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Sample records for highly potent anti-inflammatory

  1. HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid.

    PubMed

    Haj, Christeene G; Sumariwalla, Percy F; Hanuš, Lumír; Kogan, Natalya M; Yektin, Zhana; Mechoulam, Raphael; Feldmann, Mark; Gallily, Ruth

    2015-10-01

    Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Δ(9)-tetrahydrocannabinol (Δ(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-α, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Δ(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-α production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases. PMID:26272937

  2. Tricyclic Compounds Containing Non-enolizable Cyano Enones. A Novel Class of Highly Potent Anti-inflammatory and Cytoprotective Agents=

    PubMed Central

    Honda, Tadashi; Yoshizawa, Hidenori; Sundararajan, Chitra; David, Emilie; Lajoie, Marc J.; Favaloro, Frank G.; Janosik, Tomasz; Su, Xiaobo; Honda, Yukiko; Roebuck, Bill D.; Gribble, Gordon W.

    2011-01-01

    Forty-four novel tricycles containing non-enolizable cyano enones (TCEs) were designed and synthesized on the basis of a semisynthetic pentacyclic triterpenoid, bardoxolone methyl, which is currently being developed in Phase II clinical trials for the treatment of severe chronic kidney disease in diabetic patients. Most of the TCEs having two different kinds of non-enolizable cyano enones in rings A and C are highly potent suppressors of induction of inducible nitric oxide synthase stimulated with interferon-γ, and highly potent inducers of the cytoprotective enzymes heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Among these compounds, (±)-(4bS,8aR,10aS)-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile ((±)-31) is the most potent in these bioassays in our pool of drug candidates including semisynthetic triterpenoids and synthetic tricycles. These facts strongly suggest that an essential factor for potency is not a triterpenoid skeleton, but the cyano enone functionality. Notably, TCE 31 reduces hepatic tumorigenesis induced with aflatoxin in rats. Further preclinical studies and detailed mechanism studies on 31 are in progress. PMID:21361338

  3. Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects

    PubMed Central

    Ardekani, Soroush; Scott, Harry A.; Gupta, Sharad; Eum, Shane; Yang, Xiao; Brunelle, Alexander R.; Wilson, Sean M.; Mohideen, Umar; Ghosh, Kaustabh

    2015-01-01

    Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies. PMID:26584637

  4. Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects

    NASA Astrophysics Data System (ADS)

    Ardekani, Soroush; Scott, Harry A.; Gupta, Sharad; Eum, Shane; Yang, Xiao; Brunelle, Alexander R.; Wilson, Sean M.; Mohideen, Umar; Ghosh, Kaustabh

    2015-11-01

    Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies.

  5. Esters of some non-steroidal anti-inflammatory drugs with cinnamyl alcohol are potent lipoxygenase inhibitors with enhanced anti-inflammatory activity.

    PubMed

    Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Tziona, Paraskevi; Kourounakis, Panos N; Rekka, Eleni A

    2015-11-15

    Novel esters of non steroidal anti-inflammatory drugs, α-lipoic acid and indol-3-acetic acid with cinnamyl alcohol were synthesised by a straightforward method and at high yields (60-98%). They reduced acute inflammation more than the parent acids and are potent inhibitors of soybean lipoxygenase. Selected structures decreased plasma lipidemic indices in Triton-induced hyperlipidemia to rats. Therefore, the synthesised compounds may add to the current knowledge about agents acting against various inflammatory disorders. PMID:26494261

  6. 6-Hydroxyflavone and Derivatives Exhibit Potent Anti-Inflammatory Activity among Mono-, Di- and Polyhydroxylated Flavones in Kidney Mesangial Cells

    PubMed Central

    Sidhu, Preetpal Singh; Desai, Umesh R.; Zhou, Qibing

    2015-01-01

    Inflammatory responses by kidney mesangial cells play a critical role in the glomerulonephritis. The anti-inflammatory potential of nineteen mono-, di- and polyhydroxylated flavones including fisetin, quercetin, morin, tricetin, gossypetin, apigenin and myricetin were investigated on rat mesangial cells with lipopolysaccharide (LPS) as the inflammatory stimuli. 6-Hydroxyflavone and 4′,6-dihydroxyflavone exhibited high activity with IC50 in the range of 2.0 μM, a much better inhibition potential in comparison to the well-studied polyhydroxylated flavones. Interestingly, the anti-inflammatory activity was not due to direct quenching of NO radicals. Investigation on derivatives with methylation, acetylation or sulfation of 6-hydroxyl group revealed that 6-methoxyflavone was the most potent with an IC50 of 192 nM. Mechanistic study indicated that the anti-inflammatory activity of 6-methoxyflavone arose via the inhibition of LPS-induced downstream inducible NO synthase in mesangial cells. The identification of 6-hydroxyflavone and 6-methoxyflavone with potent anti-inflammatory activity in kidney mesangial cells provides a new flavone scaffold and direction to develop naturally derived products for potential nephritis prevention and treatment. PMID:25790236

  7. The potent anti-inflammatory agent escin does not increase corticosterone secretion and immune cell apoptosis in mice.

    PubMed

    Zhang, Leiming; Wang, Hongsheng; Fan, Huaying; Wang, Tian; Jiang, Na; Yu, Pengfei; Fu, Fenghua

    2011-09-01

    Escin exerts potent glucocorticoid-like anti-inflammatory effects. The aim of this study was to investigate whether the anti-inflammatory effect of escin is through the up-regulation of glucocorticoids and if escin induces pathological changes in immune organs. Mice were administrated with escin intravenously for 7 days before observing the relevant parameters. The results showed that escin exhibits a potent anti-inflammatory effect, but does not increase corticosterone secretion in mice, and does not increase immune cell apoptosis in the spleen and thymus of mice. These findings suggest that the anti-inflammatory effect of escin is not dependent on the release of corticosterone. PMID:21596110

  8. CHF6001 I: a novel highly potent and selective phosphodiesterase 4 inhibitor with robust anti-inflammatory activity and suitable for topical pulmonary administration.

    PubMed

    Moretto, Nadia; Caruso, Paola; Bosco, Raffaella; Marchini, Gessica; Pastore, Fiorella; Armani, Elisabetta; Amari, Gabriele; Rizzi, Andrea; Ghidini, Eleonora; De Fanti, Renato; Capaldi, Carmelida; Carzaniga, Laura; Hirsch, Emilio; Buccellati, Carola; Sala, Angelo; Carnini, Chiara; Patacchini, Riccardo; Delcanale, Maurizio; Civelli, Maurizio; Villetti, Gino; Facchinetti, Fabrizio

    2015-03-01

    This study examined the pharmacologic characterization of CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide], a novel phosphodiesterase (PDE)4 inhibitor designed for treating pulmonary inflammatory diseases via inhaled administration. CHF6001 was 7- and 923-fold more potent than roflumilast and cilomilast, respectively, in inhibiting PDE4 enzymatic activity (IC50 = 0.026 ± 0.006 nM). CHF6001 inhibited PDE4 isoforms A-D with equal potency, showed an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site (i.e., >40) and displayed >20,000-fold selectivity versus PDE4 compared with a panel of PDEs. CHF6001 effectively inhibited (subnanomolar IC50 values) the release of tumor necrosis factor-α from human peripheral blood mononuclear cells, human acute monocytic leukemia cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383). Moreover, CHF6001 potently inhibited the activation of oxidative burst in neutrophils and eosinophils, neutrophil chemotaxis, and the release of interferon-γ from CD4(+) T cells. In all these functional assays, CHF6001 was more potent than previously described PDE4 inhibitors, including roflumilast, UK-500,001 [2-(3,4-difluorophenoxy)-5-fluoro-N-((1S,4S)-4-(2-hydroxy-5-methylbenzamido)cyclohexyl)nicotinamide], and cilomilast, and it was comparable to GSK256066 [6-((3-(dimethylcarbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide]. When administered intratracheally to rats as a micronized dry powder, CHF6001 inhibited liposaccharide-induced pulmonary neutrophilia (ED50 = 0.205 μmol/kg) and leukocyte infiltration (ED50 = 0.188 μmol/kg) with an efficacy comparable to a high dose of budesonide (1 μmol/kg i.p.). In sum, CHF6001 has the potential to be an effective topical treatment of conditions associated with pulmonary inflammation, including

  9. Development and mechanism investigation of a new piperlongumine derivative as a potent anti-inflammatory agent.

    PubMed

    Sun, Lan-Di; Wang, Fu; Dai, Fang; Wang, Yi-Hua; Lin, Dong; Zhou, Bo

    2015-06-01

    Inflammation, especially chronic inflammation, is directly involvement in the pathogenesis of many diseases including cancer. An effective approach for managing inflammation is to employ chemicals to block activation of nuclear factor-κB (NF-κB), a key regulator for inflammatory processes. Piperlongumine (piplartine, PL), an electrophilic molecule isolated from Piper longum L., possesses excellent anti-cancer and anti-inflammatory properties. In this study, a new PL analogue (PL-0N) was designed by replacing nitrogen atom of lactam in PL with carbon atom to increase its electrophilicity and thus anti-inflammatory activity. It was found that PL-0N is more potent than the parent compound in suppressing lipopolysaccharide (LPS)-induced secretion of nitric oxide and prostaglandin E2 as well as expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW264.7 macrophages. Mechanistic investigation implies that PL-0N exerts anti-inflammatory activity through inhibition of LPS-induced NF-κB transduction pathway, down-regulation of LPS-induced MAPKs activation and impairment of proteasomal activity, but also enhancement of LPS-induced autophagy; the inhibition of NF-κB by PL-0N is achieved at various stages by: (i) preventing phosphorylation of IKKα/β, (ii) stabilizing the suppressor protein IκBα, (iii) interfering with the nuclear translocation of NF-κB, and (iv) inhibiting the DNA-binding of NF-κB. These data indicate that nitrogen-atom-lacking pattern is a successful strategy to improve anti-inflammatory property of PL, and that the novel molecule, PL-0N may be served as a promising lead for developing natural product-directed anti-inflammatory agents. PMID:25850000

  10. Synthesis and biological evaluation of piperlongumine derivatives as potent anti-inflammatory agents.

    PubMed

    Seo, Young Hwa; Kim, Jin-Kyung; Jun, Jong-Gab

    2014-12-15

    Piperlongumine (PL) and its derivatives were synthesized by the direct reaction between acid chloride of 3,4,5-trimethoxycinnamic acid and various amides/lactams. Later their anti-inflammatory effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages. Of the piperlogs prepared in this study, the maximum (91%) inhibitory activity was observed with PL (IC50=3 μM) but showed cytotoxicity whereas compound 3 (IC50=6 μM) which possess α,β-unsaturated γ-butyrolactam moiety offered good level (65%) of activity with no cytotoxicity. This study revealed that amide/lactam moiety connected to cinnamoyl group with minimum 3 carbon chain length and α,β-unsaturation is fruitful to show potent anti-inflammatory activity. PMID:25453809

  11. Newer substituted beta-aminonaphthalenes as potent anti-inflammatory agents.

    PubMed

    Bansal, E; Srivastava, V K; Kumar, A

    2000-11-01

    beta-[2-(3'-Chloro-2'-oxo-4'-substituted aryl-1'-azetidinyl)-thiazol-4- yl]aminonaphthalenes 13-17 and beta-[2-(1',3'-disubstitutedphenyl-formazan-4'-yl)-thiazol-4-yl] aminonaphthalenes 8-12 were synthesized from beta-(2-arylideneamino-thiazol-4-yl)aminonaphthalenes 3-7 by diazotisation and by cycloaddition with monochloroacetyl chloride, respectively, on the azomethine group of the compounds 3-7. The newly synthesized compounds showed potent anti-inflammatory and analgesic activities and were less ulcerogenic than phenylbutazone. PMID:11148856

  12. Stereocontrolled total synthesis of the potent anti-inflammatory and pro-resolving lipid mediator resolvin D3 and its aspirin-triggered 17R-epimer.

    PubMed

    Winkler, Jeremy W; Uddin, Jasim; Serhan, Charles N; Petasis, Nicos A

    2013-04-01

    The first total synthesis of stereochemically pure resolvin D3 and aspirin-triggered resolvin D3 is reported. These enzymatic metabolites of docosahexaenoic acid (DHA) have potent anti-inflammatory and pro-resolving actions. The convergent synthetic strategy is based on enantiomerically pure starting materials, and it is highly stereocontrolled. PMID:23510485

  13. Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drugs

    PubMed Central

    Boukhatem, Mohamed Nadjib; Ferhat, Mohamed Amine; Kameli, Abdelkrim; Saidi, Fairouz; Kebir, Hadjer Tchoketch

    2014-01-01

    Background Volatile oils obtained from lemon grass [Cymbopogon citratus (DC.) Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases. Aims In the present study, lemon grass essential oil (LGEO) was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases. Methods The chemical profile of LGEO as determined by gas chromatography–mass spectrometry analysis revealed two major components: geranial (42.2%), and neral (31.5%). The antifungal activity of LGEO was evaluated against several pathogenic yeasts and filamentous fungi using disc diffusion and vapor diffusion methods. Results LGEO exhibited promising antifungal effect against Candida albicans, C. tropicalis, and Aspergillus niger, with different inhibition zone diameters (IZDs) (35–90 mm). IZD increased with increasing oil volume. Significantly, higher anti-Candida activity was observed in the vapor phase. For the evaluation of the anti-inflammatory effect, LGEO (10 mg/kg, administered orally) significantly reduced carrageenan-induced paw edema with a similar effect to that observed for oral diclofenac (50 mg/kg), which was used as the positive control. Oral administration of LGEO showed dose-dependent anti-inflammatory activity. In addition, topical application of LGEO in vivo resulted in a potent anti-inflammatory effect, as demonstrated by using the mouse model of croton oil-induced ear edema. To our knowledge, this is the first such report to be published. The topical application of LGEO at doses of 5 and 10 µL/ear significantly reduced acute ear edema induced by croton oil in 62.5 and 75% of the mice, respectively. In addition, histological analysis clearly confirmed that LGEO inhibits the skin inflammatory response in animal models. Conclusion Results of the present study indicate that LGEO has a noteworthy potential for the development of drugs for the treatment of

  14. A Novel Anti-Inflammatory Effect for High Density Lipoprotein

    PubMed Central

    Cameron, Scott J.; Morrell, Craig N.; Bao, Clare; Swaim, AnneMarie F.; Rodriguez, Annabelle; Lowenstein, Charles J.

    2015-01-01

    High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL) are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC). Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis. PMID:26680360

  15. A Novel Anti-Inflammatory Effect for High Density Lipoprotein.

    PubMed

    Cameron, Scott J; Morrell, Craig N; Bao, Clare; Swaim, AnneMarie F; Rodriguez, Annabelle; Lowenstein, Charles J

    2015-01-01

    High density lipoprotein has anti-inflammatory effects in addition to mediating reverse cholesterol transport. While many of the chronic anti-inflammatory effects of high density lipoprotein (HDL) are attributed to changes in cell adhesion molecules, little is known about acute signal transduction events elicited by HDL in endothelial cells. We now show that high density lipoprotein decreases endothelial cell exocytosis, the first step in leukocyte trafficking. ApoA-I, a major apolipoprotein of HDL, mediates inhibition of endothelial cell exocytosis by interacting with endothelial scavenger receptor-BI which triggers an intracellular protective signaling cascade involving protein kinase C (PKC). Other apolipoproteins within the HDL particle have only modest effects upon endothelial exocytosis. Using a human primary culture of endothelial cells and murine apo-AI knockout mice, we show that apo-AI prevents endothelial cell exocytosis which limits leukocyte recruitment. These data suggest that high density lipoprotein may inhibit diseases associated with vascular inflammation in part by blocking endothelial exocytosis. PMID:26680360

  16. Design and synthesis of aloe-emodin derivatives as potent anti-tyrosinase, antibacterial and anti-inflammatory agents.

    PubMed

    Liu, Jinbing; Wu, Fengyan; Chen, Changhong

    2015-11-15

    Twenty aloe-emodin derivatives were designed, synthesized, and their biological activities were evaluated. Some compounds displayed potent tyrosinase inhibitory activities, especially, compounds with thiosemicarbazide moiety showed more potent inhibitory effects than the other compounds. The structure-activity relationships (SARs) were preliminarily discussed. The inhibition mechanism of selected compounds 1 and 13 were investigated. The results showed compound 1 was reversible inhibitor, however, compound 13 was irreversible. Kinetic analysis indicated that compound 1 was competitive tyrosinase inhibitor. Furthermore, the antibacterial activities and anti-inflammatory activities of some selected compounds were also screened. The results showed that compound 3 exhibited more potent antibacterial activity than the aloe-emodin, compounds 5 and 6 possessed more potent anti-inflammatory activities than the diacerein. PMID:26471089

  17. Centrally Synthesized Estradiol Is a Potent Anti-Inflammatory in the Injured Zebra Finch Brain.

    PubMed

    Pedersen, Alyssa L; Nelson, Lars H; Saldanha, Colin J

    2016-05-01

    In homeotherms, injury to the brain, such as a penetrating wound, increases microglial cytokine expression and astroglial aromatase (estrogen synthase). In songbirds, injury-induced synthesis of estrogens is neuroprotective as aromatase inhibition and replacement with estradiol (E2) exacerbates and mitigates the extent of damage, respectively. The influence of induced aromatization on inflammation, however, remains unstudied. We hypothesized that injury-induced aromatization, via E2 synthesis, may affect neuroinflammation after a penetrating brain injury. Using adult zebra finches, we first documented an increase in the transcription of cytokines but not aromatase, 2 hours after the injury. Twenty-four hours after the injury, however, aromatase was dramatically elevated and cytokine expression had returned to baseline, suggesting that aromatization may be involved in the decrease of cytokines and neuroinflammation. In two subsequent experiments, we tested the influence of the inhibition of induced aromatization and aromatase inhibition with concomitant central E2 replacement on the transcription of the cytokines TNF-α, IL-1β, and IL-6, the enzyme cyclooxygenase-2 (cox-2), and its product prostaglandin E2 (PGE2). Administration of fadrozole, an aromatase inhibitor, caused a sustained elevation of IL-1β in females and TNF-α, cox-2, and PGE2 in both sexes. This prolonged neuroinflammation appears to be due to a failure to synthesize E2 locally because intracranial E2 replacement lowered IL-1β in females, TNF-α in males, and cox-2 and PGE2 in both sexes. IL-6 was not affected by injury, aromatase inhibition, or E2 replacement in either sex. These data suggest that E2 synthesis after a penetrating brain injury is a potent and inducible anti-inflammatory signal, with specific modulation of discrete cytokine signaling. PMID:26963472

  18. One-Step Synthesis of Chiral Oxindole-type Analogues with Potent Anti-inflammatory and Analgesic Activities

    PubMed Central

    Sun, Yulong; Liu, Jia; Jiang, Xianxing; Sun, Tao; Liu, Luping; Zhang, Xiaoyuan; Ding, Shaoli; Li, Jingyi; Zhuang, Yan; Wang, Yiqing; Wang, Rui

    2015-01-01

    Here we report a facile approach to synthesize highly optically active oxindole-type analogues with both high yield and enantioselectivity. This single-step synthesis strategy represents a substantial improvement upon existing methods that are often involved with multi-step routes and have suboptimal atomic economy. One such compound, namely Q4c, showed remarkable in vivo anti-inflammatory activity with efficiency approaching to that of a steroidal compound dexamethasone. Moreover, Q4c alleviated pain in mouse models with comparable activity to morphine. Further investigation suggested that nitric oxide signaling pathway is involved in the anti-inflammatory and analgesic activities of Q4c. Notably, this is the first time that chiral oxindole-type analogues have been identified to be both anti-inflammatory and analgesic, and our study also paved the way for future development of oxindoles as drug candidates in this field. PMID:26324065

  19. One-Step Synthesis of Chiral Oxindole-type Analogues with Potent Anti-inflammatory and Analgesic Activities.

    PubMed

    Sun, Yulong; Liu, Jia; Jiang, Xianxing; Sun, Tao; Liu, Luping; Zhang, Xiaoyuan; Ding, Shaoli; Li, Jingyi; Zhuang, Yan; Wang, Yiqing; Wang, Rui

    2015-01-01

    Here we report a facile approach to synthesize highly optically active oxindole-type analogues with both high yield and enantioselectivity. This single-step synthesis strategy represents a substantial improvement upon existing methods that are often involved with multi-step routes and have suboptimal atomic economy. One such compound, namely Q4c, showed remarkable in vivo anti-inflammatory activity with efficiency approaching to that of a steroidal compound dexamethasone. Moreover, Q4c alleviated pain in mouse models with comparable activity to morphine. Further investigation suggested that nitric oxide signaling pathway is involved in the anti-inflammatory and analgesic activities of Q4c. Notably, this is the first time that chiral oxindole-type analogues have been identified to be both anti-inflammatory and analgesic, and our study also paved the way for future development of oxindoles as drug candidates in this field. PMID:26324065

  20. Potent Anti-Inflammatory Activity of Tetramethylpyrazine Is Mediated through Suppression of NF-k

    PubMed Central

    Chen, Wei; Chen, Weixiong; Zhu, Jinshui; Chen, Niwei; Lu, Yunmin

    2016-01-01

    The purpose of the current study was to evaluate the anti-inflammatory activity of tetramethlpyrazine on oxazolone-induced colitis mice. Spleen mononuclear cells (SMC), lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were isolated from oxazolone-induced colitis and normal mice. The colitis cells treated by oxazolone were randomly divided into model, low dose, middle dose and high dose groups treated with 0, 0.5, 1.0 and 2.0 g/L tetramethlpyrazine, respectively. The apoptotic rate of SMC and LPMC in the oxazolone-induced group was lower than that in the normal group. Compared with model group, apoptotic rate of SMC was significantly increased in the high dose group, while the apoptotic rate of LPMC in the middle dose group was increased. Compared with SMC, LPMC and PBMC of normal group, the mRNA level of nuclear factor kappa B (NF-kB), transcription factor-activated protein-1 (AP-1) and nuclear factor of activated T cells (NF-AT) were higher in model group. Tetramethylpyrazine inhibited the increase of NF-kB, AP-1 and NF-AT mRNA induced by oxazolone. For SMC, LPMC and PBMC there was significant difference in the mRNA level of AP-1 among the three different doses of tetramethylpyrazine treated groups. However, no significant difference was observed in the mRNA levels of NF-AT and NF-κB between normal and middle groups. Tetramethylpyrazine promoted the apoptotic rate of SMC and LPMC in-vitro, and suppressed the expression of transcription factors in SMC, LPMC and PBMC isolated from oxazolone-induced colitis mice. The study provides a novel insight into the mechanism behind the effect of etramethylpyrazine on colitis. PMID:27610159

  1. Potent Anti-Inflammatory Activity of Tetramethylpyrazine Is Mediated through Suppression of NF-k.

    PubMed

    Chen, Wei; Chen, Weixiong; Zhu, Jinshui; Chen, Niwei; Lu, Yunmin

    2016-01-01

    The purpose of the current study was to evaluate the anti-inflammatory activity of tetramethlpyrazine on oxazolone-induced colitis mice. Spleen mononuclear cells (SMC), lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were isolated from oxazolone-induced colitis and normal mice. The colitis cells treated by oxazolone were randomly divided into model, low dose, middle dose and high dose groups treated with 0, 0.5, 1.0 and 2.0 g/L tetramethlpyrazine, respectively. The apoptotic rate of SMC and LPMC in the oxazolone-induced group was lower than that in the normal group. Compared with model group, apoptotic rate of SMC was significantly increased in the high dose group, while the apoptotic rate of LPMC in the middle dose group was increased. Compared with SMC, LPMC and PBMC of normal group, the mRNA level of nuclear factor kappa B (NF-kB), transcription factor-activated protein-1 (AP-1) and nuclear factor of activated T cells (NF-AT) were higher in model group. Tetramethylpyrazine inhibited the increase of NF-kB, AP-1 and NF-AT mRNA induced by oxazolone. For SMC, LPMC and PBMC there was significant difference in the mRNA level of AP-1 among the three different doses of tetramethylpyrazine treated groups. However, no significant difference was observed in the mRNA levels of NF-AT and NF-κB between normal and middle groups. Tetramethylpyrazine promoted the apoptotic rate of SMC and LPMC in-vitro, and suppressed the expression of transcription factors in SMC, LPMC and PBMC isolated from oxazolone-induced colitis mice. The study provides a novel insight into the mechanism behind the effect of etramethylpyrazine on colitis. PMID:27610159

  2. Berteroin Present in Cruciferous Vegetables Exerts Potent Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin

    PubMed Central

    Jung, Yoo Jin; Jung, Jae In; Cho, Han Jin; Choi, Myung-Sook; Sung, Mi-Kyung; Yu, Rina; Kang, Young-Hee; Park, Jung Han Yoon

    2014-01-01

    Berteroin (5-methylthiopentyl isothiocyanate) is a sulforaphane analog present in cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and mustard oil. We examined whether berteroin exerts anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin inflammation models. Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced degradation of inhibitor of κBα (IκBα) and nuclear factor-κB p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor β activated kinase-1. Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin effectively suppressed TPA-induced edema formation and down-regulated iNOS and COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results demonstrate that berteroin exhibits potent anti-inflammatory properties and suggest that berteroin can be developed as a skin anti-inflammatory agent. PMID:25393510

  3. A Short Peptide That Mimics the Binding Domain of TGF-β1 Presents Potent Anti-Inflammatory Activity

    PubMed Central

    Vaz, Emília R.; Fujimura, Patrícia T.; Araujo, Galber R.; da Silva, Carlos A. T.; Silva, Rangel L.; Cunha, Thiago M.; Lopes-Ferreira, Mônica; Lima, Carla; Ferreira, Márcio J.; Cunha-Junior, Jair P.; Taketomi, Ernesto A.; Goulart, Luiz R.; Ueira-Vieira, Carlos

    2015-01-01

    The transforming growth factor beta 1 (TGF-β1) is a pleiotropic cytokine with multiple roles in development, wound healing, and immune regulation. TGF-β1-mediated immune dysfunction may lead to pathological conditions, such as inflammation. Chronic inflammatory process is characterized by a continuous release of pro-inflammatory cytokines, and the inhibition or the blockage of these cytokines signaling pathways are considered a target treatment. In this context, despite the high numbers of TGF-β-targeted pathways, the inducible regulatory T cells (iTreg) to control inflammation seems to be a promising approach. Our aim was to develop novel peptides through phage display (PhD) technology that could mimic TGF-β1 function with higher potency. Specific mimetic peptides were obtained through a PhD subtraction strategy from whole cell binding using TGF-β1 recombinant as a competitor during elution step. We have selected a peptide that seems to play an important role on cellular differentiation and modulation of TNF-α and IL-10 cytokines. The synthetic pm26TGF-β1 peptide tested in PBMC significantly down-modulated TNF-α and up-regulated IL-10 responses, leading to regulatory T cells (Treg) phenotype differentiation. Furthermore, the synthetic peptide was able to decrease leukocytes rolling in BALB/C mice and neutrophils migration during inflammatory process in C57BL/6 mice. These data suggest that this peptide may be useful for the treatment of inflammatory diseases, especially because it displays potent anti-inflammatory properties and do not exhibit neutrophils’ chemoattraction. PMID:26312490

  4. Arzanol, a Potent mPGES-1 Inhibitor: Novel Anti-Inflammatory Agent

    PubMed Central

    Kothavade, Pankaj S.; Nagmoti, Dnyaneshwar M.; Bulani, Vipin D.; Juvekar, Archana R.

    2013-01-01

    Arzanol is a novel phloroglucinol α-pyrone, isolated from a Mediterranean plant Helichrysum italicum (Roth) Don ssp. microphyllum which belongs to the family Asteraceae. Arzanol has been reported to possess a variety of pharmacological activities. However, anti-inflammatory, anti-HIV, and antioxidant activities have been studied in some detail. Arzanol has been reported to inhibit inflammatory transcription factor NFκB activation, HIV replication in T cells, releases of IL-1β, IL-6, IL-8, and TNF-α, and biosynthesis of PGE2 by potentially inhibiting mPGES-1 enzyme. Diversity of mechanisms of actions of arzanol may be useful in treatment of disease involving these inflammatory mediators such as autoimmune diseases and cancer. This review presents comprehensive information on the chemistry, structure-activity relationship, and pharmacological activities of arzanol. In addition this review discusses recent developments and the scope for future research in these aspects. PMID:24198734

  5. Design, synthesis and biological evaluation of piperic acid triazolyl derivatives as potent anti-inflammatory agents.

    PubMed

    Ali, Yakub; Alam, Mohammad Sarwar; Hamid, Hinna; Husain, Asif; Bano, Sameena; Dhulap, Abhijeet; Kharbanda, Chetna; Nazreen, Syed; Haider, Saqlain

    2015-03-01

    Nineteen novel piperine based triazoles have been synthesized using click chemistry approach and were tested for in vivo anti-inflammatory activity. The most active compounds were evaluated for in vitro TNF-α expression. Compounds 3g and 3f were found to show significant in vivo inhibition of inflammation, 80.40% and 76.71%, respectively after 5 h in comparison to piperine (54.72%) and the standard drug indomethacin (77.02%) without causing any damage to the stomach. Compounds 3g and 3f suppressed TNF-α level by 73.73% and 70.64%, respectively and protein expression of COX-2, NF-κB and TNF-α more than indomethacin. Moreover, the compound 3g was found to show significant analgesic activity of 54.09% which was comparable with the indomethacin (57.43%). PMID:25596479

  6. Some new 2,3,6-trisubstituted quinazolinones as potent anti-inflammatory, analgesic and COX-II inhibitors.

    PubMed

    Kumar, Ashok; Sharma, Shalabh; Archana; Bajaj, Kiran; Sharma, Shipra; Panwar, Hemant; Singh, Tripti; Srivastava, V K

    2003-11-17

    Various 2-(substitutedphenylmethyleneimino)aminoacetylmethylene-3-(2'-substitutedindol-3'-yl)-halosubstituted-4(3H)quinazolinones (5a-5i) and 2-(substituted phenylaminomethyleneacetyl-4'-oxo-1'-thiazolidinyl-3-(2"-substitutedindol-3"-yl) 4(3H)-quinazolinones (6a-6i) have been synthesized in the present studies. The structure of these compounds have been elucidated by elemental (C, H, N) and spectral (IR, 1H NMR and mass) analysis. Furthermore, above said compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic activities and acute toxicity study. Compound 6d was found to be most potent. Compound exihibiting less ulcerogenic liability and ALD(50) >2000mg/kg po. PMID:14604693

  7. Pitavastatin is a potent anti-inflammatory agent in the rat paw model of acute inflammation.

    PubMed

    Qadir, Farida; Alam, Syed Mahboob; Siddiqi, Abeer Qamar; Kamran, Afshan

    2014-11-01

    Statins are used extensively as anti-hyperlipidemic agents. In addition to curtailing cholesterol synthesis they have been found to have multiple actions unrelated to cholesterol lowering "the pleiotropic effects," which includes inhibition of inflammation. We aimed at investigating the effect of pitavastatin a 3rd generation statin, in suppressing acute inflammation in rat paw edema model. Male Sprague-Dawley rats were randomly assigned to one of five groups (n=8): Control, indomethacin and pitavastatin (0.2mg/kg, 0.4mg/kg, 0.8mg/kg) treated. 1hour following treatment, inflammation was induced by sub-planter injection of egg albumin into the hind paw. Anti-inflammatory effect was evaluated by measurement of edema formation every half hour for three hours, assessment of polymorphonuclear leukocyte (PMNL) infiltration and measurement of tissue damage in skin biopsies. Ascending doses of pitavastatin were found to attenuate these parameters. The lowest dose of pitavastatin (0.2mg/kg) was found to significantly reduce edema volume, PMNL infiltration and tissue damage. The efficacy of the smallest dose was found comparable to indomethacin. PMID:26045381

  8. Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders

    PubMed Central

    Johnson, Tyler A.; Sohn, Johann; Inman, Wayne D.; Bjeldanes, Leonard F.; Rayburn, Keith

    2012-01-01

    Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica, (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activity in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves were also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with the standard anti-inflammatory agent celastrol (1) but was moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves plant portions displayed moderate to weak anti-inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity. In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti-inflammatory effects ≥ 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of the roots, stems or leaves of stinging nettle may be more effective then traditional tinctures (water, methanol, ethanol) to undergo clinical evaluations for the treatment of inflammatory disorders including arthritis. A chemical investigation into the lipophillic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted. PMID:23092723

  9. TOPICAL ANTIHISTAMINES DISPLAY POTENT ANTI-INFLAMMATORY ACTIVITY LINKED IN PART TO ENHANCED PERMEABILITY BARRIER FUNCTION

    PubMed Central

    Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis; Park, Kyungho; Roelandt, Truus; Oda, Yuko; Hupe, Melanie; Crumrine, Debra; Lee, Hae-Jin; Gschwandtner, Maria; Thyssen, Jacob P.; Trullas, Carles; Tschachler, Erwin; Feingold, Kenneth R.; Elias, Peter M.

    2012-01-01

    Systemic antagonists of the histamine type 1 and 2 receptors (H1/2r) are widely used as anti-pruritics and central sedatives, but demonstrate only modest anti-inflammatory activity. Because many inflammatory dermatoses result from defects in cutaneous barrier function, and because keratinocytes express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective, if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by: i) stimulation of epidermal differentiation, leading to thickened cornified envelopes; and ii) enhanced epidermal lipid synthesis and secretion. Since barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r antagonists likely oppose mast cell-derived histamine. In four immunologically-diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis), or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic dermatitis), topical H1/2r agonists aggravated, while H1/2r antagonists improved inflammation and/or barrier function. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function. These results could shift current paradigms of antihistamine utilization from a predominantly-systemic to a topical approach. PMID:23014339

  10. Anti-allergic and anti-inflammatory properties of a potent histamine H1 receptor antagonist, desloratadine citrate disodium injection, and its anti-inflammatory mechanism on EA.hy926 endothelial cells.

    PubMed

    Jie, Qiong; Kodithuwakku, Nandani Darshika; Yuan, Xin; He, Guangwei; Chen, Meiling; Xu, Shuhong; Wu, Yulin

    2015-05-01

    The present study, demonstrates that, desloratadine citrate disodium injection (DLC) possesses antihistaminic, anti-allergic and anti-inflammatory properties and elucidates its molecular mechanisms of anti-inflammatory properties. In vitro antihistamine activity of DLC was determined in guinea pig isolated tissues. In vivo antihistamine effects were evaluated after following intravenous administration of DLC in mice with histamine- induced paw edema and in rats with increased capillary permeability. Anti-allergic effects were assessed through passive cutaneous anaphylactic (PCA) reactions in sensitized rodents and ovalbumin-induced allergic rhinitis in rats. Anti-inflammatory properties and molecular mechanisms of DLC were determined on histamine- and lipopolysaccharide (LPS)-induced EA.hy926 endothelial cells. DLC exhibited significant and reversible inhibition of histamine-induced contractions of isolated guinea pig ileum with pA2 value of 8.88. Histamine-induced paw edema and increased capillary permeability were notably inhibited by DLC intravenous administration. In the model of PCA reactions, DLC showed significant activity in a dose-dependent nd potently inhibited both the early-phase and late-phase allergic reaction of ovalbumin-induced allergic rhinitis in rats. DLC alleviated the rhinitis symptoms and inhibited inflammatory cell infiltration, IL-4 and protein leakage in nasal lavage fluid (NLF). In EA.hy926 cells, DLC significantly inhibited the histamine- and LPS- induced IL-6 and IL-8 production and P-selectin and intercellular cell adhesion molecule-1 (ICAM-1) expression. Moreover, DLC reduced translocation of nuclear factor-kappaB (NF-κB) to the nucleus in activated EA.hy926 cells. These results provide evidence that DLC possesses potent antihistaminic, anti-allergic and, anti-inflammatory properties via suppressing IL-6, IL-8, P-selectin and ICAM-1 expression. PMID:25704613

  11. Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism*

    PubMed Central

    Wei, Lin; Gao, Jiuxiang; Zhang, Shumin; Wu, Sijin; Xie, Zeping; Ling, Guiying; Kuang, Yi-Qun; Yang, Yongliang; Yu, Haining; Wang, Yipeng

    2015-01-01

    Cathelicidins are a family of gene-encoded peptide effectors of innate immunity found exclusively in vertebrates. They play pivotal roles in host immune defense against microbial invasions. Dozens of cathelicidins have been identified from several vertebrate species. However, no cathelicidin from marine reptiles has been characterized previously. Here we report the identification and characterization of a novel cathelicidin (Hc-CATH) from the sea snake Hydrophis cyanocinctus. Hc-CATH is composed of 30 amino acids, and the sequence is KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL. Circular dichroism spectroscopy and structure modeling analysis indicated that Hc-CATH mainly assumes an amphipathic α-helical conformation in bacterial membrane-mimetic solutions. It possesses potent broad-spectrum and rapid antimicrobial activity. Meanwhile, it is highly stable and shows low cytotoxicity toward mammalian cells. The microbial killing activity of Hc-CATH is executed through the disruption of cell membrane and lysis of bacterial cells. In addition, Hc-CATH exhibited potent anti-inflammatory activity by inhibiting the LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Hc-CATH directly binds with LPS to neutralize its toxicity, and it also binds to Toll-like receptor 4 (TLR4/MD2 complex), which therefore inhibits the binding of LPS to TLR4/MD2 complex and the subsequent activation of LPS-induced inflammatory response pathways. Taken together, our study demonstrates that Hc-CATH, the first cathelicidin from sea snake discovered to have both antimicrobial and anti-inflammatory activity, is a potent candidate for the development of peptide antibiotics. PMID:26013823

  12. Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism.

    PubMed

    Wei, Lin; Gao, Jiuxiang; Zhang, Shumin; Wu, Sijin; Xie, Zeping; Ling, Guiying; Kuang, Yi-Qun; Yang, Yongliang; Yu, Haining; Wang, Yipeng

    2015-07-01

    Cathelicidins are a family of gene-encoded peptide effectors of innate immunity found exclusively in vertebrates. They play pivotal roles in host immune defense against microbial invasions. Dozens of cathelicidins have been identified from several vertebrate species. However, no cathelicidin from marine reptiles has been characterized previously. Here we report the identification and characterization of a novel cathelicidin (Hc-CATH) from the sea snake Hydrophis cyanocinctus. Hc-CATH is composed of 30 amino acids, and the sequence is KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL. Circular dichroism spectroscopy and structure modeling analysis indicated that Hc-CATH mainly assumes an amphipathic α-helical conformation in bacterial membrane-mimetic solutions. It possesses potent broad-spectrum and rapid antimicrobial activity. Meanwhile, it is highly stable and shows low cytotoxicity toward mammalian cells. The microbial killing activity of Hc-CATH is executed through the disruption of cell membrane and lysis of bacterial cells. In addition, Hc-CATH exhibited potent anti-inflammatory activity by inhibiting the LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Hc-CATH directly binds with LPS to neutralize its toxicity, and it also binds to Toll-like receptor 4 (TLR4/MD2 complex), which therefore inhibits the binding of LPS to TLR4/MD2 complex and the subsequent activation of LPS-induced inflammatory response pathways. Taken together, our study demonstrates that Hc-CATH, the first cathelicidin from sea snake discovered to have both antimicrobial and anti-inflammatory activity, is a potent candidate for the development of peptide antibiotics. PMID:26013823

  13. Rational Development of a Potent 15-Lipoxygenase-1 Inhibitor with in Vitro and ex Vivo Anti-inflammatory Properties.

    PubMed

    Eleftheriadis, Nikolaos; Neochoritis, Constantinos G; Leus, Niek G J; van der Wouden, Petra E; Dömling, Alexander; Dekker, Frank J

    2015-10-01

    Human 15-lipoxygenase-1 (h-15-LOX-1) is a mammalian lipoxygenase and plays an important role in several inflammatory lung diseases such as asthma, COPD, and chronic bronchitis. Novel potent inhibitors of h-15-LOX-1 are required to explore the role of this enzyme further and to enable drug discovery efforts. In this study, we applied an approach in which we screened a fragment collection that is focused on a diverse substitution pattern of nitrogen-containing heterocycles such as indoles, quinolones, pyrazoles, and others. We denoted this approach substitution-oriented fragment screening (SOS) because it focuses on the identification of novel substitution patterns rather than on novel scaffolds. This approach enabled the identification of hits with good potency and clear structure-activity relationships (SAR) for h-1-5-LOX-1 inhibition. Molecular modeling enabled the rationalization of the observed SAR and supported structure-based design for further optimization to obtain inhibitor 14 d that binds with a Ki of 36 nM to the enzyme. In vitro and ex vivo biological evaluations of our best inhibitor demonstrate a significant increase of interleukin-10 (IL-10) gene expression, which indicates its anti-inflammatory properties. PMID:26331552

  14. Rational development of a potent 15-lipoxygenase-1 inhibitor with in vitro and ex vivo anti-inflammatory properties

    PubMed Central

    Eleftheriadis, Nikolaos; Neochoritis, Constantinos G.; Leus, Niek G.J.; van der Wouden, Petra E.; Dömling, Alexander; Dekker, Frank J.

