary phytochemical screening showed the presence of saponins, flavonoids, terpenoids, triterpenens and glycosides. The data obtained from the present study indicates that the extract possessed a significant analgesic and anti-inflammatory activity, upholding the folkloric use of the plant. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

A study of oxidative stress induced by non-thermal plasma-activated water for bacterial damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Qian; Ma, Ruonan; Tian, Ying

2013-05-20

Ar/O{sub 2} (2%) cold plasma microjet was used to create plasma-activated water (PAW). The disinfection efficacy of PAW against Staphylococcus aureus showed that PAW can effectively disinfect bacteria. Optical emission spectra and oxidation reduction potential results demonstrated the inactivation is attributed to oxidative stress induced by reactive oxygen species in PAW. Moreover, the results of X-ray photoelectron spectroscopy, atomic absorption spectrometry, and transmission electron microscopy suggested that the chemical state of cell surface, the integrity of cell membrane, as well as the cell internal components and structure were damaged by the oxidative stress.

Substance P-induced inflammatory responses in guinea-pig skin: the effect of specific NK1 receptor antagonists and the role of endogenous mediators.

PubMed Central

Walsh, D T; Weg, V B; Williams, T J; Nourshargh, S

1995-01-01

1. The sensory neuropeptide substance P (SP), when released from sensory nerves, has been implicated in the development of neurogenic inflammation. In the present study, using an in vivo model system, we have characterized and investigated the mechanisms underlying SP-induced leukocyte accumulation and oedema formation in the guinea-pig. 2. Intradermally injected SP (i.d., 10(-13) - 10(-9) mol per site), induced a dose- and time-dependent accumulation of 111In-neutrophils, 111In-eosinophils and oedema formation as measured by the local accumulation of i.v. injected 125I-albumin. The leukocyte accumulation evoked by SP was significant at 10(-10) and 10(-9) mol per site, whereas oedema formation was significant at the lowest dose tested (10(-13) mol per site). 3. The NK1 receptor antagonists, CP-96,345 (1 mg kg-1, i.v.) and RP-67,580 (10 micrograms per site, i.d.), significantly attenuated the oedema formation induced by the lower doses of SP. Oedema formation and leukocyte accumulation induced by 10(-9) mol per site SP were unaffected by either antagonist. 4. SP-elicited responses were not significantly affected by the platelet activating factor (PAF) receptor antagonist, UK-74,505 (2.5 mg kg-1, i.v.) or the H1 histamine receptor antagonist, chlorpheniramine (10(-8) mol per site, i.d.). However, the 111In-eosinophil accumulation, but not the 111In-neutrophil accumulation or oedema formation, induced by SP was significantly inhibited by the specific 5-lipoxygenase (5-LO) inhibitor, ZM-230,487 (10(-8) mol per site, i.d.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7541689

Application of Box-Behnken design for ultrasonic-assisted extraction of polysaccharides from Paeonia emodi.

PubMed

Ahmad, Ajaz; Alkharfy, Khalid M; Wani, Tanveer A; Raish, Mohammad

2015-01-01

The objective of the present work was to study the ultrasonic assisted extraction and optimization of polysaccharides from Paeonia emodi and evaluation of its anti-inflammatory response. Specifically, the optimization of polysaccharides was carried out using Box-Behnken statistical experimental design. Response surface methodology (RSM) of three factors (extraction temperature, extraction time and liquid solid ratio) was employed to optimize the percentage yield of the polysaccharides. The experimental data were fitted to quadratic response surface models using multiple regression analysis with high coefficient of determination value (R) of 0.9906. The highest polysaccharide yield (8.69%) as per the Derringer's desirability prediction tool was obtained under the optimal extraction condition (extraction temperature 47.03 °C, extraction time 15.68 min, and liquid solid ratio 1.29 ml/g) with a desirability value of 0.98. These optimized values of tested parameters were validated under similar conditions (n = 6), an average of 8.13 ± 2.08% of polysaccharide yield was obtained in an optimized extraction conditions with 93.55% validity. The anti-inflammatory effect of polysaccharides of P. emodi were studied on carrageenan induced paw edema. In vivo results showed that the P. emodi 200mg/kg of polysaccharide extract exhibited strong potential against inflammatory response induced by 1% suspension of carrageenean in normal saline. Copyright © 2014 Elsevier B.V. All rights reserved.

Anti-rheumatoid Arthritis Effect of Kaejadan via Analgesic and Antiinflammatory Activity in vivo and in vitro.

PubMed

Yoon, Jung Jae; Sohn, Eun Jung; Kim, Jung Hyo; Seo, Jai Wha; Kim, Sung-Hoon

2017-03-01

Although Kaejadan (KJD), an herbal cocktail of three medicinal plants (Lithospermum erythrorhizon, Cinnamomum loureirii, and Salvia miltiorrhiza), has been traditionally used for the treatment of rheumatoid arthritis, its scientific evidence is not fully understood. Hence, we investigated antiinflammatory and analgesic mechanism of KJD in vivo and in vitro. Kaejadan suppressed the number of writhing responses in mice treated by acetic acid and showed antinociceptive effect by tail-flick test. Kaejadan abrogated serotonin or carrageenan or Freund's complete adjuvant (FCA)-induced paw edema and also reduced the level of Evans Blue for vascular permeability. Furthermore, KJD effectively reduced the positive responses for C-reactive protein and rheumatoid arthritis test in FCA-treated rats. Of note, KJD inhibited the level of lipid peroxide malondialdehyde and enhanced the level of superoxide dismutase in the hepatic tissues of FCA-treated rats. Additionally, KJD abrogated the levels of IL-1β and IL-6 in lipopolysaccharide and IFN-γ-exposed RAW 264.7 cells. Also, KJD reduced the expression of cyclooxygenase 2 or inducible nitric oxide synthase at protein and mRNA levels in IFN-γ and lipopolysaccharide-exposed RAW 264.7 cells. Overall, our findings demonstrate that KJD exerts antiinflammatory and analgesic effects via enhancement of antioxidant activity and inhibition of proinflammatory cytokines. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin.

PubMed

Lee, Jin-Ah; Ha, Sang Keun; Cho, EunJung; Choi, Inwook

2015-11-19

The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs) in HepG2 cells were stimulated with lipopolysaccharide (LPS). ARMs prominently inhibited (p < 0.05) the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs). ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%). Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin's anti-inflammatory activities in the body.

Diacerein niosomal gel for topical delivery: development, in vitro and in vivo assessment.

PubMed

El-Say, Khalid M; Abd-Allah, Fathy I; Lila, Ahmed E; Hassan, Abd El-Saboor A; Kassem, Alaa Eldin A

2016-01-01

The purpose of this study was to load diacerein (DCR) in niosomes by applying response surface methodology and incorporate these niosomes in gel base for topical delivery. Box-Behnken design was used to investigate the effect of charge-inducing agent (X1), surfactant HLB (X2) and sonication time (X3) on the vesicle size (Y1), entrapment efficiency (Y2) and cumulative drug released (Y3). DCR niosomal formulations were prepared by thin film hydration method. The optimized formula was incorporated in different gel bases. DCR niosomal gels were evaluated for homogeneity, rheological behavior; in vitro release and pharmacodynamic activity by carrageenan-induced hind paw edema method in the rat compared with DCR commercial gel. The results revealed that the mean vesicle sizes of the prepared niosomes ranged from 7.33 to 23.72 µm and the entrapment efficiency ranged from 9.52% to 58.43% with controlled release pattern over 8 h. DCR niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant, 37.66%, maximum inhibition of edema size in comparison with 20.83% for the commercial gel (p < 0.05). These results recommended the incorporation of DCR niosomes in 3% HPMC for topical application as a potent anti-inflammatory drug for the treatment of osteoarthritis.

λ-Carrageenan improves the antitumor effect of dendritic cellbased vaccine.

PubMed

Li, Jinyao; Aipire, Adila; Li, Jinyu; Zhu, Hongge; Wang, Yanping; Guo, Wenjia; Li, Xiaoqin; Yang, Jia; Liu, Chunling

2017-05-02

In this study, we investigated the effect of λ-carrageenan on the maturation and function of dendritic cells (DCs) and its adjuvant effect on DC-based vaccine. We found that λ-carrageenan dose-dependently decreased the endocytosis of DCs, promoted DC maturation and increased cytokine production through TLR4 mediated signaling pathway. λ-carrageenan treatment also enhanced the ability of DCs in the stimulating allogenic splenocyte proliferation. In TC-1 tumor mouse model, HPV peptides pulsed λ-carrageenan-DC (HPV-CGN-DC) significantly inhibited tumor growth compared with control group. The frequencies of CD4+ and CD8+ T cells in spleens of tumor mice and their activation status were significantly increased in HPV-CGN-DC group, but the frequencies of natural regulatory T cells and CD11b+Gr-1+ cells were significantly decreased. Further, HPV-CGN-DC induced strong CD8+ T cell responses, which are negatively correlated with tumor volumes. The results suggested that λ-carrageenan promoted DC maturation through TLR4 signaling pathway and could be used as the adjuvant in DC-based vaccines.

Bee venom stimulation into lung meridian acupoint reduces inflammation in a mouse model of carrageenan-induced pleurisy: an alternative therapeutic approach for the respiratory inflammatory disease.

PubMed

Choi, Hoon-Seong; Kang, Suk-Yun; Roh, Dae-Hyun; Choi, Sheu-Ran; Ryu, Yeonhee; Lee, Jang-Hern

2018-06-21

Respiratory inflammation is frequent and fatal pathologic state encountered in veterinary medicine. Although diluted bee venom (dBV) has potent anti-inflammatory effects, the clinical use of dBV is limited to several chronic inflammatory diseases. The present study was designed to propose the acupoint treatment of dBV as a novel therapeutic strategy for respiratory inflammatory disease. Experimental pleurisy was induced by injection of carrageenan into left pleural space in mouse. dBV was injected into a specific lung meridian acupoint (LU-5) or into arbitrary non-acupoint located near the midline of the back in mouse. The inflammatory responses were evaluated by analysis the inflammatory indicators in pleural exudate. dBV injection into LU-5 acupoint significantly suppressed the increase of pleural exudate volume, leukocyte accumulation, MPO activity. Moreover, dBV acupoint treatment effectively inhibited the production of IL-1β, but not TNF-α in pleural exudate. On the other hand, dBV treatment on non-acupoint did not inhibit the inflammatory responses in carrageenan-induced pleurisy. The present results demonstrate that dBV stimulation into the LU-5 lung meridian acupoint produces significant anti-inflammatory effects on carrageenan-induced pleurisy suggesting that dBV acupuncture as a promising alternative medicine therapy for respiratory inflammatory diseases.

(E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one ameliorates the collagen-arthritis via blocking ERK/JNK and NF-κB signaling pathway.

PubMed

Li, Xiuxia; Peng, Fei; Xie, Caifeng; Wu, Wenshuang; Han, Xiaolei; Chen, Lijuan

2013-12-01

Our previous report has shown a natural pyranochalcones-derived compound, (E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one (5b), that exerted protection against carrageenan-induced hind paw edema and adjuvant-induced arthritis. In this study, collagen-induced arthritis (CIA) model was used to further examine the anti-arthritic effects of 5b in vivo; the underlying molecular mechanisms of action were also investigated using a murine monocytic cell line, RAW264.7 cells. Here we showed that oral administration of 5b (20mg/kg) significantly suppressed the progression of arthritis. Improvement in disease severity was accompanied by inhibition of CD68-positive cells in knee joint and reduced pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in serum. In vitro, 5b suppressed expressions of iNOS, cyclooxygenase-2 (COX-2), TNF-α, IL-6 and IL-1β as well as productions of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-treated macrophages. This compound also significantly suppressed LPS-induced NF-κB activation, including phosphorylation of I-κB, degradation of I-κB, and nuclear translocation of p65 and p50. Treatment with 5b also blocked LPS-induced expression of TLR4 remarkably, suppressed degradation of IRAKs and phosphorylations of JNK and ERK, but had little effect to p38 kinase activation. These findings indicated that 5b might be a therapeutic agent for rheumatoid arthritis, and exerted an anti-inflammatory effect mainly through mediating TLR4, NF-κB and ERK/JNK signaling pathways in monocytes. © 2013.