    2016-01-01

    Human 15-lipoxygenase-1 (h-15-LOX-1) is an important mammalian lipoxygenase and plays an important role in several inflammatory lung diseases such as asthma, COPD and chronic bronchitis. Novel potent inhibitors of h-15-LOX-1 are required to explore the role of this enzyme further and to enable drug discovery efforts. In this study, we applied an approach in which we screened a fragment collection that is focused on a diverse substitution pattern of nitrogen containing heterocycles such as indoles, quinolones, pyrazoles etc. We denoted this approach Substitution Oriented fragment Screening (SOS), because it is focuses on identification of novel substitution patterns rather than on novel scaffolds. This approach enabled the identification of hits with good potency and clear structure activity relationships (SAR) for h-1-5-LOX-1 inhibition. A molecular modeling enabled the rationalization of the observed SAR and supported structure-based design for further optimization to obtain inhibitor 14d that binds with a Ki of 36 nM to the enzyme. In vitro and ex vivo biological evaluations of our best inhibitor demonstrate significant increase of interleukin-10 (IL-10) gene expression, which indicates anti-inflammatory properties. PMID:26331552

  15. Highly oxygenated triterpenoids from the roots of Schisandra chinensis and their anti-inflammatory activities.

    PubMed

    Song, Qiu-Yan; Gao, Kun; Nan, Zhi-Biao

    2016-01-01

    A new highly oxygenated triterpenoid, schinchinenlactone D (1), and three known compounds (2-4) were isolated from the roots of Schisandra chinensis. Their structures were determined by combining the spectroscopic analysis with the theoretical computations. The anti-inflammatory activities of compounds 1-4 were evaluated, and compound 3 exhibits the most significant activity in the inhibition of NO production with an IC50 value of 10.6 μM. PMID:26313467

  16. High-Throughput Yeast-Based Reporter Assay to Identify Compounds with Anti-inflammatory Potential.

    PubMed

    Garcia, G; Santos, C Nunes do; Menezes, R

    2016-01-01

    The association between altered proteostasis and inflammatory responses has been increasingly recognized, therefore the identification and characterization of novel compounds with anti-inflammatory potential will certainly have a great impact in the therapeutics of protein-misfolding diseases such as degenerative disorders. Although cell-based screens are powerful approaches to identify potential therapeutic compounds, establishing robust inflammation models amenable to high-throughput screening remains a challenge. To bridge this gap, we have exploited the use of yeasts as a platform to identify lead compounds with anti-inflammatory properties. The yeast cell model described here relies on the high-degree homology between mammalian and yeast Ca(2+)/calcineurin pathways converging into the activation of NFAT and Crz1 orthologous proteins, respectively. It consists of a recombinant yeast strain encoding the lacZ gene under the control of Crz1-recongition elements to facilitate the identification of compounds interfering with Crz1 activation through the easy monitoring of β-galactosidase activity. Here, we describe in detail a protocol optimized for high-throughput screening of compounds with potential anti-inflammatory activity as well as a protocol to validate the positive hits using an alternative β-galactosidase substrate. PMID:27613055

  17. The anti-inflammatory compound BAY 11-7082 is a potent inhibitor of Protein Tyrosine Phosphatases

    PubMed Central

    Krishnan, Navasona; Bencze, Gyula; Cohen, Philip; Tonks, Nicholas K.

    2013-01-01

    Summary The families of protein tyrosine phosphatases (PTPs) and protein tyrosine kinases (PTKs) function in a coordinated manner to regulate signal transduction events that are critical for cellular homeostasis. Aberrant tyrosine phosphorylation, resulting from disruption of either PTP or PTK function, has been shown to be the cause of major human diseases, including cancer and diabetes. Consequently, the characterization of small molecule inhibitors of these kinases and phosphatases may not only provide molecular probes with which to define the significance of particular signalling events, but also may have therapeutic implications. BAY 11-7082 is an anti-inflammatory compound that has been reported to inhibit IκB kinase activity. The compound has an α,β-unsaturated electrophilic center, which confers the property of being a Michael acceptor; this suggests that it may react with nucleophilic cysteine-containing proteins, such as PTPs. In this study, we demonstrated that BAY 11-7082 was a potent, irreversible inhibitor of PTPs. Using mass spectrometry, we have shown that BAY 11-7082 inactivated PTPs by forming a covalent adduct with the active site cysteine. Administration of the compound caused an increase in protein tyrosine phosphorylation in RAW 264 macrophages, similar to the effects of the generic PTP inhibitor sodium orthovanadate. These data illustrate that BAY 11-7082 is an effective pan-PTP inhibitor with cell permeability, revealing its potential as a new probe for chemical biology approaches to the study of PTP function. Furthermore, the data suggest that inhibition of PTP function may contribute to the many biological effects of BAY 11-7082 that have been reported to date. PMID:23578302

  18. The anti-inflammatory compound BAY-11-7082 is a potent inhibitor of protein tyrosine phosphatases.

    PubMed

    Krishnan, Navasona; Bencze, Gyula; Cohen, Philip; Tonks, Nicholas K

    2013-06-01

    The families of protein tyrosine phosphatases (PTPs) and protein tyrosine kinases (PTKs) function in a coordinated manner to regulate signal transduction events that are critical for cellular homeostasis. Aberrant tyrosine phosphorylation, resulting from disruption of either PTP or PTK function, has been shown to be the cause of major human diseases, including cancer and diabetes. Consequently, the characterization of small-molecule inhibitors of these kinases and phosphatases may not only provide molecular probes with which to define the significance of particular signaling events, but also may have therapeutic implications. BAY-11-7082 is an anti-inflammatory compound that has been reported to inhibit IκB kinase activity. The compound has an α,β-unsaturated electrophilic center, which confers the property of being a Michael acceptor; this suggests that it may react with nucleophilic cysteine-containing proteins, such as PTPs. In this study, we demonstrated that BAY-11-7082 was a potent, irreversible inhibitor of PTPs. Using mass spectrometry, we have shown that BAY-11-7082 inactivated PTPs by forming a covalent adduct with the active-site cysteine. Administration of the compound caused an increase in protein tyrosine phosphorylation in RAW 264 macrophages, similar to the effects of the generic PTP inhibitor sodium orthovanadate. These data illustrate that BAY-11-7082 is an effective pan-PTP inhibitor with cell permeability, revealing its potential as a new probe for chemical biology approaches to the study of PTP function. Furthermore, the data suggest that inhibition of PTP function may contribute to the many biological effects of BAY-11-7082 that have been reported to date. PMID:23578302

  19. Anti-inflammatory activity of cinnamon (C. zeylanicum and C. cassia) extracts - identification of E-cinnamaldehyde and o-methoxy cinnamaldehyde as the most potent bioactive compounds.

    PubMed

    Gunawardena, Dhanushka; Karunaweera, Niloo; Lee, Samiuela; van Der Kooy, Frank; Harman, David G; Raju, Ritesh; Bennett, Louise; Gyengesi, Erika; Sucher, Nikolaus J; Münch, Gerald

    2015-03-01

    Chronic inflammation is a contributing factor in many age-related diseases. In a previous study, we have shown that Sri Lankan cinnamon (C. zeylanicum) was one of the most potent anti-inflammatory foods out of 115 foods tested. However, knowledge about the exact nature of the anti-inflammatory compounds and their distribution in the two major cinnamon species used for human consumption is limited. The aim of this investigation was to determine the anti-inflammatory activity of C. zeylanicum and C. cassia and elucidate their main phytochemical compounds. When extracts were tested in LPS and IFN-γ activated RAW 264.7 macrophages, most of the anti-inflammatory activity, measured by down-regulation of nitric oxide and TNF-α production, was observed in the organic extracts. The most abundant compounds in these extracts were E-cinnamaldehyde and o-methoxycinnamaldehyde. The highest concentration of E-cinnamaldehyde was found in the DCM extract of C. zeylanicum or C. cassia (31 and 34 mg g(-1) of cinnamon, respectively). When these and other constituents were tested for their anti-inflammatory activity in RAW 264.7 and J774A.1 macrophages, the most potent compounds were E-cinnamaldehyde and o-methoxycinnamaldehyde, which exhibited IC₅₀ values for NO with RAW 264.7 cells of 55 ± 9 μM (7.3 ± 1.2 μg mL(-1)) and 35 ± 9 μM (5.7 ± 1.5 μg mL(-1)), respectively; and IC₅₀ values for TNF-α of 63 ± 9 μM (8.3 ± 1.2 μg mL(-1)) and 78 ± 16 μM (12.6 ± 2.6 μg mL(-1)), respectively. If therapeutic concentrations can be achieved in target tissues, cinnamon and its components may be useful in the treatment of age-related inflammatory conditions. PMID:25629927

  20. Identification of Magnolia officinalis L. bark extract as the most potent anti-inflammatory of four plant extracts.

    PubMed

    Walker, Joel M; Maitra, Amarnath; Walker, Jessica; Ehrnhoefer-Ressler, Miriam M; Inui, Taichi; Somoza, Veronika

    2013-01-01

    This study was designed to compare the anti-inflammatory potential of a Magnolia officinalis L. bark extract solely or in combination with extracts prepared from either Polygonum aviculare L., Sambucus nigra L., or Isodon japonicus L. in bacterial lipopolysaccharide (LPS) stimulated human gingival fibroblasts (HGF-1) and human U-937 monocytes, as cell models of periodontal disease. HGF-1 and U-937 cells were incubated with LPS from either Porphyromonas gingivalis or Escherichia coli together with the four plant extracts alone or in combination. Secretion of anti-inflammatory cytokines from HGF-1 and U-937 cells was measured by means of a multiplexed bead assay system. Magnolia officinalis L. bark extract, at concentrations of 1 μg/mL and 10 μg/mL, reduced interleukin 6 (IL-6) and interleukin-8 (IL-8) secretion from HGF-1 cells to 72.5 ± 28.6% and reduced matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) secretion from U-937 cells to 8.87 ± 7.97% compared to LPS-treated cells (100%). The other three extracts also reduced secretion of these inflammatory markers but were not as effective. Combination of 9 μg/mL Magnolia officinalis L. extract with 1 μg/mL of each of the other extracts maintained the anti-inflammatory effect of Magnolia officinalis L. extract. Combination of 5 μg/mL Magnolia officinalis L. extract with 5 μg/mL Isodon japonicus L. extract also maintained the anti-inflammatory potential of the Magnolia officinalis L. extract, whereas increasing concentrations of any of the other plant extracts in the combination experiments reduced the Magnolia officinalis L. extract efficacy in U-937 cells. PMID:23711140

  1. Identification of plumericin as a potent new inhibitor of the NF-κB pathway with anti-inflammatory activity in vitro and in vivo

    PubMed Central

    Fakhrudin, N; Waltenberger, B; Cabaravdic, M; Atanasov, A G; Malainer, C; Schachner, D; Heiss, E H; Liu, R; Noha, S M; Grzywacz, A M; Mihaly-Bison, J; Awad, E M; Schuster, D; Breuss, J M; Rollinger, J M; Bochkov, V; Stuppner, H; Dirsch, V M

    2014-01-01

    BACKGROUND AND PURPOSE The transcription factor NF-κB orchestrates many pro-inflammatory signals and its inhibition is considered a promising strategy to combat inflammation. Here we report the characterization of the natural product plumericin as a highly potent inhibitor of the NF-κB pathway with a novel chemical scaffold, which was isolated via a bioactivity-guided approach, from extracts of Himatanthus sucuuba, an Amazonian plant traditionally used to treat inflammation-related disorders. EXPERIMENTAL APPROACH A NF-κB luciferase reporter gene assay was used to identify NF-κB pathway inhibitors from H. sucuuba extracts. Monitoring of TNF-α-induced expression of the adhesion molecules VCAM-1, ICAM-1 and E-selectin by flow cytometry was used to confirm NF-κB inhibition in endothelial cells, and thioglycollate-induced peritonitis in mice to confirm effects in vivo. Western blotting and transfection experiments were used to investigate the mechanism of action of plumericin. KEY RESULTS Plumericin inhibited NF-κB-mediated transactivation of a luciferase reporter gene (IC50 1 μM), abolished TNF-α-induced expression of the adhesion molecules VCAM-1, ICAM-1 and E-selectin in endothelial cells and suppressed thioglycollate-induced peritonitis in mice. Plumericin exerted its NF-κB pathway inhibitory effect by blocking IκB phosphorylation and degradation. Plumericin also inhibited NF-κB activation induced by transfection with the constitutively active catalytic subunit of the IκB kinase (IKK-β), suggesting IKK involvement in the inhibitory action of this natural product. CONCLUSION AND IMPLICATIONS Plumericin is a potent inhibitor of NF-κB pathways with a new chemical scaffold. It could be further explored as a novel anti-inflammatory lead compound. PMID:24329519

  2. Synthesis and biological evaluation of 2-aroylbenzofurans, rugchalcones A, B and their derivatives as potent anti-inflammatory agents.

    PubMed

    Seo, Young Hwa; Damodar, Kongara; Kim, Jin-Kyung; Jun, Jong-Gab

    2016-03-15

    An efficient synthesis of 2-aroylbenzofurans, rugchalcones A, B and their derivatives was accomplished in excellent yields by the Rap-Stoermer reaction between substituted salicylaldehydes and phenacyl bromides. Later their anti-inflammatory effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages. The compounds were exhibited exceptional potency against inflammatory mediated NO production with no cytotoxicity at 10 μM concentration and IC50 values are found in the range from 0.75 to 13.27 μM. Among the 2-aroylbenzofurans prepared in this study, compounds 4 (99.6%; IC50=0.57), rugchalcone B (2) (99.3%; IC50=4.13), 7 (96.8%; IC50=1.90) and 8 (74.3%; IC50=0.99) were showed the maximum inhibitory activity. This study suggests that compounds 2, 4, 7 and 8 which are having 4-hydroxyphenyl group and/or hydroxy (-OH) group at 5- and/or 6-position of benzofuran motif could be considered as a promising scaffolds for the further development of iNOS inhibitors for potential anti-inflammatory applications. PMID:26898337

  3. Synthesis, molecular properties, toxicity and biological evaluation of some new substituted imidazolidine derivatives in search of potent anti-inflammatory agents.

    PubMed

    Husain, Asif; Ahmad, Aftab; Khan, Shah Alam; Asif, Mohd; Bhutani, Rubina; Al-Abbasi, Fahad A

    2016-01-01

    The aim of this study was to design and synthesize pharmaceutical agents containing imidazolidine heterocyclic ring in the hope of developing potent, safe and orally active anti-inflammatory agents. A number of substituted-imidazolidine derivatives (3a-k) were synthesized starting from ethylene diamine and aromatic aldehydes. The imidazolidine derivatives (3a-k) were investigated for their anticipated anti-inflammatory, and analgesic activity in Wistar albino rats and Swiss albino mice, respectively. Bioactivity score, molecular and pharmacokinetic properties of the imidazolidine derivatives were calculated by online computer software programs viz. Molinspiration and Osiris property explorer. The results of biological testing indicated that among the synthesized compounds only three imidazolidine derivatives namely 4-[1,3-Bis(2,6-dichlorobenzyl)-2-imidazolidinyl]phenyl-diethylamine (3g), 4-[1,3-Bis(3-hydroxy-4-methoxybenzyl)-2-imidazolidinyl]phenyl-diethylamine (3i) and 4-(1,3-Bis(4-methoxybenzyl)-4-methylimidazolidin-2-yl)-phenyl-diethylamine (3j) possess promising anti-inflammatory and analgesic actions. Additionally these derivatives displayed superior GI safety profile (low severity index) with respect to the positive control, Indomethacin. All synthesized compounds showed promising bioactivity score for drug targets by Molinspiration software. Almost all the compounds were predicted to have very low toxicity risk by Osiris online software. Compound number (3i) emerged as a potential candidate for further research as it obeyed Lipinski's rule of five for drug likeness, exhibited promising biological activity in-vivo and showed no risk of toxicity in computer aided screening. PMID:26903774

  4. Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

    PubMed

    Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

    2014-02-01

    The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production. PMID:24365491

  5. Rational Design of Small Peptides for Optimal Inhibition of Cyclooxygenase-2: Development of a Highly Effective Anti-Inflammatory Agent.

    PubMed

    Singh, Palwinder; Kaur, Sukhmeet; Kaur, Jagroop; Singh, Gurjit; Bhatti, Rajbir

    2016-04-28

    Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg(-1) dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of compound 30 for targeting COX-2, iNOS, and VGSC was investigated by using substance P, l-arginine, and veratrine, respectively, as biomarkers. The interactions of 30 with COX-2 were supported by isothermal calorimetry experiments showing a Ka of 6.10 ± 1.10 × 10(4) M(-1) and ΔG of -100.3 kJ mol(-1) in comparison to a Ka 0.41 × 10(3) ± 0.09 M(-1) and ΔG of -19.2 ± 0.06 kJ mol(-1) for COX-1. Moreover, compound 30 did not show toxicity up to a 2000 mg kg(-1) dose. Hence, we suggest peptide 30 as a highly potent and promising candidate for further development into an anti-inflammatory drug. PMID:27019010

  6. Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics.

    PubMed

    Luz, John Gately; Antonysamy, Stephen; Kuklish, Steven L; Condon, Bradley; Lee, Matthew R; Allison, Dagart; Yu, Xiao-Peng; Chandrasekhar, Srinivasan; Backer, Ryan; Zhang, Aiping; Russell, Marijane; Chang, Shawn S; Harvey, Anita; Sloan, Ashley V; Fisher, Matthew J

    2015-06-11

    Microsomal prostaglandin E synthase 1 (mPGES-1) is an α-helical homotrimeric integral membrane inducible enzyme that catalyzes the formation of prostaglandin E2 (PGE2) from prostaglandin H2 (PGH2). Inhibition of mPGES-1 has been proposed as a therapeutic strategy for the treatment of pain, inflammation, and some cancers. Interest in mPGES-1 inhibition can, in part, be attributed to the potential circumvention of cardiovascular risks associated with anti-inflammatory cyclooxygenase 2 inhibitors (coxibs) by targeting the prostaglandin pathway downstream of PGH2 synthesis and avoiding suppression of antithrombotic prostacyclin production. We determined the crystal structure of mPGES-1 bound to four potent inhibitors in order to understand their structure-activity relationships and provide a framework for the rational design of improved molecules. In addition, we developed a light-scattering-based thermal stability assay to identify molecules for crystallographic studies. PMID:25961169

  7. Investigation on Toxicity and Teratogenicity in Rats of a Retinoid-Polyamine Conjugate with Potent Anti-Inflammatory Properties.

    PubMed

    Petridis, Theodoros; Giannakopoulou, Dimitra; Stamatopoulou, Vassiliki; Grafanaki, Katerina; Kostopoulos, Christos G; Papadaki, Helen; Malavaki, Christina J; Karamanos, Nikos K; Douroumi, Stathianna; Papachristou, Dionysios; Magoulas, George E; Papaioannou, Dionissios; Drainas, Denis

    2016-02-01

    Previous studies have shown that N(1),N(12)-bis(all-trans-retinoyl)spermine (RASP), a retinoid analog, inhibits RNase P activity and angiogenesis in the chicken embryo chorioallantoic membrane, demonstrates anti-tumor activity on prostate cancer cells, and acts as anti-inflammatory agent, being more effective and less toxic than all-trans retinoic acid. In an attempt to further characterize the biological profile of RASP, we tested its effects on organ toxicity and teratogenicity by daily oral gavage of RASP at a level of 50 mg/Kg of body weight in two generations of rats. We found that this compound does not induce changes to the body growth, the appearance of physical features, and the animal's reflexes. Additionally, no substantial histopathological lesions were found in brain, heart, lung, thymus, liver, thyroid gland, adrenal gland, pituitary gland, kidneys, spleen, skin, femora, prostate, testis, epididymis, vagina, uterus, and ovaries of RASP-treated animals. These results suggest RASP, as a promising lead compound for the treatment of several dermatological disorders and certain cancer types, has apparently minimal toxic side-effects as revealed in this two-generation reproduction study in rats. PMID:26762583

  8. Anti-Inflammatory Properties of Low and High Doxycycline Doses: An In Vitro Study

    PubMed Central

    Di Caprio, Roberta; Di Costanzo, Luisa; Monfrecola, Giuseppe

    2015-01-01

    Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20–40 mg/day) do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-α, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-α, and IL-6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, our in vitro study suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled. PMID:25977597

  9. Antioxidant and anti-inflammatory effects of Marrubium alysson extracts in high cholesterol-fed rabbits

    PubMed Central

    Essawy, Soha S.; Abo-elmatty, Dina M.; Ghazy, Nabila M.; Badr, Jihan M.; Sterner, Olov

    2013-01-01

    The antioxidant and anti-inflammatory effects of hexane (HEXA), chloroform (CHLORO), ethyl acetate (EA) and total alcoholic (T. ALCOH) extracts of Marrubium alysson in hypercholesterolemic-fed rabbits were evaluated. Hypercholesterolemia was induced in male rabbits by high cholesterol diet (HCD) (350 mg/kg) for 8 weeks. Hypercholesterolemic rabbits were allocated into groups, treated with simvastatin (SIM 5 mg/kg), different extracts of M. alysson at two doses of 250, 500 mg/kg. A normal control group and an HCD control one were used for comparison. Lipid profile, as well as oxidized low density lipoprotein-cholesterol (ox-LDL-C), myeloperoxidase activity (MPO) and superoxide anion production (O2•−), C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) were also evaluated. In addition, histological examination of ascending aorta was performed. We found dyslipidemia associated with significant increases in ox-LDL-C 123.5 ± 9.8 nmol MDA/mg non-HDL, MPO activity 0.08 ± 0.05 U/100 mg tissue and O2•− production 3.5 ± 0.3 nmol cytochrome C reduced/min/g tissue × 10−4 in hypercholerterolemic rabbits. In addition, there was a significant increase in CRP 6.6 ± 0.49 μmol/L and MCP-1 190.9 ± 6.4 pg/ml and its mRNA expression in HCD. Intima appeared thick with thick plaques surrounding the intima and luminal narrowing. SIM, EA and HEXA extracts of M. alysson had lipid lowering effect, decrease in ox-LDL-C, MPO, O2•−, CRP and MCP-1 mRNA expression with improvement of the pathological picture. M. alysson enhanced the stability of plaque, had lipid lowering, anti-inflammatory and antioxidant activities. PMID:25473336

  10. Polysaccharide Constituents of Three Types of Sea Urchin Shells and Their Anti-Inflammatory Activities

    PubMed Central

    Jiao, Heng; Shang, Xiaohui; Dong, Qi; Wang, Shuang; Liu, Xiaoyu; Zheng, Heng; Lu, Xiaoling

    2015-01-01

    As a source of potent anti-inflammatory traditional medicines, the quantitative chromatographic fingerprints of sea urchin shell polysaccharides were well established via pre-column derivatization high performance liquid chromatography (HPLC) analysis. Based on the quantitative results, the content of fucose and glucose could be used as preliminary distinguishing indicators among three sea urchin shell species. Besides, the anti-inflammatory activities of the polysaccharides from sea urchin shells and their gonads were also determined. The gonad polysaccharide of Anthocidaris crassispina showed the most potent anti-inflammatory activity among all samples tested. PMID:26389925

  11. In vitro and in vivo characterization of A-940894: a potent histamine H4 receptor antagonist with anti-inflammatory properties

    PubMed Central

    Strakhova, MI; Cuff, CA; Manelli, AM; Carr, TL; Witte, DG; Baranowski, JL; Vortherms, TA; Miller, TR; Rundell, L; McPherson, MJ; Adair, RM; Brito, AA; Bettencourt, BM; Yao, BB; Wetter, JM; Marsh, KC; Liu, H; Cowart, MD; Brioni, JD; Esbenshade, TA

    2009-01-01

    Background and purpose: The histamine H4 receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H4 receptor antagonist, A-940894 (4-piperazin-1-yl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine). Experimental approach: We have analysed the pharmacological profile of A-940894 at mouse native, rat recombinant and human recombinant and native, histamine H4 receptors by radioligand binding, calcium mobilization, mast cell shape change, eosinophil chemotaxis assays and in the mouse model of zymosan-induced peritonitis. Key results: A-940894 potently binds to both human and rat histamine H4 receptors and exhibits considerably lower affinity for the human histamine H1, H2 or H3 receptors. It potently blocked histamine-evoked calcium mobilization in the fluorometric imaging plate reader assays and inhibited histamine-induced shape change of mouse bone marrow-derived mast cells and chemotaxis of human eosinophils in vitro. In a mouse mast cell-dependent model of zymosan-induced peritonitis, A-940894 significantly blocked neutrophil influx and reduced intraperitoneal prostaglandin D2 levels. Finally, A-940894 has good pharmacokinetic properties, including half-life and oral bioavailability in rats and mice. Conclusions and Implications: These data suggest that A-940894 is a potent and selective histamine H4 receptor antagonist with pharmacokinetic properties suitable for long-term in vivo testing and could serve as a useful tool for the further characterization of histamine H4 receptor pharmacology. PMID:19413570

  12. In vitro anti-inflammatory and antioxidant activities and protein quality of high hydrostatic pressure treated squids (Todarodes pacificus).

    PubMed

    Zhang, Yifeng; Dai, Bona; Deng, Yun; Zhao, Yanyun

    2016-07-15

    This study investigated the in vitro anti-inflammatory and antioxidant properties, protein quality, and other related characteristics obtained by the single-cycle and two-cycle high hydrostatic pressure (HHP at 200, 400 and 600 MPa) treatment of squids (Todarodes pacificus). The soluble protein nitrogen content and in vitro protein digestibility increased significantly (p<0.05) after all HHP treatments, and the two-cycle 600 MPa HHP treatments yielded the highest values, 7.59% and 84.42%, respectively. The estimated protein efficiency ratios, and antioxidant and anti-inflammatory properties of squids significantly increased by all HHP treatments. (1)H nuclear magnetic resonance (NMR) showed that the main spectral changes associated to the anti-inflammatory properties of proteins following HHP treatment were in the range of 3.00-3.19 and 3.60-3.79 ppm. This indicates that the HHP treatments modified the protein and functional properties of squids and gave the relevant chemical shifts in NMR signals, either migrated or disappeared. PMID:26948613

  13. A Herbal Composition of Scutellaria baicalensis and Eleutherococcus senticosus Shows Potent Anti-Inflammatory Effects in an Ex Vivo Human Mucosal Tissue Model

    PubMed Central

    Zhang, Nan; Van Crombruggen, Koen; Holtappels, Gabriele; Bachert, Claus

    2012-01-01

    Background. Patients seek an effective alternative to pharmacotherapy including herbal treatment options for allergic rhinitis and rhinosinusitis. Material and Methods. Nasal mucosal tissue was obtained from 12 patients, fragmented, preincubated with tissue culture medium, S. baicalensis and/or E. senticosus and/or vitamin C (each compound 0.2 μg/mL and 2 μg/mL) for 1 hour at 37°C/5% CO2, and stimulated with anti-IgE for 30 minutes and 6 hours to imitate the allergic early and late phases. Furthermore, Staphylococcus aureus superantigen B (SEB) stimulation for 6 hours was used to imitate T-cell activation. Results. The combination of S. baicalensis and E. senticosus had a more potent suppressive effect on the release of PGD2, histamine, and IL-5 than S. baicalensis alone. The combination also resulted in a significant inhibition of SEB-induced cytokines comparable or superior to an established topical corticosteroid, fluticasone propionate. Vitamin C increased ciliary beat frequency, but had no anti-inflammatory effects. Discussion. The combination of S. baicalensis and E. senticosus may be able to significantly block allergic early-and late-phase mediators and substantially suppress the release of proinflammatory, and Th1-, Th2-, and Th17—derived cytokines. PMID:22272213

  14. Potent anti-inflammatory agent escin does not affect the healing of tibia fracture and abdominal wound in an animal model.

    PubMed

    Zhang, Leiming; Wang, Hongsheng; Wang, Tian; Jiang, Na; Yu, Pengfei; Liu, Feiyan; Chong, Yating; Fu, Fenghua

    2012-04-01

    Escin, a potent anti-inflammatory and anti-edematous agent, has been widely used clinically in preventing inflammatory edema after trauma, such as fracture and surgery. The aim of this study was to investigate whether escin has an inhibitory effect on fracture healing, and whether escin has an inhibitory effect on wound healing after surgery. Male New Zealand white rabbits underwent tibial mid-diaphyseal osteotomy, and were administered escin once per day for 10 days. At weeks 2, 4 and 6, bone fracture healing and bone mineral density were measured. The histologic examination of callus, osteocalcin, alkaline phosphatase, calcium and phosphate in the serum were also assayed. In another experiment, the rats underwent midline laparotomy, and received escin once prior to or after the operation. Six days later, the abdominal incision wounds were excised for measuring hydroxyproline levels. The results showed that there were no significant differences in fracture healing between the model and rabbits administered escin, and escin did not affect the hydroxyproline levels in the abdominal incision wounds of the rats. These findings suggest that escin has no inhibitory effect on fracture and wound healing in animal models. PMID:22969961

  15. Potent anti-inflammatory agent escin does not affect the healing of tibia fracture and abdominal wound in an animal model

    PubMed Central

    ZHANG, LEIMING; WANG, HONGSHENG; WANG, TIAN; JIANG, NA; YU, PENGFEI; LIU, FEIYAN; CHONG, YATING; FU, FENGHUA

    2012-01-01

    Escin, a potent anti-inflammatory and anti-edematous agent, has been widely used clinically in preventing inflammatory edema after trauma, such as fracture and surgery. The aim of this study was to investigate whether escin has an inhibitory effect on fracture healing, and whether escin has an inhibitory effect on wound healing after surgery. Male New Zealand white rabbits underwent tibial mid-diaphyseal osteotomy, and were administered escin once per day for 10 days. At weeks 2, 4 and 6, bone fracture healing and bone mineral density were measured. The histologic examination of callus, osteocalcin, alkaline phosphatase, calcium and phosphate in the serum were also assayed. In another experiment, the rats underwent midline laparotomy, and received escin once prior to or after the operation. Six days later, the abdominal incision wounds were excised for measuring hydroxyproline levels. The results showed that there were no significant differences in fracture healing between the model and rabbits administered escin, and escin did not affect the hydroxyproline levels in the abdominal incision wounds of the rats. These findings suggest that escin has no inhibitory effect on fracture and wound healing in animal models. PMID:22969961

  16. PGH1, the precursor for the anti-inflammatory prostaglandins of the 1-series, is a potent activator of the pro-inflammatory receptor CRTH2/DP2.

    PubMed

    Schröder, Ralf; Xue, Luzheng; Konya, Viktoria; Martini, Lene; Kampitsch, Nora; Whistler, Jennifer L; Ulven, Trond; Heinemann, Akos; Pettipher, Roy; Kostenis, Evi

    2012-01-01

    Prostaglandin H(1) (PGH(1)) is the cyclo-oxygenase metabolite of dihomo-γ-linolenic acid (DGLA) and the precursor for the 1-series of prostaglandins which are often viewed as "anti-inflammatory". Herein we present evidence that PGH(1) is a potent activator of the pro-inflammatory PGD(2) receptor CRTH2, an attractive therapeutic target to treat allergic diseases such as asthma and atopic dermatitis. Non-invasive, real time dynamic mass redistribution analysis of living human CRTH2 transfectants and Ca(2+) flux studies reveal that PGH(1) activates CRTH2 as PGH(2), PGD(2) or PGD(1) do. The PGH(1) precursor DGLA and the other PGH(1) metabolites did not display such effect. PGH(1) specifically internalizes CRTH2 in stable CRTH2 transfectants as assessed by antibody feeding assays. Physiological relevance of CRTH2 ligation by PGH(1) is demonstrated in several primary human hematopoietic lineages, which endogenously express CRTH2: PGH(1) mediates migration of and Ca(2+) flux in Th2 lymphocytes, shape change of eosinophils, and their adhesion to human pulmonary microvascular endothelial cells under physiological flow conditions. All these effects are abrogated in the presence of the CRTH2 specific antagonist TM30089. Together, our results identify PGH(1) as an important lipid intermediate and novel CRTH2 agonist which may trigger CRTH2 activation in vivo in the absence of functional prostaglandin D synthase. PMID:22442685

  17. The JAK-3 inhibitor CP-690550 is a potent anti-inflammatory agent in a murine model of pulmonary eosinophilia.

    PubMed

    Kudlacz, Elizabeth; Conklyn, Maryrose; Andresen, Catharine; Whitney-Pickett, Carrie; Changelian, Paul

    2008-03-17

    Janus kinase 3 (JAK-3) is a tyrosine kinase that has been shown to participate in the signaling of several cytokines that are believed to play a role in allergic airway disease, e.g. IL-2, 4 and 9. The current study describes the immunosuppressive effects of CP-690550, a novel, small molecule inhibitor of JAK-3, in a murine model of allergic pulmonary inflammation. In vitro, CP-690550 potently inhibited IL-4 induced upregulation of CD23 (IC(50)=57 nM) and class II major histocompatibility complex (MHCII) expression (IC(50)=71 nM) on murine B cells. Repeat aerosol exposure to ovalbumin in wild-type mice sensitized to the antigen resulted in preferential recruitment of Th2-like cells (IL-4+ and IL-5+) into bronchoalveolar lavage fluid (BAL). The importance of IL-4 in the development of pulmonary eosinophilia was supported by a marked (90%) reduction in the influx of these cells in IL-4KO mice similarly sensitized and ovalbumin exposed. Animals dosed with CP-690550 (15 mg/kg/d) during the period of antigen sensitization and boost demonstrated marked reductions in BAL eosinophils and levels of IL-13 and eotaxin following ovalbumin aerosol exposure. The JAK-3 inhibitor (1.5-15 mg/kg/d) also effectively reduced the same parameters when administered during the period of antigen challenge. In contrast, the calcineurin inhibitor tacrolimus (10 mg/kg) was effective only when administered during the period of ovalbumin aerosol exposure. These data support the participation of JAK-3 in processes that contribute to pulmonary eosinophilia in the allergic mouse model. CP-690550 represents an intriguing novel therapy for treatment of allergic conditions associated with airway eosinophilia including asthma and rhinitis. PMID:18242596

  18. Correction: The anti-inflammatory effect of a glycosylation product derived from the high hydrostatic pressure enzymatic hydrolysate of a flatfish byproduct.

    PubMed

    Choe, In-Hu; Jeon, Hyeon Jin; Eom, Sung-Hwan; Han, Young-Ki; Kim, Yoon Sook; Lee, Sang-Hoon

    2016-08-10

    Correction for 'The anti-inflammatory effect of a glycosylation product derived from the high hydrostatic pressure enzymatic hydrolysate of a flatfish byproduct' by In-Hu Choe, et al., Food Funct., 2016, 7, 2557-2565. PMID:27396872

  19. A high performance liquid chromatography with ultraviolet method for Eschweilera nana leaves and their anti-inflammatory and antioxidant activities

    PubMed Central

    Outuki, Priscila M.; Lazzeri, Nides S.; de Francisco, Lizziane M. B.; Bersani-Amado, Ciomar A.; Ferreira, Izabel C. P.; Cardoso, Mara Lane C.

    2015-01-01

    Background: Eschweilera nana Miers is a tree widely distributed in Cerrado, Brazil. Objective: In this study, we aimed to describe its phytochemical properties and antioxidant and topical anti-inflammatory effects for the first time, as well validate an high performance liquid chromatography with ultraviolet/visible (HPLC-UV-Vis) method for the separation and quantification of the main components (hyperoside and rutin) in the hydroalcoholic extract of E. nana leaves. Materials and Methods: Structural identification of compounds in E. nana extract was performed by analysis of spectral data by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance and/or ESI/EM. The HPLC-UV-Vis method was validated according International Conference on Harmonization (ICH) parameters. The 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) method were used for determination of in vitro antioxidant activities and the croton oil-induced inflammation for evaluation of in vivo anti-inflammatory effects. Results: Hyperoside, rutin, α-amirin, β-amirin, β-sitosterol, and stigmasterol were identified in the hydroalcoholic extract of E. nana leaves. HPLC-UV-Vis was validated according to ICH parameters. Furthermore, in vitro and in vivo assays demonstrated that the hydroalcoholic extract and methanol fraction showed significant antioxidant and topical anti-inflammatory effects, as they were able to reduce ear edema induced by croton-oil application. Conclusions: This research showed the first phytochemical study of E. nana extract and their biological activities may be associated with the presence of flavonoids in the extracts. PMID:26246741

  20. Potent Anti-Inflammatory Activity of Pyrenocine A Isolated from the Marine-Derived Fungus Penicillium paxilli Ma(G)K

    PubMed Central

    Toledo, Thaís Regina; Dejani, Naiara N.; Monnazzi, Luis Gustavo Silva; Kossuga, Miriam H.; Berlinck, Roberto G. S.; Sette, Lara D.; Medeiros, Alexandra I.

    2014-01-01

    Very little is known about the immunomodulatory potential of secondary metabolites isolated from marine microorganisms. In the present study, we characterized pyrenocine A, which is produced by the marine-derived fungus Penicillium paxilli Ma(G)K and possesses anti-inflammatory activity. Pyrenocine A was able to suppress, both pretreatment and posttreatment, the LPS-induced activation of macrophages via the inhibition of nitrite production and the synthesis of inflammatory cytokines and PGE2. Pyrenocine A also exhibited anti-inflammatory effects on the expression of receptors directly related to cell migration (Mac-1) as well as costimulatory molecules involved in lymphocyte activation (B7.1). Nitrite production was inhibited by pyrenocine A in macrophages stimulated with CpG but not Poly I:C, suggesting that pyrenocine A acts through the MyD88-dependent intracellular signaling pathway. Moreover, pyrenocine A is also able to inhibit the expression of genes related to NFκB-mediated signal transduction on macrophages stimulated by LPS. Our results indicate that pyrenocine A has promissory anti-inflammatory properties and additional experiments are necessary to confirm this finding in vivo model. PMID:24574582

  1. Potent anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R. Br. ex Cass., a Q'eqchi' Maya traditional medicine.

    PubMed

    Walshe-Roussel, Brendan; Choueiri, Christine; Saleem, Ammar; Asim, Muhammd; Caal, Federico; Cal, Victor; Rojas, Marco Otarola; Pesek, Todd; Durst, Tony; Arnason, John Thor

    2013-08-01

    The widespread use of Neurolaena lobata (L.) R. Br. ex Cass. by Q'eqchi' Maya and indigenous healers throughout the Caribbean for inflammatory conditions prompted the study of the anti-inflammatory activity of this traditional medicine. The objectives of this study were to conduct a detailed ethnobotanical investigation of the uses of N. lobata by the Q'eqchi' Maya of Belize for a variety of inflammatory symptoms and to evaluate the in vitro anti-inflammatory activity of leaf extract and isolated sesquiterpene lactones. The crude 80% EtOH extract of N. lobata leaves administered at 100 μg/mL reduced LPS-stimulated TNF-α production in THP-1 monocytes by 72% relative to the stimulated vehicle control. Isolated sesquiterpene lactones, neurolenins B, C+D, lobatin B and 9α-hydroxy-8β-isovalerianyloxy-calyculatolide were more active (IC50=0.17-2.32 μM) than the positive control parthenolide (IC50=4.79 μM). The results provide a pharmacological and phytochemical basis for the traditional use of this leaf for inflammatory conditions. PMID:23747054

  2. Similar Anti-Inflammatory Acute Responses from Moderate-Intensity Continuous and High-Intensity Intermittent Exercise

    PubMed Central

    Cabral-Santos, Carolina; Gerosa-Neto, José; Inoue, Daniela Sayuri; Panissa, Valéria Leme Gonçalves; Gobbo, Luís Alberto; Zagatto, Alessandro Moura; Campos, Eduardo Zapaterra; Lira, Fábio Santos

    2015-01-01

    The purpose of this study was to compare the effect of high-intensity intermittent exercise (HIIE) versus volume matched steady state exercise (SSE) on inflammatory and metabolic responses. Eight physically active male subjects completed two experimental sessions, a 5-km run on a treadmill either continuously (70% vVO2max) or intermittently (1:1 min at vVO2max). Blood samples were collected at rest, immediately, 30 and 60 minutes after the exercise session. Blood was analyzed for glucose, non-ester fatty acid (NEFA), uric acid, lactate, cortisol, and cytokines (IL-6, IL-10 and TNF-α) levels. The lactate levels exhibited higher values immediately post-exercise than at rest (HIIE 1.34 ± 0.24 to 7.11 ± 2.85, and SSE 1.35 ± 0.14 to 4.06±1.60 mmol·L-1, p < 0.05), but HIIE promoted higher values than SSE (p < 0.05); the NEFA levels were higher immediately post-exercise than at rest only in the SSE condition (0.71 ± 0.04 to 0.82±0.09 mEq/L, respectively, p < 0.05), yet, SSE promoted higher values than HIIE immediately after exercise (HIIE 0.72±0.03 vs SSE 0.82±0.09 mEq·L-1, p < 0.05). Glucose and uric acid levels did not show changes under the different conditions (p > 0.05). Cortisol, IL-6, IL-10 and TNF-α levels showed time-dependent changes under the different conditions (p < 0.05), however, the area under the curve of TNF-α in the SSE were higher than HIIE (p < 0.05), and the area under the curve of IL-6 in the HIIE showed higher values than SSE (p < 0.05). In addition, both exercise conditions promote increased IL-10 levels and IL-10/TNF-α ratio (p < 0.05). In conclusion, our results demonstrated that both exercise protocols, when volume is matched, promote similar inflammatory responses, leading to an anti-inflammatory status; however, the metabolic responses are different. Key points Metabolic contribution of both exercise, HIIE and SSE, was different. Both protocols leading to an anti-inflammatory status. HIIE induce a higher energy expenditure take

  3. Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo

    PubMed Central

    Aerts, J.; Vandenbroucke, R. E.; Dera, R.; Balusu, S.; Van Wonterghem, E.; Moons, L.; Libert, C.; Dehaen, W.; Arckens, L.

    2015-01-01

    A hydroxypyrone-based matrix metalloproteinase (MMP) inhibitor was synthesized and assayed for its inhibitory capacity towards a panel of ten different MMPs. The compound exhibited selective inhibition towards MMP-12. The effects of inhibition of MMP-12 on endotoxemia and inflammation-induced blood-cerebrospinal fluid barrier (BCSFB) disruption were assessed both in vitro and in vivo. Similar to MMP-12 deficient mice, inhibitor-treated mice displayed significantly lower lipopolysaccharide- (LPS-) induced lethality compared to vehicle treated controls. Following LPS injection Mmp-12 mRNA expression was massively upregulated in choroid plexus tissue and a concomitant increase in BCSFB permeability was observed, which was restricted in inhibitor-treated mice. Moreover, an LPS-induced decrease in tight junction permeability of primary choroid plexus epithelial cells was attenuated by inhibitor application in vitro. Taken together, this hydroxypyrone-based inhibitor is selective towards MMP-12 and displays anti-inflammatory activity in vitro and in vivo. PMID:26351407

  4. Anti-inflammatory and antiobesity effects of mulberry leaf and fruit extract on high fat diet-induced obesity.

    PubMed

    Lim, Hyun Hwa; Lee, Sung Ok; Kim, Sun Yeou; Yang, Soo Jin; Lim, Yunsook

    2013-10-01

    The purpose of this study was to investigate the anti-inflammatory and antiobesity effect of combinational mulberry leaf extract (MLE) and mulberry fruit extract (MFE) in a high-fat (HF) diet-induced obese mice. Mice were fed a control diet or a HF diet for nine weeks. After obesity was induced, the mice were administered with single MLE at low dose (133 mg/kg/day, LMLE) and high dose (333 mg/kg/day, HMLE) or combinational MLE and MFE (MLFE) at low dose (133 mg MLE and 67 mg MFE/kg/day, LMLFE) and high dose (333 mg MLE and 167 mg MFE/kg/day, HMLFE) by stomach gavage for 12 weeks. The mulberry leaf and fruit extract treatment for 12 weeks did not show liver toxicity. The single MLE and combinational MLFE treatments significantly decreased plasma triglyceride, liver lipid peroxidation levels and adipocyte size and improved hepatic steatosis as compared with the HF group. The combinational MLFE treatment significantly decreased body weight gain, fasting plasma glucose and insulin, and homeostasis model assessment of insulin resistance. HMLFE treatment significantly improved glucose control during intraperitoneal glucose tolerance test compared with the HF group. Moreover, HMLFE treatment reduced protein levels of oxidative stress markers (manganese superoxide dismutase) and inflammatory markers (monocyte chemoattractant protein-1, inducible nitric oxide synthase, C-reactive protein, tumour necrosis factor-α and interleukin-1) in liver and adipose tissue. Taken together, combinational MLFE treatment has potential antiobesity and antidiabetic effects through modulation of obesity-induced inflammation and oxidative stress in HF diet-induced obesity. PMID:24000381

  5. Anti-inflammatory and anti-diabetic effects of brown seaweeds in high-fat diet-induced obese mice

    PubMed Central

    Oh, Ji-Hyun; Kim, Jaehoon

    2016-01-01

    BACKGROUND/OBJECTIVES Seaweeds have been reported to have various health beneficial effects. In this study, we investigated the potential anti-obesity and anti-inflammatory effects of four types of domestic brown seaweeds in a high-fat diet-induced obese mouse model and bone marrow-derived macrophages (BMDM). MATERIALS/METHODS Male C57BL/6N mice were fed low-fat diet (LFD), high-fat diet (HFD) or HFD containing Undaria Pinnatifida, HFD containing Laminaria Japonica (LJ), HFD containing Sargassum Fulvellum, or HFD containing Hizikia Fusiforme (HF) for 16 weeks. RESULTS Brown seaweed supplementation did not affect long-term HFD-associated changes in body weight or adiposity, although mice fed HFD + LJ or HFD + HF gained slightly less body weight compared with those fed HFD at the beginning of feeding. Despite being obese, mice fed HFD + LJ appeared to show improved insulin sensitivity compared to mice fed HFD. Consistently, we observed significantly reduced blood glucose concentrations in mice fed HFD + LJ compared with those of mice fed HFD. Although no significant differences in adipocyte size were detected among the HFD-fed groups, consumption of seaweeds decreased formation of HFD-induced crown-like structures in gonadal adipose tissue as well as plasma inflammatory cytokines. BMDM from mice fed HFDs with seaweeds showed differential regulation of pro-inflammatory cytokines such as IL-1β and IL-6 compared with BMDM from mice fed HFD by LPS stimulation. CONCLUSION Although seaweed consumption did not prevent long-term HFD-induced obesity in C57BL/6N mice, it reduced insulin resistance (IR) and circulation of pro-inflammatory cytokines. Therefore, seaweeds may ameliorate systemic inflammation and IR in obesity partially due to inhibition of inflammatory signaling in adipose tissue cells as well as bone marrow-derived immune cells. PMID:26865915

  6. Anti-inflammatory Activity.

    PubMed

    2016-01-01

    Inflammation is the body's first response to infection or injury and is critical for both innate and adaptive immunity. It can be considered as part of the complex biological response of vascular tissues to harmful stimuli such as pathogens, damaged cells, or irritants. The search for natural compounds and phytoconstituents that are able to interfere with these mechanisms by preventing a prolonged inflammation could be useful for human health. Here, the anti-inflammatory properties of plant-based drugs are put together with both in vitro and acute (carrageenan, egg albumin and croton oil) and chronic (cotton pellet) in vivo models. PMID:26939273

  7. Rosuvastatin Alters the Proteome of High Density Lipoproteins: Generation of alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties.

    PubMed

    Gordon, Scott M; McKenzie, Benjamin; Kemeh, Georgina; Sampson, Maureen; Perl, Shira; Young, Neal S; Fessler, Michael B; Remaley, Alan T

    2015-12-01

    Statins lower plasma cholesterol by as much as 50%, thus reducing future cardiovascular events. However, the physiological effects of statins are diverse and not all are related to low density lipoprotein cholesterol (LDL-C) lowering. We performed a small clinical pilot study to assess the impact of statins on lipoprotein-associated proteins in healthy individuals (n = 10) with normal LDL-C (<130 mg/dL), who were treated with rosuvastatin (20 mg/day) for 28 days. Proteomic analysis of size-exclusion chromatography isolated LDL, large high density lipoprotein (HDL-L), and small HDL (HDL-S) fractions and spectral counting was used to compare relative protein detection before and after statin therapy. Significant protein changes were found in each lipoprotein pool and included both increases and decreases in several proteins involved in lipoprotein metabolism, complement regulation and acute phase response. The most dramatic effect of the rosuvastatin treatment was an increase in α-1-antirypsin (A1AT) spectral counts associated with HDL-L particles. Quantitative measurement by ELISA confirmed an average 5.7-fold increase in HDL-L associated A1AT. Molecular modeling predictions indicated that the hydrophobic reactive center loop of A1AT, the functional domain responsible for its protease inhibitor activity, is likely involved in lipid binding and association with HDL was found to protect A1AT against oxidative inactivation. Cell culture experiments, using J774 macrophages, demonstrated that the association of A1AT with HDL enhances its antiprotease activity, preventing elastase induced production of tumor necrosis factor α. In conclusion, we show that statins can significantly alter the protein composition of both LDL and HDL and our studies reveal a novel functional relationship between A1AT and HDL. The up-regulation of A1AT on HDL enhances its anti-inflammatory functionality, which may contribute to the non-lipid lowering beneficial effects of statins. PMID

  8. A new insight into viral proteins as Immunomodulatory therapeutic agents: KSHV vOX2 a homolog of human CD200 as a potent anti-inflammatory protein

    PubMed Central

    Mousavinezhad-Moghaddam, Maryam; Amin, Abbas Ali; Rafatpanah, Houshang; Rezaee, Seyed Abdol Rahim

    2016-01-01

    The physiologic function of the immune system is defense against infectious microbes and internal tumour cells, Therefore, need to have precise modulatory mechanisms to maintain the body homeostasis. The mammalian cellular CD200 (OX2)/CD200R interaction is one of such modulatory mechanisms in which myeloid and lymphoid cells are regulated. CD200 and CD200R molecules are membrane proteins that their immunomodulatory effects are able to suppress inflammatory responses, particularly in the privilege sites such as CNS and eyes. Kaposi’s sarcoma-associated herpesvirus (KSHV), encodes a wide variety of immunoregulatory proteins which play central roles in modulating inflammatory and anti-inflammatory responses in favour of virus dissemination. One such protein is a homologue of the, encoded by open reading frame (ORF) K14 and therefore called vOX2. Based on its gene expression profile during the KSHV life cycle, it is hypothesised that vOX2 modulates host inflammatory responses. Moreover, it seems that vOX2 involves in cell adhesion and modulates innate immunity and promotes Th2 immune responses. In this review the activities of mammalian CD200 and KSHV CD200 in cell adhesion and immune system modulation are reviewed in the context of potential therapeutic agents. PMID:27096058

  9. A new insight into viral proteins as Immunomodulatory therapeutic agents: KSHV vOX2 a homolog of human CD200 as a potent anti-inflammatory protein.

    PubMed

    Mousavinezhad-Moghaddam, Maryam; Amin, Abbas Ali; Rafatpanah, Houshang; Rezaee, Seyed Abdol Rahim

    2016-01-01

    The physiologic function of the immune system is defense against infectious microbes and internal tumour cells, Therefore, need to have precise modulatory mechanisms to maintain the body homeostasis. The mammalian cellular CD200 (OX2)/CD200R interaction is one of such modulatory mechanisms in which myeloid and lymphoid cells are regulated. CD200 and CD200R molecules are membrane proteins that their immunomodulatory effects are able to suppress inflammatory responses, particularly in the privilege sites such as CNS and eyes. Kaposi's sarcoma-associated herpesvirus (KSHV), encodes a wide variety of immunoregulatory proteins which play central roles in modulating inflammatory and anti-inflammatory responses in favour of virus dissemination. One such protein is a homologue of the, encoded by open reading frame (ORF) K14 and therefore called vOX2. Based on its gene expression profile during the KSHV life cycle, it is hypothesised that vOX2 modulates host inflammatory responses. Moreover, it seems that vOX2 involves in cell adhesion and modulates innate immunity and promotes Th2 immune responses. In this review the activities of mammalian CD200 and KSHV CD200 in cell adhesion and immune system modulation are reviewed in the context of potential therapeutic agents. PMID:27096058

  10. Rapid identification of anti-inflammatory compounds from Tongmai Yangxin Pills by liquid chromatography with high-resolution mass spectrometry and chemometric analysis.

    PubMed

    Tao, Shan; Huang, Yi; Chen, Zhui; Chen, Yaqi; Wang, Yi; Wang, Yi

    2015-06-01

    We present an integrated approach to rapidly identify anti-inflammatory compounds of TongmaiYangxin Pills (TMYXP), a botanical drug for the treatment of cardiovascular disease. Liquid chromatography coupled with high-resolution mass spectrometry was used to analyze the chemical composition of TMYXP. Eighty compounds of TMYXP including flavonoids, coumarins, iridoid glycosides, saponins, and lignans, were identified unambiguously or tentatively. After the rapid isolation and bioassay, 18 fractions of TMYXP were obtained and their anti-inflammatory activities were evaluated in lipopolysaccharide-stimulated RAW 264.7 macrophages. We performed chemometric analysis to reveal the correlation between the chemical and pharmacological information of the fractions to facilitate the identification of active compounds. To verify the reliability of the proposed method in discovering active components from a complex mixture, activities of seven compounds, which were positively or negatively related to bioactivity according to calculation, were validated in vitro. Results indicated that six active compounds with high R values exerted certain anti-inflammatory effects in a dose-dependent manner with IC50 values of 53.6-204.1 μM. Our findings suggest that the integrated use of identification based on high-resolution mass spectrometry and chemometric methods could rapidly identify active compounds from complex mixture of natural products. PMID:25943824

  11. Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed exert prebiotics and anti-inflammatory activities in Caco-2 cells

    PubMed Central

    Hwang, Pai-An; Phan, Nam Nhut; Lu, Wen-Jung; Ngoc Hieu, Bui Thi; Lin, Yen-Chang

    2016-01-01

    Background The aim of this study is to investigate the anti-inflammatory effects of low-molecular-weight fucoidan (LMF) and high-stability fucoxanthin (HS-Fucox) in a lipopolysaccharide-induced inflammatory Caco-2 cell line co-culture with B. lactis. Methods We used various methods such as transepithelial resistance (TER) assay, cytokine secretion assay, and tight junction protein mRNA expression assay to examine LMF and HS-Fucox anti-inflammatory properties. Results LMF and HS-Fucox activated probiotic growth and reduced the inflammation of the intestinal epithelial cells. Moreover, the combination of LMFHS-Fucox dramatically enhanced the intestinal epithelial barrier and immune function against the lipopolysaccharide effect by inhibiting IL-1β and TNF-α and promoting IL-10 and IFN-γ. Conclusion These findings suggested that LMF and HS-Fucox, alone or in combination, could be the potential natural compounds to enhance the immune system and have an anti-inflammatory effect on the intestinal cells. PMID:27487850

  12. Mushrooms: A Potential Natural Source of Anti-Inflammatory Compounds for Medical Applications

    PubMed Central

    Elsayed, Elsayed A.; El Enshasy, Hesham; Wadaan, Mohammad A. M.; Aziz, Ramlan

    2014-01-01

    For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents. PMID:25505823

  13. Anti-Inflammatory Iridoids of Botanical Origin

    PubMed Central

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer’s disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective anti-inflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  14. Natural products and anti-inflammatory activity.

    PubMed

    Yuan, Gaofeng; Wahlqvist, Mark L; He, Guoqing; Yang, Min; Li, Duo

    2006-01-01

    The aim of this review paper was to summarise some commonly available natural products and their anti-inflammatory activity. We have collected data from MEDLINE, Current Contents and scientific journals, which included 92 publications. There are numerous natural products detailed in this literature; however we have summarized a few of the most commonly available and potent ones. In this paper, the natural products with anti-inflammatory activity including curcumin, parthenolide, cucurbitacins, 1,8-cineole, pseudopterosins, lyprinol, bromelain, flavonoids, saponins, marine sponge natural products and Boswellia serrata gum resin were reviewed. Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Further studies are being conducted to investigate the mechanism of action, metabolism, safety and long term side effect of these natural products, as well as interactions between these natural products with food and drug components. PMID:16672197

  15. Evaluation of Caesalpinia bonducella flower extract for anti-inflammatory action in rats and its high performance thin layer chromatography chemical fingerprinting

    PubMed Central

    Arunadevi, Rathinam; Murugammal, Shanmugam; Kumar, Dinesh; Tandan, Surendra Kumar

    2015-01-01

    Objective: The study is aimed to evaluate anti-inflammatory activity of Caesalpinia bonducella Fleming (Caesalpiniaceae) flower extract (CBFE) and to study its effect on radiographic outcome in adjuvant induced arthritis and authentication by high performance thin layer chromatography (HPTLC) chemical fingerprinting. Materials and Methods: CBFE was administered orally (30, 100, and 300 mg/kg b.wt.) and tested for its anti-inflammatory activity in carrageenan-induced inflammation, cotton pellet induced chronic granulomatous inflammation and autacoids-induced inflammation. Effect on radiographic outcome was tested in adjuvant-induced arthritis. CBFE was HPTLC fingerprinted in suitable solvent system. Result: In carrageenan-induced inflammation, CBFE produced significant inhibition in edema volume at all the doses (30, 100 and 300 mg/kg b.wt.) and percentage of inhibition was 28.68, 31.00, and 22.48, respectively as compared to control at 5 h of its administration. In cotton pellet granuloma assay, CBFE significantly decreased the granuloma weight at 300 mg/kg dose level by 22.53%. CBFE (300 mg/kg) caused significant inhibition by 37.5, 44.44, and 35.29% edema volume, at ½, 1 and 3 h after 5-hydroxytryptamine injection, respectively. Radiographic score of animals treated with 300 mg/kg CBFE was significantly decreased when compared to arthritic control animals. Conclusion: The extract was found to possess significant anti-inflammatory activity. CBFE treatment improved the bony architecture in adjuvant-induced arthritis in rats. The developed HPTLC fingerprint would be helpful in the authentication of C. bonducella flower extract. PMID:26729956

  16. Structural Insights into the Interaction Between a Potent Anti-Inflammatory Protein, Viral CC Chemokine Inhibitor (vCCI), and the Human CC Chemokine, Eotaxin-1

    SciTech Connect

    Kuo, Nai-Wei; Gao, Yong; Schill, Megan S.; Isern, Nancy G.; Dupureur, Cynthia M.; Liwang, Patricia J.

    2014-01-30

    Chemokines play important roles in the immune system, not only recruiting leukocytes to the site of infection and inflammation but also guiding cell homing and cell development. The soluble poxvirusencoded protein vCCI, a CC chemokine inhibitor, can bind to human CC chemokines tightly to impair the host immune defense. This protein has no known homologs in eukaryotes, and may represent a potent method to stop inflammation. Previously, our structure of the vCCI:MIP-1β complex indicated that vCCI uses negatively charged residues in β-sheet II to interact with positively charged residues in the MIP-1βN-terminus, 20’s region and 40’s loop. However, the interactions between vCCI and other CC chemokines have not yet been fully explored. Here, we used NMR and fluorescence anisotropy to study the interaction between vCCI and eotaxin-1 (CCL11), another CC chemokine that is an important factor in the asthma response. NMR results reveal that the binding pattern is very similar to the vCCI:MIP-1βcomplex, and suggest that electrostatic interactions provide a major contribution to binding. Fluorescence anisotropy results on variants of eotaxin-1 further confirm the critical roles of the charged residues in eotaxin. Compared to wild-type eotaxin, single, double, or triple mutations at these critical charged residues weaken the binding. One exception is the K47A mutation that exhibits increased affinity for vCCI, which can be explained structurally. In addition, the binding affinity between vCCI and other wild type CC chemokines, MCP-1, MIP-1β and RANTES, were determined as 1.09 nM, 1.16 nM, and 0.22 nM, respectively. To our knowledge, this is the first work quantitatively measuring the binding affinity between vCCI and different CC chemokines.

  17. Anti-inflammatory iridoids of botanical origin.

    PubMed

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer's disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective antiinflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  18. The anti-inflammatory effect of a glycosylation product derived from the high hydrostatic pressure enzymatic hydrolysate of a flatfish byproduct.

    PubMed

    Choe, In-Hu; Jeon, Hyeon Jin; Eom, Sung-Hwan; Han, Young-Ki; Kim, Yoon Sook; Lee, Sang-Hoon

    2016-06-15

    In this study, flatfish byproducts were hydrolyzed by Protamex at high hydrostatic pressure and glycosylated with ribose to utilize the protein of flatfish byproducts as a nutraceutical. We investigated the anti-inflammatory effects of glycosylated fish byproduct protein hydrolysate (GFPH) and its anti-inflammatory mechanisms were elucidated in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophage. The results showed that GFPH suppresses LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) dose-dependently. The enzyme-linked immunosorbent assay (ELISA) kit clearly demonstrated that GFPH significantly reduced the production of pro-inflammatory cytokines such as, interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1. Moreover, GFPH reduced nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) activation. These results indicate that the inhibitory effects of GFPH on LPS-induced NO and PGE2 production might be due to the suppression of the NF-κB and MAPKs signaling pathways. Therefore, these results suggest that flatfish byproducts are latent bioactive resources and GFPH may have potential as a therapeutic agent in the treatment of various inflammatory diseases. PMID:27068102

  19. Amides of non-steroidal anti-inflammatory drugs with thiomorpholine can yield hypolipidemic agents with improved anti-inflammatory activity.

    PubMed

    Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Gavalas, Antonios; Rekka, Eleni A

    2016-02-01

    Novel amides of non steroidal anti-inflammatory drugs (NSAIDs), α-lipoic acid and indole-3-acetic acid with thiomorpholine were synthesised by a simple method and at high yields (60-92%). All the NSAID derivatives highly decreased lipidemic indices in the plasma of Triton treated hyperlipidemic rats. The most potent compound was the indomethacin derivative, which decreased total cholesterol, triglycerides and LDL cholesterol by 73%, 80% and 83%, respectively. They reduced acute inflammation equally or more than most parent acids. Hence, it could be concluded that amides of common NSAIDs with thiomorpholine acquire considerable hypolipidemic potency, while they preserve or augment their anti-inflammatory activity, thus addressing significant risk factors for atherogenesis. PMID:26750253

  20. Pharmacological potential of Populus nigra extract as antioxidant, anti-inflammatory, cardiovascular and hepatoprotective agent

    PubMed Central

    Debbache-Benaida, Nadjet; Atmani-Kilani, Dina; Schini-Keirth, Valérie Barbara; Djebbli, Nouredine; Atmani, Djebbar

    2013-01-01

    Objective To evaluate antioxidant, anti-inflammatory, hepatoprotective and vasorelaxant activities of Populus nigra flower buds ethanolic extract. Methods Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw edema. Protection from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver sections. Vasorelaxant effect was estimated in endothelium-intact and -rubbed rings of porcine coronary arteries precontracted with high concentration of U46619. Results The results showed a moderate antioxidant activity (40%), but potent anti-inflammatory activity (49.9%) on carrageenan-induced mice paw edema, and also as revealed by histopathologic examination, complete protection against AlCl3-induced hepatic toxicity. Relaxant effects of the same extract on vascular preparation from porcine aorta precontracted with high concentration of U46619 were considerable at 10−1 g/L, and comparable (P>0.05) between endothelium-intact (67.74%, IC50=0.04 mg/mL) and -rubbed (72.72%, IC50=0.075 mg/mL) aortic rings. Conclusions The extract exerted significant anti-inflammatory, hepatoprotective and vasorelaxant activities, the latter being endothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties, probably related to an inhibition of Ca2+ influx. PMID:23998009

  1. Two new proanthocyanidin trimers isolated from Cistus incanus L. demonstrate potent anti-inflammatory activity and selectivity to cyclooxygenase isoenzymes inhibition.

    PubMed

    Mansoor, K A; Matalka, K Z; Qa'dan, F S; Awad, R; Schmidt, M

    2016-09-01

    Two new proanthocyanidin trimers have been isolated from Cistus incanus herb; gallocatechin-(4α→6)-gallocatechin-(4α→8)-gallocatechin (compound 1) and epigallocatechin-3-O-gallate-(4ß→8)-epigallocatechin-3-O-gallate-(4ß→8)-gallocatechin (compound 2). The structures were determined on the basis of 1D- and 2D-NMR (HSQC, HMBC) of their peracetylated derivatives, MALDI-TOF-MS and by acid-catalysed degradation with phloroglucinol. A more abundant proanthocyanidin oligomer was also isolated, purified and its chemical constitution studied by (13)C-NMR and phloroglucinol degradation. The mean molecular weight of the polymer was estimated to be about 7 to 8 flavan-3-ol-units with a ratio of procyanidin : prodelphinidin units at 1:5, some of which are derivatised by gallic acid. Water extract and higher oligomeric proanthocyanidin fractions of C. incanus significantly inhibited TPA-induced oedema when applied topically at doses of 0.5 and 1 mg/ear in mice. Furthermore, the extracts and the pure compounds inhibited COX-1 and COX-2 activities. In addition, compound 2 exhibited an IC50 of 4.5 μM against COX-2 indicating its high selectivity towards COX-2. PMID:26414773

  2. High Spinal Anesthesia Enhances Anti-Inflammatory Responses in Patients Undergoing Coronary Artery Bypass Graft Surgery and Aortic Valve Replacement: Randomized Pilot Study

    PubMed Central

    Lee, Trevor W. R.; Kowalski, Stephen; Falk, Kelsey; Maguire, Doug; Freed, Darren H.; HayGlass, Kent T.

    2016-01-01

    Background Cardiac surgery induces many physiologic changes including major inflammatory and sympathetic nervous system responses. Here, we conducted a single-centre pilot study to generate hypotheses on the potential immune impact of adding high spinal anaesthesia to general anaesthesia during cardiac surgery in adults. We hypothesized that this strategy, previously shown to blunt the sympathetic response and improve pain management, could reduce the undesirable systemic inflammatory responses caused by cardiac surgery. Methods This prospective randomized unblinded pilot study was conducted on 14 patients undergoing cardiac surgery for coronary artery bypass grafting and/or aortic valve replacement secondary to severe aortic stenosis. The primary outcome measures examined longitudinally were serum pro-inflammatory (IL-6, IL-1b, CCL2), anti-inflammatory (IL-10, TNF-RII, IL-1Ra), acute phase protein (CRP, PTX3) and cardiovascular risk (sST2) biomarkers. Results The kinetics of pro- and anti-inflammatory biomarker was determined following surgery. All pro-inflammatory and acute phase reactant biomarker responses induced by surgical stress were indistinguishable in intensity and duration between control groups and those who also received high spinal anaesthesia. Conversely, IL-10 levels were markedly elevated in both intensity and duration in the group receiving high spinal anesthesia (p = 0.005). Conclusions This hypothesis generating pilot study suggests that high spinal anesthesia can alter the net inflammatory response that results from cardiac surgery. In appropriately selected populations, this may add incremental benefit by dampening the net systemic inflammatory response during the week following surgery. Larger population studies, powered to assess immune, physiologic and clinical outcomes in both acute and longer term settings, will be required to better assess potential benefits of incorporating high spinal anesthesia. Trial Registration Clinical

  3. Anti-inflammatory treatment.

    PubMed

    Fistarol, Susanna K; Itin, Peter H

    2011-01-01

    Inflammatory mucosal disorders are treated conventionally with potent or superpotent topical corticosteroids. For more than 20 years, topical cyclosporine has been used in the management of oral mucous membrane affections. Recently other topically applied calcineurin inhibitors, namely tacrolimus and pimecrolimus, expanded the armamentarium for the treatment of inflammatory mucosal diseases. This chapter places its main emphasis on the efficacy and safety of topical calcineurin inhibitors in the management of different oral and genital conditions, including anogenital lichen sclerosus (LS), oral and genital lichen planus, plasma cell balanitis and vulvitis, mucous membrane pemphigoid and pemphigus vulgaris, all conditions having usually a protracted course, requiring long-lasting treatment. There is current evidence for the effectiveness of both pimecrolimus and tacrolimus in the topical treatment of inflammatory oral mucosal diseases and genital dermatoses, especially oral lichen planus and genital LS. PMID:21325840

  4. Synthesis and anti-inflammatory activity of aromatic glucosinolates.

    PubMed

    Vo, Quan V; Trenerry, Craige; Rochfort, Simone; Wadeson, Jenny; Leyton, Carolina; Hughes, Andrew B

    2013-10-01

    Aromatic GLs are important members of the glucosinolate family of compounds because of their potential biological activity and medicinal properties. This study has shown success in the high yielding synthesis of some important aromatic GLs as well as the results of testing for anti-inflammatory properties of the synthetic GLs. 3,4-Dimethoxyphenylglucosinolate was found to be the most active anti-inflammatory of the seven glucosinolates assayed. PMID:23978357

  5. Rapid Anti-Inflammatory Effects of Gonadotropin-Releasing Hormone Antagonism in Rheumatoid Arthritis Patients with High Gonadotropin Levels in the AGRA Trial

    PubMed Central

    Kåss, Anita; Hollan, Ivana; Fagerland, Morten Wang; Gulseth, Hans Christian; Torjesen, Peter Abusdal; Førre, Øystein Torleiv

    2015-01-01

    Objectives Gonadotropin-releasing hormone (GnRH) and pituitary gonadotropins, which appear to be proinflammatory, undergo profound secretory changes during events associated with rheumatoid arthritis (RA) onset, flares, or improvement e.g. menopausal transition, postpartum, or pregnancy. Potential anti-inflammatory effects of GnRH-antagonists may be most pronounced in patients with high GnRH and gonadotropin levels. Therefore, we investigated the efficacy and safety of a GnRH-antagonist, cetrorelix, in RA patients with high gonadotropin levels. Methods We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99). Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1–2; 3mg days 3–5) or placebo, were followed through day 15. Only predefined primary and secondary endpoints were analyzed. Results The primary endpoint, Disease Activity Score of 28-joint counts with C-reactive protein (DAS28-CRP), improved with cetrorelix compared with placebo by day 5 (-1.0 vs. -0.4, P = 0∙010). By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049), DAS28-CRP≤3.2 (24% vs. 0%, P = 0.012), and European League against Rheumatism ‘Good-responses’ (19% vs. 0%, P = 0.026). Tumor necrosis factor-α, interleukin-1β, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively) compared with placebo by day 15. Adverse event rates were similar between groups. Conclusions GnRH-antagonism produced rapid anti-inflammatory effects in RA patients with high gonadotropin levels. GnRH should be investigated further in RA. Trial Registration ClinicalTrials.gov NCT00667758 PMID:26460564

  6. Simultaneous analysis of several non-steroidal anti-inflammatory drugs in human urine by high-performance liquid chromatography with normal solid-phase extraction.

    PubMed

    Hirai, T; Matsumoto, S; Kishi, I

    1997-05-01

    A practical and reproducible high-performance liquid chromatographic method using normal solid-phase extraction has been developed for the simultaneous analysis of twelve non-steroidal anti-inflammatory drugs (NSAIDs) in human urine. A urine specimen mixed with acetate buffer pH 5.0 was purified by solid-phase extraction on a Sep-Pak Silica cartridge. The analyte was chromatographed by a reversed-phase Inertsil ODS-2 column using a phosphate buffer-acetonitrile at pH 5.0 as the mobile phase, and the effluent from the column was monitored at 230 or 320 nm. Absolute recoveries were greater than 73% for all of the twelve NSAIDs. The present method enabled simple manipulation and isocratic HPLC with UV analysis as well as high sensitivity of 0.005 microg/ml for naproxen, and 0.05 microg/ml for sulindac, piroxicam, loxoprofen, ketoprofen, felbinac, fenbufen, flurbiprofen, diclofenac, ibuprofen and mefenamic acid as the quantitation limit in human urine using indomethacin as an internal standard. PMID:9188827

  7. Development of high-throughput multi-residue method for non-steroidal anti-inflammatory drugs monitoring in swine muscle by LC-MS/MS.

    PubMed

    Castilhos, Tamara S; Barreto, Fabiano; Meneghini, Leonardo; Bergold, Ana Maria

    2016-07-01

    A reliable and simple method for the detection and quantification of residues of 14 non-steroidal anti-inflammatory drugs and a metamizole metabolite in swine muscle was developed using liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS). The samples were extracted with acetonitrile (ACN) in solid-liquid extraction followed by a low-temperature partitioning (LLE-LTP) process at -20 ± 2°C. After evaporation to dryness, the residue was reconstituted with hexane and a mixture of water:acetonitrile (1:1). LC separation was achieved on a reversed-phase (RP18) column with gradient elution using water (phase A) and ACN (phase B) both containing 1 mmol l(-)(1) ammonium acetate (NH4COO) with 0.025% acetic acid. Analysis was carried out on a triple-quadrupole tandem mass spectrometer (LC-MS/MS) in multiple reaction monitoring mode using an electrospray interface in negative and positive mode in a single run. Method validation was performed according to the criteria of Commission Decision No. 2002/657/EC. The matrix effect and linearity were evaluated. Decision limit (CCα), detection capability (CCβ), accuracy and repeatability of the method are also reported. The proposed method proved to be simple, easy and adequate for high-throughput analysis and was applied to routine analysis by the Brazilian Ministry of Agriculture, Livestock and Food Supply. PMID:27268755

  8. Optimisation by response surface methodology of microextraction by packed sorbent of non steroidal anti-inflammatory drugs and ultra-high performance liquid chromatography analysis of dialyzed samples.

    PubMed

    D'Archivio, Angelo Antonio; Maggi, Maria Anna; Ruggieri, Fabrizio; Carlucci, Maura; Ferrone, Vincenzo; Carlucci, Giuseppe

    2016-06-01

    A procedure based on microextraction by packed sorbent (MEPS) followed by ultra-high performance liquid chromatography (UHPLC) with photodiode array (PDA) detection has been developed for the analysis of seven selected non steroidal anti-inflammatory drugs (NSAIDs) in human dialysates. The influence on MEPS efficiency of pH of the sample, pH of the washing solvent and methanol content in the hydro-alcoholic elution mixture has been investigated by response surface methodology based on a Box-Behnken design of experiments. Among the above factors, pH of sample is the variable that mostly influences MEPS recovery. UHPLC separation of the NSAIDs was completed within less than 4min under isocratic elution conditions on a Fortis SpeedCore C18 column (150×4.6mm I.D., 2.6μm) using acetonitrile-phosphate buffer as the mobile phase. Calibration curves of the NSAIDs were linear over the concentration range 0.025-15μg/mL, with correlation coefficients≥0.998. Intra- and inter-assay relative standard deviations were <8% and recovery values ranged from 94% to 100% for the quality control samples. The results reveal that the developed MEPS/PDA-UHPLC method exhibits a good accuracy and precision and is well suited for the rapid analysis of human dialysate from patients treated with the selected NSAIDs. PMID:27017570

  9. The anti-inflammatory action of fermented soybean products in kidney of high-fat-fed rats.

    PubMed

    Choi, Jehun; Kwon, Sun-Hwa; Park, Kun-Young; Yu, Byung Pal; Kim, Nam Deuk; Jung, Jee H; Chung, Hae Young

    2011-03-01

    Soybean has many compounds with a variety of biological properties that potentially benefit human health; among them, isoflavones have inhibitory effects on lipid oxidation in adipose tissue. In this study, we examined two Korean traditional fermented soybean products--doenjang (DNJ) and cheonggukjang (CGJ)--for their ability to suppress redox-sensitive nuclear factor κB (NF-κB) activation in the kidney of rats fed a high-fat diet. Sprague-Dawley rats, 4 weeks old, were fed soybean, DNJ, or CGJ (1 g/kg/day) with a 20% fat diet for 6 weeks. Body weight and food intake were carefully monitored. NF-κB-related activities of genes for inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and vascular cell adhesion molecule-1 (VCAM-1), were determined. The soybean products exhibited antioxidative action by maintaining redox regulation, suppressing NF-κB activation, and modulating the expression of genes for NF-κB-induced inflammatory proteins such as COX-2, iNOS, and VCAM-1. Based on these results, we conclude that Korean traditional soybean fermented products, especially CGJ, suppress the generation of reactive species, NF-κB activity, and NF-κB-related inflammatory genes. PMID:21332402

  10. NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties

    PubMed Central

    Kashfi, Khosrow; Chattopadhyay, Mitali; Kodela, Ravinder

    2015-01-01

    Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac and NOSH-sulindac administered orally to rats at equimolar doses. Gastrointestinal safety: 6 h post-administration, number/size of hemorrhagic lesions in stomachs were counted. Tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1 h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5 h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5 h. 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. Anti-cancer: We examined the effects of NOSH-sulindac on the growth properties of 12 human cancer cell lines of six different tissue origins. Both agents reduced PGE2 levels in stomach tissue; however, NOSH-sulindac did not cause any stomach ulcers, whereas sulindac caused significant bleeding. Lipid peroxidation induced by sulindac was higher than that from NOSH-sulindac. SOD activity was significantly lowered by sulindac but increased by NOSH-sulindac. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Sulindac increased plasma TNFα whereas this rise was lower in the NOSH-sulindac-treated animals. NOSH-sulindac inhibited the growth of all cancer cell lines studied, with potencies of 1000- to 9000-fold greater than that of sulindac. NOSH-sulindac inhibited cell proliferation, induced apoptosis, and caused G2/M

  11. In vivo photoprotective and anti-inflammatory effect of hyperforin is associated with high antioxidant activity in vitro and ex vivo.

    PubMed

    Meinke, Martina C; Schanzer, Sabine; Haag, Stefan F; Casetti, Federica; Müller, Marcel L; Wölfle, Ute; Kleemann, Anke; Lademann, Juergen; Schempp, Christoph M

    2012-06-01

    Hyperforin, a major constituent of St. John's Wort (Hypericum perforatum, HP), provides anti-inflammatory, anti-tumor, and anti-bacterial properties. Previous studies have shown anti-oxidative properties of St. John's Wort extracts; however, its free radical scavenging activity in skin cells or skin has not been assessed in detail so far. Therefore, the free radical scavenging activity of hyperforin was tested in the H(2)DCFDA-assay in vitro in HaCaT keratinocytes irradiated with solar simulated radiation. Hyperforin (EC(50) 0.7 μM corresponding to 0.42 μg/ml) was much more effective compared to Trolox (EC(50) 12 μg/ml) and N-acetylcysteine (EC(50) 847 μg/ml) without showing phototoxicity. The radical protection factor of a cream containing 1.5%w/w of a hyperforin-rich HP extract was determined to be 200 × 10(14) radicals/mg, indicating a high radical scavenging activity. The cream was further applied ex vivo on porcine ear skin and significantly reduced radical formation after infrared irradiation. Finally, the UV-protective effect of the HP cream was tested on 20 volunteers in a randomized, double-blind, vehicle-controlled study. HP cream significantly reduced UVB-induced erythema as opposed to the vehicle. Occlusive application of HP cream on non-irradiated test sites did not cause any skin irritation. Taken together, these results demonstrate that hyperforin is a powerful free radical scavenger. PMID:22430217

  12. Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.

    PubMed

    Talaat, Roba; El-Sayed, Waheba; Agwa, Hussein S; Gamal-Eldeen, Amira M; Moawia, Shaden; Zahran, Magdy A H

    2015-08-01

    Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage functions and their antioxidant activity. MTT assay was used to assess the cytotoxic effect of thalidomide analogs against splenocytes. Tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB-P65) were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was estimated by colorimetric assay. Antioxidant activity was examined by ORAC assay. Our results demonstrated that thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 produced a slight increase in splenocyte proliferation compared with thalidomide. Thalidomide dithiocarbamate analog 1 is a potent inhibitor of TNF-α production, whereas thalidomide dithiocarbamate analog 5 is a potent inhibitor of both TNF-α and NO. Analog 2 has a pronounced inhibitory effect on NF-κB-P65 production level. All thalidomide analogs showed prooxidant activity against hydroxyl (OH) radical. Analog 1 and thalidomide dithioate analog 3 have prooxidant activity against peroxyl (ROO) radical in relation to thalidomide. On the other hand, analog 4 has a potent scavenging capacity against peroxyl (ROO) radical compared with thalidomide. Taken together, the results of this study suggest that thalidomide analogs might have valuable anti-inflammatory activities with more pronounced effect than thalidomide itself. PMID:26051520

  13. Bioactive Compounds, Antioxidant, Xanthine Oxidase Inhibitory, Tyrosinase Inhibitory and Anti-Inflammatory Activities of Selected Agro-Industrial By-products

    PubMed Central

    Oskoueian, Ehsan; Abdullah, Norhani; Hendra, Rudi; Karimi, Ehsan

    2011-01-01

    Evaluation of abundantly available agro-industrial by-products for their bioactive compounds and biological activities is beneficial in particular for the food and pharmaceutical industries. In this study, rapeseed meal, cottonseed meal and soybean meal were investigated for the presence of bioactive compounds and antioxidant, anti-inflammatory, xanthine oxidase and tyrosinase inhibitory activities. Methanolic extracts of rapeseed meal showed significantly (P < 0.01) higher phenolics and flavonoids contents; and significantly (P < 0.01) higher DPPH and nitric oxide free radical scavenging activities when compared to that of cottonseed meal and soybean meal extracts. Ferric thiocyanate and thiobarbituric acid tests results showed rapeseed meal with the highest antioxidant activity (P < 0.01) followed by BHT, cotton seed meal and soybean meal. Rapeseed meal extract in xanthine oxidase and tyrosinase inhibitory assays showed the lowest IC50 values followed by cottonseed and soybean meals. Anti-inflammatory assay using IFN-γ/LPS stimulated RAW 264.7 cells indicated rapeseed meal is a potent source of anti-inflammatory agent. Correlation analysis showed that phenolics and flavonoids were highly correlated to both antioxidant and anti-inflammatory activities. Rapeseed meal was found to be promising as a natural source of bioactive compounds with high antioxidant, anti-inflammatory, xanthine oxidase and tyrosinase inhibitory activities in contrast to cotton and soybean meals. PMID:22272095

  14. Potent anti-inflammatory effect of dioscin mediated by suppression of TNF-α-induced VCAM-1, ICAM-1and EL expression via the NF-κB pathway.

    PubMed

    Wu, Shan; Xu, Hui; Peng, Jinyong; Wang, Changyuan; Jin, Yue; Liu, Kexin; Sun, Huijun; Qin, Jianhua

    2015-03-01

    The modulation of adhesion molecule expression and the reduction of aberrant leukocyte adhesion to the endothelium are attractive approaches for treating inflammation-related vascular complications, including atherosclerosis. Dioscin has a variety of biological activities including anti-inflammatory activity. However, the molecular mechanisms behind dioscin's anti-inflammatory effects are not fully understood. In this study, we investigated the molecular mechanism involved in the effects of dioscin on inflammatory mediators in tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs). In vitro, dioscin decreased monocyte adhesion to TNF-α-treated HUVECs by reducing vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression and inhibiting endothelial lipase (EL) expression in TNF-α-treated HUVECs and macrophages by blocking the nuclear factor-κB (NF-κB) pathway. Thus, dioscin might inhibit inflammation by interrupting the NF-κB signaling pathway and could potentially contribute to treatments for inflammatory diseases and atherosclerosis. PMID:25577996

  15. Systematic Analysis of Absorbed Anti-Inflammatory Constituents and Metabolites of Sarcandra glabra in Rat Plasma Using Ultra-High-Pressure Liquid Chromatography Coupled with Linear Trap Quadrupole Orbitrap Mass Spectrometry

    PubMed Central

    Li, Xiong; Zhao, Jin; Liu, Jianxing; Li, Geng; Zhao, Ya; Zeng, Xing

    2016-01-01

    Ultra-high-pressure liquid chromatography (UHPLC) was coupled with linear ion trap quadrupole Orbitrap mass spectrometry (LTQ-Orbitrap) and was used for the first time to systematically analyze the absorbed components and metabolites in rat plasma after oral administration of the water extract of Sarcandra glabra. This extract is a well-known Chinese herbal medicine for the treatment of inflammation and immunity related diseases. The anti-inflammatory activities of the absorbed components were evaluated by measuring nitric oxide (NO) production and proinflammatory genes expression in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. As a result, 54 components in Sarcandra glabra were detected in dosed rat plasma, and 36 of them were positively identified. Moreover, 23 metabolites were characterized and their originations were traced. Furthermore, 20 of the 24 studied components showed anti-inflammatory activities. These results provide evidence that this method efficiency detected constituents in plasma based on the anti-inflammatory mechanism of multiple components and would be a useful technique for screening multiple targets for natural medicine research. PMID:26974321

  16. Systematic Analysis of Absorbed Anti-Inflammatory Constituents and Metabolites of Sarcandra glabra in Rat Plasma Using Ultra-High-Pressure Liquid Chromatography Coupled with Linear Trap Quadrupole Orbitrap Mass Spectrometry.