Gold(I) Complexes of 9-Deazahypoxanthine as Selective Antitumor and Anti-Inflammatory Agents

PubMed Central

Vančo, Ján; Gáliková, Jana; Hošek, Jan; Dvořák, Zdeněk; Paráková, Lenka; Trávníček, Zdeněk

2014-01-01

The gold(I) mixed-ligand complexes involving O-substituted derivatives of 9-deazahypoxanthine (HLn) and triphenylphosphine (PPh3) with the general formula [Au(Ln)(PPh3)] (1–5) were prepared and thoroughly characterized by elemental analysis, FT-IR and multinuclear NMR spectroscopy, ESI+ mass spectrometry, single crystal X-ray (HL5 and complex 2) and TG/DTA analyses. Complexes 1–5 were evaluated for their in vitro antitumor activity against nine human cancer lines, i.e. MCF7 (breast carcinoma), HOS (osteosarcoma), A549 (adenocarcinoma), G361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) and THP-1 (monocytic leukaemia), for their in vitro anti-inflammatory activity using a model of LPS-activated macrophages, and for their in vivo antiedematous activity by λ-carrageenan-induced hind paw edema model on rats. The results showed that the complexes 1–5 exhibit selective in vitro cytotoxicity against MCF7, HOS, 22Rv1, A2780 and A2780R, with submicromolar IC50 values for 2 against the MCF7 (0.6 µM) and HOS (0.9 µM). The results of in vitro cytotoxicity screening on primary culture of human hepatocytes (HEP220) revealed up to 30-times lower toxicity of compounds against healthy cells as compared with cancer cells. Additionally, the complexes 1–5 significantly influence the secretion and expression of pro-inflammatory cytokines TNF-α and IL-1β by a similar manner as a commercially used anti-arthritic drug Auranofin. The tested complexes also significantly influence the rate and overall volume of the edema, caused by the intraplantar application of λ-carrageenan polysaccharide to rats. Based on these promising results, the presented compounds could qualify to become feasible candidates for advanced testing as potential antitumor and anti-inflammatory drug-like compounds. PMID:25333949

Anti-inflammatory, gastroprotective, free-radical-scavenging, and antimicrobial activities of hawthorn berries ethanol extract.

PubMed

Tadić, Vanja M; Dobrić, Silva; Marković, Goran M; Dordević, Sofija M; Arsić, Ivana A; Menković, Nebojsa R; Stević, Tanja

2008-09-10

Hawthorn [Crataegus monogyna Jacq. and Crataegus oxyacantha L.; sin. Crataegus laevigata (Poiret) DC., Rosaceae] leaves, flowers, and berries are used in traditional medicine in the treatment of chronic heart failure, high blood pressure, arrhythmia, and various digestive ailments, as well as geriatric and antiarteriosclerosis remedies. According to European Pharmacopoeia 6.0, hawthorn berries consist of the dried false fruits of these two species or their mixture. The present study was carried out to test free-radical-scavenging, anti-inflammatory, gastroprotective, and antimicrobial activities of hawthorn berries ethanol extract. Phenolic compounds represented 3.54%, expressed as gallic acid equivalents. Determination of total flavonoid aglycones content yielded 0.18%. The percentage of hyperoside, as the main flavonol component, was 0.14%. With respect to procyanidins content, the obtained value was 0.44%. DPPH radical-scavenging capacity of the extract was concentration-dependent, with EC50 value of 52.04 microg/mL (calculation based on the total phenolic compounds content in the extract). Oral administration of investigated extract caused dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. The obtained anti-inflammatory effect was 20.8, 23.0, and 36.3% for the extract doses of 50, 100, and 200 mg/kg, respectively. In comparison to indomethacin, given in a dose producing 50% reduction of rat paw edema, the extract given in the highest tested dose (200 mg/kg) showed 72.4% of its activity. Gastroprotective activity of the extract was investigated using an ethanol-induced acute stress ulcer in rats with ranitidine as a reference drug. Hawthorn extract produced dose-dependent gastroprotective activity (3.8 +/- 2.1, 1.9 +/- 1.7, and 0.7 +/- 0.5 for doses of 50, 100, and 200 mg/kg, respectively), with the efficacy comparable to that of the reference drug. Antimicrobial testing of the extract revealed its moderate bactericidal activity, especially against gram-positive bacteria Micrococcus flavus, Bacillus subtilis, and Lysteria monocytogenes, with no effect on Candida albicans. All active components identified in the extract might be responsible for activities observed.

Jobelyn® attenuates inflammatory responses and neurobehavioural deficits associated with complete Freund-adjuvant-induced arthritis in mice.

PubMed

Omorogbe, Osarume; Ajayi, Abayomi M; Ben-Azu, Benneth; Oghwere, Ejiroghene E; Adebesin, Adaeze; Aderibigbe, Adegbuyi O; Okubena, Olajuwon; Umukoro, Solomon

2018-02-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the physical and psychosocial wellbeing of the patients and a major cause of work disability. Current drugs for its treatment only provide palliative effect, as cure for the disease still remains elusive. Jobelyn ® (JB), a potent anti-oxidant and anti-inflammatory dietary supplement obtained from Sorghum bicolor, has been claimed to relieve arthritic pain. Thus, this study was designed to evaluate its effect on inflammatory and biochemical changes as well as neurobehavioural deficits associated with complete Freund-adjuvant (CFA)-induced arthritis in mice. The effect of JB (50, 100 and 200 mg/kg) on inflammatory oedema, neurobehavioural deficits, levels of biomarkers of oxidative stress and inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) induced by 0.1 mL of CFA (10 mg/mL) was evaluated in male Swiss mice. Oral administration of JB (100 and 200 mg/kg) reduced inflammatory paw volume and reversed sensorimotor deficits induced by CFA. JB also reduced pain episodes, anxiety and depressive-like symptoms in CFA-mice. The increased level of oxidative stress in the joint and brain tissues of CFA-mice was reduced by JB. It also decreased tumor necrosis factor-alpha and interleukin-6 levels induced by CFA in the joint tissue of mice. These findings suggest that Jobelyn ® attenuates inflammatory responses induced by CFA in mice via inhibition of oxidative stress and release of inflammatory cytokines. The ability of JB to attenuate CFA-induced nociception, sensorimotor deficits and depressive-like symptom suggests it might improve the quality of life of patients with arthritic conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Synthesis, biological evaluation and molecular modeling of novel series of pyridine derivatives as anticancer, anti-inflammatory and analgesic agents

NASA Astrophysics Data System (ADS)

Helal, M. H.; El-Awdan, S. A.; Salem, M. A.; Abd-elaziz, T. A.; Moahamed, Y. A.; El-Sherif, A. A.; Mohamed, G. A. M.

2015-01-01

This paper presents a combined synthesis; characterization, computational and biological activity studies of novel series of pyridines heterocyclic compounds. The compounds have been characterized by elemental analyses and spectral like IR, 1H NMR, 13C NMR and MS studies. Michael addition of substituted-2-methoxycarbonylacetanilide 2a,b on the α-substituted cinnamonitriles 3a-d gave the corresponding 2-pyridone derivatives 5-10. Structures of the titled compounds cited in this article were elucidated by spectrometric data (IR, 1H NMR, 13C NMR and MS). The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. Also, valuable information is obtained from the calculation of molecular parameters including electronegativity, net dipole moment of the compounds, total energy, electronic energy, binding energy, HOMO and LUMO energy. Various in vitro antitumor as well as in vivo anti-inflammatory and analgesic activities of the synthesized compounds were investigated. Evaluation of anti-inflammatory activity of test compounds was performed using carrageenan induced paw edema in rats. All the tested compounds showed moderate to good activity. The SAR results indicate that all compounds showed moderate to good activity, among these 7 and 10 compounds having -N(CH3)2 group are most effective.

Synergistic effect of the interaction between naproxen and citral on inflammation in rats.

PubMed

Ortiz, Mario I; González-García, Martha P; Ponce-Monter, Héctor A; Castañeda-Hernández, Gilberto; Aguilar-Robles, Paulina

2010-12-15

The combination of non-steroidal anti-inflammatory drugs with herbs having analgesic effects can increase their antinociceptive activity and limit their side effects. The aim of the present study was to examine the effects on inflammation and gastric injury in rats resulting from the interaction between naproxen and citral. Naproxen, citral, or fixed-dose naproxen-citral combinations were administered orally and their anti-inflammation (carrageenan-induced paw edema) and gastric damage were assessed in rats. The pharmacological interaction type was evaluated by the isobolographic analysis. Naproxen, citral, or combinations of naproxen and citral produced anti-inflammatory effects. The sole administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or combinations. ED(30) values were estimated for the individual drugs, and isobolograms were constructed. The derived theoretical ED(30) for the anti-inflammatory effect was 504.4 mg/kg; this was significantly higher than the observed experimental value (190.6 mg/kg). These results indicate that a synergistic interaction underlies the anti-inflammatory effect. The data suggests that the naproxen-citral combination can interact and to produce minor gastric damage and may have therapeutic advantages for the clinical treatment of inflammation. Copyright © 2010 Elsevier GmbH. All rights reserved.

Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway

PubMed Central

Franchin, Marcelo; da Cunha, Marcos Guilherme; Denny, Carina; Napimoga, Marcelo Henrique; Cunha, Thiago Mattar; Bueno-Silva, Bruno; Matias de Alencar, Severino; Ikegaki, Masaharu; Luiz Rosalen, Pedro

2013-01-01

The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO) pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion) with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1) was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity. PMID:23737853

Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway.

PubMed

Franchin, Marcelo; da Cunha, Marcos Guilherme; Denny, Carina; Napimoga, Marcelo Henrique; Cunha, Thiago Mattar; Bueno-Silva, Bruno; Matias de Alencar, Severino; Ikegaki, Masaharu; Luiz Rosalen, Pedro

2013-01-01

The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO) pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion) with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1) was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity.

Anti-Inflammatory and Antioxidant Activities of Salvia fruticosa: An HPLC Determination of Phenolic Contents

PubMed Central

Boukhary, Rima; Ghoneim, Asser I.; Aboul-Ela, Maha; El-Lakany, Abdalla

2016-01-01

Objectives. Salvia fruticosa Mill. (S. fruticosa) is widely used in folk medicine. Accordingly, the present study was designed to evaluate the antioxidant and anti-inflammatory activities of S. fruticosa, and to determine the phenolic constituents of its extracts. Methods. The antioxidant activity was determined using 2,2-diphenylpicrylhydrazyl assay. Total phenolic contents were estimated using Folin-Ciocalteu reagent, and high-performance liquid chromatography was performed to identify phenolic constituents. To evaluate the anti-inflammatory activity, carrageenan-induced mouse paw edema was determined plethysmographically. Key Findings. Different plant extracts demonstrated strong radical scavenging activity, where the ethyl acetate extract had the highest value in the roots and the lowest in the aerial parts. This antioxidant activity was correlated to the total phenolic content of different extracts, where rutin and luteolin were the most abundant constituents. Interestingly, both the roots and aerial parts revealed a significant anti-inflammatory activity comparable to diclofenac. Conclusions. This study is the first to demonstrate pharmacologic evidence of the potential anti-inflammatory activity of S. fruticosa. This activity may partly be due to the radical scavenging effects of its polyphenolic contents. These findings warrant the popular use of the East Mediterranean sage and highlight the potential of its active constituents in the development of new anti-inflammatory drugs. PMID:26881007

Analgesic and anti-inflammatory controlled-released injectable microemulsion: Pseudo-ternary phase diagrams, in vitro, ex vivo and in vivo evaluation.

PubMed

Pineros, Isabel; Slowing, Karla; Serrano, Dolores R; de Pablo, Esther; Ballesteros, Maria Paloma

2017-04-01

Development of analgesic and anti-inflammatory controlled-released injectable microemulsions utilising lysine clonixinate (LC) as model drug and generally regarded as safe (GRAS) excipients. Different microemulsions were optimised through pseudo-ternary phase diagrams and characterised measuring droplet size, viscosity, ex vivo haemolytic activity and in vitro drug release. The anti-inflammatory and analgesic activity was tested in mice (Hot plate test) and rats (Carrageenan-induced paw edema test) respectively and their activity was compared to an aqueous solution of LC salt. The aqueous solution showed a faster and shorter response whereas the optimised microemulsion increased significantly (p<0.01) the potency and duration of the analgesic and anti-inflammatory activity after deep intramuscular injection. The droplet size and the viscosity were key factors to control the drug release from the systems and enhance the effect of the formulations. The microemulsion consisting of Labrafil®/Lauroglycol®/Polysorbate 80/water with LC (56.25/18.75/15/10, w/w) could be a promising formulation after buccal surgery due to its ability to control the drug release and significantly achieve greater analgesic and anti-inflammatory effect over 24h. Copyright © 2016. Published by Elsevier B.V.

Date seed oil loaded niosomes: development, optimization and anti-inflammatory effect evaluation on rats.

PubMed

Soliman, Mahmoud S; Abd-Allah, Fathy I; Hussain, Talib; Saeed, Noha M; El-Sawy, Hossam S

2018-07-01

An optimized date seed oil (DSO) loaded niosomes was formulated. Maximize the extract anti-inflammatory efficacy and govern its release characteristics from nanoparticles for osteoarthritis prevention and treatment purposes. By using Box-Behnken Design, the effect of three formulation factors on the entrapment efficiency percentage (Y 1 ), initial DSO release percentage after 2 h (Y 2 ), and cumulative DSO release percentage of DSO after 12 h (Y 3 ), were optimized and studied. The optimized DSO formulation was specified, elaborated, particle size and zeta potential assessed, examined morphologically under electron and light microscope, and in vivo evaluated via carrageenan-induced rat paw edema study. 65.89%, 18.39%, and 58.27% were the measured responses of the optimized niosomes for Y 1 , Y 2 , and Y 3 , respectively. The vesicular structure of the optimized DSO loaded nano-vesicles with nano-size range and good stability features were confirmed. Furthermore, a distinguished anti-inflammatory activity in both prompt and sustained effectiveness were exhibited via the optimized DSO niosomes. Interestingly, the delayed efficacy outcomes of the extract loaded nanoparticles showed a similarity profile as well as the negative control group outcomes. To emphasize, DSO loading in niosomes revealed a significant enhancement toward inflammation alleviation, which offers a promising implement in osteoarthritis remediation and prohibition.

Screening of Bauhinia purpurea Linn. for analgesic and anti-inflammatory activities

PubMed Central

Shreedhara, C.S.; Vaidya, V.P.; Vagdevi, H.M.; Latha, K.P.; Muralikrishna, K.S.; Krupanidhi, A.M.

2009-01-01

Objectives: Ethanol extract of the stem of Bauhinia purpurea Linn. was subjected to analgesic and anti-inflammatory activities in animal models. Materials and Methods: Albino Wistar rats and mice were the experimental animals respectively. Different CNS depressant paradigms like analgesic activity (determined by Eddy's hot plate method and acetic acid writhing method) and anti-inflammatory activity determined by carrageenan induced paw edema using plethysmometer in albino rats) were carried out, following the intra-peritoneal administration of ethanol extract of Bauhinia purpurea Linn. (BP) at the dose level of 50 mg/kg and 100 mg/kg. Results: The analgesic and anti-inflammatory activities of ethanol extracts of BP were significant (P < 0.001). The maximum analgesic effect was observed at 120 min at the dose of 100 mg/kg (i.p.) and was comparable to that of standard analgin (150 mg/kg) and the percentage of edema inhibition effect was 46.4% and 77% for 50 mg/kg and 100 mg/kg (i.p) respectively. Anti-inflammatory activity was compared with standard Diclofenac sodium (5 mg/kg). Conclusion: Ethanol extract of Bauhinia purpurea has shown significant analgesic and anti-inflammatory activities at the dose of 100 mg/kg and was comparable with corresponding standard drugs. The activity was attributed to the presence of phytoconstituents in the tested extract. PMID:20336222

Transformation of Lettuce with rol ABC Genes: Extracts Show Enhanced Antioxidant, Analgesic, Anti-Inflammatory, Antidepressant, and Anticoagulant Activities in Rats.

PubMed

Ismail, Hammad; Dilshad, Erum; Waheed, Mohammad Tahir; Mirza, Bushra

2017-03-01

Lettuce is an edible crop that is well known for dietary and antioxidant benefits. The present study was conducted to investigate the effects of rol ABC genes on antioxidant and medicinal potential of lettuce by Agrobacterium-mediated transformation. Transgene integration and expression was confirmed through PCR and real-time RT-PCR, respectively. The transformed plants showed 91-102 % increase in total phenolic contents and 53-65 % increase in total flavonoid contents compared to untransformed plants. Total antioxidant capacity and total reducing power increased up to 112 and 133 % in transformed plants, respectively. Results of DPPH assay showed maximum 51 % increase, and lipid peroxidation assay exhibited 20 % increase in antioxidant activity of transformed plants compared to controls. Different in vivo assays were carried out in rats. The transgenic plants showed up to 80 % inhibition in both hot plate analgesic assay and carrageenan-induced hind paw edema test, while untransformed plants showed only 45 % inhibition. Antidepressant and anticoagulant potential of transformed plants was also significantly enhanced compared to untransformed plants. Taken together, the present work highlights the use of rol genes to enhance the secondary metabolite production in lettuce and improve its analgesic, anti-inflammatory, antidepressant, and anticoagulatory properties.

HPLC profiling, antioxidant and in vivo anti-inflammatory activity of the ethanol extract of Syzygium jambos available in Bangladesh.

PubMed

Hossain, Hemayet; Rahman, Shaikh Emdadur; Akbar, Proity Nayeeb; Khan, Tanzir Ahmed; Rahman, Md Mahfuzur; Jahan, Ismet Ara

2016-03-28

Syzygium jambos has been used as a traditional medicine for the treatment of inflammatory diseases in Bangladesh. The study investigates the high performance liquid chromatography (HPLC) profiling of phenolic compounds, and evaluates the antioxidant and anti-inflammatory activities of ethanol extract of S. jambos available in Bangladesh. The extract was subjected to HPLC for the identification and quantification of the major bioactive polyphenols present in S. jambos. Antioxidant activity was determined using 2, 2'-azino bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging, reducing power assay, total antioxidant capacity, total phenolic and flavonoid content. Furthermore, the anti-inflammatory effect of the extract in rats for two different test models: carrageenan and histamine-induced paw edema was inspected. High levels of catechin hydrate and rutin hydrate (99.00 and 79.20 mg/100 g extract, respectively) and moderate amounts of ellagic acid and quercetin (59.40 and 69.30 mg/100 g extract, respectively) were quantified in HPLC. Catechin hydrate from this plant extract was determined for the first time through HPLC. For ABTS scavenging assay, the median inhibition concentration (IC50) value of S. jambos was 57.80 µg/ml, which was significant to that of ascorbic acid (12.01 µg/ml). The maximum absorbance for reducing power assay was found to be 0.4934. The total antioxidant capacity, phenolic and flavonoid contents were calculated to be 628.50 mg/g of ascorbic acid, 230.82 mg/g of gallic acid and 11.84 mg/g of quercetin equivalent, respectively. At a dose of 400 mg/kg, a significant acute anti-inflammatory activity (P < 0.01) was observed in rats for both the test models with a reduction in the paw volume of 58.04 and 53.95 %, in comparison to those of indomethacin (62.94 and 65.79 %), respectively. The results suggest that the phenolic and flavonoid compounds are responsible for acute anti-inflammatory and antioxidant activities of S. jambos.

Levetiracetam interacts synergistically with nonsteroidal analgesics and caffeine to produce antihyperalgesia in rats.

PubMed

Tomić, Maja A; Micov, Ana M; Stepanović-Petrović, Radica M

2013-11-01

Levetiracetam is a novel anticonvulsant with antihyperalgesic efficacy in inflammatory pain. Nonsteroidal analgesics and caffeine, as analgesic adjuvant, are widely used against inflammatory pain. This study characterized the manner in which levetiracetam interacts with analgesics (ibuprofen, celecoxib, and paracetamol) and caffeine to suppress hyperalgesia in a model of localized inflammation. Rat paw inflammation was induced by intraplantar carrageenan (.1 mL, 1%). Hyperalgesia and antihyperalgesic effects of levetiracetam (orally), analgesics (orally), and caffeine (intraperitoneally) alone and 2-drug combinations of levetiracetam with analgesics or caffeine were examined by a modified paw pressure test. The type of interaction between components was determined by isobolographic analysis or by analysis of the log dose-response curves for drug combination and drugs alone. Levetiracetam (10-200 mg/kg), ibuprofen (12.5-100 mg/kg), celecoxib (3.75-30 mg/kg), paracetamol (50-200 mg/kg), caffeine (15-100 mg/kg), and 2-drug combinations of levetiracetam with analgesics/caffeine produced a significant, dose-dependent reduction of inflammatory hyperalgesia. Isobolographic analysis revealed that levetiracetam exerts a synergistic interaction with analgesics, with approximately 7-, 9-, and 11-fold reduction of doses of both drugs in combination of levetiracetam with paracetamol, celecoxib, and ibuprofen, respectively. Analysis of the log dose-response curves for levetiracetam (1-50 mg/kg) in the presence of caffeine (10 mg/kg) and levetiracetam applied alone also revealed a synergistic interaction. Levetiracetam's ED50 in the presence of caffeine was reduced approximately 11-fold. The presented data suggest that 2-drug combinations of levetiracetam and nonsteroidal analgesics or caffeine could be useful in treatment of inflammatory pain. The efficacy and the adverse effects of those mixtures should be explored further in clinical settings. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Inflammation enhances Y1 receptor signaling, neuropeptide Y-mediated inhibition of hyperalgesia, and substance P release from primary afferent neurons

PubMed Central

Taylor, Bradley K.; Fu, Weisi; Kuphal, Karen E.; Stiller, Carl-Olav; Winter, Michelle K.; Chen, Wenling; Corder, Gregory F.; Urban, Janice H.; McCarson, Kenneth E.; Marvizon, Juan Carlos

2014-01-01

Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. NPY decreased capsaicin-evoked SP-like immunoreactivity in microdialysate of the dorsal horn. NPY also decreased non-noxious stimulus (paw brush)-evoked NK1R internalization (as well as mechanical hyperalgesia and mechanical and cold allodynia) after intraplantar injection of carrageenan. Similarly, in rat spinal cord slices with dorsal root attached, [Leu31, Pro34]-NPY inhibited dorsal root stimulus-evoked NK1R internalization. In rat dorsal root ganglion neurons, Y1 receptors colocalized extensively with calcitonin gene-related peptide (CGRP). In dorsal horn neurons, Y1 receptors were extensively expressed and this may have masked detection of terminal co-localization with CGRP or SP. To determine whether the pain inhibitory actions of Y1 receptors are enhanced by inflammation, we administered [Leu31, Pro34]-NPY after intraplantar injection of complete Freund's adjuvant (CFA) in rat. We found that [Leu31, Pro34]-NPY reduced paw clamp-induced NK1R internalization in CFA rats but not uninjured controls. To determine the contribution of increased Y1 receptor-G protein coupling, we measured [35S]GTPγS binding simulated by [Leu31, Pro34]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception. PMID:24184981

The 5-lipoxygenase inhibitor RF-22c potently suppresses leukotriene biosynthesis in cellulo and blocks bronchoconstriction and inflammation in vivo.