    PubMed

    Li, Xiong; Zhao, Jin; Liu, Jianxing; Li, Geng; Zhao, Ya; Zeng, Xing

    2016-01-01

    Ultra-high-pressure liquid chromatography (UHPLC) was coupled with linear ion trap quadrupole Orbitrap mass spectrometry (LTQ-Orbitrap) and was used for the first time to systematically analyze the absorbed components and metabolites in rat plasma after oral administration of the water extract of Sarcandra glabra. This extract is a well-known Chinese herbal medicine for the treatment of inflammation and immunity related diseases. The anti-inflammatory activities of the absorbed components were evaluated by measuring nitric oxide (NO) production and proinflammatory genes expression in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. As a result, 54 components in Sarcandra glabra were detected in dosed rat plasma, and 36 of them were positively identified. Moreover, 23 metabolites were characterized and their originations were traced. Furthermore, 20 of the 24 studied components showed anti-inflammatory activities. These results provide evidence that this method efficiency detected constituents in plasma based on the anti-inflammatory mechanism of multiple components and would be a useful technique for screening multiple targets for natural medicine research. PMID:26974321

  17. Boswellia carterii liquisolid systems with promoted anti-inflammatory activity.

    PubMed

    Mostafa, Dina Mahmoud; Ammar, Nagwa Mohammed; Abd El-Alim, Sameh Hosam; Kassem, Ahmed Alaa; Hussein, Rehab Ali; Awad, Gamal; El-Awdan, Sally Abdul-Wanees

    2015-01-01

    Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance. PMID:25895614

  18. Potent anti-inflammatory effect of a novel furan-2,5-dione derivative, BPD, mediated by dual suppression of COX-2 activity and LPS-induced inflammatory gene expression via NF-κB inactivation

    PubMed Central

    Shin, Ji-Sun; Park, Seung-Jae; Ryu, Suran; Kang, Han Byul; Kim, Tae Woo; Choi, Jung-Hye; Lee, Jae-Yeol; Cho, Young-Wuk; Lee, Kyung-Tae

    2012-01-01

    BACKGROUND AND PURPOSE We previously reported that 3-(benzo[d]-1,3-dioxol-5-yl)-4-phenylfuran-2,5-dione (BPD) showed strong inhibitory effects on PGE2 production. However, the exact mechanism for the anti-inflammatory effect of BPD is not completely understood. In this study, we investigated the molecular mechanism involved in the effects of BPD on inflammatory mediators in LPS-stimulated macrophages and animal models of inflammation. EXPERIMENTAL APPROACH The expressions of COX-2, inducible NOS (iNOS), TNF-α, IL-6 and IL-1β, in LPS-stimulated RAW 264.7 cells and murine peritoneal macrophages, were determined by Western blot and/or qRT-PCR, respectively. NF-κB activation was investigated by EMSA, reporter gene assay and Western blotting. Anti-inflammatory effects of BPD were evaluated in vivo in carrageenan-induced paw oedema in rats and LPS-induced septic shock in mice. KEY RESULTS BPD not only inhibited COX-2 activity but also reduced the expression of COX-2. In addition, BPD inhibited the expression of iNOS, TNF-α, IL-6 and IL-1β at the transcriptional level. BPD attenuated LPS-induced DNA-binding activity and the transcription activity of NF-κB; this was associated with a decrease in the phosphorylation level of inhibitory κB-α (IκB-α) and reduced nuclear translocation of NF-κB. Furthermore, BPD suppressed the formation of TGF-β-activated kinase-1 (TAK1)/TAK-binding protein1 (TAB1), which was accompanied by a parallel reduction of phosphorylation of TAK1 and IκB kinase (IKK). Pretreatment with BPD inhibited carrageenan-induced paw oedema and LPS-induced septic death. CONCLUSION AND IMPLICATIONS Taken together, our data indicate that BPD is involved in the dual inhibition of COX-2 activity and TAK1-NF-κB pathway, providing a molecular basis for the anti-inflammatory properties of BPD. PMID:21913901

  19. Synthesis and optimization of novel allylated mono-carbonyl analogs of curcumin (MACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI) in rats.

    PubMed

    Zhu, Heping; Xu, Tingting; Qiu, Chenyu; Wu, Beibei; Zhang, Yali; Chen, Lingfeng; Xia, Qinqin; Li, Chenglong; Zhou, Bin; Liu, Zhiguo; Liang, Guang

    2016-10-01

    A series of novel symmetric and asymmetric allylated mono-carbonyl analogs of curcumin (MACs) were synthesized using an appropriate synthetic route and evaluated experimentally thru the LPS-induced expression of TNF-α and IL-6. Most of the obtained compounds exhibited improved water solubility as a hydrochloride salt compared to lead molecule 8f. The most active compound 7a was effective in reducing the Wet/Dry ratio in the lungs and protein concentration in bronchoalveolar lavage fluid. Meanwhile, 7a also inhibited mRNA expression of several inflammatory cytokines, including TNF-α, IL-6, IL-1β, and VCAM-1, in Beas-2B cells after Lipopolysaccharide (LPS) challenge. These results suggest that 7a could be therapeutically beneficial for use as an anti-inflammatory agent in the clinical treatment of acute lung injury (ALI). PMID:27240273

  20. Gastrointestinal and Cardiovascular Risk of Nonsteroidal Anti-inflammatory Drugs

    PubMed Central

    Al-Saeed, Abdulwahed

    2011-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) confer a gastrointestinal (GI) side effect profile and concerns regarding adverse cardiovascular effects have emerged associated with considerable morbidity and mortality. NSAIDs are highly effective in treating pain and inflammation, but it is well recognized that these agents are associated with substantial gastrointestinal toxicity. Cyclo-oxygenase-2 inhibitors may also reduce the risk for gastrointestinal events, although they may increase cardiovascular adverse events. The selection of an appropriate analgesic or anti-inflammatory agent with or without gastroprotective therapy should be individualized. PMID:22253945

  1. Role of effective composition on antioxidant, anti-inflammatory, sedative-hypnotic capacities of 6 common edible Lilium varieties.

    PubMed

    Wang, Tingting; Huang, Hanhan; Zhang, Yao; Li, Xia; Li, Hongfa; Jiang, Qianqian; Gao, Wenyuan

    2015-04-01

    Nine Lilium samples (belong to 6 different cultivars with different maturity stage) were qualitatively and quantitatively analyzed of total phenolics (TP), total flavonoids (TF), total saponins (TS), total carbohydrates (TC, polysaccharides), and soluble proteins contents (SP), and the monomeric components were quantified utilizing high-performance liquid chromatography with photodiode array detector (HPLC-PAD) associated with liquid chromatography-mass spectrometry (HPLC-MS). Antioxidant activity (reducing power and DPPH radical scavenging activity), anti-inflammatory (xylene-induced mouse ear edema detumescent assay and carrageenan-induced mouse paw edema detumescent assay), and sedative-hypnotic capacities (sodium pentobarbital-induced sleep assay) were comparatively evaluated in mouse model. Additionally, correlation analysis and principal component analysis were carried out to detect clustering and elucidate relationships between components' concentrations and bioactivities to clarify the role of effective composition. Lilium bulbs in later maturity stage preliminary evidenced higher saponins content, and lower phenolic acids and flavonoids content. The result demonstrated that Lilium bulbs generally had distinct antioxidant, anti-inflammatory, and sedative-hypnotic capacities. Varieties statistically differed (P < 0.05) in chemical composition and bioactivities. Lilium varieties of Dongbei and Lanzhou presented potent sedative-hypnotic effect and anti-inflammatory activity. The antioxidant capacity was related to the phenolic acids and flavonoids contents, the anti-inflammatory and sedative-hypnotic capacities were related to the saponins content. This is first study presenting comprehensive description of common edible Lilium bulbs' chemical compositions, sedative-hypnotic, and anti-inflammatory capacities grown in China. It would informatively benefit the genetic selection and cultivated optimization of Lilium varieties to improve nutritional quality, and

  2. Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents

    PubMed Central

    Bala, Suman; Sharma, Neha; Saini, Vipin

    2014-01-01

    Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents. PMID:25383223

  3. Anti-inflammatory properties of α- and γ-tocopherol

    PubMed Central

    Reiter, Elke; Jiang, Qing; Christen, Stephan

    2007-01-01

    Natural vitamin E consists of four different tocopherol and four different tocotrienol homologues (α, β, γ, δ) that all have antioxidant activity. However, recent data indicate that the different vitamin E homologues also have biological activity unrelated to their antioxidant activity. In this review, we discuss the anti-inflammatory properties of the two major forms of vitamin E, α-tocopherol (αT) and γ-tocopherol (γT), and discuss the potential molecular mechanisms involved in these effects. While both tocopherols exhibit anti-inflammatory activity in vitro and in vivo, supplementation with mixed (γT-enriched) tocopherols seems to be more potent than supplementation with αT alone. This may explain the mostly negative outcomes of the recent large-scale interventional chronic disease prevention trials with αT and thus warrants further investigation. PMID:17316780

  4. Inhibition of soluble epoxide hydrolase contributes to the anti-inflammatory effect of antimicrobial triclocarban in a murine model

    PubMed Central

    Liu, Jun-Yan; Qiu, Hong; Morisseau, Christophe; Hwang, Sung Hee; Tsai, Hsing-Ju; Ulu, Arzu; Chiamvimonvat, Nipavan; Hammock, Bruce D

    2011-01-01

    The increasing use of the anti-microbial triclocarban (TCC) in personal care products (PCPs) has resulted in concern regarding environmental pollution. TCC is a potent inhibitor of soluble epoxide hydrolase (sEH). Inhibitors of sEH (sEHIs) are anti-inflammatory, anti-hypertensive and cardio-protective in multiple animal models. However, the in vivo effects anticipated from a sEHI have not been reported for TCC. Here we demonstrated the anti-inflammatory effects in vivo of TCC in a murine model. TCC was employed in a lipopolysaccharide (LPS)-challenged murine model. Systolic blood pressure, plasma levels of several inflammatory cytokines and chemokine, and metabolomic profile of plasma oxylipins were determined. TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. TCC significantly repressed the increased release of inflammatory cytokines and chemokine caused by LPS. Furthermore, TCC significantly shifted the oxylipin profile in vivo in a time-dependent manner towards resolution of inflammation as expected from a sEHI. These results demonstrated that at the doses used TCC is anti-inflammatory in the murine model. This study suggests that TCC may provide some benefits in humans in addition to its antimicrobial activities due to its potent inhibition of sEH. It may be a promising starting point for developing new low volume high value applications of TCC. However these biological effects also caution against the general over use of TCC in PCPs. PMID:21741984

  5. Fructose 1,6-bisphosphate, a high-energy intermediate of glycolysis, attenuates experimental arthritis by activating anti-inflammatory adenosinergic pathway

    PubMed Central

    Veras, Flávio P.; Peres, Raphael S.; Saraiva, André L. L.; Pinto, Larissa G.; Louzada-Junior, Paulo; Cunha, Thiago M.; Paschoal, Jonas A. R.; Cunha, Fernando Q.; Alves-Filho, José C.

    2015-01-01

    Fructose 1,6-bisphosphate (FBP) is an endogenous intermediate of the glycolytic pathway. Exogenous administration of FBP has been shown to exert protective effects in a variety of ischemic injury models, which are attributed to its ability to sustain glycolysis and increase ATP production. Here, we demonstrated that a single treatment with FBP markedly attenuated arthritis, assessed by reduction of articular hyperalgesia, joint swelling, neutrophil infiltration and production of inflammatory cytokines, TNF and IL-6, while enhancing IL-10 production in two mouse models of arthritis. Our mechanistic studies showed that FBP reduces joint inflammation through the systemic generation of extracellular adenosine and subsequent activation of adenosine receptor A2a (A2aR). Moreover, we showed that FBP-induced adenosine generation requires hydrolysis of extracellular ATP through the activity of the ectonucleosides triphosphate diphosphohydrolase-1 (ENTPD1, also known as CD39) and ecto-5′-nucleotidase (E5NT, also known as CD73). In accordance, inhibition of CD39 and CD73 abolished anti-arthritic effects of FBP. Taken together, our findings provide a new insight into the molecular mechanism underlying the anti-inflammatory effect of FBP, showing that it effectively attenuates experimental arthritis by activating the anti-inflammatory adenosinergic pathway. Therefore, FBP may represent a new therapeutic strategy for treatment of rheumatoid arthritis (RA). PMID:26478088

  6. Inhibition of soluble epoxide hydrolase contributes to the anti-inflammatory effect of antimicrobial triclocarban in a murine model

    SciTech Connect

    Liu Junyan; Qiu Hong; Morisseau, Christophe; Hwang, Sung Hee; Tsai, Hsing-Ju; Ulu, Arzu; Chiamvimonvat, Nipavan; Hammock, Bruce D.

    2011-09-01

    The increasing use of the antimicrobial triclocarban (TCC) in personal care products (PCPs) has resulted in concern regarding environmental pollution. TCC is a potent inhibitor of soluble epoxide hydrolase (sEH). Inhibitors of sEH (sEHIs) are anti-inflammatory, anti-hypertensive and cardio-protective in multiple animal models. However, the in vivo effects anticipated from a sEHI have not been reported for TCC. Here we demonstrated the anti-inflammatory effects in vivo of TCC in a murine model. TCC was employed in a lipopolysaccharide (LPS)-challenged murine model. Systolic blood pressure, plasma levels of several inflammatory cytokines and chemokine, and metabolomic profile of plasma oxylipins were determined. TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. TCC significantly repressed the increased release of inflammatory cytokines and chemokine caused by LPS. Furthermore, TCC significantly shifted the oxylipin profile in vivo in a time-dependent manner towards resolution of inflammation as expected from a sEHI. These results demonstrated that at the doses used TCC is anti-inflammatory in the murine model. This study suggests that TCC may provide some benefits in humans in addition to its antimicrobial activities due to its potent inhibition of sEH. It may be a promising starting point for developing new low volume high value applications of TCC. However these biological effects also caution against the general over use of TCC in PCPs. - Graphical abstract: Display Omitted Research Highlights: > Anti-microbial triclocarban (TCC) is anti-inflammatory in a murine model. > TCC significantly shifted the oxylipin profile in vivo as expected from a sEHI. > TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. > TCC significantly repressed LPS-induced increased release of inflammatory cytokines.

  7. Marine Diterpenoids as Potential Anti-Inflammatory Agents.

    PubMed

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E; Fernandez, Patricia L

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  8. Marine Diterpenoids as Potential Anti-Inflammatory Agents

    PubMed Central

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  9. Anti-inflammatory activity of (polyphenolic)-sulfonates and their sodium salts in rodents.

    PubMed

    Hall, I H; Murphy, M E; Elkins, A L

    1998-01-01

    A series of polyphenolic-sulfonated compounds were observed to have potent anti-inflammatory activity and were protective against induced endotoxic shock in mice at 8 and 16 mg/kg, I.P. These agents proved to be potent elastase inhibitors in human leukocytes and J774-AI and IC-21 mouse macrophages as well as prostaglandin cyclo-oxygenase inhibitors in J774-AI macrophages. The compounds from 5 to 50 muM inhibited TNFalpha release from IC-21 macrophages and IL-1 release from mouse P388(D1) macrophages induced by LPS. The binding of these cytokines to high affinity receptors on target cells, e.g. L929 fibroblasts and IL-2 in HuT78 T lymphoma cells, were also suppressed by the agents. These compounds blocked the adhesion of leukocytes and macrophages to the plasma membranes of L929 fibroblasts. PMID:18475825

  10. Anti-Inflammatory Activity of (Polyphenolic)-Sulfonates and Their Sodium Salts in Rodents

    PubMed Central

    Murphy, Margaret E.; Elkins, Amy L.

    1998-01-01

    A series of polyphenolic-sulfonated compounds were observed to have potent anti-inflammatory activity and were protective against induced endotoxic shock in mice at 8 and 16 mg/kg, I.P. These agents proved to be potent elastase inhibitors in human leukocytes and J774-AI and IC-21 mouse macrophages as well as prostaglandin cyclo-oxygenase inhibitors in J774-AI macrophages. The compounds from 5 to 50 μM inhibited TNFα release from IC-21 macrophages and IL-1 release from mouse P388D1 macrophages induced by LPS. The binding of these cytokines to high affinity receptors on target cells, e.g. L929 fibroblasts and IL-2 in HuT78 T lymphoma cells, were also suppressed by the agents. These compounds blocked the adhesion of leukocytes and macrophages to the plasma membranes of L929 fibroblasts. PMID:18475825

  11. In vitro analysis of the cytotoxic and anti-inflammatory effects of antioxidant compounds used as additives in ultra high-molecular weight polyethylene in total joint replacement components

    PubMed Central

    Bladen, C L; Tzu-Yin, L; Fisher, J; Tipper, J L

    2013-01-01

    Ultra high-molecular weight polyethylene (UHMWPE) remains the most commonly used material in modern joint replacement prostheses. However, UHMWPE wear particles, formed as the bearing articulates, are one of the main factors leading to joint replacement failure via the induction of osteolysis and subsequent aseptic loosening. Previous studies have shown that the addition of antioxidants such as vitamin E to UHMWPE can improve wear resistance of the polymer and reduce oxidative fatigue. However, little is known regarding the biological consequences of such antioxidant chemicals. This study investigated the cytotoxic and anti-inflammatory effects of a variety of antioxidant compounds currently being tested experimentally for use in hip and knee prostheses, including nitroxides, hindered phenols, and lanthanides on U937 human histocyte cells and human peripheral blood mononuclear cells (PBMNCs) in vitro. After addition of the compounds, cell viability was determined by dose response cytotoxicity studies. Anti-inflammatory effects were determined by quantitation of TNF-α release in lipopolysaccharide (LPS)-stimulated cells. This study has shown that many of these compounds were cytotoxic to U937 cells and PBMNCs, at relatively low concentrations (micromolar), specifically the hindered phenol 3,5-di-tert-butyl-4-hydroxyhydrocinnamate (HPAO1), and the nitroxide 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO). Lanthanides were only cytotoxic at very high concentrations and were well tolerated by the cells at lower concentrations. Cytotoxic compounds also showed reduced anti-inflammatory effects, particularly in PBMNCs. Careful consideration should therefore be given to the use of any of these compounds as potential additives to UHMWPE. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 101B: 407–413, 2013. PMID:22915524

  12. Terpenoids with anti-inflammatory activity from Abies chensiensis.

    PubMed

    Zhao, Qian-Qian; Wang, Shu-Fang; Li, Ya; Song, Qiu-Yan; Gao, Kun

    2016-06-01

    The phytochemical investigation of Abies chensiensis led to the isolation and identification of nine new compounds including eight triterpenoids (1-8) and a new abietane-type diterpene (9), along with three known compounds (10-12). The absolute configuration of 9 was assigned by X-ray diffraction analysis. Compounds 1-11 were evaluated for the anti-inflammatory activity. Among the tested compounds, 1, 2, 5 and 6 exhibited potent inhibitory activity with IC50 values of 15.97, 18.73, 20.18 and 10.97μM, respectively. PMID:27080759

  13. Bioengineered Colorectal Cancer Drugs: Orally Delivered Anti-Inflammatory Agents.

    PubMed

    Urbanska, Aleksandra Malgorzata; Zhang, Xiaoying; Prakash, Satya

    2015-07-01

    Intestinal inflammation is one of the major factors that increase colorectal cancer (CRC) incidence worldwide. Inflammation in the gastrointestinal tract is directly linked to tumor development at the early stages of the disease, thus a key issue toward the prevention and the treatment of colonic neoplasia. Thus, the use of anti-inflammatory drugs has emerged first as a strategy to reduce chronic inflammation in case of many inflammatory bowel diseases (IBD), but it has proven its efficacy by reducing the risk of colonic neoplasia. This comprehensive review highlights the role of chronic inflammation, mainly in IBD, in the development of CRC including molecular and immune mechanisms that have tumorigenic effects. Multiple lines of evidence indicate that several bioactive and phytochemical compounds used as anti-inflammatory drugs have also antitumoral attributes. The uses of orally delivered cytokines and small molecules, as well as key dietary supplementation as anti-inflammatory therapeutics are discussed. In addition, comprehensive knowledge about CRC and intestinal inflammation, and the importance of the intestinal mucosal wall as a mucosal immunological barrier that comes into play during interactions with gut microbiota (pathogens and commensal), luminal secretions (bile acids, and bacterial and epithelial metabolites), and ingested chemicals (food components, high fat content, heterocyclic amines, and low intake of dietary fiber) are underscored. The multifunctionality of several anti-inflammatory drugs opens a line for their application in the treatment and prevention not only in IBD but also in CRC. Current bioengineering approaches for oral delivery of anti-inflammatory agents including cytokines, genetically modified bacteria, or small molecule inhibitors of inflammation directly contribute to the early management of CRC. Limitations of the current therapeutics, which stem from the lack of complete understanding of the complex molecular interactions

  14. The promotion of functional urinary bladder regeneration using anti-inflammatory nanofibers.

    PubMed

    Bury, Matthew I; Fuller, Natalie J; Meisner, Jay W; Hofer, Matthias D; Webber, Matthew J; Chow, Lesley W; Prasad, Sheba; Thaker, Hatim; Yue, Xuan; Menon, Vani S; Diaz, Edward C; Stupp, Samuel I; Cheng, Earl Y; Sharma, Arun K

    2014-11-01

    Current attempts at tissue regeneration utilizing synthetic and decellularized biologic-based materials have typically been met in part by innate immune responses in the form of a robust inflammatory reaction at the site of implantation or grafting. This can ultimately lead to tissue fibrosis with direct negative impact on tissue growth, development, and function. In order to temper the innate inflammatory response, anti-inflammatory signals were incorporated through display on self-assembling peptide nanofibers to promote tissue healing and subsequent graft compliance throughout the regenerative process. Utilizing an established urinary bladder augmentation model, the highly pro-inflammatory biologic scaffold (decellularized small intestinal submucosa) was treated with anti-inflammatory peptide amphiphiles (AIF-PAs) or control peptide amphiphiles and used for augmentation. Significant regenerative advantages of the AIF-PAs were observed including potent angiogenic responses, limited tissue collagen accumulation, and the modulation of macrophage and neutrophil responses in regenerated bladder tissue. Upon further characterization, a reduction in the levels of M2 macrophages was observed, but not in M1 macrophages in control groups, while treatment groups exhibited decreased levels of M1 macrophages and stabilized levels of M2 macrophages. Pro-inflammatory cytokine production was decreased while anti-inflammatory cytokines were up-regulated in treatment groups. This resulted in far fewer incidences of tissue granuloma and bladder stone formation. Finally, functional urinary bladder testing revealed greater bladder compliance and similar capacities in groups treated with AIF-PAs. Data demonstrate that AIF-PAs can alleviate galvanic innate immune responses and provide a highly conducive regenerative milieu that may be applicable in a variety of clinical settings. PMID:25145852

  15. The promotion of functional urinary bladder regeneration using anti-inflammatory nanofibers

    PubMed Central

    Bury, Matthew I.; Fuller, Natalie J.; Meisner, Jay W.; Hofer, Matthias D.; Webber, Matthew J.; Chow, Lesley W.; Prasad, Sheba; Thaker, Hatim; Yue, Xuan; Menon, Vani S.; Diaz, Edward C.; Stupp, Samuel I.; Cheng, Earl Y.; Sharma, Arun K.

    2014-01-01

    Current attempts at tissue regeneration utilizing synthetic and decellularized biologic-based materials have typically been met in part by innate immune responses in the form of a robust inflammatory reaction at the site of implantation or grafting. This can ultimately lead to tissue fibrosis with direct negative impact on tissue growth, development, and function. In order to temper the innate inflammatory response, anti-inflammatory signals were incorporated through display on self-assembling peptide nanofibers to promote tissue healing and subsequent graft compliance throughout the regenerative process. Utilizing an established urinary bladder augmentation model, the highly pro-inflammatory biologic scaffold (decellularized small intestinal submucosa) was treated with anti-inflammatory peptide amphiphiles (AIF-PAs) or control peptide amphiphiles and used for augmentation. Significant regenerative advantages of the AIF-PAs were observed including potent angiogenic responses, limited tissue collagen accumulation, and the modulation of macrophage and neutrophil responses in regenerated bladder tissue. Upon further characterization, a reduction in the levels of M2 macrophages was observed, but not in M1 macrophages in control groups, while treatment groups exhibited decreased levels of M1 macrophages and stabilized levels of M2 macrophages. Pro-inflammatory cytokine production was decreased while anti-inflammatory cytokines were up-regulated in treatment groups. This resulted in far fewer incidences of tissue granuloma and bladder stone formation. Finally, functional urinary bladder testing revealed greater bladder compliance and similar capacities in groups treated with AIF-PAs. Data demonstrate that AIF-PAs can alleviate galvanic innate immune responses and provide a highly conducive regenerative milieu that may be applicable in a variety of clinical settings. PMID:25145852

  16. Studies on tracheorelaxant and anti-inflammatory activities of rhizomes of Polygonatum verticillatum

    PubMed Central

    2013-01-01

    Background The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders. Methods The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode’s solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the lipoxygenase inhibitory activity was performed in the in-vitro assay. Various chromatographic and spectroscopic techniques were used for the isolation and characterization of pure molecules. Results In isolated guinea-pig tracheal preparations, PR caused complete inhibition of the high K+ (80 mM) and carbachol-induced contractions however, it was more potent against K+ than CCh, similar to verapamil. Pretreatment of the tissue with PR, displaced the Ca2+ concentration-response curves to the right, similar to that induced by verapamil, indicating the presence of Ca2+ channel blocking like activity. When tested on carrageenan-induced rat paw edema, PR demonstrated a marked reduction in edema with 65.22% protection at 200 mg/kg, similar to aspirin. In the in-vitro assay, PR showed lipoxygenase inhibitory activity (IC50: 102 ± 0.19 μg/mL), similar to baicalein. Bioactivity-guided fractionation led to the isolation of 2-hydroxybenzoic acid and β-sitosterol. Conclusions These results indicate that the plant possesses tracheorelaxant, mediated possibly through a Ca2+ channel blockade mechanism, and anti-inflammatory activities, which may explain the medicinal use of this plant in airway disorders and inflammation. PMID:23895558

  17. [In vitro anti-inflammatory and free radical scavenging activities of flavans from Ilex centrochinensis].

    PubMed

    Li, Lu-jun; Yu, Li-juan; Li, Yan-ci; Liu, Meng-yuan; Wu, Zheng-zhi

    2015-04-01

    This study was carried out to evaluate the anti-inflammatory and free radical scavenging activities of flavans from flex centrochinensis S. Y. Hu in vitro and their structure-activity relationship. LPS-stimulated RAW 264.7 macrophage was used as inflammatory model. MTT assay for cell availability, Griess reaction for nitric oxide (NO) production, the content of TNF-alpha, IL-1beta, IL-6 and PGE, were detected with ELISA kits; DPPH, superoxide anion and hydroxyl free radicals scavenging activities were also investigated. According to the result, all flavans tested exhibited anti-inflammatory effect in different levels. Among them, compounds 1, 3, 4 and 6 showed potent anti-inflammatory effect through the inhibition of NO, TNF-alpha, IL-lp and IL-6, of which 1 was the most effective inhibitor, however, 2 and 5 were relatively weak or inactive. The order of free radical scavenging activities was similar to that of anti-inflammatory activities. Therefore, these results suggest that 3, 4 and 6, especially of 1, were,in part responsible for the anti-inflammatory and free radical scavenging activity of Ilex centrochinensis. Hydroxyl group at 4'-position of B-ring plays an important role in the anti-inflammatory and free radical scavenging capacities. PMID:26281592

  18. 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

  19. Analgesic and anti-inflammatory properties of the leaf extracts of Anacardium occidentalis in the laboratory rodents.

    PubMed

    Onasanwo, S A; Fabiyi, T D; Oluwole, F S; Olaleye, S B

    2012-06-01

    Anacardium occidentalis (family: Anacardiaceae) is a plant of the tropical climate widely used by folklore to treat pain and inflammation. This study was conducted to evaluate the analgesic and anti-inflammatory effects of the leaf extracts in rat and mice using different models in other to confirm folkloric claims. The aqueous, hexane, dichloromethane and methanol extracts (AEAO, HEAO, DEAO and MEAO respectively) were investigated for analgesic effects in acetic acid induced pain in mice. They significantly reduced the number of writhing (p<0.001) and the highest analgesic effect was seen in DEAO extract. DEAO was further studied on various analgesic and anti-inflammatory models in graded doses. The extract significantly reduced writhing induced by acetic acid and the number and time of paw licking induced by formalin in a dose related manner. It inhibited the neurogenic and inflammatory phases of formalin. Analgesia was shown in the inhibition of nociception induced by tail immersion in 55oC hot water. The extract prolonged the latencies of tail withdrawal to a similar degree as pentazocine. The extract caused significant inhibition of carrageenan induced paw oedema in rats in a dose dependent manner. These findings suggest that the leaf extracts of Anacardium occidentalis are highly potent analgesic and anti-inflammatory agents. Phytochemical analysis showed that the leaf extracts contain alkaloids, tannins, saponins and cardenolides. PMID:23235310

  20. Anti-inflammatory and vascularprotective properties of 8-prenylapigenin.

    PubMed

    Paoletti, Tiziana; Fallarini, Silvia; Gugliesi, Francesca; Minassi, Alberto; Appendino, Giovanni; Lombardi, Grazia

    2009-10-12

    Flavonoids display several biological activities, but exhibit poor oral absorption and rapid metabolism. To improve their pharmacological profile four C8-prenyl flavonoids, structurally related to the anti-inflammatory lead apigenin, were synthesized, and the two least cytotoxic (IC(50)>30 microM) compounds [8-prenylnaringenin (8-PN) and 8-prenylapigenin (8-PA)] in RAW 264.7 murine macrophages were assayed against a panel of biological targets. The anti-inflammatory properties of these compounds were evaluated in an in vitro model of inflammation [cells exposed to 0.1 microg/ml lipopolysaccharide (LPS) for 24h]. Both 8-PN and 8-PA were equally effective and potent in inhibiting the LPS-induced gene expression [tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2] (RT-PCR) and release (ELISA) of pro-inflammatory mediators [TNF-alpha, NO, prostaglandin (PG)E(2)], through mechanisms involving the inhibition of nuclear factor-kappaB (NF-kappaB) activation (EMSA) and reactive oxygen species accumulation [2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) determination]. One-digit nM concentrations of 8-PN or 8-PA induced a significant increase in the basal production of the atheroprotective prostacyclin (PGI(2)) by human umbilical vein endothelial cells (HUVEC), with maximal effects at 10 nM. Both NS-398, a specific COX-2 inhibitor, and ICI 182 780, a non-selective estrogen receptor antagonist, abolished the activity of these compounds, suggesting a COX- and estrogen receptor-dependent mechanism of activity. 8-PA, a weaker estrogenic compound than 8-PN, resulted only 2-fold less potent than 8-PN in potentiating PGI(2) production by HUVEC, qualifying this C8-prenyl flavonoid as a lead for the rational design of new anti-inflammatory and vascularprotective compounds. PMID:19686724

  1. Identification of 14,20-dihydroxy-docosahexaenoic acid as a novel anti-inflammatory metabolite.

    PubMed

    Yokokura, Yoshiyuki; Isobe, Yosuke; Matsueda, Shinnosuke; Iwamoto, Ryo; Goto, Tomomi; Yoshioka, Takeshi; Urabe, Daisuke; Inoue, Masayuki; Arai, Hiroyuki; Arita, Makoto

    2014-12-01

    Docosahexaenoic acid (DHA) exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as D-series resolvins, protectin and maresin. Here, we analysed the lipids in inflammatory exudates using liquid chromatography-tandem mass spectrometry and identified a novel DHA metabolite, 14,20-dihydroxy-DHA (14,20-diHDHA) and showed that it is biosynthesized by eosinophils through the 12/15-lipoxygenase pathway. The chemical structure of the dominant 14,20-diHDHA isomer, which is endogenously biosynthesized by eosinophils, was identified as 14S,20R-diHDHA using chemically synthesized stereoisomers. Nanogram doses of 14,20-diHDHA displayed a potent anti-inflammatory action by limiting neutrophil infiltration in zymosan-induced peritonitis. The in vivo formation and potent anti-inflammatory action of 14,20-diHDHA may contribute to the protective effects of DHA. PMID:25012818

  2. Oxpholipin 11D: An Anti-Inflammatory Peptide That Binds Cholesterol and Oxidized Phospholipids

    PubMed Central

    Ruchala, Piotr; Navab, Mohamad; Jung, Chun-Ling; Hama-Levy, Susan; Micewicz, Ewa D.; Luong, Hai; Reyles, Jonathan E.; Sharma, Shantanu; Waring, Alan J.; Fogelman, Alan M.; Lehrer, Robert I.

    2010-01-01

    Background Many Gram-positive bacteria produce pore-forming exotoxins that contain a highly conserved, 12-residue domain (ECTGLAWEWWRT) that binds cholesterol. This domain is usually flanked N-terminally by arginine and C-terminally by valine. We used this 14-residue sequence as a template to create a small library of peptides that bind cholesterol and other lipids. Methodology/Results Several of these peptides manifested anti-inflammatory properties in a predictive in vitro monocyte chemotactic assay, and some also diminished the pro-inflammatory effects of low-density lipoprotein in apoE-deficient mice. The most potent analog, Oxpholipin-11D (OxP-11D), contained D-amino acids exclusively and was identical to the 14-residue design template except that diphenylalanine replaced cysteine-3. In surface plasmon resonance binding studies, OxP-11D bound oxidized (phospho)lipids and sterols in much the same manner as D-4F, a widely studied cardioprotective apoA-I-mimetic peptide with anti-inflammatory properties. In contrast to D-4F, which adopts a stable α-helical structure in solution, the OxP-11D structure was flexible and contained multiple turn-like features. Conclusion Given the substantial evidence that oxidized phospholipids are pro-inflammatory in vivo, OxP-11D and other Oxpholipins may have therapeutic potential. PMID:20418958

  3. Identification and evaluation of anti-inflammatory compounds from Kaempferia parviflora.

    PubMed

    Horigome, Satoru; Yoshida, Izumi; Tsuda, Aiko; Harada, Teppei; Yamaguchi, Akihiro; Yamazaki, Kumiko; Inohana, Shuichi; Isagawa, Satoshi; Kibune, Nobuyuki; Satoyama, Toshiya; Katsuda, Shin-ichi; Suzuki, Shinobu; Watai, Masatoshi; Hirose, Naoto; Mitsue, Takahiro; Shirakawa, Hitoshi; Komai, Michio

    2014-01-01

    The rhizome of Kaempferia parviflora has been used in traditional Thai medicine. In this study, we identified and compared specific compounds from the hexane extract of K. parviflora with those from other Zingiberaceous plants by using gas chromatography-mass spectrometry. We identified 5,7-dimethoxyflavone (DMF), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (TMF), estimated 3,5,7-trimethoxyflavone, 5-hydroxy-7,4'-dimethoxyflavone, 3,5,7,4'-tetramethoxyflavone, and investigated their anti-inflammatory effects in rat basophilic leukemia (RBL-2H3) cells stimulated with an IgE antigen or a calcium ionophore. We found that DMF and TMF more potently inhibited antigen-induced degranulation than did nobiletin, a well-known anti-inflammatory agent. In addition, compared to RBL-2H3 cells stimulated with a calcium ionophore, those treated with DMF and TMF showed more marked inhibition of the degranulation and the production and mRNA expression of inflammatory mediators. These results suggest that DMF and TMF inhibit an early step in the high-affinity IgE receptor signaling cascade rather than intracellular calcium release and protein kinase C activation. PMID:25035989

  4. Anti-inflammatory effects of five commercially available mushroom species determined in lipopolysaccharide and interferon-γ activated murine macrophages.

    PubMed

    Gunawardena, Dhanushka; Bennett, Louise; Shanmugam, Kirubakaran; King, Kerryn; Williams, Roderick; Zabaras, Dimitrios; Head, Richard; Ooi, Lezanne; Gyengesi, Erika; Münch, Gerald

    2014-04-01

    Inflammation is a well-known contributing factor to many age-related chronic diseases. One of the possible strategies to suppress inflammation is the employment of functional foods with anti-inflammatory properties. Edible mushrooms are attracting more and more attention as functional foods since they are rich in bioactive compounds, but their anti-inflammatory properties and the effect of food processing steps on this activity has not been systematically investigated. In the present study, White Button and Honey Brown (both Agaricus bisporus), Shiitake (Lentinus edodes), Enoki (Flammulina velutipes) and Oyster mushroom (Pleurotus ostreatus) preparations were tested for their anti-inflammatory activity in lipopolysaccharide (LPS) and interferon-γ (IFN-γ) activated murine RAW 264.7 macrophages. Potent anti-inflammatory activity (IC₅₀<0.1 mg/ml), measured as inhibition of NO production, could be detected in all raw mushroom preparations, but only raw Oyster (IC₅₀=0.035 mg/ml), Shiitake (IC₅₀=0.047 mg/ml) and Enoki mushrooms (IC₅₀=0.099 mg/ml) showed also potent inhibition of TNF-α production. When the anti-inflammatory activity was followed through two food-processing steps, which involved ultrasonication and heating, a significant portion of the anti-inflammatory activity was lost suggesting that the anti-inflammatory compounds might be susceptible to heating or prone to evaporation. PMID:24262531

  5. Antioxidant, Anti-inflammatory and Cytotoxicity of Phaleria macrocarpa (Boerl.) Scheff Fruit

    PubMed Central

    2011-01-01

    Background Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae) originates from Papua Island, Indonesia and grows in tropical areas. The different parts of the fruit of P. macrocarpa were evaluated for antioxidant, anti-inflammatory, and cytotoxic activities. Methods Phaleria macrocarpa fruit were divided into pericarp, mesocarp and seed. All parts of the fruit were reflux extracted with methanol. The antioxidant activity of the extracts were characterized in various in vitro model systems such as FTC, TBA, DPPH radical, reducing power and NO radical. Anti-inflammatory assays were done by using NO production by macrophage RAW 264.7 cell lines induced by LPS/IFN-γ and cytotoxic activities were determined by using several cancer cell lines and one normal cell line Results The results showed that different parts (pericarp, mesocarp, and seed) of Phaleria macrocarpa fruit contain various amount of total phenolic (59.2 ± 0.04, 60.5 ± 0.17, 47.7 ± 1.04 mg gallic acid equivalent/g DW) and flavonoid compounds (161.3 ± 1.58, 131.7 ± 1.66, 35.9 ± 2.47 mg rutin equivalent/g DW). Pericarp and mesocarp showed high antioxidant activities by using DPPH (71.97%, 62.41%), ferric reducing antioxidant power (92.35%, 78.78%) and NO scavenging activity (65.68%, 53.45%). Ferric thiocyanate and thiobarbituric acid tests showed appreciable antioxidant activity in the percentage hydroperoxides inhibitory activity from pericarp and mesocarp in the last day of the assay. Similarly, the pericarp and mesocarp inhibited inducible nitric oxide synthesis with values of 63.4 ± 1.4% and 69.5 ± 1.4% in macrophage RAW 264.7 cell lines induced by LPS/IFN-γ indicating their notable anti-inflammatory potential. Cytotoxic activities against HT-29, MCF-7, HeLa and Chang cell lines were observed in all parts. Conclusions These results indicated the possible application of P. macrocarpa fruit as a source of bioactive compounds, potent as an antioxidant, anti inflammatory and cytotoxic agents. PMID

  6. Photoelectron spectroscopy of non-steroidal anti-inflammatory drugs

    NASA Astrophysics Data System (ADS)

    Novak, Igor; Klasinc, Leo; Chong, Delano P.; McGlynn, Sean P.

    2013-08-01

    The electronic structures of eight non-steroidal anti-inflammatory drugs (NSAIDs) had been studied by UV photoelectron spectroscopy (UPS) and high-level Green's function (GF) calculations. Our UPS data show that the electronic structure influences the measured biological activity of NSAID, but that it is not the dominating factor. The role of electronic structure needs to be considered in conjunction with other factors like steric properties of the COX active site and orientation of relevant residues in the same site.