PubMed

Schaible, Anja M; Filosa, Rosanna; Krauth, Verena; Temml, Veronika; Pace, Simona; Garscha, Ulrike; Liening, Stefanie; Weinigel, Christina; Rummler, Silke; Schieferdecker, Sebastian; Nett, Markus; Peduto, Antonella; Collarile, Selene; Scuotto, Maria; Roviezzo, Fioretina; Spaziano, Giuseppe; de Rosa, Mario; Stuppner, Hermann; Schuster, Daniela; D'Agostino, Bruno; Werz, Oliver

2016-07-15

5-Lipoxygenase (5-LO) catalyzes the first two steps in leukotriene (LT) biosynthesis. Because LTs play pivotal roles in allergy and inflammation, 5-LO represents a valuable target for anti-inflammatory drugs. Here, we investigated the molecular mechanism, the pharmacological profile, and the in vivo effectiveness of the novel 1,2-benzoquinone-featured 5-LO inhibitor RF-22c. Compound RF-22c potently inhibited 5-LO product synthesis in neutrophils and monocytes (IC50⩾22nM) and in cell-free assays (IC50⩾140nM) without affecting 12/15-LOs, cyclooxygenase (COX)-1/2, or arachidonic acid release, in a specific and reversible manner, supported by molecular docking data. Antioxidant or iron-chelating properties were not evident for RF-22c and 5-LO-regulatory cofactors like Ca(2+) mobilization, ERK-1/2 activation, and 5-LO nuclear membrane translocation and interaction with 5-LO-activating protein (FLAP) were unaffected. RF-22c (0.1mg/kg; i.p.) impaired (I) bronchoconstriction in ovalbumin-sensitized mice challenged with acetylcholine, (II) exudate formation in carrageenan-induced paw edema, and (III) zymosan-induced leukocyte infiltration in air pouches. Taken together, RF-22c is a highly selective and potent 5-LO inhibitor in intact human leukocytes with pronounced effectiveness in different models of inflammation that warrants further preclinical analysis of this agent as anti-inflammatory drug. Copyright © 2016 Elsevier Inc. All rights reserved.

Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin

PubMed Central

Lee, Jin-Ah; Ha, Sang Keun; Cho, EunJung; Choi, Inwook

2015-01-01

The aim of this study was to improve the anti-inflammatory activities of apigenin through co-treatment with resveratrol as a bioenhancer of apigenin. RAW 264.7 cells pretreated with hepatic metabolites formed by the co-metabolism of apigenin and resveratrol (ARMs) in HepG2 cells were stimulated with lipopolysaccharide (LPS). ARMs prominently inhibited (p < 0.05) the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6 and TNF-α. Otherwise no such activity was observed by hepatic metabolites of apigenin alone (AMs). ARMs also effectively suppressed protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Co-administration of apigenin (50 mg/kg) and resveratrol (25 mg/kg) also showed a significant reduction of carrageenan-induced paw edema in mice (61.20% to 23.81%). Co-administration of apigenin and resveratrol led to a 2.39 fold increase in plasma apigenin levels compared to administration of apigenin alone, suggesting that co-administration of resveratrol could increase bioavailability of apigenin. When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM. These results suggested that resveratrol helps apigenin to bypass hepatic metabolism and maintain apigenin’s anti-inflammatory activities in the body. PMID:26610561

Spinal 5-HT2 and 5-HT3 receptors mediate low, but not high, frequency TENS-induced antihyperalgesia in rats

PubMed Central

Radhakrishnan, Rajan; King, Ellen W.; Dickman, Janelle K.; Herold, Carli A.; Johnston, Natalie F.; Spurgin, Megan L.; Sluka, Kathleen A.

2009-01-01

Transcutaneous electrical nerve stimulation (TENS) is a form of non-pharmacological treatment for pain. Involvement of descending inhibitory systems is implicated in TENS-induced analgesia. In the present study, the roles of spinal 5-HT and α2-adrenoceptors in TENS analgesia were investigated in rats. Hyperalgesia was induced by inflaming the knee joint with 3% kaolin—carrageenan mixture and assessed by measuring paw withdrawal latency (PWL) to heat before and 4 h after injection. The (1) α2-adrenergic antagonist yohimbine (30 μg), (2) 5-HT antagonist methysergide (5-HT1 and 5-HT2,30 μg), one of the 5-HT receptor subtype antagonists, (3) NAN-190 (5-HT1A, 15 μg), (4) ketanserin (5-HT2A, 30 μg), (5) MDL-72222 (5-HT3, 12 μg), or (6) vehicle was administered intrathecally prior to TENS treatment. Low (4 Hz) or high (100 Hz) frequency TENS at sensory intensity was then applied to the inflamed knee for 20 min and PWL was determined. Selectivity of the antagonists used was confirmed using respective agonists administered intrathecally. Yohimbine had no effect on the antihyperalgesia produced by low or high frequency TENS. Methysergide and MDL-72222 prevented the antihyperalgesia produced by low, but not high, frequency TENS. Ketanserin attenuated the antihyperalgesic effects of low frequency TENS whereas NAN-190 had no effect. The results from the present study show that spinal 5-HT receptors mediate low, but not high, frequency TENS-induced antihyperalgesia through activation of 5-HT2A and 5-HT3 receptors in rats. Furthermore, spinal noradrenergic receptors are not involved in either low or high frequency TENS antihyperalgesia. PMID:14499437

Pharmacological evaluation for anti-asthmatic and anti-inflammatory potential of Woodfordia fruticosa flower extracts.

PubMed

Hiralal Ghante, Mahavir; Bhusari, Kishore P; Duragkar, Nandkishore J; Ghiware, Nitin B

2014-07-01

Woodfordia fruticosa Kurz. (Lythraceae) flowers are ethnopharmacologically acclaimed in the Indian medicinal system to treat asthma. To evaluate W. fruticosa flower extracts for anti-asthmatic effect. Ethyl acetate, acetone, methanol, and hydro-alcohol extracts of W. fruticosa flowers were obtained successively and standardized. Ability of extracts to stabilize free radicals and compound-48/80-induced mast cell degranulation was evaluated. In vitro anti-inflammatory potential of extracts at 100 and 200 µg/ml by membrane stabilization and in vivo inhibition of rat paw edema up to 5 h (100 and 200 mg/ml; p.o.) was evaluated. In vitro bronchorelaxant effect was examined against histamine- and acetylcholine (1 µg/ml; independently)-induced guinea pig tracheal contraction. Extracts were evaluated for bronchoprotection (in vivo) ability against 0.1% histamine- and 2% acetylcholine-induced bronchospasm in guinea pigs at 100 and 200 mg/ml; p.o. Standardization studies revealed that the methanol extract exhibited highest polyphenolic (62.66 GAE), and flavonoid (6.32 RE) content and HPLC fingerprinting confirmed the presence of gallic acid (Rt 1.383). IC50 values for DPPH scavenging and metal chelation by the methanol extract were 40.42 and 31.50 µg/ml. Methanol and ethyl acetate extracts at 100 µg/ml exhibited 06.52 and 07.12% of histamine release. Methanol, ethyl acetate, and hydro alcohol extracts at 200 mg/kg demonstrated 32.73, 29.83, 26.75% and 32.46, 9.38, 26.75% inhibition of egg albumin and carrageenan-induced inflammation, respectively. Methanol extract exhibited 100% bronchorelaxation and 48.83% bronchoprotection. Woodfordia fruticosa flower (WFF) extracts exhibited anti-asthmatic effect by demonstrating bronchoprotection, bronchorelaxation, anti-inflammatory, antioxidant, and mast cell stabilization ability.

Acute effects of pentobarbital, thiopental and urethane on lung oedema induced by alpha-naphthythiourea (ANTU).

PubMed

Sipahi, Emine; Ustün, Hüseyin; Niyazi Ayoglu, Ferruh

2002-03-01

This study was designed to investigate the possible participation of urethane, pentobarbital sodium and thiopental sodium anaesthesia in the lung oedema induced by alpha-naphthylthiourea (ANTU), which is a well known noxious chemical agent in the lung. ANTU when injected intraperitoneally (i.p.) into rats (10 mg x kg (-1) i.p.) produced lung oedema as indicated by an increase in lung weight/body weight (LW/BW) ratio and pleural effusion (PE) reaching a maximum within 4 h. Administration of urethane prior to ANTU, at doses of 100 and 200mg(100g)(-1), elicited a significant and dose-dependent inhibition in LW/BW ratio and PE. Thiopental sodium at doses of 25, 50 mg x kg (-1), also produced a significant and dose-dependent inhibition of both parameters. Prior i.p. injection of pentobarbital sodium at a dose of 40 mg x kg (-1) elicited a significant inhibition in both parameters. These results suggest that i.p. urethane, thiopental sodium and pentobarbital sodium pretreatment have a prophylactic effect on ANTU-induced lung injury in rats. The possible role of the anaesthetics in lung oedema induced by ANTU and the possible underlying mechanisms are discussed. Copyright 2002 Elsevier Science Ltd.

Activation of tissue kallikrein-kininogen-kinin system in rabbit skin by a fraction isolated from Phoneutria nigriventer (armed spider) venom.

PubMed

Antunes, E; Marangoni, R A; Giglio, J R; Brain, S D; de Nucci, G

1993-11-01

Phoneutria nigriventer venom was fractionated by gel filtration followed by ion-exchange chromatography from which 16 fractions (I-XVI) were obtained and assayed in rabbit skin in order to identify those responsible for the increased vascular permeability observed with the whole venom. The fractions, and control mediators (tissue kallikrein, bradykinin and histamine) were intradermally injected in male New Zealand white rabbits. Local oedema formation was measured as the local accumulation of i.v. injected 125I-human serum albumin into skin sites. Fraction XIII was the only fraction assayed which significantly induced oedema formation. Fraction XIII-induced oedema was greatly reduced by either the protease inhibitor aprotinin or the bradykinin B2 receptor antagonist D-Arg,[Hyp3,Thi5,8D-Phe7]-Bk, whereas the plasma kallikrein inhibitor soybean trypsin inhibitor failed to significantly affect this oedematogenic response. The kininase II inhibitor captopril markedly potentiated fraction XIII-induced oedema. Our results indicate that the increased vascular permeability induced by fraction XIII is due to local generation of kinins in response to tissue (but not plasma) kallikrein-kinin system activation.

Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice.