  7. Anti-inflammatory activity of cationic lipids.

    PubMed

    Filion, M C; Phillips, N C

    1997-10-01

    1. The effect of liposome phospholipid composition has been assumed to be relatively unimportant because of the presumed inert nature of phospholipids. 2. We have previously shown that cationic liposome formulations used for gene therapy inhibit, through their cationic component, the synthesis by activated macrophages of the pro-inflammatory mediators nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha). 3. In this study, we have evaluated the ability of different cationic lipids to reduce footpad inflammation induced by carrageenan and by sheep red blood cell challenge. 4. Parenteral (i.p. or s.c) or local injection of the positively charged lipids dimethyldioctadecylammomium bromide (DDAB), dioleyoltrimethylammonium propane (DOTAP), dimyristoyltrimethylammonium propane (DMTAP) or dimethylaminoethanecarbamoyl cholesterol (DC-Chol) significantly reduced the inflammation observed in both models in a dose-dependent manner (maximum inhibition: 70-95%). 5. Cationic lipids associated with dioleyol- or dipalmitoyl-phosphatidylethanolamine retained their anti-inflammatory activity while cationic lipids associated with dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylglycerol (DMPG) showed no anti-inflammatory activity, indicating that the release of cationic lipids into the macrophage cytoplasm is a necessary step for anti-inflammatory activity. The anti-inflammatory activity of cationic lipids was abrogated by the addition of dipalmitoylphosphatidylethanolamine-poly(ethylene)glycol-2000 (DPPE-PEG2000) which blocks the interaction of cationic lipids with macrophages. 6. Because of the significant role of protein kinase C (PKC) in the inflammatory process we have determined whether the cationic lipids used in this study inhibit PKC activity. The cationic lipids significantly inhibited the activity of PKC but not the activity of a non-related protein kinase, PKA. The synthesis of interleukin-6 (IL-6), which is not dependent on PKC activity for its

  8. Anti-inflammatory and antimicrobial activities of novel pyrazole analogues.

    PubMed

    Surendra Kumar, R; Arif, Ibrahim A; Ahamed, Anis; Idhayadhulla, Akbar

    2016-09-01

    A new sequence of pyrazole derivatives (1-6) was synthesized from condensation technique under utilizing ultrasound irradiation. Synthesized compounds were characterized from IR, (1)H NMR, (13)C NMR, Mass and elemental analysis. Synthesized compounds (1-6) were screened for antimicrobial activity. Among the compounds 3 (MIC: 0.25 μg/mL) was exceedingly antibacterially active against gram negative bacteria of Escherichia coli and compound 4 (MIC: 0.25 μg/mL) was highly active against gram positive bacteria of Streptococcus epidermidis compared with standard Ciprofloxacin. Compound 2 (MIC: 1 μg/mL) was highly antifungal active against Aspergillus niger proportionate to Clotrimazole. Synthesized compounds (1-6) were screened for anti-inflammatory activity and the compound 2-((5-hydroxy-3-methyl-1H-pyrazol-4-yl)(4-nitrophenyl)methyl)hydrazinecarboxamide (4) was better activity against anti-inflammatory when compared with standard drugs (Diclofenac sodium). Compounds (2, 3 and 4) are the most important molecules and hence the need to develop new drugs of antibacterial, antifungal and anti-inflammatory agents. PMID:27579011

  9. Anti-Inflammatory and Antinociceptive Activities of Bufalin in Rodents

    PubMed Central

    Huang, Yang; Yin, Junqiang; Lin, Wenqian

    2014-01-01

    The aims of this study were to evaluate the anti-inflammatory and analgesic effects of bufalin, a major component of “Chan-su.” We used a carrageenan-induced paw edema model to assess the anti-inflammatory activity of this compound, and Western blot analysis detected NF-κB signaling during this effect. The antinociceptive activities were evaluated by acetic acid-induced writhing, formalin, and hot-plate tests; open-field test investigated effects on the central nervous system. Our data showed that bufalin (0.3 and 0.6 mg/kg, i.p.) potently decreased carrageenan-induced paw edema. Bufalin down regulated the expression levels of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) during these treatments. Further studies demonstrated that bufalin significantly inhibited the activation of NF-κB signaling. Bufalin also reduced acetic acid-induced writhing and the licking time in the formalin test and increased hot-plate reaction latencies. Naloxone pretreatment (2 mg/kg, i.p.) in the early phases of the formalin test and hot-plate test significantly attenuated the bufalin-induced antinociception effects, which suggests the involvement of the opioid system. A reduction in locomotion was not observed in the open-field test after bufalin administration. Taken together, bufalin treatment resulted in in vivo anti-inflammatory and analgesic effects, and bufalin may be a novel, potential drug for the treatment of inflammatory diseases. PMID:24719521

  10. Anti-Inflammatory Activities of Natural Products Isolated from Soft Corals of Taiwan between 2008 and 2012

    PubMed Central

    Wei, Wen-Chi; Sung, Ping-Jyun; Duh, Chang-Yih; Chen, Bo-Wei; Sheu, Jyh-Horng; Yang, Ning-Sun

    2013-01-01

    This review reports details on the natural products isolated from Taiwan soft corals during the period 2008–2012 focusing on their in vitro and/or in vivo anti-inflammatory activities. Chemical structures, names, and literature references are also reported. This review provides useful and specific information on potent anti-inflammatory marine metabolites for future development of immune-modulatory therapeutics. PMID:24152566

  11. Structural characterization of anti-inflammatory Immunoglobulin G Fc proteins

    PubMed Central

    Ahmed, Alysia A.; Giddens, John; Pincetic, Andrew; Lomino, Joseph V.; Ravetch, Jeffrey V.; Wang, Lai-Xi; Bjorkman, Pamela J.

    2014-01-01

    Immunoglobulin G (IgG) is a central mediator of host defense due to its ability to recognize and eliminate pathogens. The recognition and effector responses are encoded on distinct regions of IgGs. The diversity of the antigen recognition Fab domains accounts for IgG's ability to bind with high specificity to essentially any antigen. Recent studies have indicated that the Fc effector domain also displays considerable heterogeneity, accounting for its complex effector functions of inflammation, modulation and immune suppression. Therapeutic anti-tumor antibodies, for example, require the pro-inflammatory properties of the IgG Fc to eliminate tumor cells, while the anti-inflammatory activity of Intravenous Immunoglobulin G (IVIG) requires specific Fc glycans for activity. In particular, the anti-inflammatory activity of IVIG is ascribed to a small population of IgGs in which the Asn297-linked complex N-glycans attached to each Fc CH2 domain include terminal α2,6-linked sialic acids. We used chemoenzymatic glycoengineering to prepare fully di-sialylated IgG Fc and solved its crystal structure. Comparison of the structures of asialylated Fc, sialylated Fc, and F241A Fc, a mutant that displays increased glycan sialylation, suggests that increased conformational flexibility of the CH2 domain is associated with the switch from pro- to anti-inflammatory activity of the Fc. PMID:25036289

  12. Anti-inflammatory activities of selected synthetic homoisoflavanones.

    PubMed

    Shaikh, Mahidansha M; Kruger, Hendrik G; Bodenstein, Johannes; Smith, Peter; du Toit, Karen

    2012-01-01

    Four homoisoflavanones of the 3-benzylidene-4-chromanone type, some of which were previously isolated from Caesalpinia pulcherrima, were synthesised to determine their anti-inflammatory activity and cytotoxicity. A range of four different homoisoflavanones (compounds 4a-4d) were synthesised from the corresponding substituted phenols. ¹H- and ¹³C-NMR data together with high-resolution mass spectroscopy data were employed to elucidate the structures. Anti-inflammatory activity was determined in mice with acute croton oil-induced auricular dermatitis. In vitro cytotoxicity was tested against a Chinese hamster ovarian cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Compound 4a exhibited a tendency to inhibit oedema in a dose-dependent manner after 3 and 6 h of treatment. Compounds 4b-4d also inhibited oedema, although a clear dose-response relationship was not observed. Compounds 4a-4c were found to be less cytotoxic than compound 4d. Compound 4b was the least cytotoxic. Compounds 4a-4d exhibited anti-inflammatory activity and varying levels of cytotoxicity. PMID:21950651

  13. Molecular Targets of Dietary Polyphenols with Anti-inflammatory Properties

    PubMed Central

    Yoon, Joo-Heon

    2005-01-01

    There is persuasive epidemiological and experimental evidence that dietary polyphenols have anti-inflammatory activity. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to combat inflammation. Recently, cyclooxygenase (COX) inhibitors have been developed and recommended for treatment of rheumatoid arthritis (RA) and osteoarthritis (OA). However, two COX inhibitors have been withdrawn from the market due to unexpected side effects. Because conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of many inflammatory diseases, there is an urgent need to find safer compounds and to develop mechanism-based approaches for the management of these diseases. Polyphenols are found in many dietary plant products, including fruits, vegetables, beverages, herbs, and spices. Several of these compounds have been found to inhibit the inflammation process as well as tumorigenesis in experimental animals; they can also exhibit potent biological properties. In addition, epidemiological studies have indicated that populations who consume foods rich in specific polyphenols have lower incidences of inflammatory disease. This paper provides an overview of the research approaches that can be used to unravel the biology and health effects of polyphenols. Polyphenols have diverse biological effects, however, this review will focus on some of the pivotal molecular targets that directly affect the inflammation process. PMID:16259055

  14. Anti-inflammatory properties of new bioisosteres of indomethacin synthesized from safrole which are sulindac analogues.

    PubMed

    Pereira, E F; Pereira, N A; Lima, M E; Coelho, F A; Barreiro, E J

    1989-01-01

    The anti-inflammatory activities of new compounds (I, II, III and IV) synthesized in 30% overall yield from the abundant natural product safrole, the principal chemical constituent of the oil of sassafras (Ocotea pretiosa, Lauraceae), were determined in mice. The synthesis of these new indenyl-acetic acids (I and II) and indenyl-propionic acids (III and IV) was based on the minimal structural features of non-steroid anti-inflammatory agents of the aryl- or heteroarylcarboxylic acid group. The compounds exhibited potencies 4- to 10-fold less than that of indomethacin in inhibiting carrageenan-induced hindpaw edema. In contrast, like sulindac, all the new compounds were more potent than indomethacin in antagonizing writhing pain and increased vascular permeability caused by acetic acid. The results confirm the anticipated bioisosteric relationship between these synthetic derivatives, designed as sulindac analogues, and the classical non-steroidal anti-inflammatory agent, indomethacin. PMID:2638933

  15. Synthesis and anti-inflammatory activity of some potential cyclic phenothiazines.

    PubMed

    Kumar, A; Ram, T; Tyagi, R; Goel, B; Bansal, E; Srivastava, V K

    1998-05-01

    Some new schiff's bases (IVa-IVe), thiazolidinones (Va-Ve), delta 2-triazolines (VIa-VIe) and formazans (VIIa-VIIe) of 2-chlorophenothiazine have been synthesized and screened against Carrageenin induced oedema in albino rats. Some compounds of the series have shown promising activity. The most active compound is 2-chloro-10[5-(2-fluorophenyl-2-oxo-4 thiazolidin-1-yl)-amino acetyl] phenothiazine was found to be most potent. This compound (Vb) was further evaluated in detail and compared with phenylbutazone for its relative anti inflammatory potency (ED50), ulcerogenic liabilities (UD50) and acute toxicity (ALD50). It was found to be almost comparable to phenylbutazone as regards anti-inflammatory activity was concerned but and minimum ulcerogenic liability and cardiovascular effects. Hence, it seems promising as an anti-inflammatory agent in our preliminary studies. PMID:9689901

  16. Intravital Microscopic Methods to Evaluate Anti-inflammatory Effects and Signaling Mechanisms Evoked by Hydrogen Sulfide

    PubMed Central

    Zuidema, Mozow Y.; Korthuis, Ronald J.

    2016-01-01

    Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule with potent anti-inflammatory properties. Exogenous application of H2S donors, administered either acutely during an inflammatory response or as an antecedent preconditioning intervention that invokes the activation of anti-inflammatory cell survival programs, effectively limits leukocyte rolling, adhesion and emigration, generation of reactive oxygen species, chemokine and cell adhesion molecule expression, endothelial barrier disruption,capillary perfusion deficits, and parenchymal cell dysfunction and injury. This chapter focuses on intravital microscopic methods that can be used to assess the anti-inflammatory effects exerted by H2S, as well as to explore the cellular signaling mechanisms by which this gaseous molecule limits the aforementioned inflammatory responses. Recent advances include use of intravital multiphoton microscopy and optical biosensor technology to explore signaling mechanisms in vivo. PMID:25747477

  17. Synthesis and Biological Evaluation of Novel Resveratrol-NSAID Derivatives as Anti-inflammatory Agents.

    PubMed

    Peng, Wei; Ma, Yan-Yan; Zhang, Kun; Zhou, Ai-Yu; Zhang, Yu; Wang, Huaqian; Du, Zhiyun; Zhao, Deng-Gao

    2016-06-01

    Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may cause serious side effects such as gastric mucosal damage. Resveratrol, a naturally dietary polyphenol, exhibited anti-inflammatory activity and a protective effect against gastric mucosa damage induced by NSAIDs. In this regard, we synthesized a series of resveratrol-based NSAIDs derivatives and evaluated their anti-inflammatory activity against nitric oxide (NO) overproduction in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We identified mono-substituted resveratrol-ibuprofen combination 21 as the most potent anti-inflammatory agent, which is more active than a physical mixture of ibuprofen and resveratrol, individual ibuprofen, or individual resveratrol. In addition, compound 21 exerted potent inhibitory effects on the LPS-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Furthermore, compound 21 significantly increased the survival rate in an LPS-induced acute inflammatory model and produced markedly less gastric damage than ibuprofen. It was found that compound 21 may be a potent anti-inflammatory agent for the treatment of inflammation-related diseases. PMID:27009373

  18. QSAR and Docking Studies on Capsazepine Derivatives for Immunomodulatory and Anti-Inflammatory Activity

    PubMed Central

    Shukla, Aparna; Sharma, Pooja; Prakash, Om; Singh, Monika; Kalani, Komal; Khan, Feroz; Bawankule, Dnyaneshwar Umrao; Luqman, Suaib; Srivastava, Santosh Kumar

    2014-01-01

    Capsazepine, an antagonist of capsaicin, is discovered by the structure and activity relationship. In previous studies it has been found that capsazepine has potency for immunomodulation and anti-inflammatory activity and emerging as a favourable target in quest for efficacious and safe anti-inflammatory drug. Thus, a 2D quantitative structural activity relationship (QSAR) model against target tumor necrosis factor-α (TNF-α) was developed using multiple linear regression method (MLR) with good internal prediction (r2 = 0.8779) and external prediction (r2pred = 0.5865) using Discovery Studio v3.5 (Accelrys, USA). The predicted activity was further validated by in vitro experiment. Capsazepine was tested in lipopolysaccharide (LPS) induced inflammation in peritoneal mouse macrophages. Anti-inflammatory profile of capsazepine was assessed by its potency to inhibit the production of inflammatory mediator TNF-α. The in vitro experiment indicated that capsazepine is an efficient anti-inflammatory agent. Since, the developed QSAR model showed significant correlations between chemical structure and anti-inflammatory activity, it was successfully applied in the screening of forty-four virtual derivatives of capsazepine, which finally afforded six potent derivatives, CPZ-29, CPZ-30, CPZ-33, CPZ-34, CPZ-35 and CPZ-36. To gain more insights into the molecular mechanism of action of capsazepine and its derivatives, molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were performed. The results of QSAR, molecular docking, in silico ADMET screening and in vitro experimental studies provide guideline and mechanistic scope for the identification of more potent anti-inflammatory & immunomodulatory drug. PMID:25003344

  19. Medicinal plants with anti-inflammatory activities.

    PubMed

    Maione, Francesco; Russo, Rosa; Khan, Haroon; Mascolo, Nicola

    2016-06-01

    Medicinal plants have been the main remedy to treat various ailments for a long time and nowadays, many drugs have been developed from traditional medicine. This paper reviews some medicinal plants and their main constituents which possess anti-inflammatory activities useful for curing joint inflammation, inflammatory skin disorders, cardiovascular inflammation and other inflammatory diseases. Here, we provide a brief overview of quick and easy reading on the role of medicinal plants and their main constituents in these inflammatory diseases. We hope that this overview will shed some light on the function of these natural anti-inflammatory compounds and attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions. PMID:26221780

  20. Ethanesulfohydroxamic acid ester prodrugs of nonsteroidal anti-inflammatory drugs (NSAIDs): synthesis, nitric oxide and nitroxyl release, cyclooxygenase inhibition, anti-inflammatory, and ulcerogenicity index studies.

    PubMed

    Huang, Zhangjian; Velázquez, Carlos A; Abdellatif, Khaled R A; Chowdhury, Morshed A; Reisz, Julie A; DuMond, Jenna F; King, S Bruce; Knaus, Edward E

    2011-03-10

    The carboxylic acid group of the anti-inflammatory (AI) drugs indo-methacin, (S)-naproxen and ibuprofen was covalently linked via a two-carbon ethyl spacer to a sulfohydroxamic acid moiety (CH(2)CH(2)SO(2)NHOH) to furnish a group of hybrid ester prodrugs that release nitric oxide (NO) and nitroxyl (HNO). Biological data acquired for this hitherto unknown class of ethanesulfohydroxamic acid ester prodrugs showed (i) all compounds exhibited superior NO, but similar HNO, release properties relative to arylsulfohydroxamic acids, (ii) the (S)-naproxen and ibuprofen prodrug esters are more potent AI agents than their parent NSAID, (iii) the indomethacin prodrug ester, in contrast to indomethacin which is highly ulcerogenic, showed no visible stomach lesions [ulcer index (UI) = 0 for a 80 μmol/kg oral dose] while retaining potent AI activity, and iv) that the indomethacin prodrug ester, unlike indomethacin which is an ulcerogenic selective COX-1 inhibitor, is a selective COX-2 inhibitor (COX-2 selectivity index = 184) devoid of ulcerogenicity that is attributed to its high COX-2 SI and/or ability to release cytoprotective NO. PMID:21280601

  1. The new nonsteroidal anti-inflammatory drugs.

    PubMed

    Scherbel, A L; Wilke, W S

    1981-10-01

    Most physicians regard to newer short-acting anti-inflammatory drugs as a substitute for aspirin because they are less toxic. Although these drugs cannot induce remissions of rheumatoid arthritis, they do afford symptomatic relief and exert both a moderate algesic and anti-inflammatory effect in conditions like osteoarthritis, gout, pseudogout, and a variety of musculoskeletal syndromes. The many adverse reactions and toxic effects associated with these drugs are probably related to the inhibition of prostaglandin synthetase, which in turn reduces the biosynthesis of prostaglandins in widespread areas of the body. Thus limited in number, these compounds cannot play an effective role in the body's defense mechanisms. Researchers postulate that this failure accounts for the gastrointestinal and renal lesions--as well as other, as yet unexplained toxic manifestations--noted in patients taking these drugs. For safety's sake, the newer anti-inflammatory drugs should be used with large doses of aspirin, other agents that inhibit prostaglandin synthetase, or drugs that are potentially nephro-toxic. PMID:6974117

  2. Anti-inflammatory properties of cryptolepine.

    PubMed

    Olajide, Olumayokun A; Ajayi, Abayomi M; Wright, Colin W

    2009-10-01

    Cryptolepine is the major alkaloid of the West African shrub, Cryptolepis sanguinolenta. Cryptolepine has been shown to inhibit nitric oxide production, and DNA binding of Nuclear Factor-kappa B following inflammatory stimuli in vitro. In order to validate the anti-inflammatory property of this compound in vivo, we investigated its effects on a number of animal models of inflammation. Cryptolepine (10-40 mg/kg i.p.) produced significant dose-dependent inhibition of the carrageenan-induced rat paw oedema, and carrageenan-induced pleurisy in rats. These effects were compared with those of the non-steroidal anti-inflammatory drug indomethacin (10 mg/kg). At doses of 10-40 mg/kg i.p., cryptolepine inhibited lipopolysaccharide (LPS)-induced microvascular permeability in mice in a dose-related fashion. Oral administration of up to 40 mg/kg of the compound for four consecutive days did not induce gastric lesion formation in rats. Analgesic activity was also exhibited by cryptolepine through a dose-related (10-40 mg/kg i.p.) inhibition of writhing induced by i.p. administration of acetic acid in mice. The results of this study reveal that cryptolepine possesses in vivo anti-inflammatory activity. PMID:19288476

  3. Synthesis and Anti-Inflammatory Activity of New Alkyl-Substituted Phthalimide 1H-1,2,3-Triazole Derivatives

    PubMed Central

    Assis, Shalom Pôrto de Oliveira; da Silva, Moara Targino; de Oliveira, Ronaldo Nascimento; Lima, Vera Lúcia de Menezes

    2012-01-01

    Four new 1,2,3-triazole phthalimide derivatives with a potent anti-inflammatory activity have been synthesized in the good yields by the 1,3-dipolar cycloaddition reaction from N-(azido-alkyl)phthalimides and terminal alkynes. The anti-inflammatory activity was determined by injecting carrageenan through the plantar tissue of the right hind paw of Swiss white mice to produce inflammation. All the compounds 3a–c and 5a–c exhibited an important anti-inflammatory activity; the best activity was found for the compounds 3b and 5c, which showed to be able to decrease by 69% and 56.2% carrageenan-induced edema in mice. These compounds may also offer a future promise as a new anti-inflammatory agent. PMID:23304092

  4. Anti-inflammatory potential of allyl-isothiocyanate--role of Nrf2, NF-(κ) B and microRNA-155.

    PubMed

    Wagner, Anika Eva; Boesch-Saadatmandi, Christine; Dose, Janina; Schultheiss, Gerhard; Rimbach, Gerald

    2012-04-01

    In this study, the underlying mechanisms of the potential anti-inflammatory properties of allyl-isothiocyanate (AITC) were analysed in vitro and in vivo. Murine RAW264.7 macrophages stimulated with lipopolysaccharide (LPS) were supplemented with increasing concentrations of AITC. In addition, C57BL/6 mice (n= 10 per group) were fed a pro-inflammatory high-fat diet and AITC was administered orally via gavage for 7 days. Biomarkers of inflammation were determined both in cultured cells and in mice. AITC significantly decreased tumour necrosis factor α mRNA levels and its secretion in LPS stimulated RAW264.7 macrophages. Furthermore, gene expression of other pro-inflammatory markers including interleukin-1β and inducible nitric oxide synthase were down-regulated following AITC treatment. AITC decreased nuclear p65 protein levels, a subunit of the transcription factor NF-κB. Importantly, our data indicate that AITC significantly attenuated microRNA-155 levels in LPS-stimulated RAW264.7 macrophages in a dose-dependent manner. The anti-inflammatory effects of AITC were accompanied by an increase in Nrf2 nuclear translocation and consequently by an increase of mRNA and protein levels of the Nrf2 target gene heme-oxygenase 1. AITC was slightly less potent than sulforaphane (used as a positive control) in down-regulating inflammation in LPS-stimulated macrophages. A significant increase in nuclear Nrf2 and heme-oxygenase 1 gene expression and only a moderate down-regulation of interleukin-1β and microRNA-155 levels due to AITC was found in mouse liver. Present data suggest that AITC exhibits potent anti-inflammatory activity in cultured macrophages in vitro but has only little anti-inflammatory activity in mice in vivo. PMID:21692985

  5. Quantitative Analysis and In vitro Anti-inflammatory Effects of Gallic Acid, Ellagic Acid, and Quercetin from Radix Sanguisorbae

    PubMed Central

    Seo, Chang-Seob; Jeong, Soo-Jin; Yoo, Sae-Rom; Lee, Na-Ri; Shin, Hyeun-Kyoo

    2016-01-01

    Background: Radix Sanguisorbae has long been used to treat diarrhea, enteritis, duodenal ulcers, and internal hemorrhage. Objective: We investigated the in vitro anti-inflammatory effects of Radix Sanguisorbae and performed quantitative analyses of three marker components, namely gallic acid, ellagic acid, and quercetin, using high-performance liquid chromatography coupled with a photodiode array detector. Materials and Methods: The three marker components were separated using a reversed-phase Gemini C18 analytical column maintained at 40°C by the gradient elution with two solvent systems. We examined the biological effects of the three marker compounds, gallic acid, ellagic acid, and quercetin, by determining their anti-inflammatory activities in the murine macrophage cell line RAW 264.7. Results: All of the marker compounds exhibited inhibitory effects on prostaglandin E2 production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, with no cytotoxicity. Particularly, ellagic acid significantly inhibited production of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-6 in LPS-treated RAW 264.7 cells. Conclusion: Our results suggest that ellagic acid is the most potent bioactive phytochemical component of radix Sanguisorbae in the treatment of inflammatory diseases. SUMMARY Established high-performance liquid chromatography method was applied in the quantitative analysis of gallic acid, ellagic acid, and quercetin present in an extract from radix SanguisorbaeAmong the three compounds, the ellagic acid.(7.65.mg/g) is main component in radix SanguisorbaeEllagic acid significantly inhibited production of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-6 in lipopolysaccharide-treated RAW 264.7 cells. Abbreviations used: HPLC: High-performance liquid chromatography, PDA: Photodiode array, TNF-α: Tumor necrosis factor alpha, IL: Interleukin, LPS: Lipopolysaccharide, PGE2: Prostaglandin E2, NSAIDs

  6. Erdosteine: antitussive and anti-inflammatory effects.

    PubMed

    Dal Negro, Roberto W

    2008-01-01

    Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on

  7. New Anti-Inflammatory Metabolites by Microbial Transformation of Medrysone

    PubMed Central

    Bano, Saira; Wahab, Atia-tul-; Yousuf, Sammer; Jabeen, Almas; Mesaik, Mohammad Ahmed; Rahman, Atta-ur-; Choudhary, M. Iqbal

    2016-01-01

    Microbial transformation of the anti-inflammatory steroid medrysone (1) was carried out for the first time with the filamentous fungi Cunninghamella blakesleeana (ATCC 8688a), Neurospora crassa (ATCC 18419), and Rhizopus stolonifer (TSY 0471). The objective was to evaluate the anti-inflammatory potential of the substrate (1) and its metabolites. This yielded seven new metabolites, 14α-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (2), 6β-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (3), 15β-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (4), 6β,17α-dihydroxy-6α-methylpregn-4-ene-3,11,20-trione (5), 6β,20S-dihydroxy-6α-methylpregn-4-ene-3,11-dione (6), 11β,16β-dihydroxy-6α-methylpregn-4-ene-3,11-dione (7), and 15β,20R-dihydroxy-6α-methylpregn-4-ene-3,11-dione (8). Single-crystal X-ray diffraction technique unambiguously established the structures of the metabolites 2, 4, 6, and 8. Fungal transformation of 1 yielded oxidation at the C-6β, -11β, -14α, -15β, -16β positions. Various cellular anti-inflammatory assays, including inhibition of phagocyte oxidative burst, T-cell proliferation, and cytokine were performed. Among all the tested compounds, metabolite 6 (IC50 = 30.3 μg/mL) moderately inhibited the reactive oxygen species (ROS) produced from zymosan-induced human whole blood cells. Compounds 1, 4, 5, 7, and 8 strongly inhibited the proliferation of T-cells with IC50 values between <0.2–10.4 μg/mL. Compound 7 was found to be the most potent inhibitor (IC50 < 0.2 μg/mL), whereas compounds 2, 3, and 6 showed moderate levels of inhibition (IC50 = 14.6–20.0 μg/mL). Compounds 1, and 7 also inhibited the production of pro-inflammatory cytokine TNF-α. All these compounds were found to be non-toxic to 3T3 cells (mouse fibroblast), and also showed no activity when tested against HeLa (human epithelial carcinoma), or against PC3 (prostate cancer) cancer cell lines. PMID:27104348

  8. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

    SciTech Connect

    Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

    2014-08-15

    Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.

  9. Anti-Inflammatory Effects of Agrimoniin-Enriched Fractions of Potentilla erecta.

    PubMed

    Hoffmann, Julia; Casetti, Federica; Bullerkotte, Ute; Haarhaus, Birgit; Vagedes, Jan; Schempp, Christoph M; Wölfle, Ute

    2016-01-01

    Potentilla erecta (PE) is a small herbaceous plant with four yellow petals belonging to the Rosaceae family. The rhizome of PE has traditionally been used as an antidiarrheal, hemostatic and antihemorrhoidal remedy. PE contains up to 20% tannins and 5% ellagitannins, mainly agrimoniin. Agrimoniin is a hydrolyzable tannin that is a potent radical scavenger. In this study we tested the anti-inflammatory effect of four PE fractions with increasing amounts of agrimoniin obtained by Sephadex column separation. First, we analyzed in HaCaT keratinocytes the expression of cyclooxygenase-2 (COX-2) induced by ultraviolet-B (UVB) irradiation. As COX-2 catalyzes the metabolism of arachidonic acid to prostanoids such as PGE₂, we also measured the PGE₂ concentration in cell culture supernatants. PE inhibited UVB-induced COX-2 expression in HaCaT cells and dose-dependently reduced PGE₂. The PE fraction with the highest agrimoniin amount (PE4) was the most effective in this experiment, whereas fraction PE1 containing mainly sugars had no effect. PE4 also dose dependently inhibited the phosphorylation of the epidermal growth factor receptor (EGFR) which plays a crucial role in UVB-mediated COX-2 upregulation. A placebo-controlled UV-erythema study with increasing concentrations of PE4 demonstrated a dose dependent inhibition of UVB-induced inflammation in vivo. Similarly, PE4 significantly reduced UVB-induced PGE₂ production in suction blister fluid in vivo. In summary, PE fractions with a high agrimoniin content display anti-inflammatory effects in vitro and in vivo in models of UVB-induced inflammation. PMID:27322232

  10. Activity of antimicrobial peptide mimetics in the oral cavity: II. Activity against periopathogenic biofilms and anti-inflammatory activity.

    PubMed

    Hua, J; Scott, R W; Diamond, G

    2010-12-01

    Whereas periodontal disease is ultimately of bacterial etiology, from multispecies biofilms of gram-negative anaerobic microorganisms, much of the deleterious effects are caused by the resultant epithelial inflammatory response. Hence, development of a treatment that combines anti-biofilm antibiotic activity with anti-inflammatory activity would be of great utility. Antimicrobial peptides (AMPs) such as defensins are naturally occurring peptides that exhibit broad-spectrum activity as well as a variety of immunomodulatory activities. Furthermore, bacteria do not readily develop resistance to these agents. However, clinical studies have suggested that they do not represent optimal candidates for exogenous therapeutic agents. Small-molecule mimetics of these AMPs exhibit similar activities to the parent peptides, in addition to having low toxicity, high stability and low cost. To determine whether AMP mimetics have the potential for treatment of periodontal disease, we examined the activity of one mimetic, mPE, against biofilm cultures of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Metabolic assays as well as culture and biomass measurement assays demonstrated that mPE exhibits potent activity against biofilm cultures of both species. Furthermore, as little as 2 μg ml(-1) mPE was sufficient to inhibit interleukin-1β-induced secretion of interleukin-8 in both gingival epithelial cells and THP-1 cells. This anti-inflammatory activity is associated with a reduction in activation of nuclear factor-κB, suggesting that mPE can act both as an anti-biofilm agent in an anaerobic environment and as an anti-inflammatory agent in infected tissues. PMID:21040516

  11. 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. PMID:25338213

  12. Anti-inflammatory effects of isoketocharbroic acid from brown alga, Sargassum micracanthum.

    PubMed

    Ham, Young Min; Yoon, Weon-Jong; Lee, Wook Jae; Kim, Sang-Cheol; Baik, Jong Seok; Kim, Jin Hwa; Lee, Geun Soo; Lee, Nam Ho; Hyun, Chang-Gu

    2015-01-01

    During our on-going screening program designed to isolate natural compounds from marine environments, we isolated isoketochabrolic acid (IKCA) from Sargassum micracanthum, an important brown algae distributed in Jeju Island, Korea. Furthermore, we evaluated the inhibitory effects of IKCA on nitric oxide (NO) production in lipopolysaccharide (LPS)-triggered macrophages. IKCA strongly inhibited NO production, with an IC50 value of 58.31 μM. Subsequent studies demonstrated that IKCA potently and concentration-dependently reduced prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 cytokine production. In conclusion, to the best of our knowledge, this is the first study to show that IKCA isolated from S. micracanthum has a potent anti-inflammatory activity. Therefore, IKCA might be useful as an anti-inflammatory health supplement or functional cosmetics. PMID:26600756

  13. Anti-inflammatory effects of isoketocharbroic acid from brown alga, Sargassum micracanthum

    PubMed Central

    Ham, Young Min; Yoon, Weon-Jong; Lee, Wook Jae; Kim, Sang-Cheol; Baik, Jong Seok; Kim, Jin Hwa; Lee, Geun Soo; Lee, Nam Ho; Hyun, Chang-Gu

    2015-01-01

    During our on-going screening program designed to isolate natural compounds from marine environments, we isolated isoketochabrolic acid (IKCA) from Sargassum micracanthum, an important brown algae distributed in Jeju Island, Korea. Furthermore, we evaluated the inhibitory effects of IKCA on nitric oxide (NO) production in lipopolysaccharide (LPS)-triggered macrophages. IKCA strongly inhibited NO production, with an IC50 value of 58.31 μM. Subsequent studies demonstrated that IKCA potently and concentration-dependently reduced prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 cytokine production. In conclusion, to the best of our knowledge, this is the first study to show that IKCA isolated from S. micracanthum has a potent anti-inflammatory activity. Therefore, IKCA might be useful as an anti-inflammatory health supplement or functional cosmetics. PMID:26600756

  14. Investigation of Pharmacological Activity of Caralluma penicillata: Anti-Inflammatory Properties and Gastritis Protection against Indomethacin in Adult Guinea Pigs

    PubMed Central

    Albaser, Nabil; Ghanem, Najeeb; Shehab, Mohanad; Al-Adhal, Adnan

    2014-01-01

    Caralluma is a plant that possessing a great therapeutic potential in folk medicine in Yemen, namely, Caralluma penicillata (C. penicillata) as antiulcer. The study aims to evaluate the anti-inflammatory properties and gastritis protection activity of C. penicillata against indomethacin in adult guinea pigs. The study was divided into four parts: firstly, the optimum dose of extract as anti-inflammatory effect was determined. Secondly, the acute anti-inflammatory effect of extract were estimated. Thirdly, the repeated doses of extract against chronic inflammation was estimated. The anti-inflammatory activity of extract was compared with indomethacin as a prototype of drug against inflammation. Fourthly, the gastritis protection properties of extract with/without indomethacin were performed. The results showed that a 400 mg/kg of 10% ethanol extract produced the maximum of anti-inflammatory effect. Also, the single dose of extract was equipotent for indomethacin (10 mg/kg), but shorter in duration with regard to acute anti-inflammatory effect. In addition, the repeated doses of extract against chronic inflammation were less potent than indomethacin with regard to ulcerogenic effect. On the other hand, extract-indomethacin combination reduced the gastritis effect of indomethacin based on ulcer index and histological study.

  15. A COMPARATIVE EVALUATION OF ANTI-INFLAMMATORY ACTIVITY OF THE BARK OF FICUS BENGALENSIS IN PLANTS OF DIFFERENT AGE

    PubMed Central

    Patil, Vikas V.; Patil, Vijay R.

    2010-01-01

    The medicinal plants have been selected for thorough studies from indigenous folk medicines, Ayurvedic, Unani and Siddha systems of medicines. The aim of this study deals with the comparative evaluation of anti-inflammatory activity of the bark of Ficus bengalensis in plants of different age. The anti-inflammatory activity was evaluated by rat paw edema model induced by carrageenan for acute inflammation and cotton pellet granuloma model for chronic inflammation. Indomethacin was used as a standard drug. The various extracts were studied for their anti-inflammatory activity in carrageenan-induced hind paw edema in rats and the paw volume was measured plethysmometrically from 0 to 3h after injection. We have determined the anti-inflammatory activity of various extracts of the bark of Ficus bengalensis with oral administration doses of 300 and 600 mg/kg/day of body weight to healthy animals. Positive results for flavonoids, sterols, and triterpene, tannins and saponins compounds were investigated by phytochemical analysis. The ethanolic extract of younger plant showed a greater anti-inflammatory effect compared with the standard drug indomethacin. Present studies besides confirming anti-inflammatory activity of the ethanolic extract of younger more potent than mature plant help to identify from the comparative study of the bark of Ficus bengalensis. PMID:24825975

  16. Characterization of the anti-inflammatory activity and reduced potential for dermal atrophy of (11 beta, 16 beta)-9-fluoro-1',2',3', 4'-tetrahydro-11,21-dihydroxypregna-1,4-dieno[16,17-b]naph thalene-3, 20-dione hydrate (1 : 1) (SQ 26,490), a topically active corticoid.

    PubMed

    Wojnar, R J; Alpaugh, W C; Dzelzkalns, E

    1985-01-01

    SQ 26,490, (11 beta, 16 beta)-9-fluoro-1',2',3',4'-tetrahydro-11, 21-dihydroxypregna-1,4-dieno[16,17-b]naphthalene 3,20-dione hydrate (1 : 1), was a moderately potent inhibitor of edema formation in the rat. After extended topical application, SQ 26,490 totally inhibited edema formation without appreciable production of skin atrophy, measured under identical conditions. This atrophy was maintained at a low plateau level of 15-20% at doses beyond those necessary to achieve optimal anti-inflammatory activity. In contrast, the potent corticoids, fluocinolone acetonide and halcinonide, and the moderately potent corticoid, clobetasone butyrate, produced inhibition of edema with a concomitant dose-related atrophy. Hydrocortisone, a weakly potent corticoid, totally inhibited edema and produced at high doses a low atrophy. SQ 26,490 possesses the property for a greater separation of anti-inflammatory and atrophogenic activities than comparative corticoids. PMID:4074443

  17. Mangiferin suppressed advanced glycation end products (AGEs) through NF-κB deactivation and displayed anti-inflammatory effects in streptozotocin and high fat diet-diabetic cardiomyopathy rats.

    PubMed

    Hou, Jun; Zheng, Dezhi; Fung, Gabriel; Deng, Haoyu; Chen, Lin; Liang, Jiali; Jiang, Yan; Hu, Yonghe

    2016-03-01

    Given the importance of the aggregation of advanced glycation end products (AGEs) and cardiac inflammation in the onset and progression of diabetic cardiomyopathy (DCM), our objective in this study was to demonstrate the cardioprotective effect of mangiferin, an antidiabetic and anti-inflammatory agent, on diabetic rat model. The DCM model was established by a high-fat diet and a low dose of streptozotocin. DCM rats were treated orally with mangiferin (20 mg/kg) for 16 weeks. Serum and left ventricular myocardium were collected for determination of inflammatory cytokines. AGEs mRNA and protein expression of nuclear factor kappa B (NF-κB) and receptor for AGEs (RAGE) in myocardium were assayed by real-time PCR and Western blot. ROS levels were measured by dihydroethidium fluorescence staining. NF-κB binding activity was assayed by TransAM NF-κB p65 ELISA kit. Chronic treatment with mangiferin decreased the levels of myocardial enzymes (CK-MB, LDH) and inflammatory mediators (TNF-α, IL-1β). Meanwhile, NF-κB is inhibited by the reduction of nuclear translocation of p65 subunit, and mangiferin reduced AGE production and decreased the mRNA and protein expression of RAGE in DCM rats. Our data indicated that mangiferin could significantly ameliorate DCM by preventing the release of inflammatory cytokines, and inhibiting ROS accumulation, AGE/RAGE production, and NF-κB nuclear translocation, suggesting that mangiferin treatment might be beneficial in DCM. PMID:26751764

  18. Simultaneous quantification of an anti-inflammatory compound (DuP 697) and a potential metabolite (X6882) in human plasma and urine by high-performance liquid chromatography.

    PubMed

    Joshi, A S; Raghavan, N; Williams, R M; Takahashi, K; Shingu, H; King, S Y

    1994-10-01

    A high-performance liquid chromatographic (HPLC) method using fluorescence detection has been developed for the simultaneous analysis of low nanogram concentrations of an anti-inflammatory drug, 5-Bromo-2-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]thiophene (DuP 697), and a potential metabolite (X6882) in human plasma and of DuP 697 in human urine. This assay method used an EM Separations Lichrospher C18 endcapped column. The mobile phase was acetonitrile-water (75:25, v/v). The detection of DuP 697 and X6882 was by fluorescence at excitation and emission wavelengths of 256 and 419 nm, respectively. The chromatographic system could separate DuP 697 from X6882, the external standard (anthracene), and other endogenous substances present in human plasma. In human plasma the limits of quantification for DuP 697 and X6882 were 3 and 20 ng/ml, respectively; the limit of quantification for DuP 697 in human urine was 5 ng/ml. These compounds were shown to be stable in frozen (-20 degrees C) human plasma and urine for at least 9 weeks. The assay described has been used to characterize DuP 697 pharmacokinetics after oral administration in humans. PMID:7858707

  19. Sesquiterpenes from Essential Oils and Anti-Inflammatory Activity.

    PubMed

    da Silveira e Sá, Rita de Cássia; Andrade, Luciana Nalone; de Sousa, Damião Pergentino

    2015-10-01

    This review is aimed at presenting relevant information on the therapeutic potential of essential oil sesquiterpenes with anti-inflammatory activity. The data reviewed provide a basis for seeking new anti-inflammatory drugs from natural products that do not exhibit the undesirable side effects often displayed by anti-inflammatory drugs. In this review the experimental models, possible mechanisms of action, and chemical structures of 12 sesquiterpenes are presented. PMID:26669122

  20. Anti-inflammatory activity of extracts from Conyza canadensis.

    PubMed

    Lenfeld, J; Motl, O; Trka, A

    1986-04-01

    The petroleum ether and ethanolic extract from the epigean part of Conyza canadensis exhibits a significant anti-inflammatory effect on rats with a carrageenin and formalin oedema. Eight sesquiterpenic hydrocarbons with the highest anti-inflammatory activity were found in the petroleum ether fraction (beta-santalene, beta-himachalene, cuparene, alpha-curcumene, gamma-cadinene and three other unidentified hydrocarbons). Of these substances, beta-himachalene was further studied and its anti-inflammatory activity was demonstrated. PMID:3725873

  1. The anti-inflammatory effects of venlafaxine in the rat model of carrageenan-induced paw edema

    PubMed Central

    Hajhashemi, Valiollah; Minaiyan, Mohsen; Banafshe, Hamid Reza; Mesdaghinia, Azam; Abed, Alireza

    2015-01-01

    Objective(s): Recently anti-inflammatory effects of antidepressants have been demonstrated. Venlafaxine belongs to newer antidepressants with serotonin norepinephrine reuptake inhibition property. The pain alleviating properties of venlafaxine in different pain models such as neurogenic pain, diabetic neuropathy, and fibromyalgia have been demonstrated. Anti-inflammatory effects of venlafaxine and also its underlying mechanisms remain unclear. The present study was designed to evaluate the anti-inflammatory effects of venlafaxine and determine possible underlying mechanisms. Materials and Methods: We examined the anti-inflammatory effects of intraperitoneal (IP) and intracerebroventricular (ICV) administration of venlafaxine in the rat model of carrageenan-induced paw edema. Results: Our results showed that both IP (50 and 100 mg/kg) and ICV (50 and 100 μg/rat) injection of venlafaxine inhibited carrageenan-induced paw edema. Also IP and ICV administration of venlafaxine significantly decreased myeloperoxidase (MPO) activity and interleukin (IL)-1β and tumor necrosis factor (TNF)-α production. Finally, we tried to reverse the anti-inflammatory effect of venlafaxine by yohimbine (5 mg/kg, IP), an alpha2-adrenergic antagonist. Our results showed that applied antagonist failed to change the anti-inflammatory effect of venlafaxine. Conclusion: These results demonstrated that venlafaxine has potent anti-inflammatory effect which is related to the peripheral and central effects of this drug. Also we have shown that anti-inflammatory effect of venlafaxine is mediated mostly through the inhibition of IL-1β and TNF-α production and decreases MPO activity in the site of inflammation. PMID:26351555

  2. Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates.