PubMed

Serafim, Karla G G; Navarro, Suelen A; Zarpelon, Ana C; Pinho-Ribeiro, Felipe A; Fattori, Victor; Cunha, Thiago M; Alves-Filho, Jose C; Cunha, Fernando Q; Casagrande, Rubia; Verri, Waldiceu A

2015-11-01

Bosentan is a mixed endothelin receptor antagonist widely used to treat patients with pulmonary arterial hypertension, and the emerging literature suggests bosentan as a potent anti-inflammatory drug. Superoxide anion is produced in large amounts during inflammation, stimulates cytokine production, and thus contributes to inflammation and pain. However, it remains to be determined whether endothelin contributes to the inflammatory response triggered by the superoxide anion. The present study investigated the effects of bosentan in a mouse model of inflammation and pain induced by potassium superoxide, a superoxide anion donor. Male Swiss mice were treated with bosentan (10-100 mg/kg) by oral gavage, 1 h before potassium superoxide injection, and the inflammatory response was evaluated locally and at spinal cord (L4-L6) levels. Bosentan (100 mg/kg) inhibited superoxide anion-induced mechanical and thermal hyperalgesia, overt pain-like behavior (abdominal writhings, paw flinching, and licking), paw edema, myeloperoxidase activity (neutrophil marker) in the paw skin, and leukocyte recruitment in the peritoneal cavity. Bosentan also inhibited superoxide anion-induced interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) production, while it enhanced IL-10 production in the paw skin and spinal cord. Bosentan inhibited the reduction of antioxidant capacity (reduced glutathione, ferric reducing antioxidant power, and ABTS radical scavenging ability) induced by the superoxide anion. Finally, we demonstrated that intraplantar injection of potassium superoxide induces the mRNA expression of prepro-endothelin-1 in the paw skin and spinal cord. In conclusion, our results demonstrated that superoxide anion-induced inflammation, pain, cytokine production, and oxidative stress depend on endothelin; therefore, these responses are amenable to bosentan treatment.

Effects of Liver × receptor agonist treatment on signal transduction pathways in acute lung inflammation

PubMed Central

2010-01-01

Background Liver × receptor α (LXRα) and β (LXRβ) are members of the nuclear receptor super family of ligand-activated transcription factors, a super family which includes the perhaps better known glucocorticoid receptor, estrogen receptor, thyroid receptor, and peroxisome proliferator-activated receptors. There is limited evidence that LXL activation may reduces acute lung inflammation. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse model of carrageenan-induced pleurisy. Methods Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), tumor necrosis factor-α, (TNF-α) and interleukin-1β (IL-1β). Furthermore, carrageenan induced the expression of iNOS, nitrotyrosine and PARP, as well as induced apoptosis (TUNEL staining and Bax and Bcl-2 expression) in the lung tissues. Results Administration of T0901317, 30 min after the challenge with carrageenan, caused a significant reduction in a dose dependent manner of all the parameters of inflammation measured. Conclusions Thus, based on these findings we propose that LXR ligand such as T0901317, may be useful in the treatment of various inflammatory diseases. PMID:20175894

The Effect of Lactic Acid Bacteria-fermented Soybean Milk Products on Carrageenan-induced Tail Thrombosis in Rats

PubMed Central

KAMIYA, Seitaro; OGASAWARA, Masayoshi; ARAKAWA, Masayuki; HAGIMORI, Masayori

2013-01-01

Thrombosis is characterized by congenital and acquired procatarxis. Lactic acid bacteria-fermented soybean milk products (FS-LAB) inhibit hepatic lipid accumulation and prevent atherosclerotic plaque formation. However, the therapeutic efficacy of FS-LAB against thrombosis has yet to be investigated. In this study, FS-LAB were administered subcutaneously into the tails of rats, with the subsequent intravenous administration of κ-carrageenan 12 hr after the initial injection. In general, administration of κ-carrageenan induces thrombosis. The length of the infarcted tail regions was significantly shorter in the rats administered a single-fold or double-fold concentration of the FS-LAB solution compared with the region in control rats. Therefore, FS-LAB exhibited significant antithrombotic effects. Our study is the first to characterize the properties of FS-LAB and, by testing their efficacy on an in vivo rat model of thrombosis, demonstrate the potency of their antithrombotic effect. PMID:24936368

Effect of α-trinositol on interstitial fluid pressure, oedema generation and albumin extravasation in experimental frostbite in the rat

PubMed Central

Berg, A; Aas, P; Gustafsson, T; Reed, R K

1999-01-01

The anti-inflammatory effect of α-trinositol (D-myo-inositol-1,2,6-trisphosphate) on oedema formation, microvascular protein leakage and interstitial fluid pressure (Pif) in rat skin after frostbite injury, was investigated. α-Trinositol (40 mg kg body weight−1) was administered intravenously as a bolus both before and/or in the interval between freezing and thawing of the tissue. Pif was measured in rat paw skin with micropipettes connected to a servo-controlled counterpressure system. Oedema formation was estimated by measuring the increase in total tissue water content (wet weight minus dry weight divided by dry weight). Albumin extravasation (i.e., the difference between the plasma equivalent space for 125I- and 131I-human serum albumin (HSA) circulating for different time intervals) was used to estimate the microvascular leakage. Compared to untreated animals, α-trinositol given pre- and/or post-freeze reduced total tissue water and albumin extravasation as well as the fall in Pif in injured tissue significantly (P<0.05). α-Trinositol given only post-freeze reduced total tissue water and albumin extravasation from 4.46±0.93 and 2.37±1.12 to 2.51±0.29 and 0.36±0.18 ml g dry weight−1, respectively (P<0.05). Pif fell from −0.8±0.2 mmHg pre-freeze to −3.4±1.0 mmHg (P<0.05) at 20 min after tissue injury (circulatory arrest) and was attenuated by treatment with α-trinositol. We conclude that α-trinositol exerts its anti-oedematous effect by acting on the extracellular matrix, attenuating the lowering of Pif as well as on the microvascular wall, thereby decreasing the protein extravasation. PMID:10217530

Pharmacological Basis for Use of Selaginella moellendorffii in Gouty Arthritis: Antihyperuricemic, Anti-Inflammatory, and Xanthine Oxidase Inhibition

PubMed Central

Zhao, Ping; Chen, Ke-li; Zhang, Guo-li

2017-01-01

This study was aimed at evaluating the effects of Selaginella moellendorffii Hieron. (SM) on gouty arthritis and getting an insight of the possible mechanisms. HPLC method was developed for chemical analysis. The paw oedema, the neutrophil accumulation, inflammatory mediators, lipid peroxidation, and histopathological changes of the joints were analyzed in gouty arthritis rat model, and the kidney injury and serum urate were detected in hyperuricemic mice. Pharmacokinetic result demonstrated that the main apigenin glycosides might be quantitatively transformed into apigenin in the mammalian body. Among these compounds, the apigenin exhibited the strongest effect on xanthine oxidase (XOD). SM aqueous extract has proved to be active in reducing hyperuricemia in dose-dependent manner, and the levels of blood urea nitrogen (BUN) and creatinine (Cr) in high dose group were decreased significantly as compared with hyperuricemic control group (P < 0.01). The high dose of SM extract could significantly prevent the paw swelling, reduce gouty joint inflammatory features, reduce the release of IL-1β and TNF-α, lower malondialdehyde (MDA) and myeloperoxidase (MPO) levels, and increase superoxide dismutase (SOD) level (P < 0.01). For the first time, this study provides a rational basis for the traditional use of SM aqueous extract against gout in folk medicine. PMID:28250791

Silk fibroin/kappa-carrageenan composite scaffolds with enhanced biomimetic mineralization for bone regeneration applications.

PubMed

Nourmohammadi, Jhamak; Roshanfar, Fahimeh; Farokhi, Mehdi; Haghbin Nazarpak, Masoumeh

2017-07-01

The combination of protein-polysaccharide in scaffolding together with the ability to induce bone-like apatite formation has become a promising approach to mimic extracellular matrix composition. In the present study, we developed and characterized new bioactive composite scaffolds from kappa-carrageenan/silk fibroin for bone regeneration applications. Three dimensional (3D) scaffolds were fabricated by adding various amounts of carrageenan to a silk fibroin solution, followed by freeze-drying. Various characterization techniques were applied to analyze such items as the structure, morphology, compressive strength, and bone-like apatite mineralization of the composites, which were then compared to those of pure fibroin scaffolds. The results demonstrated the formation of a highly porous structure with interconnected pores. The mean pore size and porosity both increased by increasing carrageenan content. Moreover, the addition of carrageenan to silk fibroin led to the formation of a bone-like apatite layer throughout the scaffolds after 7days of soaking them in simulated body fluid. Osteoblast-like cell (MG 63) culture experiments indicated that all scaffolds are biocompatible. The cells attached well to the surfaces of all scaffolds and tended to join their adjacent cells. However, higher carrageenan content led to better cellular proliferation and higher Alkaline phosphatase expression. Copyright © 2017 Elsevier B.V. All rights reserved.

Combined NMR and GC-MS analyses revealed dynamic metabolic changes associated with the carrageenan-induced rat pleurisy.

PubMed

Li, Huihui; An, Yanpeng; Zhang, Lulu; Lei, Hehua; Zhang, Limin; Wang, Yulan; Tang, Huiru

2013-12-06

Inflammation is closely associated with pathogenesis of various metabolic disorders, cardiovascular diseases, and cancers. To understand the systems responses to localized inflammation, we analyzed the dynamic metabolic changes in rat plasma and urine associated with the carrageenan-induced self-limiting pleurisy using NMR spectroscopy in conjunction with multivariate data analysis. Fatty acids in plasma were also analyzed using GC-FID/MS with the data from clinical chemistry and histopathology as complementary information. We found that in the acute phase of inflammation rats with pleurisy had significantly lower levels in serum albumin, fatty acids, and lipoproteins but higher globulin level and larger quantity of pleural exudate than controls. The carrageenan-induced inflammation was accompanied by significant metabolic alterations involving TCA cycle, glycolysis, biosyntheses of acute phase proteins, and metabolisms of amino acids, fatty acids, ketone bodies, and choline in acute phase. The resolution process of pleurisy was heterogeneous, and two subgroups were observed for the inflammatory rats at day-6 post treatment with different metabolic features together with the quantity of pleural exudate and weights of thymus and spleen. The metabolic differences between these subgroups were reflected in the levels of albumin and acute-phase proteins, the degree of returning to normality for multiple metabolic pathways including glycolysis, TCA cycle, gut microbiota functions, and metabolisms of lipids, choline and vitamin B3. These findings provided some essential details for the dynamic metabolic changes associated with the carrageenan-induced self-limiting inflammation and demonstrated the combined NMR and GC-FID/MS analysis as a powerful approach for understanding biochemical aspects of inflammation.

Evaluation of the protective effect of pentoxifylline on carrageenan-induced chronic non-bacterial prostatitis in rats.

PubMed

Hajighorbani, Mahboobeh; Ahmadi-Hamedani, Mahmood; Shahab, Elaheh; Hayati, Farzad; Kafshdoozan, Khatereh; Keramati, Keivan; Amini, Amin Hossein

2017-06-01

Chronic non-bacterial prostatitis (CNP) is the most common type of prostatitis and oxidative stress (OS) was shown to be highly elevated in prostatitis patients. This study aimed to investigate the protective effect of pentoxifylline (PTX) on CNP induced by carrageenan in rats. Male adult Wistar rats (n = 30) were divided into control, CNP and three treatment groups (n = 6) including CNP + cernilton and CNP + PTX groups. CNP was induced by single intraprostatic injection of 1% carrageenan (100 µl). Rats in treatment groups received orally cernilton 100 mg/kg and PTX at 50 and 100 mg/kg 1 week after CNP induction for 21 days. Prostatic index (PI), prostatic specific antigen (PSA), tumor-necrosis factor alpha (TNF-α), serum lipid peroxidation (MDA), blood urea nitrogen, creatinine and histopathological changes were compared between groups. There were significant increase of PI, serum levels of PSA, TNF-α and MDA in CNP group at 29 day. In treatment groups, significant reduction in PI, serum levels of PSA, TNF-α, MDA and creatinine was observed especially in rats treated with dose of 50 mg/kg of PTX. In CNP group, histopathological changes of the prostate such as leucocyte infiltration, large involutions and projection into the lumen and reducing the volume of the lumen were observed as well. Whereas PTX, especially at dose of 50 mg/kg, could improve the above-mentioned changes remarkably in CNP treated rats. For the first time, our findings indicated that PTX improved CNP induced by carrageenan in rats.

Effect of long-term ketamine administration on vocalization to paw pressure and on spinal wind-up activity in monoarthritic rats.

PubMed

Pelissier, Teresa; Alvarez, Pedro; Hernández, Alejandro

2003-09-01

The antinociceptive effect of long-lasting ketamine administration (mini-osmotic pump) was studied in monoarthritic rats by using hindpaw pressure testing and wind-up measurement in a C-fiber reflex paradigm. Chronic ketamine induced antinociception in the monoarthritic paw and significantly suppressed mechanical hyperalgesia during the 14-day treatment period. The treatment also reduced C-reflex wind-up in the monoarthritic hindpaw. After pump removal, vocalization thresholds and spinal wind-up scores from the monoarthritic paw returned to control values, while hyperalgesia developed in the normal paw. Results suggest that ketamine upregulates NMDA receptors upon long-term administration, resulting in hyperalgesic response in the normal paw after drug withdrawal.

Anti-inflammatory activity of Heliotropium strigosum in animal models.

PubMed

Khan, Haroon; Khan, Murad Ali; Gul, Farah; Hussain, Sajjid; Ashraf, Nadeem

2015-12-01

The current project was designed to evaluate the anti-inflammatory activity of crude extract of Heliotropium strigosum and its subsequent solvent fractions in post carrageenan-induced edema and post xylene-induced ear edema at 50, 100, and 200 mg/kg intraperitoneally. The results revealed marked attenuation of edema induced by carrageenan injection in a dose-dependent manner. The ethyl acetate fraction was most dominant with 73.33% inhibition followed by hexane fraction (70.66%). When the extracts were challenged against xylene-induced ear edema, again ethyl acetate and hexane fractions were most impressive with 38.21 and 35.77% inhibition, respectively. It is concluded that various extracts of H. strigosum possessed strong anti-inflammatory activity in animal models. © The Author(s) 2012.

Inhibitory effect of vasopressin receptor antagonist OPC-31260 on experimental brain oedema induced by global cerebral ischaemia.

PubMed

Molnár, A H; Varga, C; Berkó, A; Rojik, I; Párducz, A; László, F; László, F A

2008-03-01

The effects of the non-peptide vasopressin V(2) receptor antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats. The general cerebral hypoxia was produced by bilateral common carotid ligation in Sprague-Dawley rats of the CFY strain. By 6 h after the ligation, half of the rats had died, but the survival rate was significantly higher following OPC-31260 administration. Electron microscopic examinations revealed typical ischaemic changes after the carotid ligation. The carotid ligation increased the brain contents of water and Na(+) and enhanced the plasma vasopressin level. The increased brain water and Na(+) accumulation was prevented by OPC-31260 administration, but the plasma vasopressin level was further enhanced by OPC-31260. These results demonstrate the important role of vasopressin in the development of the disturbances in brain water and electrolyte balance in response to general cerebral hypoxia. The carotid ligation-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on the renal vasopressin V(2) receptors. These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans.

Antinociceptive effect in mice of a hydroalcoholic extract of Neurolaena lobata (L.) R. Br. and its organic fractions.

PubMed

Gracioso, J S; Paulo, M Q; Hiruma Lima, C A; Souza Brito, A R

1998-12-01

An infusion of the aerial parts of Neurolaena lobata (L.) R. Br. (Compositae-Asteraceae) is used in Caribbean folk medicine to treat several kinds of pain. In this investigation we studied the acute oral toxicity of the hydroalcoholic extract of the plant and the antinociceptive effect of the extract and of its hexane- and chloroform-partitioned fractions, given orally, in nociception and inflammatory models in mice. No signs of toxicity were observed for oral doses up to 5000 mg kg(-1) in mice. Morphine hydrochloride (100 mg kg(-1)), dipyrone sodium (200 mg kg(-1)), the hydroalcoholic extract (1000 mg kg(-1)), and its chloroform- and hexane-partitioned fractions (100 mg kg(-1)) significantly inhibited acetic acid-induced abdominal constriction in mice (100, 95, 47, 62 and 60% inhibition, respectively when compared with the negative control). In the hot-plate test in mice, morphine hydrochloride, the chloroform- and hexane-partitioned fractions, but not the hydroalcoholic extract, resulted in a significant latency increase in all observation times. In the acetic acid-induced abdominal constriction in mice, pretreatment of the animals with naloxone significantly reversed the analgesic effect of morphine, but not that of the hydroalcoholic extract or of its hexane- and chloroform-partitioned fractions. Finally, administration of the hexane- and chloroform-partitioned fractions (100 mg kg(-1)) had a significant anti-oedematogenic effect on carrageenan-induced oedema in mice. These data show that the hydroalcoholic extract of N. lobata and, in particular, its partitioned fractions have significant analgesic properties when assessed through these pain models. Their antinociceptive effect might be the result of interference with the inflammatory process.

A quantitative model for dermal infection and oedema in BALB/c mice pinna.

PubMed

Marino-Marmolejo, Erika Nahomy; Flores-Hernández, Flor Yohana; Flores-Valdez, Mario Alberto; García-Morales, Luis Felipe; González-Villegas, Ana Cecilia; Bravo-Madrigal, Jorge

2016-12-12

Pharmaceutical industry demands innovation for developing new molecules to improve effectiveness and safety of therapeutic medicines. Preclinical assays are the first tests performed to evaluate new therapeutic molecules using animal models. Currently, there are several models for evaluation of treatments, for dermal oedema or infection. However, the most common or usual way is to induce the inflammation with chemical substances instead of infectious agents. On the other hand, this kind of models require the implementation of histological techniques and the interpretation of pathologies to verify the effectiveness of the therapy under assessment. This work was focused on developing a quantitative model of infection and oedema in mouse pinna. The infection was achieved with a strain of Streptococcus pyogenes that was inoculated in an injury induced at the auricle of BALB/c mice, the induced oedema was recorded by measuring the ear thickness with a digital micrometer and histopathological analysis was performed to verify the damage. The presence of S. pyogenes at the infection site was determined every day by culture. Our results showed that S. pyogenes can infect the mouse pinna and that it can be recovered at least for up to 4 days from the infected site; we also found that S. pyogenes can induce a bigger oedema than the PBS-treated control for at least 7 days; our results were validated with an antibacterial and anti-inflammatory formulation made with ciprofloxacin and hydrocortisone. The model we developed led us to emulate a dermal infection and allowed us to objectively evaluate the increase or decrease of the oedema by measuring the thickness of the ear pinna, and to determine the presence of the pathogen in the infection site. We consider that the model could be useful for assessment of new anti-inflammatory or antibacterial therapies for dermal infections.

Quantitative nuclear magnetic resonance imaging: characterisation of experimental cerebral oedema.

PubMed Central

Barnes, D; McDonald, W I; Johnson, G; Tofts, P S; Landon, D N

1987-01-01

Magnetic resonance imaging (MRI) has been used quantitatively to define the characteristics of two different models of experimental cerebral oedema in cats: vasogenic oedema produced by cortical freezing and cytotoxic oedema induced by triethyl tin. The MRI results have been correlated with the ultrastructural changes. The images accurately delineated the anatomical extent of the oedema in the two lesions, but did not otherwise discriminate between them. The patterns of measured increase in T1' and T2' were, however, characteristic for each type of oedema, and reflected the protein content. The magnetisation decay characteristics of both normal and oedematous white matter were monoexponential for T1 but biexponential for T2 decay. The relative sizes of the two component exponentials of the latter corresponded with the physical sizes of the major tissue water compartments. Quantitative MRI data can provide reliable information about the physico-chemical environment of tissue water in normal and oedematous cerebral tissue, and are useful for distinguishing between acute and chronic lesions in multiple sclerosis. Images PMID:3572428

Assessing the role of metabotropic glutamate receptor 5 in multiple nociceptive modalities.

PubMed

Zhu, Chang Z; Wilson, Sonya G; Mikusa, Joseph P; Wismer, Carol T; Gauvin, Donna M; Lynch, James J; Wade, Carrie L; Decker, Michael W; Honore, Prisca

2004-12-15

Preclinical data, performed in a limited number of pain models, suggest that functional blockade of metabotropic glutamate (mGlu) receptors may be beneficial for pain management. In the present study, effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective mGlu5 receptor antagonist, were examined in a wide variety of rodent nociceptive and hypersensitivity models in order to fully characterize the potential analgesic profile of mGlu5 receptor blockade. Effects of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), as potent and selective as MPEP at mGlu5/mGlu1 receptors but more selective than MPEP at N-methyl-aspartate (NMDA) receptors, were also evaluated in selected nociceptive and side effect models. MPEP (3-30 mg/kg, i.p.) produced a dose-dependent reversal of thermal and mechanical hyperalgesia following complete Freund's adjuvant (CFA)-induced inflammatory hypersensitivity. Additionally, MPEP (3-30 mg/kg, i.p.) decreased thermal hyperalgesia observed in carrageenan-induced inflammatory hypersensitivity without affecting paw edema, abolished acetic acid-induced writhing activity in mice, and was shown to reduce mechanical allodynia and thermal hyperalgesia observed in a model of post-operative hypersensitivity and formalin-induced spontaneous pain. Furthermore, at 30 mg/kg, i.p., MPEP significantly attenuated mechanical allodynia observed in three neuropathic pain models, i.e. spinal nerve ligation, sciatic nerve constriction and vincristine-induced neuropathic pain. MTEP (3-30 mg/kg, i.p.) also potently reduced CFA-induced thermal hyperalgesia. However, at 100 mg/kg, i.p., MPEP and MTEP produced central nerve system (CNS) side effects as measured by rotarod performance and exploratory locomotor activity. These results suggest a role for mGlu5 receptors in multiple nociceptive modalities, though CNS side effects may be a limiting factor in developing mGlu5 receptor analgesic compounds.

Pharmacological insight into the anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R.Br. ex Cass.

PubMed

McKinnon, R; Binder, M; Zupkó, I; Afonyushkin, T; Lajter, I; Vasas, A; de Martin, R; Unger, C; Dolznig, H; Diaz, R; Frisch, R; Passreiter, C M; Krupitza, G; Hohmann, J; Kopp, B; Bochkov, V N

2014-10-15

Neurolaena lobata is a Caribbean medicinal plant used for the treatment of several conditions including inflammation. Recent data regarding potent anti-inflammatory activity of the plant and isolated sesquiterpene lactones raised our interest in further pharmacological studies. The present work aimed at providing a mechanistic insight into the anti-inflammatory activity of N. lobata and eight isolated sesquiterpene lactones, as well as a structure-activity relationship and in vivo anti-inflammatory data. The effect of the extract and its compounds on the generation of pro-inflammatory proteins was assessed in vitro in endothelial and monocytic cells by enzyme-linked immunosorbent assay. Their potential to modulate the expression of inflammatory genes was further studied at the mRNA level. In vivo anti-inflammatory activity of the chemically characterized extract was evaluated using carrageenan-induced paw edema model in rats. The compounds and extract inhibited LPS- and TNF-α-induced upregulation of the pro-inflammatory molecules E-selectin and interleukin-8 in HUVECtert and THP-1 cells. LPS-induced elevation of mRNA encoding for E-selectin and interleukin-8 was also suppressed. Furthermore, the extract inhibited the development of acute inflammation in rats. Sesquiterpene lactones from N. lobata interfered with the induction of inflammatory cell adhesion molecules and chemokines in cells stimulated with bacterial products and cytokines. Structure-activity analysis revealed the importance of the double bond at C-4-C-5 and C-2-C-3 and the acetyl group at C-9 for the anti-inflammatory activity. The effect was confirmed in vivo, which raises further interest in the therapeutic potential of the compounds for the treatment of inflammatory diseases. Copyright © 2014 Elsevier GmbH. All rights reserved.

Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia-induced vascular leakage and oedema in rat brain.