    PubMed

    Naumov, Roman N; Panda, Siva S; Girgis, Adel S; George, Riham F; Farhat, Michel; Katritzky, Alan R

    2015-06-01

    Novel, mesalazine, metronidazole conjugates 6a-e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties. PMID:25937011

  3. Develop Anti-Inflammatory Nanotherapies to Treat Cardiovascular Disease

    NASA Astrophysics Data System (ADS)

    Tang, Jun

    Cardiovascular disease (CVD) is the leading cause of disease-related death in the world, accounting for 30 % global mortality. The majority of CVD is caused by atherosclerosis, a chronic inflammatory disease of major arteries featured by the deposition of lipids and cholesterol. Inflammation of atherosclerosis is mainly promoted by the pathological macrophages and monocytes, and modulating their functions has been proposed as a promising therapeutic target. This dissertation first presents the development of a novel simvastatin-loaded high-density lipoprotein (HDL) based nanoparticle ([S]-rHDL), which was able to deliver anti-inflammatory simvastatin preferentially to inflammatory monocytes in the blood and to macrophages in advanced atherosclerotic plaques, leading to the reduced inflammation in the tissue. Second, extensive in vivo characterization of [S]-rHDL in a mouse atherosclerosis model revealed that the anti-inflammatory capability of [S]-rHDL derived from its effects on blood monocytes, endothelial layer, monocyte recruitment, and plaque macrophage function. Third, a translational study that integrated the use of [S]-rHDL into oral statin treatment demonstrated a great potential for this nanomedicine as an attractive addition to the current high-dose oral statin standard-of-care for acute coronary syndrome. Finally, preliminary results suggested potential applications of the rHDL platform to other macrophage-implicated diseases.

  4. Antimicrobial and anti-inflammatory activities of leaf extract of Valeriana wallichii DC.

    PubMed

    Khuda, Fazli; Iqbal, Zafar; Zakiullah; Khan, Ayub; Nasir, Fazli

    2012-10-01

    Valeriana wallichii DC (Valerianaceae) is one of the most widely used traditional remedies for various complications associated with nervous system and digestion. No antimicrobial and anti-inflammatory studies have so far been carried out on the aerial parts of the plant. The present work was focused to evaluate the antimicrobial (antifungal and antibacterial) and anti-inflammatory properties of V. wallichii using reported methods. Chloroform fraction (VW-2) and hexane fraction (VW-3) exhibited significant activity against S. aureus and B. subtilus, respectively. The chloroform fraction (VW-2) showed significant activity against S. aureus with 0.27 mg/ml MIC, where 0.31 mg/ml MIC was deduced for VW-3 fraction against B. subtilus. VW-3 fraction was also found to be the most potent inhibitor of M. canis, showing 70% inhibition with an MIC value of 0.19 mg/ml. Considerable inhibitory activity was also observed for VW-2 and water fraction (VW-6) against M. canis and A. flavus. A remarkable anti-inflammatory like activity was observed for the crude extract at a dose of 200 mg/kg at all observed durations. Other doses of the sample also showed excellent activity. Looking to these results it may be concluded that V. wallichii may be a potential source for activity guided isolation of natural products with antimicrobial and anti-inflammatory-like properties. PMID:23009985

  5. Synthesis and pharmacological evaluation of pyrazolopyrimidopyrimidine derivatives: anti-inflammatory agents with gastroprotective effect in rats.

    PubMed

    Karoui, Amine; Allouche, Fatma; Deghrigue, Monia; Agrebi, Asma; Bouraoui, Abderrahman; Chabchoub, Fakher

    2014-01-01

    We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3',4':4,5]pyrimido[1,6-a]pyrimidine 5 from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 5a, b, f (50-100 mg/kg, i.p) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay, and their effects are comparable to that of acetylsalicylic-lysine (300 mg/kg, i.p.), used as a reference drug. The nature of substituent (Y, R3) had a pronounced effect on the anti-inflammatory activity. Studies of structure-activity relationships have led to selection of compound ethyl-3,5-dimethyl-7-imino-N (1)-phenyl-1,7-dihydropyrazolo[3',4':4,5]pyrimido[1,6-a]pyrimidine-6-carboxylate, 5f which exhibited the most potent anti-inflammatory activity. In addition, the compounds 5a, b, f showed a significant gastroprotective effect against HCl/EtOH-induced gastric ulcer. PMID:24489456

  6. Anti-inflammatory effects of the novel inhaled phosphodiesterase type 4 inhibitor CHF6001 on virus-inducible cytokines.

    PubMed

    Edwards, Michael R; Facchinetti, Fabrizio; Civelli, Maurizio; Villetti, Gino; Johnston, Sebastian L

    2016-02-01

    Respiratory virus infections precipitate asthma and chronic obstructive pulmonary disease (COPD) exacerbations, with most exacerbations due to rhinovirus infection. Both asthma and COPD exacerbations are not well controlled by steroid therapies, and there is a much research interest in finding improved therapies or combinations of therapies for controlling exacerbations. CHF6001 is a new, inhaled highly potent and selective phosphodiesterase type 4 (PDE4) inhibitor. Using in vitro human bronchial epithelial cells (BEAS-2B), we investigated the potential anti-inflammatory effects of CHF6001 on rhinovirus (RV1B)-induced cytokines. Cytokine mRNA was measured by real-time PCR, while protein release was measured by ELISA. CHF6001 was used in a 7-point dose-response curve (1000-0.001 nmol/L) as a 1.5-h pretreatment prior to infection in comparison with roflumilast. Both roflumilast and CHF6001 reduced RV1B-induced IL-8, IL-29, IP-10, and RANTES mRNA and protein in a concentration-dependent manner. Generally, CHF6001 was 13- to 16-fold more potent (subnanomolar EC 50 values) than roflumilast at reducing IL-8, IL-29, IP-10, and RANTES mRNA and protein release, but had similar efficacies. In combination with the steroid fluticasone propionate (1 nmol/L), CHF6001 had additive effects, significantly reducing RV-induced cytokines when compared with steroid or CHF6001 alone. Combined low-dose steroid and low-dose CHF6001 had a similar efficacy as high-dose steroid or CHF6001 alone, indicating the combination had steroid and PDE4 inhibitor sparing effects. Overall results indicate that PDE4 inhibitors have anti-inflammatory activity against virus-induced inflammatory mediators and that CHF6001 is more potent than roflumilast. PMID:26977295

  7. Anti-Inflammatory and Antinociceptive Activities of Untreated, Germinated, and Fermented Mung Bean Aqueous Extract

    PubMed Central

    Ali, Norlaily Mohd; Mohd Yusof, Hamidah; Yeap, Swee-Keong; Ho, Wan-Yong; Beh, Boon-Kee; Koh, Soo-Peng; Abdullah, Mohd Puad; Alitheen, Noorjahan Banu

    2014-01-01

    Evaluation of anti-inflammatory and antinociceptive activities of untreated mung bean (MB), germinated mung bean (GMB), and fermented mung bean (FMB) was performed on both in vitro (inhibition of inflammatory mediator, nitric oxide(NO)) and in vivo (inhibition of ear oedema and reduction of response to pain stimulus) studies. Results showed that both GMB and FMB aqueous extract exhibited potent anti-inflammatory and antinociceptive activities in a dose-dependent manner. In vitro results showed that GMB and FMB were potent inflammatory mediator (NO) inhibitors at both 2.5 and 5 mg/mL. Further in vivo studies showed that GMB and FMB aqueous extract at 1000 mg/kg can significantly reduce ear oedema in mice caused by arachidonic acid. Besides, both 200 mg/kg and 1000 mg/kg concentrations of GMB and FMB were found to exhibit potent antinociceptive effects towards hotplate induced pain. With these, it can be concluded that GMB and FMB aqueous extract exhibited potential anti-inflammatory and antinociceptive effects. PMID:25045389

  8. Topical anti-inflammatory activity of Solanum corymbiflorum leaves.

    PubMed

    Piana, Mariana; Camponogara, Camila; Boligon, Aline Augusti; Machado, Michel Mansur; de Brum, Thiele Faccim; Oliveira, Sara Marchesan; de Freitas Bauermann, Liliane

    2016-02-17

    Solanum corymbiflorum is popularly known as "baga-de-veado" and its leaves are applied on inflamed legs, scabies, tick bite, boils, mastitis, low back pain and otitis. The aim of this study was evaluate anti-inflammatory in vivo activity and relate this activity with antioxidant compounds present in the extract of S. corymbiflorum leaves. The extract from S. corymbiflorum leaves topically applied was able to reduce the croton oil-induced ear edema and myeloperoxidase (MPO) activity with maximum inhibition of 87±3% and 45±7%, rescpectively in the dose of 1mg/ear. Similar results were found for positive control dexamethasone, which presented inhibitions of ear edema and MPO activity of 89±3% and 50±3%, respectively in a dose of 0.1mg/ear. These findings are due, at least in part, the presence of polyphenols (195.28mg GAE/g) and flavonoids, as chlorogenic acid (59.27mg/g), rutin (12.72mg/g), rosmarinic acid, caffeic acid and gallic acid found by high performance liquid chromatography (HPLC) analysis. This species showed potencial antioxidant by 1,1-diphenyl-2-picrylhydrazyl (DPPH), and carbonyl groups in proteins methods which may be related with the presence of this compounds. This species possess anti-inflammatory activity confirming their popular use for the local treatment of skin inflammatory disorders. PMID:26721215

  9. A novel anti-inflammatory peptide from human lipocortin 5.

    PubMed Central

    Perretti, M.; Becherucci, C.; Mugridge, K. G.; Solito, E.; Silvestri, S.; Parente, L.

    1991-01-01

    1. A novel anti-inflammatory peptide (residues 204-212) of human recombinant lipocortin 5 (hrLC5) found on the high similarity region with uteroglobin is described. 2. Peptide 204-212 dose-dependently inhibited the contractions of rat isolated stomach strips elicited by porcine pancreatic phospholipase A2 (PLA2). Contractions caused by arachidonic acid (AA), prostaglandin E2 (PGE2) and 5-hydroxytryptamine were not affected. No direct enzyme inhibition was observed in a radiochemical assay. 3. PGE2 release by both human fibroblasts and rat macrophages was reduced by peptide 204-212 in a dose-dependent manner. 4. The development of carrageenin-induced oedema in rats was significantly inhibited by the local administration of peptide 204-212. 5. The pattern and potency of the biological effects of peptide 204-212 are similar to those of antiflammin 2, a lipocortin 1-derived peptide. 6. It is suggested that peptide 204-212 may represent the active site responsible for the anti-inflammatory properties of lipocortin 5. PMID:1832064

  10. Brucella CβG induces a dual pro- and anti-inflammatory response leading to a transient neutrophil recruitment

    PubMed Central

    Degos, Clara; Gagnaire, Aurélie; Banchereau, Romain; Moriyón, Ignacio; Gorvel, Jean-Pierre

    2015-01-01

    Brucella is the causing agent of a chronic zoonosis called brucellosis. The Brucella β-1,2 cyclic glucan (CβG) is a virulence factor, which has been described as a potent immune stimulator, albeit with no toxicity for cells and animals. We first used a genome-wide approach to characterize human myeloid dendritic cell (mDC) responses to CβG. Transcripts related to inflammation (IL-6, IL2RA, PTGS2), chemokine (CXCR7, CXCL2) and anti-inflammatory pathways (TNFAIP6, SOCS3) were highly expressed in CβG-treated mDC. In mouse GMCSF-derived DC, CβG triggered the expression of both activation (CXCL2, KC) and inhibition (SOCS3 and TNFAIP6) molecules. We then characterized the inflammatory infiltrates at the level of mouse ear when injected with CβG or LPS. CβG yielded a lower and transient recruitment of neutrophils compared to LPS. The consequence of these dual pro- and anti-inflammatory signals triggered by CβG corresponds to the induction of a controlled local inflammation. PMID:25654761

  11. Antibacterial, anti-inflammatory and probiotic potential of Enterococcus hirae isolated from the rumen of Bos primigenius.

    PubMed

    Arokiyaraj, Selvaraj; Hairul Islam, Villianur Ibrahim; Bharanidharan, R; Raveendar, Sebastian; Lee, Jinwook; Kim, Do Hyung; Oh, Young Kyoon; Kim, Eun-Kyung; Kim, Kyoung Hoon

    2014-07-01

    In the present study bacterial strains were isolated from the rumen fluids of Bos primigenius and investigated their in vitro probiotic properties with potent antibacterial activity and anti-inflammatory effects. 9 g positive bacterial isolates were obtained and three isolates could able to tolerate gastric conditions, high bile salt concentrations and exhibited significant bactericidal effect against the enteric pathogens Vibrio cholera, Enterococcus faecalis, Enterobacter aerogens, Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi. Moreover it showed above 70% cell surface hydrophobicity, significant low-invasion ability and potential adherence capacity in Caco-2 cells when compared with the control. The proinflammatory cytokines (TNF-α) was greatly reduced in rumen bacteria treatment and ARBS-1 modulate the immune response by activating the IL-4 secretion in parallel to TNF-α suppression. The 16s rRNA gene sequence of the active isolates were identified as Enterococcus hirae (ARBS-1), Pediococcus acidilactici (ARBS-4) and Bacillus licheniformis (ARBS-7). This study revealed the probiotic bactericidal properties of E. hirae obtained from the rumen of B. primigenius with potential antibacterial and anti-inflammatory effects. Future studies with the strains may yield some novel probiotic product for livestock's. PMID:24609495

  12. Review of Anti-Inflammatory Herbal Medicines

    PubMed Central

    Ghasemian, Mona; Owlia, Sina; Owlia, Mohammad Bagher

    2016-01-01

    Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil's claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle. PMID:27247570

  13. Review of Anti-Inflammatory Herbal Medicines.

    PubMed

    Ghasemian, Mona; Owlia, Sina; Owlia, Mohammad Bagher

    2016-01-01

    Medicinal plants and their secondary metabolites are progressively used in the treatment of diseases as a complementary medicine. Inflammation is a pathologic condition that includes a wide range of diseases such as rheumatic and immune-mediated conditions, diabetes, cardiovascular accident, and etcetera. We introduce some herbs which their anti-inflammatory effects have been evaluated in clinical and experimental studies. Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, evening primrose, and Devil's claw are some of the introduced medicinal herbs in this review. Since the treatment of inflammation is not a one-dimensional remedy, this review tries to reach a multidimensional therapeutic approach to inflammation with the help of herbal medicine and modification in lifestyle. PMID:27247570

  14. Corneal reepithelialization and anti-inflammatory agents.

    PubMed Central

    Srinivasan, B D

    1982-01-01

    These studies have demonstrated that nonsteroidal anti-inflammatory agents (cyclooxygenase and lipoxygenase inhibitors) can inhibit PMN arrival in the tear fluid following corneal injury but do not inhibit the reepithelialization either by corneal epithelial cells or by conjunctival epithelial cells. Therefore, they can be used safely in ocular inflammatory conditions even when corneal epithelial defects are present. Corticosteroids, on the other hand, inhibit reepithelialization by conjunctival epithelial cells and not by corneal epithelial cells in the doses tested. This inhibition does not occur with pretreatment prior to injury, suggesting that corticosteroids can be used clinically in conditions that have intact corneal epithelium without fear of slowing down wound healing should epithelial defects occur when not on steroid therapy. Furthermore, the steroid inhibition is temporary since there is a breakthrough in steroid inhibition with time, and occurs only if the steroids have been used shortly after deepithelialization. The steroid inhibition can be reversed by specific steroid antagonist, indicating that the steroid effect is mediated through specific receptors. An exciting and new hypothesis proposes that corticosteroids induce the formation of an inhibitory protein that inhibits the phospholipase enzyme to cause a block in arachidonic acid release from cell membranes. This mechanism of action may also be prevalent in the steroid effect on corneal reepithelialization, and experiments are under way to isolate this inhibitory protein from steroid-treated conjunctival epithelium. This isolation and pharmacologic characterization of this inhibitory protein is of obvious advantage to the field of ophthalmic therapeutics since this protein may have the anti-inflammatory potential of the steroids without their steroid sideeffects. Images FIGURE 3 a FIGURE 3 b PMID:6763806

  15. Anti-Inflammatory and Antioxidant Activities of Salvia fruticosa: An HPLC Determination of Phenolic Contents.

    PubMed

    Boukhary, Rima; Raafat, Karim; 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

  16. Anti-Inflammatory Properties and Chemical Characterization of the Essential Oils of Four Citrus Species.

    PubMed

    Amorim, Jorge Luis; Simas, Daniel Luiz Reis; Pinheiro, Mariana Martins Gomes; Moreno, Daniela Sales Alviano; Alviano, Celuta Sales; da Silva, Antonio Jorge Ribeiro; Fernandes, Patricia Dias

    2016-01-01

    Citrus fruits have potential health-promoting properties and their essential oils have long been used in several applications. Due to biological effects described to some citrus species in this study our objectives were to analyze and compare the phytochemical composition and evaluate the anti-inflammatory effect of essential oils (EO) obtained from four different Citrus species. Mice were treated with EO obtained from C. limon, C. latifolia, C. aurantifolia or C. limonia (10 to 100 mg/kg, p.o.) and their anti-inflammatory effects were evaluated in chemical induced inflammation (formalin-induced licking response) and carrageenan-induced inflammation in the subcutaneous air pouch model. A possible antinociceptive effect was evaluated in the hot plate model. Phytochemical analyses indicated the presence of geranial, limonene, γ-terpinene and others. EOs from C. limon, C. aurantifolia and C. limonia exhibited anti-inflammatory effects by reducing cell migration, cytokine production and protein extravasation induced by carrageenan. These effects were also obtained with similar amounts of pure limonene. It was also observed that C. aurantifolia induced myelotoxicity in mice. Anti-inflammatory effect of C. limon and C. limonia is probably due to their large quantities of limonene, while the myelotoxicity observed with C. aurantifolia is most likely due to the high concentration of citral. Our results indicate that these EOs from C. limon, C. aurantifolia and C. limonia have a significant anti-inflammatory effect; however, care should be taken with C. aurantifolia. PMID:27088973

  17. Anti-Inflammatory Properties and Chemical Characterization of the Essential Oils of Four Citrus Species

    PubMed Central

    Amorim, Jorge Luis; Simas, Daniel Luiz Reis; Pinheiro, Mariana Martins Gomes; Moreno, Daniela Sales Alviano; Alviano, Celuta Sales; da Silva, Antonio Jorge Ribeiro

    2016-01-01

    Citrus fruits have potential health-promoting properties and their essential oils have long been used in several applications. Due to biological effects described to some citrus species in this study our objectives were to analyze and compare the phytochemical composition and evaluate the anti-inflammatory effect of essential oils (EO) obtained from four different Citrus species. Mice were treated with EO obtained from C. limon, C. latifolia, C. aurantifolia or C. limonia (10 to 100 mg/kg, p.o.) and their anti-inflammatory effects were evaluated in chemical induced inflammation (formalin-induced licking response) and carrageenan-induced inflammation in the subcutaneous air pouch model. A possible antinociceptive effect was evaluated in the hot plate model. Phytochemical analyses indicated the presence of geranial, limonene, γ-terpinene and others. EOs from C. limon, C. aurantifolia and C. limonia exhibited anti-inflammatory effects by reducing cell migration, cytokine production and protein extravasation induced by carrageenan. These effects were also obtained with similar amounts of pure limonene. It was also observed that C. aurantifolia induced myelotoxicity in mice. Anti-inflammatory effect of C. limon and C. limonia is probably due to their large quantities of limonene, while the myelotoxicity observed with C. aurantifolia is most likely due to the high concentration of citral. Our results indicate that these EOs from C. limon, C. aurantifolia and C. limonia have a significant anti-inflammatory effect; however, care should be taken with C. aurantifolia. PMID:27088973

  18. 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

  19. Anti-inflammatory activity of D-002: an active product isolated from beeswax.

    PubMed

    Carbajal, D; Molina, V; Valdés, S; Arruzazabala, M L; Más, R; Magraner, J

    1998-10-01

    D-002 is a natural mixture of high molecular weight alcohols isolated and purified from beeswax, which contains triacontanol among its main components. This study was undertaken to investigate the anti-inflammatory effects of D-002 administered by the oral route in two animal models commonly used in the pharmacological screening of anti-inflammatory drugs. D-002 administered orally to rats (100 and 200 mg/kg) produced a mild but significant reduction of exudate volume in carrageenan-induced pleuritic inflammation that was accompanied by a marked and significant decrease of leukotriene B4 (LTB4) levels in the exudate. D-002 (25, 50 and 200 mg/kg) also significantly diminished the granuloma weight in the cotton pellet granuloma in rats. In both cases, D-002 was less effective than indomethacin, which was used as an established anti-inflammatory reference drug. On the other hand, D-002 administered from 25-1000 mg/kg did not induce erosions or gastromucosal lesions in rats, which differs from results usually obtained with non steroidal anti-inflammatory drugs. These results indicate that D-002 is a mild anti-inflammatory agent without any ulcerogenic effect associated. The results suggest that these effects are probably not mediated through an inhibition of cyclooxygenase, but a reduction in LTB4 levels induced by D-002 could explain these results. PMID:9849648

  20. Sol-gel-derived magnetic SiO2/TiO2 nanocomposite reinforced hollow fiber-solid phase microextraction for enrichment of non-steroidal anti-inflammatory drugs from human hair prior to high performance liquid chromatography.

    PubMed

    Es'haghi, Zarrin; Esmaeili-Shahri, Effat

    2014-10-01

    Hollow fiber-solid phase micro-extraction (HF-SPME) technique containing sol-gel-derived Fe3O4/SiO2/TiO2 core-double shell nanocomposite as a novel high efficiency sorbent, coupled with high performance liquid chromatography was used to extraction and determination of six non-steroidal anti-inflammatory drugs; acetylsalicylic acid, naproxen, piroxicam, diclofenac, indomethacin and mefenamic acid, in hair samples. First, magnetite nanoparticles (Fe3O4-NPs) were synthesized by chemical co-precipitation of Fe(II) and Fe(III) ions (where the ratio of Fe(II) to Fe(III) is 1:2 and a non-oxidizing environment), in alkaline medium to produce magnetite particles. Subsequently, surface of Fe3O4-NPs was modified with SiO2 and TiO2 using layer-by-layer chemical technique. A core-shell structure of Fe3O4/SiO2/TiO2 composite was prepared by coating magnetite core particles with silica and titania layers. In the proposed method, NSAIDs were extracted by the synthesized nanocomposite and analyzed by HPLC. The parameters affecting the efficiency of magnetic nanoparticle (MNPs) assisted HF-SPME were investigated and optimized. The method validation was included and satisfying results with high pre-concentration factors (405 up to 2450) were obtained. It owes large surface area and porosity of the nano-adsorbent. Under the optimal conditions, the method detection limits (S/N=3) were in the range of 0.01-0.10μgml(-1) and the limits of quantification (S/N=10) between 0.04 and 0.30μgml(-1). Relative standard deviations were 3.09-6.61%. Eventually, the method was successfully applied to human hair after administration of NSAIDs. PMID:25464107

  1. A novel anti-inflammatory mechanism of high density lipoprotein through up-regulating annexin A1 in vascular endothelial cells.

    PubMed

    Pan, Bing; Kong, Jinge; Jin, Jingru; Kong, Jian; He, Yubin; Dong, Shuying; Ji, Liang; Liu, Donghui; He, Dan; Kong, Liming; Jin, David K; Willard, Belinda; Pennathur, Subramaniam; Zheng, Lemin

    2016-06-01

    High density lipoprotein (HDL) as well as annexin A1 have been reported to be associated with cardiovascular protection. However, the correlation between HDL and annexin A1 was still unknown. In this study, HDL increased endothelial annexin A1 and prevented the decrease of annexin A1 in TNF-α-activated endothelial cells in vitro and in vivo, and above effects were attenuated after knockdown of annexin A1. Annexin A1 modulation affected HDL-mediated inhibition of monocyte adhesion to TNF-α-activated endothelium (45.2±13.7% decrease for annexin A1 RNA interference; 78.7±16.3% decrease for anti-Annexin A1 antibody blocking; 11.2±6.9% increase for Ad-ANXA1 transfection). Additionally, HDL up-regulated annexin A1 through scavenger receptor class B type I, involving ERK, p38MAPK, Akt and PKC signaling pathways, and respective inhibitors of these pathways attenuated HDL-induced annexin A1 expression as well as impaired HDL-mediated inhibition of monocyte-endothelial cell adhesion. Apolipoprotein AI also increased annexin A1 and activated similar signaling pathways. Endothelial annexin A1 from apolipoprotein AI knockout mice was decreased in comparison to that from wild type mice. Finally, HDL-induced annexin A1 inhibited cell surface VCAM-1, ICAM-1 and E-selectin, and secretion of MCP-1, IL-8, VCAM-1 and E-selectin, thereby inhibiting monocyte adhesion. PMID:27012521

  2. [Anti-inflammatory effects of prednisolone 17-valerate 21-acetate, a new topical corticosteroid (author's transl)].

    PubMed

    Wada, Y; Etoh, Y; Ohira, A; Ikuta, J; Kato, Y; Sano, N

    1980-09-01

    Anti-inflammatory activities of prednisolone 17-valerate 21-acetate(PVA) were studied in rats and guinea pigs and results compared with data on topical steroids, such as betamethasone 17-valerate(BV) and hydrocortisone 17-butyrate(HB). PVA given subcutaneously inhibited dose-dependently carrageenin- and kaolin-induced edema. These anti-inflammatory activities of PVA were the weakest among the steroids tested. A local administration of PVA into the site of inflammation, however, had the same or more potent activities than BV and HB in carrageenin-induced edema and paper disk granuloma. Topical application of PVA ointment in carrageenin-induced edema exhibited an inhibitory effect which was dependent on the concentrations (0.1-1.0%). The anti-inflammatory activity of 0.3% PVA ointment was equivalent to that of 0.12% BV ointment. For the other experimental models, i.e. exuberant granulation, croton oil-induced ear edema, passive cutaneous anaphylaxis and tuberculin-induced delayed type hypersensitivity, the activity of 0.3% PVA ointment was the same or somewhat more potent than 0.12% BV and 0.1% HB ointments. The thymolytic activity of PVA ointment in the exuberant granulation model was similar to the activity seen with HB ointment and weaker than of BV ointment. Thus, the anti-inflammatory activities of PVA were equivalent to or more potent than those of BV and HB, and with topical application, the systemic effect of PVA was weaker than the other steroids examined. PMID:7203275

  3. Repositioning drugs for inflammatory disease – fishing for new anti-inflammatory agents

    PubMed Central

    Hall, Christopher J.; Wicker, Sophie M.; Chien, An-Tzu; Tromp, Alisha; Lawrence, Lisa M.; Sun, Xueying; Krissansen, Geoffrey W.; Crosier, Kathryn E.; Crosier, Philip S.

    2014-01-01

    Inflammation is an important and appropriate host response to infection or injury. However, dysregulation of this response, with resulting persistent or inappropriate inflammation, underlies a broad range of pathological processes, from inflammatory dermatoses to type 2 diabetes and cancer. As such, identifying new drugs to suppress inflammation is an area of intense interest. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat inflammation. Traditional drug discovery, including structure-based drug design, have largely fallen short of satisfying this unmet need. With faster development times and reduced safety and pharmacokinetic uncertainty, drug repositioning – the process of finding new uses for existing drugs – is emerging as an alternative strategy to traditional drug design that promises an improved risk-reward trade-off. Using a zebrafish in vivo neutrophil migration assay, we undertook a drug repositioning screen to identify unknown anti-inflammatory activities for known drugs. By interrogating a library of 1280 approved drugs for their ability to suppress the recruitment of neutrophils to tail fin injury, we identified a number of drugs with significant anti-inflammatory activity that have not previously been characterized as general anti-inflammatories. Importantly, we reveal that the ten most potent repositioned drugs from our zebrafish screen displayed conserved anti-inflammatory activity in a mouse model of skin inflammation (atopic dermatitis). This study provides compelling evidence that exploiting the zebrafish as an in vivo drug repositioning platform holds promise as a strategy to reveal new anti-inflammatory activities for existing drugs. PMID:25038060

  4. Anti-inflammatory effects of methoxyphenolic compounds on human airway cells

    PubMed Central

    2012-01-01

    Background The respiratory epithelium plays a central role in the inflammatory response in asthma and other diseases. Methoxyphenolic compounds are purported to be effective anti-inflammatory agents, but their effects on the airway epithelium have not been well characterized. Methods Human airway cells were stimulated with TNF-α in the presence or absence of 4-substituted methoxyphenols and resveratrol. The expression of various cytokines was measured by qPCR, ELISAs, and protein arrays. Reactive oxygen species (ROS) production was measured with a reactive fluorescent probe (3',6'-diacetate-2',7'-dichlorofluorescein). Activation of NF-κB was measured by nuclear translocation and phosphorylation. Ribonuclear protein association with mRNA was assessed with a biotin-RNA affinity isolation assay. Results Multiple inflammatory mediators were inhibited by methoxyphenols, including: CCL2, CCL5, IL-6, IL-8, ICAM-1, MIF, CXCL1, CXCL10, and Serpin E1. IC50 values were obtained for each compound that showed significant anti-inflammatory activity: diapocynin (20.3 μM), resveratrol (42.7 μM), 2-methoxyhydroquinone (64.3 μM), apocynin (146.6 μM), and 4-amino-2-methoxyphenol (410 μM). The anti-inflammatory activity did not correlate with inhibition of reactive oxygen species production or NF-κB activation. However, methoxyphenols inhibited binding of the RNA-binding protein HuR to mRNA, indicating that they may act post-transcriptionally. Conclusions Methoxyphenols demonstrate anti-inflammatory activity in human airway cells. More potent compounds that act via similar mechanisms may have therapeutic potential as novel anti-inflammatory agents. PMID:22414048

  5. Evaluation of antinociceptive and anti-inflammatory activity of hydromethanol extract of Cocos nucifera L.

    PubMed

    Naskar, Sagar; Mazumder, U K; Pramanik, G; Saha, P; Haldar, P K; Gupta, M

    2013-02-01

    Cocos nucifera L. (family: arecaceae) is generally straight unbranched plant, traditionally cultivated for its fruit (coconut) in home gardens. In the present study, anti-inflammatory and antinociceptive (analgesic) activity of hydromethanol extract of Cocos nucifera L. (HECN) was evaluated in animal models. HECN showed significant (p < 0.05) and dosedependent anti-inflammatory activity in carrageenan induced paw oedema models of inflammation and the result was comparable with the standard drug diclofenac. In addition, the extract also showed highly significant (p < 0.01) antinociceptive activity. HECN treated group showed increase in the reaction time in hot plate method and decrease the writhing induced by acetic acid in mice when compared with control group animal. The anti-inflammatory and antinociceptive activity observed in the present study could be attributed largely to the presence of its antioxidant phytoconstituents such as flavonoid, saponin and polyphenols. PMID:22527352

  6. A RECOMBINANT IgG Fc THAT RECAPITULATES THE ANTI-INFLAMMATORY ACTIVITY OF IVIG

    PubMed Central

    Anthony, Robert M.; Nimmerjahn, Falk; Ashline, David J.; Reinhold, Vernon N.; Paulson, James C.; Ravetch, Jeffrey V.

    2008-01-01

    High doses of monomeric IgG purified from pooled human plasma confer anti-inflammatory activity for a wide variety of autoimmune diseases. The heterogeneity of IVIG, derived from its Fab specificity, IgG subclass distribution and variable glycosylation have confounded efforts to develop a recombinant substitute for this blood-derived product. Recent studies have demonstrated that this paradoxical anti-inflammatory activity of IgG is completely dependent on sialylation of the N-linked glycan of the IgG Fc fragment. Determining the precise glycan requirements for this anti-inflammatory activity allowed appropriate glycan engineering of an IgG1 Fc fragment, leading to the generation of a fully recombinant, sialylated IgG1 Fc with greatly enhanced potency. PMID:18420934

  7. Anti-inflammatory and immunomodulatory properties of Carica papaya.

    PubMed

    Pandey, Saurabh; Cabot, Peter J; Shaw, P Nicholas; Hewavitharana, Amitha K

    2016-07-01

    Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking. PMID:27416522

  8. Luteolin exhibits anti-inflammatory effects by blocking the activity of heat shock protein 90 in macrophages.

    PubMed

    Chen, Dan; Bi, Aijing; Dong, Xiaoliang; Jiang, Yi; Rui, Bing; Liu, Jinjiao; Yin, Zhimin; Luo, Lan

    2014-01-01

    Septic diseases represent the prevalent complications in intensive care units. Luteolin, a plant flavonoid, has potent anti-inflammatory properties; however, the molecular mechanism beneath luteolin mediated immune modulation remains unclear. Here in vitro investigations showed that luteolin dose-dependently inhibited LPS-triggered secretion and relocation of high mobility group B-1 (HMGB1) and LPS-induced production of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) in macrophages. The mechanism analysis demonstrated that luteolin reduced the release of HMGB1 through destabilizing c-Jun and suppressed HMGB1-induced aggravation of inflammatory cascade through reducing Akt protein level. As an inhibitor of Hsp90, luteolin destabilized Hsp90 client protein c-Jun and Akt. In vivo investigations showed that luteolin effectively protected mice from lipopolysaccharide (LPS)-induced lethality. In conclusion, the present study suggested that luteolin may act as a potential therapeutic reagent for treating septic diseases. PMID:24321097

  9. Anti-inflammatory effects of escin are correlated with the glucocorticoid receptor/NF-κB signaling pathway, but not the COX/PGF2α signaling pathway.

    PubMed

    Wang, Hongsheng; Zhang, Leiming; Jiang, Na; Wang, Zhenhua; Chong, Yating; Fu, Fenghua

    2013-08-01

    In China, escin has been widely used in the clinic as a potent anti-inflammatory drug. Previous studies have indicated that escin exerts its anti-inflammatory effect by enhancing the release of glucocorticoids (GCs) and prostaglandin-F2α (PGF2α), and this has been documented in the drug description. However, our previous studies demonstrated that escin did not increase the secretion of GCs, but instead elevated the protein expression of the GC receptor (GR), which may have repressed nuclear factor (NF)-κB-mediated gene expression. The aim of this study was to determine the functions of NF-κB and PGF2α with regard to the anti-inflammatory effect of escin. We investigated the anti-inflammatory effects of dexamethasone, diclofenac and escin against carrageenan-induced paw edema in rats, and observed that escin exerted a GC-like anti-inflammatory effect. In addition, we studied the role of PGF2α in the anti-inflammatory effect exerted by escin in an acetic acid-induced capillary permeability model in mice. The results revealed that the coadministration of escin and diclofenac, a potent prostaglandin-synthesis inhibitor, did not affect the anti-inflammatory effect of escin. Furthermore, we investigated the function of NF-κB with regard to the anti-inflammatory effect exerted by escin in lipopolysaccharide (LPS)-treated mice, and demonstrated that escin significantly inhibited the expression of NF-κB. These results suggest that escin has a GC-like anti-inflammatory effect, and that its mechanisms may be correlated with the GC receptor/NF-κB signaling pathway, but not the COX/PGF2α signaling pathway. PMID:24137201

  10. Anti-inflammatory effects of escin are correlated with the glucocorticoid receptor/NF-κB signaling pathway, but not the COX/PGF2α signaling pathway

    PubMed Central

    WANG, HONGSHENG; ZHANG, LEIMING; JIANG, NA; WANG, ZHENHUA; CHONG, YATING; FU, FENGHUA

    2013-01-01

    In China, escin has been widely used in the clinic as a potent anti-inflammatory drug. Previous studies have indicated that escin exerts its anti-inflammatory effect by enhancing the release of glucocorticoids (GCs) and prostaglandin-F2α (PGF2α), and this has been documented in the drug description. However, our previous studies demonstrated that escin did not increase the secretion of GCs, but instead elevated the protein expression of the GC receptor (GR), which may have repressed nuclear factor (NF)-κB-mediated gene expression. The aim of this study was to determine the functions of NF-κB and PGF2α with regard to the anti-inflammatory effect of escin. We investigated the anti-inflammatory effects of dexamethasone, diclofenac and escin against carrageenan-induced paw edema in rats, and observed that escin exerted a GC-like anti-inflammatory effect. In addition, we studied the role of PGF2α in the anti-inflammatory effect exerted by escin in an acetic acid-induced capillary permeability model in mice. The results revealed that the coadministration of escin and diclofenac, a potent prostaglandin-synthesis inhibitor, did not affect the anti-inflammatory effect of escin. Furthermore, we investigated the function of NF-κB with regard to the anti-inflammatory effect exerted by escin in lipopolysaccharide (LPS)-treated mice, and demonstrated that escin significantly inhibited the expression of NF-κB. These results suggest that escin has a GC-like anti-inflammatory effect, and that its mechanisms may be correlated with the GC receptor/NF-κB signaling pathway, but not the COX/PGF2α signaling pathway. PMID:24137201

  11. Antioxidant, anti-inflammatory and anti-hyperglycaemic activities of heterocyclic homoprostanoid derivatives.

    PubMed

    Manohara Reddy, S A; Mudgal, Jayesh; Bansal, Punit; Vasanthraju, S G; Srinivasan, K K; Rao, C Mallikarjuna; Gopalan Kutty, N

    2011-01-01

    A series of 19 heterocyclic homoprostanoids were synthesized from easily available oleic and ricinoleic acids and evaluated for their possible antioxidant, anti-inflammatory and anti-hyperlipidaemic activities. Compounds with thioxo- and oxoimidazole ring (1) and (2) have shown potent antioxidant activity with IC(50) values 0.23±0.09 and 0.41±0.01mM comparable with standard ascorbic acid. Compound (3) with a quinoxaline ring showed maximum inhibition of BSA denaturation at 1mM concentration and comparable with standard diclofenac. Incorporation of electron withdrawing substitutions like chloro- and nitro-groups in the quinoxaline ring has resulted in an increase anti-inflammatory activity. Test compounds (3), (3a) and (3c) showed modest inhibition of DPP-IV in vitro. However, the unsubstituted quinoxaline (3) and substituted quinoxalines (3b and 3c) reduced plasma glucose levels indicating the presence of hypoglycemic activity. PMID:21146413

  12. Anti-inflammatory and cytotoxic neoflavonoids and benzofurans from Pterocarpus santalinus.

    PubMed

    Wu, Shou-Fang; Chang, Fang-Rong; Wang, Sheng-Yang; Hwang, Tsong-Long; Lee, Chia-Lin; Chen, Shu-Li; Wu, Chin-Chung; Wu, Yang-Chang

    2011-05-27

    Five new benzofurans, pterolinuses A-E (1-5), six new neoflavonoids, pterolinuses F-J (8-13), and five known compounds (6, 7, 14-16) were isolated from an extract of Pterocarpus santalinus heartwood. All new structures were elucidated by spectroscopic methods, and configurations were confirmed by CD spectral data and optical rotation values. The isolates were evaluated for anti-inflammatory and cytotoxic activities. Six compounds (1, 2, 4, 6, 7, and 15) showed significant inhibition in at least one anti-inflammatory assay. Compound 2 showed the best selective effect against superoxide anion generation in human neutrophils with, an IC50 value of 0.19 μg/mL, and was 6.2-fold more potent than the positive control LY294002. Compound 14 showed the highest cytotoxicity against Ca9-22 cancer cells, with an IC50 value of 0.46 μg/mL. PMID:21488654

  13. Anti-leishmanial, anti-inflammatory and antimicrobial activities of phenolic derivatives from Tibouchina paratropica.

    PubMed

    Tracanna, María I; Fortuna, Antonio M; Cárdenas, Angel V Contreras; Marr, Alexandra K; McMaster, W Robert; Gómez-Velasco, Anaximandro; Sánchez-Arreola, Eugenio; Hernández, Luis Ricardo; Bach, Horacio

    2015-03-01

    A new phenolic derivative, 2,8-dihydroxy-7H-furo[2,3-f]chromen-7-one (1), together with isoquercitrin (2), was isolated from the aerial parts of Tibouchina paratropica. Compound structures were elucidated by spectroscopic methods. Both compounds show antimicrobial activity towards a panel of bacterial and fungal pathogens, and compound 1 displayed potent anti-parasitic activity against Leishmania donovani (IC50  = 0.809 µg/mL). In addition, an 85% reduction in the secretion of the pro-inflammatory cytokine IL-6 was recorded when macrophages challenged with lipopolysaccharide were exposed to compound 1, but no effect on the anti-inflammatory IL-10 was observed. Compound 2 showed neither anti-parasitic nor anti-inflammatory properties. In addition, no cytotoxic activities were observed against the human-derived macrophage THP-1 cells. PMID:25417600

  14. Anti-Inflammatory Constituents from Bidens frondosa.

    PubMed

    Le, Jiamei; Lu, Wenquan; Xiong, Xiaojuan; Wu, Zhijun; Chen, Wansheng

    2015-01-01

    A new polyacetylene glucoside (3E,5E,11E)-tridecatriene-7,9-diyne-1,2,13-triol-2-O-β-D-glucopyranoside (1), a new phenylpropanoid glucoside 2'-butoxyethylconiferin (2), and a new flavonoid glycoside 8,3',4'-trihydroxyflavone-7-O-(6''-O-p-coumaroyl)-β-D-glucopyranoside (3), have been isolated from Bidens frondosa together with fifty-three known compounds 4-56. The structures of these compounds were established by spectroscopic methods. mainly ESIMS, 1D- and 2D-NMR spectroscopic data. and comparison with literature data. Compounds 1-34, 36, 39, 43, 47, 51, and 52 were tested for inhibition of nuclear factor kappa B (NF-κB) in 293-NF-κB-luciferase report cell line induced by lipopolysaccharide (LPS), and compounds 1, 2, 3, 9, 15, 21, 24 and 51 were tested for the production of TNF-α, IL-1β, IL-6, IL-10 in RAW 264.7 macrophages induced by LPS. In conclusion, the isolated compounds 1, 2, 3, 9, 15, 21, 24 and 51 exhibited significant activity in anti-inflammatory activity assays. PMID:26473814

  15. Sterols and triterpenoids as potential anti-inflammatories: Molecular docking studies for binding to some enzymes involved in inflammatory pathways.