PubMed

Saraswat, Deepika; Nehra, Sarita; Chaudhary, Kamal; CVS, Siva Prasad

2015-05-01

Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia-induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF-A site were identified and validated with a Ramachandran plot. The active site residues of VEGF-A were detected by Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF-A blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for improvement in cellular viability and regulation of VEGF levels in N2a cells under hypoxia (0.5% O2 ). Additionally, the best candidate molecule's efficacy was assessed in male Sprague-Dawley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available VEGF blocker sunitinib. Vascular endothelial growth factor-A blocker 1 was found most effective in increasing cellular viability and maintaining normal VEGF levels under hypoxia (0.5% oxygen) in N2a cells. Vascular endothelial growth factor-A blocker 1 effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib-treated rats. Vascular endothelial growth factor-A blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia-induced vasogenic oedema by regulating VEGF levels. © 2015 Wiley Publishing Asia Pty Ltd.

Citrus hallabong [(Citrus unshiu × C. sinensis) × C. reticulata)] exerts potent anti-inflammatory properties in murine splenocytes and TPA-induced murine ear oedema model.

PubMed

Herath, Kalahe Hewage Iresha Nadeeka Madushani; Bing, So Jin; Cho, Jinhee; Kim, Areum; Kim, Gi-Ok; Lee, Jong-Chul; Jee, Youngheun

2016-12-01

Hallabong [(Citrus unshiu × C. sinensis) X C. reticulata)] (Rutaceae) is a hybrid citrus cultivated in temperate regions of South Korea. Its fruit is well-known for pharmacological properties. This study examined the anti-inflammatory effect of 80% ethanol extract of Hallabong (HE) on concanavalin A (Con A)-stimulated splenocytes and mouse oedema model induced by 12-O-tetradecanoylphorbal acetate (TPA). Murine splenocytes treated with HE were stimulated with Con A (10 μg/mL, for 24 h) were evaluated for T-cell population and production of inflammatory cytokines IL-2, IL-4 and IFN-γ. Anti-inflammatory effect of topically applied HE (100 μg/20 μL) on TPA (4 μg/20 μL/ear)-induced ear oedema was investigated in mouse model. HE-treated Con A-stimulated murine splenocytes showed a marked decrease in CD44/CD62L + memory T-cell population, an important marker for anti-inflammatory activity, and a significant inhibition in the production of IL-2 and IFN-γ. HE treatment had reduced the mouse skin oedema (47%) and myeloperoxidase (MPO) activity significantly (40%) in TPA-challenged tissues. More importantly, immunohistochemical localization revealed the suppressed (p < 0.05) expression of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX2). HE decreased the infiltration of CD3 + T cells and F4/80 + macrophages to the site of inflammation and a topical application of HE significantly suppressed the expression of TNF-α (20.2%). A topical application of HE can exert a potential anti-inflammatory effect and HE can be explored further as a putative alternative therapeutic agent for inflammatory oedema.

Prevention and treatment of hand oedema after stroke.

PubMed

Kuppens, Stefanie P M; Pijlman, Hanneke C P; Hitters, Minou W M G C; van Heugten, Caroline M

2014-01-01

As there is no evidence for a specific treatment for post-stroke-induced hand oedema, rehabilitation centre Blixembosch formalized a best practice protocol. We investigated whether the Blixembosch hand oedema protocol is usable in daily practice and leads to lower incidence (prevention) and shorter duration (treatment) compared with care as usual. In a non-randomised comparative trial, we investigated 206 post-stroke patients admitted to two Dutch rehabilitation centres. Hand volumes were measured at least bi-weekly using a volumeter. Treatment was started according the protocol (Blixembosch) or following care as usual (Leijpark). Usability was assessed with a survey among professionals. In the Blixembosch group, 16% developed oedema after admission, compared with 21% in the control group (p = 0.019). Average duration of oedema (both developed before and after admission) was 6.5 weeks in the Blixembosch group compared with 3.1 weeks in the control group (p = 0.000). Professionals were positive about the protocol. The study showed that the protocol is usable in daily practice and has a small beneficial effect on hand oedema incidence rates compared with care as usual. The negative effect on duration of hand oedema could also be caused by the difference in prognosis between the two groups.

Fabrication of micropatterned alginate-gelatin and k-carrageenan hydrogels of defined shapes using simple wax mould method as a platform for stem cell/induced Pluripotent Stem Cells (iPSC) culture.

PubMed

Vignesh, S; Gopalakrishnan, Aswathi; M R, Poorna; Nair, Shantikumar V; Jayakumar, R; Mony, Ullas

2018-06-01

Micropatterning techniques involve soft lithography, which is laborious, expensive and restricted to a narrow spectrum of biomaterials. In this work we report, first time employment of patterned wax moulds for generation of micropatterned alginate-gelatin and κ-carrageenan (κ-CRG) hydrogel systems by a novel, simple and cost effective method. We generated and characterized uniform and reproducible micropatterned hydrogels of varying sizes and shapes such as square projections, square grooves, and circular grids and crisscrossed hillocks. The rheological analysis showed that κ-carrageenan hydrogels had higher gel strength when compared to alginate-gelatin hydrogels. Human Mesenchymal stem cells (hMSCs) and Human Induced Pluripotent Stem Cells (hiPSCs) were found to be cytocompatible with these hydrogels. This micropatterned hydrogel system may have potential application in tissue engineering and also in understanding the basic biology behind the stem cell/iPSC fate. Copyright © 2018 Elsevier B.V. All rights reserved.

The anti-allergic activity of the acetate fraction of Schinus terebinthifolius leaves in IgE induced mice paw edema and pleurisy.

PubMed

Cavalher-Machado, Simone Campos; Rosas, Elaine Cruz; Brito, Fabiola de Almeida; Heringe, Alan Patrick; de Oliveira, Rodrigo Rodrigues; Kaplan, Maria Auxiliadora Coelho; Figueiredo, Maria Raquel; Henriques, Maria das Graças Müller de Oliveira

2008-11-01

Schinus is a genus of the Anacardiaceae family and contains Schinus terebinthifolius, the Brazilian pepper tree that is widely used in folk medicine. We investigate the anti-allergic activity of the ethyl acetate fraction of S. terebinthifolius Raddi (ST fraction). HPLC analysis reveled that gallic acid, methyl gallate and 1,2,3,4,6-pentagalloylglucose are the major aromatic components of the fraction. Oral pre-treatment with the ST fraction (100 mg/kg) significantly inhibited paw edema induced by compound 48/80 (100 ng/paw) and to a lesser extent, the allergic paw edema (OVA, 3 microg/paw). The ST fraction (100 and 200 mg/kg) also inhibited the edema induced by histamine (100 microg/paw), preventing mast cell degranulation and, consequently, histamine release in Wistar rat peritoneal mast cells induced by C 48/80 (5 microg/mL). This histamine inhibition was also observed after mast cell pre-treatment with both methyl gallate and 1,2,3,4,6-pentagalloylglucose (100 microg/mL), the isolated compounds from the ethyl acetate fraction. Pre-treatment with the ST fraction (100 mg/kg) significantly inhibited total leukocyte and eosinophil accumulation in pleural cavities 24 h after the intrathoracic injection of OVA (12.5 microg/cavity). This effect was related to the inhibition of CCL11/eotaxin and CCL5/RANTES in pleural lavage fluid. Pre-treatment with this fraction (100 mg/kg) failed to reduce the cell influx that was observed after LPS-injection into pleural cavity (250 ng/cavity). These findings demonstrate the anti-allergic effect of the ST fraction, which includes the inhibition of edema formation and histamine release caused by mast cell degranulation and eosinophil influx into the pleural cavity probably reflected by the decreased levels of chemokines in recovered pleural lavage fluid.

Investigation of nepetolide as a novel lead compound: Antioxidant, antimicrobial, cytotoxic, anticancer, anti-inflammatory, analgesic activities and molecular docking evaluation.

PubMed

Ur Rehman, Tanzeel; Khan, Arif-Ullah; Abbas, Azar; Hussain, Javid; Khan, Farman Ullah; Stieglitz, Kimberly; Ali, Shamsher

2018-03-01

In the present study, we describe various pharmacological effects and computational analysis of nepetolide, a tricyclic clerodane-type diterpene, isolated from Nepeta suavis . Nepetolide concentration-dependently (1.0-1000 µg/mL) exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with maximum effect of 87.01 ± 1.85%, indicating its antioxidant potential, as shown by standard drug, ascorbic acid. It was moderately active against bacterial strain of Staphylococcus aureus . In brine shrimp's lethality model, nepetolide potently showed cytotoxic effect, with LC 50 value of 8.7 µg/mL. When evaluated for antitumor activity in potato disc tumor assay, nepetolide exerted tumor inhibitory effect of 56.5 ± 1.5% at maximum tested concentration of 1000 µg/mL. Nepetolide at 20 mg/kg reduced carrageenan-induced inflammation (P < .001 vs. saline group) in rat paw. Nepetolide dose-dependently (100-500 mg/kg) decreased acetic acid evoked writhes, as exhibited by diclofenac sodium. In-silico investigation of nepetolide was carried out against cyclooxygenase-2, epidermal growth factor receptor and lipoxygenase-2 targets. Virtual screening through Patchdock online docking server identified primarily hydrophobic interactions between ligand nepetolide and receptors proteins. Enhanced hydrogen bonding was predicted with Autodock showing 6-8 hydrogen bonds per target. These results indicate that nepetolide exhibits antioxidant, antibacterial, cytotoxic, anticancer, anti-inflammatory and analgesic activities and should be considered as a lead compound for developing drugs for the remedy of oxidative stress-induced disorders, microbial infections, cancers, inflammations and pain.

Molecular docking, synthesis and biological screening of mefenamic acid derivatives as anti-inflammatory agents.

PubMed

Savjani, Jignasa K; Mulamkattil, Suja; Variya, Bhavesh; Patel, Snehal

2017-04-15

Drug induced gastrointestinal ulceration, renal side effects and hepatotoxicity are the main causes of numerous Non-Steroidal Anti-inflammatory Drugs (NSAIDs). Cyclooxygenase-2 (COX-2) inhibitors discovered to decrease the gastrointestinal issues, but unfortunately, most of them are associated with major cardiovascular adverse effects. Along these lines, various new strategies and frameworks were developed wherein basic alterations of the present medications were accounted for. The aim of the study was to prepare derivatives of mefenamic acid to evaluate anti-inflammatory activity with fewer adverse reactions. In this study, molecular docking investigations of outlined derivatives were done utilizing Protein Data Bank (PDB ID-4PH9). Synthesis of heterocyclic compounds was carried out utilizing Dicyclohexylcarbodiimide/4-Dimethylaminopyridine (DCC/DMAP) coupling. Acute toxicity prediction was performed using free online GUSAR (General Unrestricted Structure-Activity Relationships) software. The study indicated most of the compounds under safe category. In-vitro pharmacological assessment of heterocyclic compounds was done for COX-1 and COX-2 enzymes for the determination of selectivity. In vivo pharmacological screening for anti-inflammatory activity and ED 50 value were determined utilizing carrageenan induced rat paw edema. Gastro intestinal safety study was carried out on selected compounds and found to be devoid of any gastric ulcer toxicity. Most of the compounds indicated high scores as compared to standard during molecular modelling, analysis and displayed interactions with active amino acids of a COX-2 enzyme. The pharmacological screening uncovered that compound substituted with p-bromophenyl indicated maximum potency. Copyright © 2017 Elsevier B.V. All rights reserved.

Relationship between the ability of sunscreens containing 2-ethylhexyl-4'-methoxycinnamate to protect against UVR-induced inflammation, depletion of epidermal Langerhans (Ia+) cells and suppression of alloactivating capacity of murine skin in vivo.