    PubMed

    Loza-Mejía, Marco A; Salazar, Juan Rodrigo

    2015-11-01

    Triterpenes and sterols are good candidates for the development of anti-inflammatory drugs and use in chemoprevention or chemotherapy of cancer via the interaction with therapeutic targets related to inflammation, such as COX-1 and -2; LOX-5; MPO, PLA2 and i-NOS. In this study, we use molecular docking to evaluate the potential binding of a database of selected sterol and triterpenoid compounds with several skeletons against enzymes related to inflammation to propose structural requirements beneficial for anti-inflammatory activity that can be used for the design of more potent and selective anti-inflammatory and antitumor drugs. Our results suggest that the substitution pattern is important and that there is an important relationship between the class of sterol or triterpenoid skeleton and enzyme binding. PMID:26342572

  16. Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity

    PubMed Central

    Washburn, Nathaniel; Schwab, Inessa; Ortiz, Daniel; Bhatnagar, Naveen; Lansing, Jonathan C.; Medeiros, Amy; Tyler, Steven; Mekala, Divya; Cochran, Edward; Sarvaiya, Hetal; Garofalo, Kevin; Meccariello, Robin; Meador, James W.; Rutitzky, Laura; Schultes, Birgit C.; Ling, Leona; Avery, William; Nimmerjahn, Falk; Manning, Anthony M.; Kaundinya, Ganesh V.; Bosques, Carlos J.

    2015-01-01

    Despite the beneficial therapeutic effects of intravenous immunoglobulin (IVIg) in inflammatory diseases, consistent therapeutic efficacy and potency remain major limitations for patients and physicians using IVIg. These limitations have stimulated a desire to generate therapeutic alternatives that could leverage the broad mechanisms of action of IVIg while improving therapeutic consistency and potency. The identification of the important anti-inflammatory role of fragment crystallizable domain (Fc) sialylation has presented an opportunity to develop more potent Ig therapies. However, translating this concept to potent anti-inflammatory therapeutics has been hampered by the difficulty of generating suitable sialylated products for clinical use. Therefore, we set out to develop the first, to our knowledge, robust and scalable process for generating a well-qualified sialylated IVIg drug candidate with maximum Fc sialylation devoid of unwanted alterations to the IVIg mixture. Here, we describe a controlled enzymatic, scalable process to produce a tetra-Fc–sialylated (s4-IVIg) IVIg drug candidate and its qualification across a wide panel of analytic assays, including physicochemical, pharmacokinetic, biodistribution, and in vivo animal models of inflammation. Our in vivo characterization of this drug candidate revealed consistent, enhanced anti-inflammatory activity up to 10-fold higher than IVIg across different animal models. To our knowledge, this candidate represents the first s4-IVIg suitable for clinical use; it is also a valuable therapeutic alternative with more consistent and potent anti-inflammatory activity. PMID:25733881

  17. Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2.

    PubMed

    Graff, Emily C; Fang, Han; Wanders, Desiree; Judd, Robert L

    2016-02-01

    The hydroxycarboxylic acid receptors (HCA1-3) are a family of G-protein-coupled receptors that are critical for sensing endogenous intermediates of metabolism. All three receptors are predominantly expressed on adipocytes and mediate anti-lipolytic effects. In addition to adipocytes, HCA2 is highly expressed on immune cells, including macrophages, monocytes, neutrophils and dermal dendritic cells, among other cell types. The endogenous ligand for HCA2 is beta-hydroxybutyrate (β-OHB), a ketone body produced by the liver through β-oxidation when an individual is in a negative energy balance. Recent studies demonstrate that HCA2 mediates profound anti-inflammatory effects in a variety of tissues, indicating that HCA2 may be an important therapeutic target for treating inflammatory disease processes. This review summarizes the roles of HCA2 on inflammation in a number of tissues and clinical states. PMID:26773933

  18. Black Cumin (Nigella sativa) and Its Active Constituent, Thymoquinone: An Overview on the Analgesic and Anti-inflammatory Effects.

    PubMed

    Amin, Bahareh; Hosseinzadeh, Hossein

    2016-01-01

    For many centuries, seeds of Nigella sativa (black cumin), a dicotyledon of the Ranunculaceae family, have been used as a seasoning spice and food additive in the Middle East and Mediterranean areas. Traditionally, the plant is used for asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness, and gastrointestinal disturbances. The literature regarding the biological activities of seeds of this plant is extensive, citing bronchodilative, anti-inflammatory, antinociceptive, antibacterial, hypotensive, hypolipidemic, cytotoxic, antidiabetic, and hepatoprotective effects. The active ingredients of N. sativa are mainly concentrated in the fixed or essential oil of seeds, which are responsible for most health benefits. This review will provide all updated reported activities of this plant with an emphasis on the antinociceptive and anti-inflammatory effects. Results of various studies have demonstrated that the oil, extracts, and their active ingredients, in particular, thymoquinone, possess antinociceptive and anti-inflammatory effects, supporting the common folk perception of N. Sativa as a potent analgesic and anti-inflammatory agent. Many protective properties are attributed to reproducible radical scavenging activity as well as an interaction with numerous molecular targets involved in inflammation, including proinflammatory enzymes and cytokines. However, there is a need for further investigations to find out the precise mechanisms responsible for the antinociceptive and anti-inflammatory effects of this plant and its active constituents. PMID:26366755

  19. Estimation of total phenolic content, in-vitro antioxidant and anti-inflammatory activity of flowers of Moringa oleifera

    PubMed Central

    Alhakmani, Fatma; Kumar, Sokindra; Khan, Shah Alam

    2013-01-01

    Objective To evaluate and compare the antioxidant potential and anti-inflammatory activity of ethanolic extract of flowers of Moringa oleifera (M. oleifera) grown in Oman. Methods Flowers of M. oleifera were collected in the month of December 2012 and identified by a botanist. Alcoholic extract of the dry pulverized flowers of M. oleifera were obtained by cold maceration method. The ethanolic flower extract was subjected to preliminary phytochemical screening as the reported methods. Folin-Ciocalteu reagent was used to estimate total phenolic content. DPPH was used to determine in-vitro antioxidant activity and anti-inflammatory activity of flowers was investigated by protein denaturation method. Results Phytochemical analysis of extract showed presence of major classes of phytochemicals such as tannins, alkaloids, flavonoids, cardiac glycosides etc. M. oleifera flowers were found to contain 19.31 mg/g of gallic acid equivalent of total phenolics in dry extract but exhibited moderate antioxidant activity. The anti-inflammatory activity of plant extract was significant and comparable with the standard drug diclofenac sodium. Conclusions The results of our study suggest that flowers of M. oleifera possess potent anti-inflammatory activity and are also a good source of natural antioxidants. Further study is needed to identify the chemical compounds responsible for their anti-inflammatory activity. PMID:23905019

  20. Anti-inflammatory activity of intravenous immunoglobulins protects against West Nile virus encephalitis

    PubMed Central

    Srivastava, Ruchi; Ramakrishna, Chandran

    2015-01-01

    West Nile virus (WNV), an important global human pathogen, targets neurons to cause lethal encephalitis, primarily in elderly and immunocompromised patients. Currently, there are no approved therapeutic agents or vaccines to treat WNV encephalitis. Recent studies have suggested that inflammation is a major contributor to WNV encephalitis morbidity. In this study we evaluated the use of IVIG (intravenous immunoglobulins – a clinical product comprising pooled human IgG) as an anti-inflammatory treatment in a model of lethal WNV infection. We report here that IVIG and pooled human WNV convalescent sera (WNV-IVIG) inhibited development of lethal WNV encephalitis by suppressing central nervous system (CNS) infiltration by CD45high leukocytes. Pathogenic Ly6Chigh CD11b+ monocytes were the major infiltrating subset in the CNS of infected control mice, whereas IVIG profoundly reduced infiltration of these pathogenic Ly6Chigh monocytes into the CNS of infected mice. Interestingly, WNV-IVIG was more efficacious than IVIG in controlling CNS inflammation when mice were challenged with a high-dose inoculum (105 versus 104 p.f.u.) of WNV. Importantly, adsorption of WNV E-glycoprotein neutralizing antibodies did not abrogate IVIG protection, consistent with virus neutralization not being essential for IVIG protection. These findings confirmed the potent immunomodulatory activity of generic IVIG, and emphasized its potential as an effective immunotherapeutic drug for encephalitis and other virus induced inflammatory diseases. PMID:25667322

  1. Anti-inflammatory properties of quebecol and its derivatives.

    PubMed

    Cardinal, Sébastien; Azelmat, Jabrane; Grenier, Daniel; Voyer, Normand

    2016-01-15

    Herein we report our results on the anti-inflammatory activity of quebecol, a polyphenolic compound discovered in maple syrup. Bioassays demonstrated that quebecol has an anti-inflammatory effect on LPS-induced NF-κB activation and inhibits the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. We also prepared and tested precursors of quebecol and its derivatives corresponding to its substructures of interest, with the aim to study the structure-activity relationships. Comparing the results obtained for all tested compounds allowed the identification of the main moiety responsible for the anti-inflammatory activity of quebecol. PMID:26691759

  2. Acai juice attenuates atherosclerosis in apoe deficient mice through antioxidant and anti-inflammatory activities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective - Acai fruit pulp has received much attention because of its high antioxidant capacity and potential anti-inflammatory effects. In this study, athero-protective effects of açaí juice were investigated in apolipoprotein E deficient (apoE -/-) mice. Methods and Results - ApoE-/- mice were f...

  3. Phosphorylation site analysis of the anti-inflammatory and mRNA-destabilizing protein tristetraprolin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tristetraprolin (TTP/TIS11/ZFP36) is a member of the CCCH zinc finger proteins, and is an anti-inflammatory protein. Mice deficient in TTP develop a profound inflammatory syndrome with erosive arthritis, autoimmunity, and myeloid hyperplasia. TTP binds to AU-rich elements with high affinity for UUAU...

  4. Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites.

    PubMed

    Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I

    2011-01-01

    Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) to lipoxin A₄ (LXA₄) and 15-epi-LXA₄. However, it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE₂, TXB₂ and leukotriene B₄ (LTB₄) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE₂, but increased LTB₄, LXA₄ and 15-epi-LXA₄ concentrations. Both doses attenuated the LPS effects on PGE₂, and TXB₂. The increments in LXA₄ and 15-epi-LXA₄ caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA₄ and 15-epi-LXA₄ and reduce pro-inflammatory PGE₂ and TXB₂ suggests considering aspirin further for treating clinical neuroinflammation. PMID:20981485

  5. Novel chimeric peptide with enhanced cell specificity and anti-inflammatory activity.

    PubMed

    Kim, Young-Min; Kim, Nam-Hong; Lee, Jong-Wan; Jang, Jin-Sun; Park, Yung-Hoon; Park, Seong-Cheol; Jang, Mi-Kyeong

    2015-07-31

    An antimicrobial peptide (AMP), Hn-Mc, was designed by combining the N-terminus of HPA3NT3 and the C-terminus of melittin. This chimeric AMP exhibited potent antibacterial activity with low minimal inhibitory concentrations (MICs), ranging from 1 to 2 μM against four drug-susceptible bacteria and ten drug-resistant bacteria. Moreover, the hemolysis and cytotoxicity was reduced significantly compared to those of the parent peptides, highlighting its high cell selectivity. The morphological changes in the giant unilamellar vesicles and bacterial cell surfaces caused by the Hn-Mc peptide suggested that it killed the microbial cells by damaging the membrane envelope. An in vivo study also demonstrated the antibacterial activity of the Hn-Mc peptide in a mouse model infected with drug-resistant bacteria. In addition, the chimeric peptide inhibited the expression of lipopolysaccharide (LPS)-induced cytokines in RAW 264.7 cells by preventing the interaction between LPS and Toll-like receptors. These results suggest that this chimeric peptide is an antimicrobial and anti-inflammatory candidate as a pharmaceutic agent. PMID:26028561

  6. Synthesis, anti-inflammatory, analgesic and COX-1/2 inhibition activities of anilides based on 5,5-diphenylimidazolidine-2,4-dione scaffold: Molecular docking studies.

    PubMed

    Abdel-Aziz, Alaa A-M; El-Azab, Adel S; Abou-Zeid, Laila A; ElTahir, Kamal Eldin H; Abdel-Aziz, Naglaa I; Ayyad, Rezk R; Al-Obaid, Abdulrahman M

    2016-06-10

    The design, synthesis and pharmacological activities of a group of 5,5-diphenylimidazolidine-2,4-dione bearing anilide, phenacyl and benzylidene fragments 2-27 were reported. The prepared 5,5-diphenylimidazolidine-2,4-dione derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay. Among the tested compounds, derivatives 5, 9, 10, 13, and 14 showed significant and potent anti-inflammatory and analgesic activities almost equivalent to reference drug celecoxib. In COX-1/2 inhibition assay, compounds 5, 9, 10 and 14 showed high COX-2 inhibitory activity (IC50 = 0.70 μM, 0.44 μM, 0.61 μM and 0.41 μM; respectively) and selectivity index (SI) range of 142-243 comparable to celecoxib [COX-2 (SI) > 333]. These potent COX-2 inhibitors 9, 10, 13, and 14 were docked into the active site pocket of COX-2 to explore the binding mode and possible interactions of these ligands. PMID:26999325

  7. Suppression of MAPKs/NF-κB Activation Induces Intestinal Anti-Inflammatory Action of Ginsenoside Rf in HT-29 and RAW264.7 Cells.

    PubMed

    Ahn, Sungeun; Siddiqi, Muhammad Hanif; Aceituno, Veronica Castro; Simu, Shakina Yesmin; Yang, Deok Chun

    2016-07-01

    This study investigated the intestinal anti-inflammatory action of ginsenoside Rf in inflammatory bowel disease (IBD). IBD is a chronic inflammatory disease that affects the intestinal tract. It is associated with elevated levels of various inflammatory mediators, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), nitric oxide (NO), and reactive oxygen species (ROS). Ginsenosides, the main active constituents of ginseng, have been reported to exert potent therapeutic effects against diverse diseases. However, ginsenoside Rf treatment for inflammation has not yet been examined. In this study, we evaluated the inhibitory effect of ginsenoside Rf on the inflammatory mediators downstream of p38/NF-kB activation on TNF-α-stimulated intestinal epithelial cells (HT-29) and mouse macrophage cells (RAW264.7). Our results showed that ginsenoside Rf significantly reduced the production of IL-1β, IL-6, TNF-α, NO, and ROS, which are most highly activated in IBD. In addition, ginsenoside Rf significantly suppressed TNF-α/LPS-induced NF-κB transcriptional activity. These results suggest that ginsenoside Rf contains a compound that has potent intestinal anti-inflammatory effects that could be used to treat diseases such as IBD. PMID:27224660

  8. Anti-Inflammatory Activity of Chitooligosaccharides in Vivo

    PubMed Central

    Fernandes, João C.; Spindola, Humberto; de Sousa, Vanessa; Santos-Silva, Alice; Pintado, Manuela E.; Malcata, Francisco Xavier; Carvalho, João E.

    2010-01-01

    All the reports to date on the anti-inflammatory activity of chitooligosaccharides (COS) are mostly based on in vitro methods. In this work, the anti-inflammatory activity of two COS mixtures is characterized in vivo (using balb/c mice), following the carrageenan-induced paw edema method. This is a widely accepted animal model of acute inflammation to evaluate the anti-inflammatory effect of drugs. Our data suggest that COS possess anti-inflammatory activity, which is dependent on dose and, at higher doses, also on the molecular weight. A single dose of 500 mg/kg b.w. weight may be suitable to treat acute inflammation cases; however, further studies are needed to ascertain the effect upon longer inflammation periods as well as studies upon the bioavailability of these compounds. PMID:20631868

  9. Anti-Inflammatory Activity of Delonix regia (Boj. Ex. Hook)

    PubMed Central

    Shewale, Vaishali D.; Deshmukh, Tushar A.; Patil, Liladhar S.; Patil, Vijay R.

    2012-01-01

    The present work was to evaluate the anti-inflammatory activity of Delonix regia leaves (Family: Caesalpiniaceae). The powder of Delonix regia leaves was subjected to extraction with ethanol in soxhlet extractor. The ethanol extract after preliminary phytochemical investigation showed the presence of sterols, triterpenoids, phenolic compounds and flavonoids. The anti-inflammatory activity was studied using carrageenan-induced rat paw edema and cotton pellet granuloma at a three different doses (100, 200, and 400 mg/kg b.w. p.o.) of ethanol extract. The ethanol extract of Delonix regia leaves was exhibited significant anti-inflammatory activity at the dose of 400 mg/kg in both models when compared with control group. Indomethacin (10 mg/kg b.w. p.o) was also shown significant anti-inflammatory activity in both models. PMID:22110490

  10. Study of anti-inflammatory activities of α-D-glucosylated eugenol.

    PubMed

    Zhang, Peng; Zhang, Erli; Xiao, Min; Chen, Chang; Xu, Weijian

    2013-01-01

    Inflammation is an immune response against a variety of noxious stimuli, such as infection, chemicals, and physical injury. Eugenol, a natural phenolic extract, has drawn much attention for its various desirable pharmacological functions and is, therefore, broadly used in our daily life and medical practice. However, further usage of eugenol is greatly limited due to its unwanted properties, such as physicochemical instability, poor solubility, and high-dose cytotoxicity. In hopes of extending its applicability through glycosylation, we previously reported a novel, efficient, and high throughput way to biosynthesize α-D-glucosylated eugenol (α-EG). In this study, we further explored the potential superior properties of α-EG to its parent eugenol in terms of anti-inflammatory activities. We demonstrated that α-EG was an effective anti-inflammatory mediator in both non-cellular and cellular environments. In addition, the non-cellular inhibitory effect of α-EG could be amplified by α-glucosidase, which ubiquitously exists in cytoplasm. Furthermore, α-EG exhibited a superior anti-inflammatory effect to its parent eugenol in a cellular environment. In words, our findings collectively suggest that α-EG is a stronger anti-inflammatory mediator and may thereby serve as a desirable substitute for eugenol and a potential therapeutic prodrug in treating inflammatory diseases in the future. PMID:23325490

  11. Anti-inflammatory activity of polysaccharide from Schizophyllum commune as affected by ultrasonication.

    PubMed

    Du, Bin; Zeng, Huansong; Yang, Yuedong; Bian, Zhaoxiang; Xu, Baojun

    2016-10-01

    Ultrasound treatment was applied to modify the physicochemical properties of an exopolysaccharide from mycelial culture of Schizophyllum commune. Molecular weight (MW) degradation, viscosity and anti-inflammatory property of ultrasonic treated polysaccharide were optimized with response surface methodology. The best ultrasonic parameters were obtained with a three-variable-three-level Box-Behnken design. The optimized conditions for efficient anti-inflammatory activity are initial concentration at 0.4%, ultrasonic power at 600W, and duration of ultrasonic irradiation for 9min. Under these conditions, the nitric oxide inhibition rate was 95±0.03% which agreed closely with the predicted value (96%). Average MW of polysaccharide decreased after ultrasonic treatments. The viscosity of degraded polysaccharide dropped compared with native polysaccharide. The anti-inflammatory activity was improved by ultrasound treatment. The results suggested that ultrasound treatment is an effective approach to decrease the MW of polysaccharide with high anti-inflammatory activity. Ultrasonic treatment is a viable modification technology for high MW polymer materials. PMID:27189700

  12. Novel nonsteroidal anti-inflammatory drugs.

    PubMed

    Boutsen, Y; Esselinckx, W

    1999-01-01

    The authors first briefly review how the concept of COX-2 selectivity was brought to light, then tested against the known gastrotoxicity ranking of currently used NSAIDs, from the old classics to the most recent. One truly selective COX-2 agent--celecoxib--is now being marketed in an ever increasing number of countries. So far it seems to keep its main promises, i.e. high--albeit not total--safety regarding gastrointestinal adverse effects, and undisturbed platelet function. Association with warfarin drugs seems to raise no problems, but one should still be wary of possible renal side-effects. Efficacy, at least as assessed in osteoarthritis and rheumatoid patients, appears satisfactory. However, treatment of intense inflammatory crises, such as gout or ankylosing spondylitis, has not been assessed, as yet. Another COX-2 agent--rofecoxib--is on the brink of being released. Its even more potent COX-2 selectivity raises new issues. What about some COX-1 activity that several authors detected in rheumatic synovitis? On the other hand, in particular circumstances, organs such as the stomach, the kidney and small blood vessels, seem to have their homeostasis partly controlled by COX-2 mechanisms also. These questions should be answered soon, whilst clinical experience with the COX-2 agent builds up. PMID:10692773

  13. Highly potent fibrinolytic serine protease from Streptomyces.

    PubMed

    Uesugi, Yoshiko; Usuki, Hirokazu; Iwabuchi, Masaki; Hatanaka, Tadashi

    2011-01-01

    We introduce a highly potent fibrinolytic serine protease from Streptomyces omiyaensis (SOT), which belongs to the trypsin family. The fibrinolytic activity of SOT was examined using in vitro assays and was compared with those of known fibrinolytic enzymes such as plasmin, tissue-type plasminogen activator (t-PA), urokinase, and nattokinase. Compared to other enzymes, SOT showed remarkably higher hydrolytic activity toward mimic peptides of fibrin and plasminogen. The fibrinolytic activity of SOT is about 18-fold higher than that of plasmin, and is comparable to that of t-PA by fibrin plate assays. Furthermore, SOT had some plasminogen activator-like activity. Results show that SOT and nattokinase have very different fibrinolytic and fibrinogenolytic modes, engendering significant synergetic effects of SOT and nattokinase on fibrinolysis. These results suggest that SOT presents important possibilities for application in the therapy of thrombosis. PMID:22112764

  14. Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins.

    PubMed

    Tubaro, Aurelia; Giangaspero, Anna; Sosa, Silvio; Negri, Roberto; Grassi, Gianpaolo; Casano, Salvatore; Della Loggia, Roberto; Appendino, Giovanni

    2010-10-01

    A selection of seven phytocannabinoids representative of the major structural types of classic cannabinoids and their corresponding cannabivarins was investigated for in vivo topical anti-inflammatory activity in the Croton oil mouse ear dermatitis assay. Differences in the terpenoid moiety were far more important for anti-inflammatory activity than those at the C-3 alkyl residue, suggesting the involvement not only of cannabinoid receptors, but also of other inflammatory end-points targeted by phytocannabinoids. PMID:20450962

  15. Hemeoxygenase 1 partly mediates the anti-inflammatory effect of dieckol in lipopolysaccharide stimulated murine macrophages.

    PubMed

    Yayeh, Taddesse; Im, Eun Ju; Kwon, Tae-Hyung; Roh, Seong-Soo; Kim, Suk; Kim, Ji Hye; Hong, Seung-Bok; Cho, Jae Youl; Park, Nyun-Ho; Rhee, Man Hee

    2014-09-01

    Eisenia bicyclis is edible brown algae recognized as a rich source of bioactive derivatives mainly phlorotannins reported for their anti-oxidant properties. Of all phlorotannins identified so far, dieckol has shown the most potent effect in anti-inflammatory, radical scavenging and neuroprotective functions. However, whether dieckol up-regulates hemeoxygenase 1 (HO-1) and this mediates its anti-inflammatory effect in murine macrophages remains poorly understood. Dieckol (12.5-50 μM) inhibited nitric oxide production and attenuated inducible nitric oxide synthase, phospho (p)-PI-3K, p-Akt, p-IKK-α/β, p-IκB-α and nuclear p-NF-κBp65 protein expressions, and NF-κB transcriptional activity in LPS (0.1 μg/ml) stimulated murine macrophages. On the other hand, dieckol up-regulated HO-1 which partly mediated its anti-inflammatory effect in murine macrophages. Thus, dieckol appeared to be a potential therapeutic agent against inflammation through HO-1 up-regulation. PMID:24953853

  16. Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.

    PubMed Central

    van der Velden, V H

    1998-01-01

    GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized. PMID:9792333

  17. Anti-inflammatory and analgesic effects of ketoprofen in palm oil esters nanoemulsion.

    PubMed

    Sakeena, M H F; Yam, M F; Elrashid, S M; Munavvar, A S; Azmin, M N

    2010-01-01

    Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of ketoprofen produces serious gastrointestinal adverse effects. One of the promising methods to overcome these adverse effects is to administer the drug through the skin. The aim of the present work is to evaluate the anti-inflammatory and analgesic effects from topically applied ketoprofen entrapped palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen product, Fastum(®) gel. The novelty of this study is, use of POEs for the oil phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based nanoemulsion formulation and market formulation. Results indicated that there are no significant different between ketoprofen entrapped POEs nanoemulsion and market formulation in carrageenan-induced rat hind paw edema study and carrageenan-induced hyperalgesia pain threshold study. However, it shows a significant different between POEs nanoemulsion formulation and control group in these studies at p<0.05. From these results it was concluded that the developed nanoemulsion have great potential for topical application of ketoprofen. PMID:21099145

  18. Antibacterial, anti-inflammatory and neuroprotective layer-by-layer coatings for neural implants

    NASA Astrophysics Data System (ADS)

    Zhang, Zhiling; Nong, Jia; Zhong, Yinghui

    2015-08-01

    Objective. Infection, inflammation, and neuronal loss are common issues that seriously affect the functionality and longevity of chronically implanted neural prostheses. Minocycline hydrochloride (MH) is a broad-spectrum antibiotic and effective anti-inflammatory drug that also exhibits potent neuroprotective activities. In this study, we investigated the development of biocompatible thin film coatings capable of sustained release of MH for improving the long term performance of implanted neural electrodes. Approach. We developed a novel magnesium binding-mediated drug delivery mechanism for controlled and sustained release of MH from an ultrathin hydrophilic layer-by-layer (LbL) coating and characterized the parameters that control MH loading and release. The anti-biofilm, anti-inflammatory and neuroprotective potencies of the LbL coating and released MH were also examined. Main results. Sustained release of physiologically relevant amount of MH for 46 days was achieved from the Mg2+-based LbL coating at a thickness of 1.25 μm. In addition, MH release from the LbL coating is pH-sensitive. The coating and released MH demonstrated strong anti-biofilm, anti-inflammatory, and neuroprotective potencies. Significance. This study reports, for the first time, the development of a bioactive coating that can target infection, inflammation, and neuroprotection simultaneously, which may facilitate the translation of neural interfaces to clinical applications.

  19. Anti-inflammatory Activity of Constituents Isolated from Aerial Part of Angelica acutiloba Kitagawa.

    PubMed

    Uto, Takuhiro; Tung, Nguyen Huu; Taniyama, Risa; Miyanowaki, Tosihide; Morinaga, Osamu; Shoyama, Yukihiro

    2015-12-01

    Recently, the resources of medicinal plants have been exhausting. The root of Angelica acutiloba is one of the most important ingredients in Japanese Kampo medicine for the treatment of gynecological diseases. In our search for alternative medicinal plant resources of the root of A. acutiloba, we found that its aerial part has the anti-inflammatory potency as well as the root. Phytochemical investigation of the aerial part resulted in the isolation of four compounds including a new dimeric phthalide, namely tokiaerialide (2), along with Z-ligustilide (1), falcarindiol (3), and bergaptol (4). Next, we investigated the in vitro anti-inflammatory activity of 1-4 in lipopolysaccharide-stimulated RAW264 macrophages. Among the isolated compounds, 1 exhibited the most potent inhibition against lipopolysaccharide-induced production of prostaglandin E2 , nitric oxide, and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). Compounds 3 and 4 also inhibited all inflammatory mediators, but their inhibitory abilities were weaker than those of 1. Furthermore, 1, 3, and 4 strongly also induced heme oxygenase-1. These results suggest that 1, 3, and 4 potentially exert anti-inflammatory activity, and the aerial part of A. acutiloba may be considered to be a useful medicinal resource for inflammatory diseases. PMID:26463105

  20. Avicenna's Canon of Medicine: a review of analgesics and anti-inflammatory substances

    PubMed Central

    Mahdizadeh, Shahla; Khaleghi Ghadiri, Maryam; Gorji, Ali

    2015-01-01

    Naturally occurring substances mentioned in medieval medical literatures currently have, and will continue to have, a crucial place in drug discovery. Avicenna was a Persian physician who is known as the most influential medical writers in the Middle ages. Avicenna`s Canon of Medicine, the most famous books in the history of medicine, presents a clear and organized summary of all the medical knowledge of the time, including a long list of drugs. Several hundred substances and receipts from different sources are mentioned for treatment of different illnesses in this book. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs presented in this comprehensive encyclopedia of medicine. Data for this review were provided by searches of different sections of this book. Long lists of anti-inflammatory and analgesic substances used in the treatment of various diseases are provided. The efficacy of some of these drugs, such as opium, willow oil, curcuma, and garlic, was investigated by modern medicine; pointed to their potent anti-inflammatory and analgesic properties. This review will help further research into the clinical benefits of new drugs for treatment of inflammatory diseases and pain. PMID:26101752

  1. Anti-inflammatory activity of the leaf extacts of Gendarussa vulgaris Nees

    PubMed Central

    Saleem, TK Mohamed; Azeem, AK; Dilip, C; Sankar, C; Prasanth, NV; Duraisami, R

    2011-01-01

    Objective To evaluate the anti-inflammatory property of the leaf exacts of Gendarussa vulgaris (G. vulgaris) Nees. Methods G. vulgaris Nees of the family Apocynaceae is a medium sized tree grown in semishade or no shade and is common in the Ernad and Nilambur taluks of Kerala.Various parts of this plant have been used in the treatment of ulcers, sores, inflammation, dyspepsia, healing of wounds, etc. The present study aimed at the evaluation of anti-inflammatory property of the aqueous and alcoholic extracts of the leaves by both in vitro and in vivo methods. In vitro method was estimated by human red blood cell membrane stabilisation (HRBC) method and in vivo method was estimated on the carrageenan induced paw oedima. Results Both the methods showed significant anti-inflammatory property of the different extracts tested. Conclusions The alcoholic extract at a concentration of 300 mg/mL showed potent activity on comparing with the standard drug diclofenac sodium. PMID:23569746

  2. Screening of Ficus religiosa leaves fractions for analgesic and anti-inflammatory activities

    PubMed Central

    Gulecha, Vishal; Sivakumar, T; Upaganlawar, Aman; Mahajan, Manoj; Upasani, Chandrashekhar

    2011-01-01

    Objective: To evaluate the different fractions of dried leaves of Ficus religiosa Linn for analgesic and anti-inflammatory activity using different models of pain and inflammation Materials and Methods: The analgesic activity of F. religiosa carried out using acetic acid-induced writhing in mice and tail flick test in rats. The anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema and cotton pellet-granuloma formation in rats. Five different fractions (FRI, FRII, FRIII, FRIV and FRV) of F. religiosa at the dose level of 20 and 40 mg/kg, p.o were tested. Results: The fraction FRI (40 mg/kg, p.o.) and FRIII (40 mg/kg, p.o) were found to be more effective (P<0.01) in preventing carrageenan induced rat paw edema, cotton pellet granuloma formation, and acetic acid induced writhing compared to the other fractions. FRI (20 mg/kg, p.o.) and FRIII (20 mg/kg, p.o.) were also found to be more effective in increasing latency period in tail flick method. Conclusion: Out of five different fractions of F. religiosa leaves tested, FRI and FRIII possess potent analgesic and anti-inflammatory activities against different models of inflammation and pain. PMID:22144770

  3. Avicenna's Canon of Medicine: a review of analgesics and anti-inflammatory substances.

    PubMed

    Mahdizadeh, Shahla; Khaleghi Ghadiri, Maryam; Gorji, Ali

    2015-01-01

    Naturally occurring substances mentioned in medieval medical literatures currently have, and will continue to have, a crucial place in drug discovery. Avicenna was a Persian physician who is known as the most influential medical writers in the Middle ages. Avicenna`s Canon of Medicine, the most famous books in the history of medicine, presents a clear and organized summary of all the medical knowledge of the time, including a long list of drugs. Several hundred substances and receipts from different sources are mentioned for treatment of different illnesses in this book. The aim of the present study was to provide a descriptive review of all anti-inflammatory and analgesic drugs presented in this comprehensive encyclopedia of medicine. Data for this review were provided by searches of different sections of this book. Long lists of anti-inflammatory and analgesic substances used in the treatment of various diseases are provided. The efficacy of some of these drugs, such as opium, willow oil, curcuma, and garlic, was investigated by modern medicine; pointed to their potent anti-inflammatory and analgesic properties. This review will help further research into the clinical benefits of new drugs for treatment of inflammatory diseases and pain. PMID:26101752

  4. [Anti-inflammatory effects of methylprednisolone aceponate in animals].

    PubMed

    Ikoma, Y; Yamashita, M; Kamitani, K; Nakagawa, H

    1991-11-01

    In the case of dermal application of the drugs to croton oil-induced ear edema in rats and picryl chloride-induced delayed type hypersensitivity in mice, the anti-inflammatory effect of methylprednisolone aceponate (MPA) was slightly weaker than those of clobetasol 17-propionate and diflucortolone 21-valerate, but stronger than those of hydrocortisone 17-butyrate and hydrocortisone 17-butyrate 21-propionate. Betamethasone 17-valerate applied dermally was less and more effective than MPA to ear edema in rats and delayed type hypersensitivity in mice, respectively. The anti-inflammatory effect of MPA was weaker in subcutaneous administration than in topical application to the two inflammatory models. It was suggested that MPA has strong anti-inflammatory effects and weak systemic effects by topical application. Methylprednisolone 17-propionate (MP-17P) and methylprednisolone (MP), unesterified in only the C-21 position and in both the C-17 and 21 positions of MPA, respectively, showed weaker anti-inflammatory activities than MPA by topical application to croton oil-induced ear edema. The ratio of the anti-inflammatory effects by topical application to subcutaneous administration of MPA was higher than those of MP-17P and MP. The excellent characteristics of MPA as a dermal anti-inflammatory drug are suggested to be derived from di-esterification of MP, which has a weak activity intrinsically. PMID:1813371

  5. Hypoglycemic agents and potential anti-inflammatory activity

    PubMed Central

    Kothari, Vishal; Galdo, John A; Mathews, Suresh T

    2016-01-01

    Current literature shows an association of diabetes and secondary complications with chronic inflammation. Evidence of these immunological changes include altered levels of cytokines and chemokines, changes in the numbers and activation states of various leukocyte populations, apoptosis, and fibrosis during diabetes. Therefore, treatment of diabetes and its complications may include pharmacological strategies to reduce inflammation. Apart from anti-inflammatory drugs, various hypoglycemic agents have also been found to reduce inflammation that could contribute to improved outcomes. Extensive studies have been carried out with thiazolidinediones (peroxisome proliferator-activated receptor-γ agonist), dipeptidyl peptidase-4 inhibitors, and metformin (AMP-activated protein kinase activator) with each of these classes of compounds showing moderate-to-strong anti-inflammatory action. Sulfonylureas and alpha glucosidase inhibitors appeared to exert modest effects, while the injectable agents, insulin and glucagon-like peptide-1 receptor agonists, may improve secondary complications due to their anti-inflammatory potential. Currently, there is a lack of clinical data on anti-inflammatory effects of sodium–glucose cotransporter type 2 inhibitors. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and effects related to intrinsic anti-inflammatory actions of the pharmacological class of compounds. PMID:27114714

  6. Feijoa sellowiana Berg fruit juice: anti-inflammatory effect and activity on superoxide anion generation.

    PubMed

    Monforte, Maria T; Fimiani, Vincenzo; Lanuzza, Francesco; Naccari, Clara; Restuccia, Salvatore; Galati, Enza M

    2014-04-01

    Feijoa sellowiana Berg var. coolidge fruit juice was studied in vivo for the anti-inflammatory activity by carrageenin-induced paw edema test and in vitro for the effects on superoxide anion release from neutrophils in human whole blood. The fruit juice was analyzed by the high-performance liquid chromatography method, and quercetin, ellagic acid, catechin, rutin, eriodictyol, gallic acid, pyrocatechol, syringic acid, and eriocitrin were identified. The results showed a significant anti-inflammatory activity of F. sellowiana fruit juice, sustained also by an effective antioxidant activity observed in preliminary studies on 1,1-diphenyl-2-picrylhydrazyl (DPPH) test. In particular, the anti-inflammatory activity edema inhibition is significant since the first hour (44.11%) and persists until the fifth hour (44.12%) of the treatment. The effect on superoxide anion release was studied in human whole blood, in the presence of activators affecting neutrophils by different mechanisms. The juice showed an inhibiting response on neutrophils basal activity in all experimental conditions. In stimulated neutrophils, the higher inhibition of superoxide anion generation was observed at concentration of 10(-4) and 10(-2) mg/mL in whole blood stimulate with phorbol-myristate-13-acetate (PMA; 20% and 40%) and with N-formyl-methionyl-leucyl-phenylalanine (FMLP; 15% and 48%). The significant reduction of edema and the inhibition of O2(-) production, occurring mainly through interaction with protein-kinase C pathway, confirm the anti-inflammatory effect of F. sellowiana fruit juice. PMID:24433073

  7. Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies.

    PubMed

    Shahbazi, Sajad; Sahrawat, Tammanna R; Ray, Monalisa; Dash, Swagatika; Kar, Dattatreya; Singh, Shikha

    2016-01-01

    Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbβIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent. PMID:27258084

  8. Synthesis and biological evaluation studies of novel quinazolinone derivatives as antibacterial and anti-inflammatory agents

    PubMed Central

    F. Zayed, Mohamed; H. Hassan, Memy

    2013-01-01

    Some novel 6,8-diiodo-2-methyl-3-substituted-quinazolin-4(3H)-ones bearing sulfonamide derivatives (4–11) were synthesized in good yields and evaluated for their possible antibacterial, anti-inflammatory activities and acute toxicity. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. Their antibacterial activities were evaluated by the agar well diffusion method while their anti-inflammatory activities were evaluated by the carrageenan-induced hind paw edema test. All the tested compounds showed considerable antibacterial activities and high to moderate anti-inflammatory activities that last for 12 h compared to ibuprofen. All the tested compounds showed no toxic symptoms or mortality rates 24 h post-administration at tested anti-inflammatory doses. In addition, LD50 for all tested compounds was higher than that for ibuprofen implying their good safety margin. The obtained results showed that the most active compounds could be useful as a template for future design, modification and investigation to produce more active analogs. PMID:24648828

  9. Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies

    PubMed Central

    Shahbazi, Sajad; Sahrawat, Tammanna R.; Ray, Monalisa; Dash, Swagatika; Kar, Dattatreya; Singh, Shikha

    2016-01-01

    Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbβIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent. PMID:27258084

  10. Nonsteroidal Anti-inflammatory-Organometallic Anticancer Compounds.

    PubMed

    Păunescu, Emilia; McArthur, Sarah; Soudani, Mylène; Scopelliti, Rosario; Dyson, Paul J

    2016-02-15

    Compounds that combine metal-based drugs with covalently linked targeted organic agents have been shown, in some instances, to exhibit superior anticancer properties compared to the individual counterparts. Within this framework, we prepared a series of organometallic ruthenium(II)- and osmium(II)-p-cymene complexes modified with the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin and diclofenac. The NSAIDs are attached to the organometallic moieties via monodentate (pyridine/phosphine) or bidentate (bipyridine) ligands, affording piano-stool Ru(II) and Os(II) arene complexes of general formula [M(η(6)-p-cymene)Cl2(N)], where N is a pyridine-based ligand, {2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl-3-(pyridin-3-yl)propanoate} or {2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl-3-(pyridin-3-yl)propanoate}, [M(η(6)-p-cymene)Cl2(P)], where P is a phosphine ligand, {2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl-4-(diphenylphosphanyl)benzoate} or {2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl-4-(diphenylphosphanyl)benzoate, and [M(η(6)-p-cymene)Cl(N,N')][Cl], where N,N' is a bipyridine-based ligand, (4'-methyl-[2,2'-bipyridin]-4-yl)methyl-2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate), (4'-methyl-[2,2'-bipyridin]-4-yl)methyl-2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate), (bis(2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl)[2,2'-bipyridine]-5,5'-dicarboxylate), or (bis(2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl)[2,2'-bipyridine]-5,5'-dicarboxylate). The antiproliferative properties of the complexes were assessed in human ovarian cancer cells (A2780 and A2780cisR, the latter being resistant to cisplatin) and nontumorigenic human embryonic kidney (HEK-293) cells. Some of the complexes are considerably more cytotoxic than the original drugs and also display significant cancer cell selectivity. PMID:26824462

  11. Anti-inflammatory and immunomodulatory properties of 2-amino-3H-phenoxazin-3-one.

    PubMed

    Kohno, Keizo; Miyake, Masaki; Sano, Osamu; Tanaka-Kataoka, Mari; Yamamoto, Shigeto; Koya-Miyata, Satomi; Arai, Norie; Fujii, Mitsukiyo; Watanabe, Hikaru; Ushio, Shimpei; Iwaki, Kanso; Fukuda, Shigeharu

    2008-10-01

    Accumulating evidence suggests that nitric oxide (NO) and prostaglandin E(2) (PGE(2)) are involved in the pathogenesis of various chronic inflammatory diseases and cancer. During the course of a screening program to identify natural anti-inflammatory substances, we isolated the compound 2-amino-3H-phenoxazin-3-one (APO) from an extract of the edible brown mushroom Agaricus bisporus IMBACH. APO inhibited NO production by mouse peritoneal macrophages in response to the pro-inflammatory stimuli lipopolysaccharide (LPS) and interferon (IFN)-gamma (LPS/IFN-gamma) at low concentrations (IC(50)=1.5 microM) through reduced inducible NO synthase protein expression. PGE(2) production by LPS/IFN-gamma-stimulated macrophages was inhibited by APO at much lower concentrations (IC(50)=0.27 microM) than those required for the inhibition of NO production. Mechanistic analysis showed that APO inhibited both cyclooxygenase (COX)-1 and COX-2 enzyme activities with almost equal selectivity. Secretion of NO and the pro-inflammatory cytokine IL-6 by IFN-gamma-activated RAW264.7 cells, a murine macrophage-like cell line, was also dose-dependently reduced by APO. Furthermore, APO increased the secretion of the anti-inflammatory cytokine IL-4 by antigen-stimulated T cells and promoted the polarization of CD4(+) Th cells toward the anti-inflammatory Th2 phenotype at equimolar concentrations that inhibited NO production. Our results suggested that APO induced polarization toward the Th2 subset, at least in part through the down-regulation of IL-12 production. Thus, APO appears to have potent anti-inflammatory and immunoregulatory properties that may provide a promising therapeutic strategy for the treatment of T cell-mediated inflammatory autoimmune diseases as well as for bacteria-induced chronic-inflammatory diseases. PMID:18827359

  12. Topical anti-inflammatory activity of Eupatilin, a lipophilic flavonoid from mountain wormwood ( Artemisia umbelliformis Lam.).