PubMed

Walker, S L; Morris, J; Chu, A C; Young, A R

1994-01-01

The UVB sunscreen 2-ethylhexyl-4'-methoxycinnamate was evaluated in hairless albino mouse skin for its ability to inhibit UVR-induced (i) oedema, (ii) epidermal Langerhans cell (Ia+) depletion and (iii) suppression of the alloactivating capacity of epidermal cells (mixed epidermal cell-lymphocyte reaction, MECLR). The sunscreen, prepared at 9% in ethanol or a cosmetic lotion, was applied prior to UVB/UVA irradiation. In some experiments there was a second application halfway through the irradiation. Single applications in both vehicles gave varying degrees of protection from oedema and Langerhans cell depletion but afforded no protection from suppression of MECLR. When the sunscreens were applied twice there was improved protection from oedema and Langerhans cell depletion and complete protection was afforded from suppression of MECLR. There was a clear linear relationship between Langerhans cell numbers and oedema with and without sunscreen application. The relationship between Langerhans cell numbers and MECLR was more complex. These data confirm published discrepancies between protection from oedema (a model for human erythema) and endpoints with immunological significance, but show that 2-ethylhexyl-4'-methoxycinnamate can afford complete immunoprotection, although protection is dependent on the application rate and vehicle.

Dragon's blood inhibits chronic inflammatory and neuropathic pain responses by blocking the synthesis and release of substance P in rats.

PubMed

Li, Yu-Sang; Wang, Jun-Xian; Jia, Mei-Mei; Liu, Min; Li, Xiao-Jun; Tang, He-Bin

2012-01-01

As a traditional Chinese medicine, dragon's blood (DB) is widely used in treating various pains for thousands of years due to its potent anti-inflammatory and analgesic effects. In the present study, we observed that intragastric administration of DB at dosages of 0.14, 0.56, and 1.12 g/kg potently inhibited paw edema, hyperalgesia, cyclooxygenase-2 (COX-2) protein expression, or preprotachykinin-A mRNA expression in carrageenan-inflamed or sciatic nerve-injured (chronic constriction injury) rats, respectively. A short-term (15 s or 10 min) pre-exposure of cultured rat dorsal root ganglion (DRG) neurons to DB (0.3, 3, and 30 µg/ml) or its component cochinchinenin B (CB; 0.1, 1, and 10 µM) blocked capsaicin-evoked increases in both the intracellular calcium ion concentration and the substance P release. Moreover, a long-term (180 min) exposure of cultured rat DRG neurons to DB or CB significantly attenuated bradykinin-induced substance P release. These findings indicate that DB exerts anti-inflammatory and analgesic effects by blocking the synthesis and release of substance P through inhibition of COX-2 protein induction and intracellular calcium ion concentration. Therefore, DB may serve as a promising potent therapeutic agent for treatment of chronic pain, and its effective component CB might partly contribute to anti-inflammatory and analgesic effects.

Synthesis, biological evaluation and docking analysis of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones as potential cyclooxygenase-2 (COX-2) inhibitors.

PubMed

Grover, Jagdeep; Kumar, Vivek; Sobhia, M Elizabeth; Jachak, Sanjay M

2014-10-01

As a part of our continued efforts to discover new COX inhibitors, a series of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones were synthesized and evaluated for in vitro COX inhibitory potential. Within this series, seven compounds (3a-d, 3h, 3k and 3q) were identified as potential and selective COX-2 inhibitors (COX-2 IC50's in 1.79-4.35μM range; COX-2 selectivity index (SI)=6.8-16.7 range). Compound 3b emerged as most potent (COX-2 IC50=1.79μM; COX-1 IC50 >30μM) and selective COX-2 inhibitor (SI >16.7). Further, compound 3b displayed superior anti-inflammatory activity (59.86% inhibition of edema at 5h) in comparison to celecoxib (51.44% inhibition of edema at 5h) in carrageenan-induced rat paw edema assay. Structure-activity relationship studies suggested that N-phenyl ring substituted with p-CF3 substituent (3b, 3k and 3q) leads to more selective inhibition of COX-2. To corroborate obtained experimental biological data, molecular docking study was carried out which revealed that compound 3b showed stronger binding interaction with COX-2 as compared to COX-1. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antioxidant and anti-inflammatory activities of silver nanoparticles biosynthesized from aqueous leaves extracts of four Terminalia species

NASA Astrophysics Data System (ADS)

El-Rafie, Hanaa Mohamed; Abdel-Aziz Hamed, Manal

2014-09-01

The environmentally friendly synthesis of nanoparticles process is a revolutionary step in the field of nanotechnology. In recent years plant mediated biological synthesis of nanoparticles has been gaining importance due to its simplicity and eco-friendliness. In this study, a simple and an efficient eco-friendly approach for the biosynthesis of stable, monodisperse silver nanoparticles using aqueous extracts of four Terminalia species, namely, Terminalia catappa, Terminalia mellueri, Terminalia bentazoe and Terminalia bellerica were described. The silver nanoparticles were characterized in terms of synthesis, capping functionalities (polysaccharides, phenolics and flavonoidal compounds) and microscopic evaluation by UV-visible spectroscopy, Fourier transform infrared spectroscopy and transmission electron microscopy. The results showed a simple and feasible approach for obtaining stable aqueous monodispersive silver nanoparticles. Furthermore, biological activity of the biosynthesized silver nanoparticles was examined. Concerning this, dose-dependent antioxidant activity of silver nanoparticles imparted by the plant phenolic and flavonoidal components was evaluated using in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and found to be comparable to standard ascorbic acid. The same holds true for the anti-inflammatory activity where Terminalia catappa and Terminalia mellueri have a high-test inhibition percentage better than that of ascorbic acid in the carrageenan induced hind paw edema. The results also revealed that the aqueous extract of Terminallia catapa and its silver nanoparticles recorded the most potent in vivo antioxidant effect.

Nanostructured lipid carriers to enhance transdermal delivery and efficacy of diclofenac.

PubMed

Nguyen, Chien Ngoc; Nguyen, Thi Thuy Trang; Nguyen, Hanh Thuy; Tran, Tuan Hiep

2017-10-01

Lipid carrier-mediated transdermal drug delivery offers several advantages because it is non-irritating and non-toxic, provides effective control of drug release, and forms an adhesive film that hydrates the outer skin layers. However, to penetrate the deeper skin layers, these formulations need to overcome several barriers in the stratum corneum. This study evaluates factors influencing particle size and drug-loading capacity, which play a key role in drug permeation and efficacy. Diclofenac sodium was chosen as the model drug. The fabrication of diclofenac sodium-loaded lipid nanoparticles was optimized by modulating several parameters, including the lipids and surfactants employed, the drug/lipid ratio, and the pH of the aqueous phase. The physical properties and loading efficiencies of the nanoparticles were characterized. The optimized formulation was then dispersed into a polymer solution to form a gel, which demonstrated a sustained ex vivo permeation of diclofenac sodium over 24 h through excised rat skin and a higher drug penetrating capacity than that of a commercially available gel. In vivo anti-inflammatory activity was assessed in a rat carrageenan-induced paw edema model; the anti-edema effects of the prepared gel and commercially available gel over 24 h were comparable. The present findings indicate the effects of particle size and drug loading on the ability of nanostructured lipid carrier preparations to provide transdermal drug delivery.

Role of Peroxisome Proliferator-Activated Receptors in Inflammation Control

PubMed Central

Badr, Mostafa

2004-01-01

Peroxisome proliferator-activated receptors (PPARs) were discovered over a decade ago, and were classified as orphan members of the nuclear receptor superfamily. To date, three PPAR subtypes have been discovered and characterized (PPARα, β/δ, γ). Different PPAR subtypes have been shown to play crucial roles in important diseases and conditions such as obesity, diabetes, atherosclerosis, cancer, and fertility. Among the most studied roles of PPARs is their involvement in inflammatory processes. Numerous studies have revealed that agonists of PPARα and PPARγ exert anti-inflammatory effects both in vitro and in vivo. Using the carrageenan-induced paw edema model of inflammation, a recent study in our laboratories showed that these agonists hinder the initiation phase, but not the late phase of the inflammatory process. Furthermore, in the same experimental model, we recently also observed that activation of PPARδ exerted an anti-inflammatory effect. Despite the fact that exclusive dependence of these effects on PPARs has been questioned, the bulk of evidence suggests that all three PPAR subtypes, PPARα, δ, γ, play a significant role in controlling inflammatory responses. Whether these subtypes act via a common mechanism or are independent of each other remains to be elucidated. However, due to the intensity of research efforts in this area, it is anticipated that these efforts will result in the development of PPAR ligands as therapeutic agents for the treatment of inflammatory diseases. PMID:15292582

Spectroscopic, electrochemical DNA binding and in vivo anti-inflammatory studies on newly synthesized Schiff bases of 4-aminophenazone.

PubMed

Arshad, Nasima; Ahmad, Mukhtar; Ashraf, Muhammad Zaman; Nadeem, Humaira

2014-09-05

4-Aminophenazone (Ap-1) Schiff bases i.e., 4-{(3,4,5-trimethoxybenzylidine) amino}phenazone (Ap-2), 4-{(2-chlorobenzylidine) amino}phenazone (Ap-3) and 4-{(4-chlorobenzylidine)amino} phenazone (Ap-4) were synthesized and characterized by different spectroscopic techniques. Interaction of these compounds with ds.DNA was investigated through UV-Visible spectroscopy, fluorescence spectroscopy and cyclic voltammetry at stomach (4.7) and blood (7.4) pH under 37 °C (human body temperature). Instrumental findings were further quantified both kinetically and thermodynamically. Results obtained through these techniques inferred intercalative mode of binding of all the compounds with DNA. The binding constant data, "Kb", and free energy change, ΔG, indicated comparatively greater binding affinity and more spontaneity of binding of compounds with DNA at stomach pH (4.7), respectively. However, among these compounds, Ap-4 showed comparatively greater binding at both the pH. Formation of compound-DNA complex was further confirmed through the decrease in diffusion rates after the addition of DNA. The in vivo anti-inflammatory activity of the compounds was evaluated using the carrageenan-induced hind paw edema method. The results revealed that among all the compounds, Ap-4 showed greater percentage of edema inhibition compared to standard drug. Copyright © 2014 Elsevier B.V. All rights reserved.

Transformation of Lactuca sativa L. with rol C gene results in increased antioxidant potential and enhanced analgesic, anti-inflammatory and antidepressant activities in vivo.

PubMed

Ismail, Hammad; Dilshad, Erum; Waheed, Mohammad Tahir; Sajid, Moniba; Kayani, Waqas Khan; Mirza, Bushra

2016-12-01

Lettuce is an important edible crop which possesses various medicinal properties. In this study Lactuca sativa L. (cv Grand Rapids) was transformed by Agrobacterium-mediated transformation with rol C gene. Transgene integration and expression was confirmed through PCR and semiquantitative RT-PCR. The transformed extracts were evaluated for their in vitro antioxidant and in vivo analgesic, anti-inflammatory and antidepressant activities in rats. The transformed plants showed 53-98 % increase in total phenolic and 45-58 % increase in total flavonoid contents compared with untransformed plants. Results of total reducing power and total antioxidant capacity exhibited 90-118 and 61-75 % increase in transformed plants, respectively. In contrast to control, DPPH, lipid peroxidation and DNA protection assay showed up to 37, 20 and 50 % enhancement in transformed plants, respectively. The extracts showed similar but significant enhancement behavior in hot plate analgesic and carrageenan-induced hind paw edema test. The transformed extracts showed 72.1 and 78.5 % increase for analgesic and anti-inflammatory activities, respectively. The transformants of rol C gene exhibited prominent antidepressant activity with 64-73 % increase compared with untransformed plants. In conclusion, the present work suggests that transformation with rol C gene can be used to generate lettuce with enhanced medicinally important properties, such as antioxidant, analgesic, anti-inflammatory and antidepressant potential.