    PubMed

    Giangaspero, Anna; Ponti, Cristina; Pollastro, Federica; Del Favero, Giorgia; Della Loggia, Roberto; Tubaro, Aurelia; Appendino, Giovanni; Sosa, Silvio

    2009-09-01

    Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is the major lipophilic flavonoid from Artemisia umbelliformis Lam. and Artemisia genipi Weber, two mountain wormwoods used for the production of the celebrated alpine liqueur genepy. The topical anti-inflammatory activity of eupatilin was investigated using the inhibition of the Croton-oil-induced dermatitis in the mouse ear as the end point. The oedematous response and the leukocyte infiltration were evaluated up to 48 h after the induction of phlogosis, comparing eupatilin with hydrocortisone and indomethacin as representatives of steroid and non-steroid anti-inflammatory drugs, respectively. At maximum development, eupatilin significantly reduced edema in a dose-dependent manner (ID(50) = 0.28 micromol/cm(2)), showing an anti-inflammatory potency comparable to that of indomethacin (ID(50) = 0.26 micromol/cm(2)) and only 1 order of magnitude lower than that of hydrocortisone (ID(50) = 0.03 micromol/cm(2)). Within 48 h, eupatilin (0.30 micromol/cm(2)) caused a global inhibition of the oedematous response (42%) higher than that of an equimolar dose of indomethacin (18%) and fully comparable to that of 0.03 micromol/cm(2) of hydrocortisone (55%). Moreover, the effect of eupatilin on the granulocytes infiltrate (32% inhibition) was similar to that of indomethacin (35% inhibition) and comparable to that of hydrocortisone (42% reduction), as confirmed by histological analysis. When our results are taken together, they show that eupatilin is endowed with potent in vivo topical anti-inflammatory activity, qualitatively similar to that of hydrocortisone and intermediate in terms of potency between those of steroid and non-steroid drugs. PMID:19663482

  13. Anti-Inflammatory Effects of 4-Methylcyclopentadecanone on Edema Models in Mice

    PubMed Central

    Ma, Yukui; Li, Yue; Li, Xiufeng; Wu, Yingliang

    2013-01-01

    The present study evaluated the anti-inflammatory effects of 4-methylcyclopentadecanone (4-MCPC) on edema models in mice and aimed to determine the safety of 4-MCPC after acute exposure. The acute toxicity of 4-MCPC was evaluated by oral administration to rats of single doses of 0, 5, 50, 500 and 5000 mg/kg. Toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in xylene-induced mouse ear edema and carrageenan-induced mouse paw edema. The animals were treated with 4-MCPC once every day for seven consecutive days. Edema index, % inhibition, IL-1β, TNF-α, PGE2 and MPO levels in paws were detected after the treatment with xylene or carrageenan. Our results indicated that the LD50 value of 4-MCPC in rats is greater than 5000 mg/kg. The ED50 of 4-MCPC in xylene-induced mouse ear edema model was 7.5 mg/kg. 4-MCPC (8 or 16 mg/kg) remarkably inhibited carrageenan-induced mouse paw edema. Further study revealed that 4-MCPC treatment also decreased IL-1β, TNF-α, PGE2 and MPO levels in mice paws. Intragastric administration of 4-MCPC exhibited more significant anti-inflammatory activity than muscone at a dose of 16 mg/kg. Taken together, our results suggest that 4-MCPC has potent anti-inflammatory activity and the mechanisms might be related to the decreases of the levels of IL-1β, TNF-α, PGE2 and MPO in inflamed paws. PMID:24351869

  14. Local anti-inflammatory activity and systemic side effects of NM-135, a new prodrug glucocorticoid, in an experimental inflammatory rat model.

    PubMed

    Ishii, T; Kibushi, N; Nakajima, T; Kakuta, T; Tanaka, N; Sato, C; Sugai, K; Kijima-Suda, I; Kai, H; Miyata, T

    1998-12-01

    The local anti-inflammatory activity and systemic side effects of NM-135 (6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21[[2 ,3,4,6-tetrakis-O-(4-methylbenzoyl)-beta-D-glucopyranosyl]oxy]-pregna-1, 4-diene-3,20-dione) in croton oil-induced granuloma pouches and ear edema in rats were studied. The local anti-inflammatory activity of NM-135 was stronger than that of betamethasone 17-valerate (BV). As to systemic side effects, BV and diflucortolon valerate (DFV) caused thymolysis at the doses required for the anti-inflammatory activity. In contrast, no clear systemic side effect was observed in rats administered NM-135 at the dose producing the anti-inflammatory activity. These results suggest that NM-135 is a drug exhibiting a high degree of dissociation between the local anti-inflammatory activity and systemic side effects. PMID:9920209

  15. Anti-inflammatory effects of novel barbituric acid derivatives in T lymphocytes.

    PubMed

    Xu, Chenjia; Wyman, Arlene R; Alaamery, Manal A; Argueta, Shannon A; Ivey, F Douglas; Meyers, John A; Lerner, Adam; Burdo, Tricia H; Connolly, Timothy; Hoffman, Charles S; Chiles, Thomas C

    2016-09-01

    We have used a high throughput small molecule screen, using a fission yeast-based assay, to identify novel phosphodiesterase 7 (PDE7) inhibitors. One of the most effective hit compounds was BC12, a barbituric acid-based molecule that exhibits unusually potent immunosuppressive and immunomodulatory actions on T lymphocyte function, including inhibition of T cell proliferation and IL-2 cytokine production. BC12 treatment confers a >95% inhibition of IL-2 secretion in phytohaemagglutinin (PHA) plus phorbol-12-myristate-13-acetate (PMA) stimulated Jurkat T cells. The effect of BC12 on IL-2 secretion is not due to decreased cell viability; rather, BC12 blocks up-regulation of IL-2 transcription in activated T cells. BC12 also inhibits IL-2 secretion in human peripheral T lymphocytes stimulated in response to CD3/CD28 co-ligation or the combination of PMA and ionomycin, as well as the proliferation of primary murine T cells stimulated with PMA and ionomycin. A BC12 analog that lacks PDE7 inhibitory activity (BC12-4) displays similar biological activity, suggesting that BC12 does not act via PDE7 inhibition. To investigate the mechanism of inhibition of IL-2 production by BC12, we performed microarray analyses using unstimulated and stimulated Jurkat T cells in the presence or absence of BC12 or BC12-4. Our studies show these compounds affect the transcriptional response to stimulation and act via one or more shared targets to produce both anti-inflammatory and pro-stress effects. These results demonstrate potent immunomodulatory activity for BC12 and BC12-4 in T lymphocytes and suggest a potential clinical use as an immunotherapeutic to treat T lymphocyte-mediated diseases. PMID:27302770

  16. Identification of anti-inflammatory constituents in Hypericum perforatum and Hypericum gentianoides extracts using RAW 264.7 mouse macrophages

    PubMed Central

    Huang, Nan; Rizshsky, Ludmila; Hauck, Cathy; Nikolau, Basil J.; Murphy, Patricia A.; Birt, Diane F.

    2011-01-01

    Hypericum perforatum (St. John’s wort) is an herb widely used as supplement for mild to moderate depression. Our prior studies revealed synergistic anti-inflammatory activity associated with 4 bioactive compounds in a fraction of H. perforatum ethanol extract. Whether these 4 compounds also contributed to the ethanol extract activity was addressed in the research reported here. Despite the popularity of H. perforatum, other Hypericum species with different phytochemical profiles could have their anti-inflammatory potentials attributed to these or other compounds. In the current study, ethanol extracts of different Hypericum species were compared for their inhibitory effect on LPS-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 mouse macrophages. Among these extracts, those made from H. perforatum and H. gentianoides demonstrated stronger overall efficacy. LC-MS analysis indicated the 4 compounds in H. perforatum extract and pseudohypericin in all active fractions. The 4 compounds accounted for a significant part of the extract’s inhibitory activity on PGE2, NO, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW 264.7 as well as peritoneal macrophages. Pseudohypericin was the most important contributor of the anti-inflammatory potential among the 4 compounds. The lipophilic fractions of H. gentianoides extract, which did not contain the previously identified active constituents, decreased PGE2 and NO potently. These fractions were rich in acylphloroglucinols, including uliginosin A that accounted for a proportion of the anti-inflammatory activity observed with the active fractions. Overall, the current study revealed a different group of major anti-inflammatory constituents in H. gentianoides, while showing that a previously identified 4 compounds combination was important for H. perforatum’s anti-inflammatory potential. PMID:21855951

  17. The Anti-inflammatory Effects of Water Extract from Cordyceps militaris in Murine Macrophage.

    PubMed

    Jo, Wol Soon; Choi, Yoo Jin; Kim, Hyoun Ji; Lee, Jae Yun; Nam, Byung Hyouk; Lee, Jae Dong; Lee, Sang Wha; Seo, Su Yeong; Jeong, Min Ho

    2010-03-01

    The aim of this study was to determine the in vitro anti-inflammatory effect of hot water extract from Cordyceps militaris fruiting bodies (CMWE) on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release in RAW 264.7 cells. The treatment of macrophages with various concentrations of hot CMWE significantly reduced LPS-induced production as well as NO, TNF-α and IL-6 secretion in a concentration-dependent manner. These results suggest that CMWE have potent inhibitory effects on the production of these inflammatory mediators. PMID:23956624

  18. The Anti-inflammatory Effects of Water Extract from Cordyceps militaris in Murine Macrophage

    PubMed Central

    Jo, Wol Soon; Choi, Yoo Jin; Kim, Hyoun Ji; Lee, Jae Yun; Nam, Byung Hyouk; Lee, Jae Dong; Lee, Sang Wha; Seo, Su Yeong

    2010-01-01

    The aim of this study was to determine the in vitro anti-inflammatory effect of hot water extract from Cordyceps militaris fruiting bodies (CMWE) on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release in RAW 264.7 cells. The treatment of macrophages with various concentrations of hot CMWE significantly reduced LPS-induced production as well as NO, TNF-α and IL-6 secretion in a concentration-dependent manner. These results suggest that CMWE have potent inhibitory effects on the production of these inflammatory mediators. PMID:23956624

  19. 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. PMID:21905284

  20. Toxicological Evaluation of Emblica officinalis Fruit Extract and its Anti-inflammatory and Free Radical Scavenging Properties

    PubMed Central

    Middha, Sushil Kumar; Goyal, Arvind Kumar; Lokesh, Prakash; Yardi, Varsha; Mojamdar, Lavanya; Keni, Deepthi Sudhir; Babu, Dinesh; Usha, Talambedu

    2015-01-01

    officinalis fruit (MEO) has potent antioxidant activity as assessed by DPPH, ABTS and LPO assaysMEO has potent anti-inflammatory activity in carrageenan induced paw edema modelThe phenolic compounds of MEO might be a potential herbal drug for amelioration of acute inflammation. Abbreviations used: ROS, reactive oxygen species; RNS, reactive nitrogen species, LPO, lipid peroxidation, NO, nitric oxide, IL, interleukin; TNF α tumor necrosis factor alpha; NSAIDs, nonsteroidal anti inflammatory drugs; AA, ascorbic acid; MEO, methanolic extract of Emblica officinalis fruit; ABTS+; 2,2’ azino bis 3 ethylbenzthiazoline 6 sulphonic acid; DPPH, 1,1 diphenyl 2 picrylhydrazyl; HPLC, high performance liquid chromatography; MDA, malondialdehyde; DMSO, dimethyl sulphoxide; ELISA, enzyme linked immunosorbent assay. PMID:26929577

  1. Physicochemical characteristics and anti-inflammatory activities of antrodan, a novel glycoprotein isolated from Antrodia cinnamomea mycelia.

    PubMed

    Chiu, Chun-Hung; Peng, Chiung-Chi; Ker, Yaw-Bee; Chen, Chin-Chu; Lee, Arwen; Chang, Wan-Lin; Chyau, Charng-Cherng; Peng, Robert Y

    2013-01-01

    Antrodia cinnamomea (AC) is a unique fungus found inhabiting the rotten wood of Cinnamomum kanehirai. A submerged liquid culture of AC has been developed and its bioproducts have been used to meet the market demand for natural fruiting bodies. AC exhibits anti-inflammatory, antitumor, antioxidant, and immunomodulatory effects. Previously, we isolated polysaccharide AC-2 from AC mycelia by means of alkali extraction with subsequent acid precipitation and found it had a pronounced anti-inflammatory effect. In this study, a novel polysaccharide named "antrodan" was obtained by further purification of AC-2 using Sepharose CL-6B column chromatography. Antrodan exhibited a molecular weight of 442 kD and contained a particularly high content of uronic acid (152.6±0.8 mg/g). The protein content was 71.0%, apparently, higher than the carbohydrate content (14.1%), and thus antrodan was characterized as a glycoprotein. Its total glucan content was 15.65%, in which β-glucan (14.20%) was prominently higher than α-glucan (1.45%). Its FTIR confirmed the presence of β-linkages between sugars, and intramolecular amide bonds between sugars and amino acids. Its 1H-NMR spectrum showed that antrodan was a complex union of α- and β-glucans, which had (1→4)-linked α-Glcp and (1→3)-linked β-Glcp linkages to the carbohydrate chains via asparagine linked to protein site. Biologically, antrodan was confirmed to be totally non-detrimental to RAW 264.7 cell line even at dose as high as 400 μg/mL. It showed potent suppressing effect on the lipopolysaccharide-induced inflammatory responses in RAW 264.7 cell line. Moreover, antrodan significantly reduced the nitrogen oxide production at doses as low as 18.75 μg/mL. PMID:24451244

  2. Evaluation of Anticancer, Antioxidant, and Possible Anti-inflammatory Properties of Selected Medicinal Plants Used in Indian Traditional Medication

    PubMed Central

    Shaikh, Rafik; Pund, Mahesh; Dawane, Ashwini; Iliyas, Sayyed

    2014-01-01

    The present study was carried out to evaluate the anticancer, antioxidant, and possible anti-inflammatory properties of diverse medicinal plants frequently used in Indian traditional medication. The selected botanicals such as Soymida fembrifuga (Roxb.) A. Juss. (Miliaceae), Tinospora cordifolia (Willd.) Miers. (Menispermaceae), Lavandula bipinnata (L.) O. Ktze. (Lamiaceae), and Helicteres isora L. (Sterculiaceae) extracted in different solvents were evaluated for their in vitro anticancer and antioxidant activities. The results obtained indicate that H. isora has potent cytotoxic activity toward the selected cancer cells such as HeLa-B75 (34.21 ± 0.24%), HL-60 (30.25 ± 1.36%), HEP-3B (25.36 ± 1.78%), and PN-15 (29.21 ± 0.52%). Interestingly, the selected botanicals selectively inhibited cyclooxygenase-2 (COX-2) more than (COX-1), which are the key enzymes implicated in inflammation. COX-2 inhibition was observed to be in the range of 19.66-49.52% as compared to COX-1 inhibition (3.93-19.61%). The results of the antioxidant study revealed that the selected plants were found to be effective 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH), and superoxide radical (SOR) scavenging agents. High-performance thin layer chromatography (HPTLC) fingerprint of flavonoids was used as a measure of quality control of the selected plant samples. The results of the present findings strengthen the potential of the selected plants as a resource for the discovery of novel anticancer, anti-inflammatory, and antioxidant agents. PMID:25379467

  3. Evaluation of Anticancer, Antioxidant, and Possible Anti-inflammatory Properties of Selected Medicinal Plants Used in Indian Traditional Medication.

    PubMed

    Shaikh, Rafik; Pund, Mahesh; Dawane, Ashwini; Iliyas, Sayyed

    2014-10-01

    The present study was carried out to evaluate the anticancer, antioxidant, and possible anti-inflammatory properties of diverse medicinal plants frequently used in Indian traditional medication. The selected botanicals such as Soymida fembrifuga (Roxb.) A. Juss. (Miliaceae), Tinospora cordifolia (Willd.) Miers. (Menispermaceae), Lavandula bipinnata (L.) O. Ktze. (Lamiaceae), and Helicteres isora L. (Sterculiaceae) extracted in different solvents were evaluated for their in vitro anticancer and antioxidant activities. The results obtained indicate that H. isora has potent cytotoxic activity toward the selected cancer cells such as HeLa-B75 (34.21 ± 0.24%), HL-60 (30.25 ± 1.36%), HEP-3B (25.36 ± 1.78%), and PN-15 (29.21 ± 0.52%). Interestingly, the selected botanicals selectively inhibited cyclooxygenase-2 (COX-2) more than (COX-1), which are the key enzymes implicated in inflammation. COX-2 inhibition was observed to be in the range of 19.66-49.52% as compared to COX-1 inhibition (3.93-19.61%). The results of the antioxidant study revealed that the selected plants were found to be effective 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH), and superoxide radical (SOR) scavenging agents. High-performance thin layer chromatography (HPTLC) fingerprint of flavonoids was used as a measure of quality control of the selected plant samples. The results of the present findings strengthen the potential of the selected plants as a resource for the discovery of novel anticancer, anti-inflammatory, and antioxidant agents. PMID:25379467

  4. Evaluation of anti-inflammatory, analgesic, and antipyretic activities of the ethanol extract from Murdannia loriformis (Hassk.) Rolla Rao et Kammathy

    PubMed Central

    Kunnaja, Phraepakaporn; Wongpalee, Somsakul Pop; Panthong, Ampai

    2014-01-01

    Introduction: Murdannia loriformis (hassk) Rolla Roa et Kammathy, family Commelinaceae, is used by Chinese practitioners as a remedy for cancer in an early stage, and also for treating other diseases including colds, throat infections, pneumonia, diabetes mellitus, flu and inflammation. Although anticancer as well as other pharmacological effects of M. loriformis have been reported, its anti-inflammatory and other activities related to inflammation are still limited. Methods: The anti-inflammatory activity was evaluated using carrageenan- and arachidonic acid-induced paw edema in rats, and cotton pellet-induced granuloma formation in rats. The analgesic and antipyretic activities were determined by formalin test in mice and yeast-induced hyperthermia in rats, respectively. Results: The ethanol extract of the aerial part of M. loriformis exhibited anti-inflammatory activity on the rat paw edema induced by carrageenan and arachidonic acid. It also showed an inhibitory effect on the granuloma and the transudative formation of the rat implanted with cotton pellets as well as lowered the elevated serum alkaline phosphatase activity to normal level. It exerted potent analgesic effect on both the early and late phase of formalin test as well as the antipyretic effect on yeast-induced hyperthermic rats. The oral single high dose of the extract of 5,000 mg/Kg did not produce death or any abnormalities or changes of the internal organs of rats during 14 days of the observed period. Conclusion: The results obtained from this study support the use of the plant in traditional medicine for inflammatory ailments. PMID:25671174

  5. Analgesic and Anti-Inflammatory Activity of Pinus roxburghii Sarg.

    PubMed Central

    Kaushik, Dhirender; Kumar, Ajay; Kaushik, Pawan; Rana, A. C.

    2012-01-01

    The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae) is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models. PMID:22761611

  6. Anti-inflammatory and analgesic effects of Daphne retusa Hemsl.

    PubMed

    Hu, Xiaojia; Jin, Huizi; Xu, Wenzheng; Zhang, Wei; Liu, Xiaohua; Yan, Shikai; Chen, Ming; Li, Jianqiang; Zhang, Wei-dong

    2008-10-30

    Daphne retusa Hemsl. belongs to the genus Daphne, a member of Thymelaeaceae family. The barks and stems of Daphne retusa are used as a folkloric medicine 'Zhu Shi Ma' in Western China because of its effects of detumescence and acesodyne. In this paper, we investigate the anti-inflammatory and analgesic effects of the 75% ethanol extract of the stems and barks of Daphne retusa and different fractions partitioned with petroleum ether, methylene chloride, ethyl acetate and n-butanol, respectively. The anti-inflammatory effects were evaluated using xylene-induced ear oedema in mice and carrageenan-induced paw oedema in rats, while the acetic acid-induced writhing test and hot-plate test as models for evaluating the centrally and peripherally analgesic activity. The results showed the plant has significant anti-inflammatory and analgesic effects (P<0.05-0.01). Meanwhile, the result of the acute toxicity test at which the MTD was above 5g/kg indicates that the plant extract is relatively safe in, and/or non-toxic to, mice. The findings of these experimental animal studies indicate that the Daphne retusa ethanol extract possesses anti-inflammatory and analgesic properties, and thus provide pharmacological support to folkloric, ethnomedical uses of 'Zhu shima' in the treatment and/of management of anti-inflammatory and painful conditions in China. PMID:18692124

  7. Modeling Natural Anti-Inflammatory Compounds by Molecular Topology

    PubMed Central

    Galvez-Llompart, María; Zanni, Riccardo; García-Domenech, Ramón

    2011-01-01

    One of the main pharmacological problems today in the treatment of chronic inflammation diseases consists of the fact that anti-inflammatory drugs usually exhibit side effects. The natural products offer a great hope in the identification of bioactive lead compounds and their development into drugs for treating inflammatory diseases. Computer-aided drug design has proved to be a very useful tool for discovering new drugs and, specifically, Molecular Topology has become a good technique for such a goal. A topological-mathematical model, obtained by linear discriminant analysis, has been developed for the search of new anti-inflammatory natural compounds. An external validation obtained with the remaining compounds (those not used in building up the model), has been carried out. Finally, a virtual screening on natural products was performed and 74 compounds showed actual anti-inflammatory activity. From them, 54 had been previously described as anti-inflammatory in the literature. This can be seen as a plus in the model validation and as a reinforcement of the role of Molecular Topology as an efficient tool for the discovery of new anti-inflammatory natural compounds. PMID:22272145

  8. Synthesis, anti-inflammatory, analgesic, 5-lipoxygenase (5-LOX) inhibition activities, and molecular docking study of 7-substituted coumarin derivatives.

    PubMed

    Srivastava, Pavan; Vyas, Vivek K; Variya, Bhavesh; Patel, Palak; Qureshi, Gulamnizami; Ghate, Manjunath

    2016-08-01

    In the present study, 7-subsituted coumarin derivatives were synthesized using various aromatic and heterocyclic amines, and evaluated in vivo for anti-inflammatory and analgesic activity, and for ulcerogenic risk. The most active compounds were evaluated in vitro for 5-lipoxygenase (5-LOX) inhibition. Docking study was performed to predict the binding affinity, and orientation at the active site of the enzyme. In vivo anti-inflammatory and analgesic activity, and in vitro 5-LOX enzyme inhibition study revealed that compound 33 and 35 are the most potent compounds in all the screening methods. In vitro kinetic study of 35 showed mixed or non-competitive type of inhibition with 5-LOX enzyme. Presence of OCH3 group in 35 and Cl in 33 at C6-position of benzothiazole ring were found very important substitutions for potent activity. PMID:27376460

  9. The Hypolipidemic and Anti-Inflammatory Activity of Boronated Aromatic Amino Acids in CF1 Male Mice

    PubMed Central

    Miller, Merrill C.; Sood, A.; Spielvogel, Bernard F.

    1999-01-01

    The boronated aromatic amino acids were shown to be potent hypolipidemic agents in mice lowering both serum cholesterol and triglycerides after 16 days. Selective compounds were as effective as the clinical standards. Furthermore, the compounds were effective anti-inflammatory agents reducing local and central pain as well as suppressing LPS induced endotoxic shock in mice. These agents inhibited lysosomal and proteolytic enzymes of the liver and macrophages as a part of their mechanism of action. PMID:18475910

  10. Hesperetin derivatives: Synthesis and anti-inflammatory activity.

    PubMed

    Wang, Qian-Qian; Shi, Jing-Bo; Chen, Chen; Huang, Cheng; Tang, Wen-Jian; Li, Jun

    2016-03-01

    Sixteen novel hesperetin derivatives containing Mannich base moiety were designed and synthesized and their anti-inflammatory activities were evaluated by inhibiting tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in mouse RAW264.7 macrophages. Compounds 3a-3k showed better hydrophilic, while compounds 3l-3p with aromatic groups was hydrophobic. The anti-inflammatory activity of title compounds was correlated with logP values, among them, compounds 3c, 3e and 3i with minus logP values exhibited best anti-inflammatory activity through decreasing both IL-6 and TNF-α. Furthermore, the expression of LPS-induced notch1 and inos was reduced by compounds 3c, 3e, and 3i, and compound 3e attenuated LPS-induced inos protein levels in a dose-dependent manner. PMID:26848111

  11. Inflammatory Regulation Effect and Action Mechanism of Anti-Inflammatory Effective Parts of Housefly (Musca domestica) Larvae on Atherosclerosis.

    PubMed

    Chu, Fu Jiang; Jin, Xiao Bao; Xu, Yin Ye; Ma, Yan; Li, Xiao Bo; Lu, Xue Mei; Liu, Wen Bin; Zhu, Jia Yong

    2013-01-01

    The protein-enriched extracts of housefly larvae were segregated by gel-filtration chromatography (GFC) and then anti-inflammatory activity screening in RAW264.7 (induced by LPS) was carried out. After acquire the anti-inflammatory effective parts, its anti-atherosclerotic properties in vivo were then evaluated. Results showed that the anti-inflammatory effective parts of housefly larvae were low-molecular-weight parts. After treated with the effective parts oral gavaged for 4 weeks, the atherosclerotic lesions of the mouse were significantly decreased. The inflammatory and lipid parameters were also reduced (except HDL which was increased). Western blot analysis demonstrated that the effective parts exerted potent inhibitory effect on expression of p65 in nucleus and cytoplasm. The results of immunofluorescence microscopy analysis also showed that the expressions of p65 both in cytoplasm and nucleus were significantly reduced. The hypothesis that the anti-inflammatory effective parts of housefly larvae possessed anti-atherosclerosis activity in mouse and the possible mechanism could be associated with the inhibition of expression and nuclear transfer of NF- κ B p65 could be derived. PMID:23554828

  12. Anti-Inflammatory Effects of 81 Chinese Herb Extracts and Their Correlation with the Characteristics of Traditional Chinese Medicine

    PubMed Central

    Chen, Chang-Liang; Zhang, Dan-Dan

    2014-01-01

    Inducible nitrogen oxide synthase (iNOS) is the primary contributor of the overproduction of nitric oxide and its inhibitors have been actively sought as effective anti-inflammatory agents. In this study, we prepared 70% ethanol extracts from 81 Chinese herbs. These extracts were subsequently evaluated for their effect on nitrogen oxide (NO) production and cell growth in LPS/IFNγ-costimulated and unstimulated murine macrophage RAW264.7 cells by Griess reaction and MTT assay. Extracts of Daphne genkwa Sieb.et Zucc, Caesalpinia sappan L., Iles pubescens Hook.et Arn, Forsythia suspensa (Thunb.) Vahl, Zingiber officinale Rosc, Inula japonica Thunb., and Ligusticum chuanxiong Hort markedly inhibited NO production (inhibition > 90% at 100 μg/mL). Among active extracts (inhibition > 50% at 100 μg/mL), Rubia cordifolia L., Glycyrrhiza glabra L., Iles pubescens Hook.et Arn, Nigella glandulifera Freyn et Sint, Pueraria lobata (Willd.) Ohwi, and Scutellaria barbata D. Don displayed no cytotoxicity to unstimulated RAW246.7 cells while increasing the growth of LPS/IFNγ-costimulated cells. By analyzing the correlation between their activities and their Traditional Chinese Medicine (TCM) characteristics, herbs with pungent flavor displayed potent anti-inflammatory capability. Our study provides a series of potential anti-inflammatory herbs and suggests that herbs with pungent flavor are candidates of effective anti-inflammatory agents. PMID:24696703

  13. ATP-Binding Pocket-Targeted Suppression of Src and Syk by Luteolin Contributes to Its Anti-Inflammatory Action

    PubMed Central

    Lee, Jeong-Oog; Jeong, Deok; Kim, Mi-Yeon; Cho, Jae Youl

    2015-01-01

    Luteolin is a flavonoid identified as a major anti-inflammatory component of Artemisia asiatica. Numerous reports have demonstrated the ability of luteolin to suppress inflammation in a variety of inflammatory conditions. However, its exact anti-inflammatory mechanism has not been fully elucidated. In the present study, the anti-inflammatory mode of action in activated macrophages of luteolin from Artemisia asiatica was examined by employing immunoblotting analysis, a luciferase reporter gene assay, enzyme assays, and an overexpression strategy. Luteolin dose-dependently inhibited the secretion of nitric oxide (NO) and prostaglandin E2 (PGE2) and diminished the levels of mRNA transcripts of inducible NO synthase (iNOS), tumor necrosis factor- (TNF-) α, and cyclooxygenase-2 (COX-2) in lipopolysaccharide- (LPS-) and pam3CSK-treated macrophage-like RAW264.7 cells without displaying cytotoxicity. Luteolin displayed potent NO-inhibitory activity and also suppressed the nuclear translocation of NF-κB (p65 and p50) via blockade of Src and Syk, but not other mitogen-activated kinases. Overexpression of wild type Src and point mutants thereof, and molecular modelling studies, suggest that the ATP-binding pocket may be the luteolin-binding site in Src. These results strongly suggest that luteolin may exert its anti-inflammatory action by suppressing the NF-κB signaling cascade via blockade of ATP binding in Src and Syk. PMID:26236111

  14. Synthesis of Novel Substituted Thiourea and Benzimidazole Derivatives Containing a Pyrazolone Ring as Anti-Inflammatory Agents.

    PubMed

    Moneer, Ashraf A; Mohammed, Khaled O; El-Nassan, Hala B

    2016-05-01

    Two series of new 1-(alkyl/aryl)-3-{2-[(5-oxo-4,5-dihydro-1H-pyrazol-3-yl)amino]phenyl}thioureas 2a-h and 5-[2-(substituted amino)-1H-benzimidazol-1-yl]-4H-pyrazol-3-ols 3a-i were designed and synthesized as anti-inflammatory agents. The cyclooxygenase inhibitory activity of the newly synthesized compounds was investigated. All the compounds showed non-selective inhibition of COX-1 and COX-2 enzymes which was consistent with their docking results. Compounds 2c, 2f, 2g, 3b, and 3g that showed the highest COX-2 inhibitory activity were selected for further in vivo testing as anti-inflammatory agents using diclofenac as a reference drug. Two of the test compounds (2c and 3b) showed potent anti-inflammatory activity comparable to that of diclofenac with lower ulcerogenic effect relative to indomethacin. SAR study of the two series as cyclooxygenase inhibitors and anti-inflammatory agents was also provided. PMID:26684979

  15. Colonic anastomoses and non-steroidal anti-inflammatory drugs.

    PubMed

    Slim, K; Joris, J; Beloeil, H

    2016-08-01

    Nonsteroidal anti-inflammatory drugs (NSAID) play an important role in the treatment of post-operative pain, particularly in the context of enhanced recovery after colorectal surgery. Several recent articles have suggested that NSAID may have a deleterious effect on colo-colic or colo-rectal anastomoses. The aim of this review is to analyze the evidence based on meta-analyses and cohort studies in the literature. A systematic review of clinical studies identified twelve studies including two meta-analyses and ten comparative cohort studies that included a large number of patients. The data in these studies are heterogeneous, often biased, and do not permit a formal recommendation based on a high level of evidence. The main conclusion of this review is that the balance of benefit vs. risk (analgesic effect/risk of anastomotic disruption) is acceptable; it appears (with a low level of evidence) that a prescription of NSAID for 48h after surgery may be recommended for elective colon surgery. Nevertheless, it is important to respect the specific contra-indications of NSAID and avoid post-operative NSAID use if there are risk factors for anastomotic leakage: advanced age, malnutrition, severe co-morbidities, intra-operative difficulties. PMID:27480526

  16. N-Amino acid linoleoyl conjugates: anti-inflammatory activities.

    PubMed

    Burstein, Sumner; McQuain, Catherine; Salmonsen, Rebecca; Seicol, Benjamin

    2012-01-15

    Several N-linked amino acid-linoleic acid conjugates were studied for their potential as anti inflammatory agents. The parent molecule, N-linoleoylglycine was tested in an in vivo model, the mouse peritonitis assay where it showed activity in reducing leukocyte migration at doses as low as 0.3mg/kg when administered by mouth in safflower oil. Harvested peritoneal cells produced elevated levels of the inflammation-resolving eicosanoid 15-deoxy-Δ(13,14)-PGJ(2). These results are similar to those obtained in earlier studies with N-arachidonoylglycine. An in vitro model using mouse macrophage RAW cells was used to evaluate a small group of structural analogs for their ability to stimulate 15-deoxy-Δ(13,14)-PGJ(2) production. The d-alanine derivative was the most active while the d-phenylalanine showed almost no response. A high degree of stereo specificity was observed comparing the d and l alanine isomers; the latter being the less active. It was concluded that linoleic acid conjugates could provide suitable templates in a drug discovery program leading to novel agents for promoting the resolution of chronic inflammation. PMID:22217875

  17. [Non-steroidal anti-inflammatory drugs in pregnancy].

    PubMed

    Valha, P; Zmrhal, J; Feyereisl, J

    2010-02-01

    Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic (lowering an elevated body temperature and relieving pain without impairing consciousness) and, in higher doses, with anti-inflammatory effects (reducing inflammation). As inhibitors of cyclooxygenase NSAIDs given during pregnancy have the potential to cause adverse maternal and fetal effects. Maternal effects include prolongation of pregnancy and labour, whereas constriction of the ductus arteriosus, renal dysfunction and haemostatic abnormalities can occur in the fetus and neonate. As weak acids, NSAIDs are excreted in small amounts into human breast milk with little risk for adverse effects in the suckling infant. PMID:20437842

  18. Kalanchosine dimalate, an anti-inflammatory salt from Kalanchoe brasiliensis.

    PubMed

    Costa, Sônia Soares; de Souza, Maria de Lourdes Mendes; Ibrahim, Tereza; de Melo, Giany Oliveira; de Almeida, Ana Paula; Guette, Catherine; Férézou, Jean-Pierre; Koatz, Vera Lucia G

    2006-05-01

    This report describes the isolation and characterization of kalanchosine dimalate (KMC), an anti-inflammatory salt from the fresh juice of the aerial parts of Kalanchoe brasiliensis. KMC comprises the new metabolite kalanchosine (1) and malic acid (2) in a 1:2 stoichiometric ratio. Kalanchosine (1), 3,6-diamino-4,5-dihydroxyoctanedioic acid, is the first naturally occurring dimeric bis(gamma-hydroxy-beta-amino acid) and is at least partially responsible for the anti-inflammatory properties of K. brasiliensis. PMID:16724848

  19. Vasoconstrictor and the anti-inflammatory effects of 7 corticosteroids.

    PubMed

    Crijns, M B; Nater, J P; van Oostveen, F; van der Valk, P G

    1984-08-01

    The vasoconstrictor effect of 7 proprietary corticosteroid creams was compared with their effect on patches of allergic contact dermatitis provoked by patch testing in 20 subjects. A parallel between the blanching effect on the normal skin and the anti-inflammatory effect on the eczematous skin was generally found. A modified patch test method using the Finn chamber technique is described, which (with certain restrictions) offers an opportunity of studying the anti-inflammatory effect of corticosteroids on allergic dermatitis under standard conditions. PMID:6488765

  20. Biological evaluation of Phellinus linteus-fermented broths as anti-inflammatory agents.

    PubMed

    Lin, Chun-Jung; Lien, Hsiu-Man; Chang, Hsiao-Yun; Huang, Chao-Lu; Liu, Jau-Jin; Chang, Yun-Chieh; Chen, Chia-Chang; Lai, Chih-Ho

    2014-07-01

    Phellinus linteus and its constituent hispolon induce potent anti-inflammatory activity in macrophages. Efficient production of the effective constituent and the biological function of P. linteus in the regulation of innate sensing have rarely been investigated. The aim of this study was to efficiently manufacture P. linteus-fermented broth containing the effective constituent, hispolon, and evaluate its immunoregulatory functions in macrophages. Four distinct fermented broths (PL1-4) and the medium dialyzate (MD) were prepared to screen suitable culture conditions for the mycelial growth of P. linteus. The P. linteus-fermented broth exhibited a dose-responsive inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production by murine macrophages. In addition, the P. linteus-fermented broths suppressed macrophage LPS-mediated nuclear factor (NF)-κB activity and tumor necrosis factor (TNF)-α. Among the tested samples from P. linteus, PL4 contained vast amounts of hispolon and showed the greatest anti-inflammatory activity in both the RAW264.7 cells and murine primary peritoneal exudate macrophages (PEMs). This study demonstrates that the purification of the effective constituent from P. linteus-fermented broth may enable the production of a potent therapeutic agent for anti-inflammation in macrophages. PMID:24503424

  1. Tetra- and pentacyclic triterpene acids from the ancient anti-inflammatory remedy frankincense as inhibitors of microsomal prostaglandin E(2) synthase-1.

    PubMed

    Verhoff, Moritz; Seitz, Stefanie; Paul, Michael; Noha, Stefan M; Jauch, Johann; Schuster, Daniela; Werz, Oliver

    2014-06-27

    The microsomal prostaglandin E2 synthase (mPGES)-1 is the terminal enzyme in the biosynthesis of prostaglandin (PG)E2 from cyclooxygenase (COX)-derived PGH2. We previously found that mPGES-1 is inhibited by boswellic acids (IC50 = 3-30 μM), which are bioactive triterpene acids present in the anti-inflammatory remedy frankincense. Here we show that besides boswellic acids, additional known triterpene acids (i.e., tircuallic, lupeolic, and roburic acids) isolated from frankincense suppress mPGES-1 with increased potencies. In particular, 3α-acetoxy-8,24-dienetirucallic acid (6) and 3α-acetoxy-7,24-dienetirucallic acid (10) inhibited mPGES-1 activity in a cell-free assay with IC50 = 0.4 μM, each. Structure-activity relationship studies and docking simulations revealed concrete structure-related interactions with mPGES-1 and its cosubstrate glutathione. COX-1 and -2 were hardly affected by the triterpene acids (IC50 > 10 μM). Given the crucial role of mPGES-1 in inflammation and the abundance of highly active triterpene acids in frankincence extracts, our findings provide further evidence of the anti-inflammatory potential of frankincense preparations and reveal novel, potent bioactivities of tirucallic acids, roburic acids, and lupeolic acids. PMID:24844534

  2. Tetra- and Pentacyclic Triterpene Acids from the Ancient Anti-inflammatory Remedy Frankincense as Inhibitors of Microsomal Prostaglandin E2 Synthase-1

    PubMed Central

    2014-01-01

    The microsomal prostaglandin E2 synthase (mPGES)-1 is the terminal enzyme in the biosynthesis of prostaglandin (PG)E2 from cyclooxygenase (COX)-derived PGH2. We previously found that mPGES-1 is inhibited by boswellic acids (IC50 = 3–30 μM), which are bioactive triterpene acids present in the anti-inflammatory remedy frankincense. Here we show that besides boswellic acids, additional known triterpene acids (i.e., tircuallic, lupeolic, and roburic acids) isolated from frankincense suppress mPGES-1 with increased potencies. In particular, 3α-acetoxy-8,24-dienetirucallic acid (6) and 3α-acetoxy-7,24-dienetirucallic acid (10) inhibited mPGES-1 activity in a cell-free assay with IC50 = 0.4 μM, each. Structure–activity relationship studies and docking simulations revealed concrete structure-related interactions with mPGES-1 and its cosubstrate glutathione. COX-1 and -2 were hardly affected by the triterpene acids (IC50 > 10 μM). Given the crucial role of mPGES-1 in inflammation and the abundance of highly active triterpene acids in frankincence extracts, our findings provide further evidence of the anti-inflammatory potential of frankincense preparations and reveal novel, potent bioactivities of tirucallic acids, roburic acids, and lupeolic acids. PMID:24844534

  3. Antioxidant activity and anti-inflammatory activity of ethanol extract and fractions of Doenjang in LPS-stimulated RAW 264.7 macrophages

    PubMed Central

    Son, Dahee; Chung, Young-Shin; Kwon, Young Hye

    2015-01-01

    macrophages. CONCLUSIONS Twelve month-aged Doenjang has potent antioxidant and anti-inflammatory activities with high levels of phenolics and isoflavone aglycones, and can be used as a beneficial food for human health. PMID:26634044

  4. Anti-inflammatory properties of molecular hydrogen: investigation on parasite-induced liver inflammation.

    PubMed

    Gharib, B; Hanna, S; Abdallahi, O M; Lepidi, H; Gardette, B; De Reggi, M

    2001-08-01

    Molecular hydrogen reacts with the hydroxyl radical, a highly cytotoxic species produced in inflamed tissues. It has been suggested therefore to use gaseous hydrogen in a new anti-inflammatory strategy. We tested this idea, with the aid of the equipment and skills of COMEX SA in Marseille, a group who experiments with oxygen-hydrogen breathing mixtures for professional deep-sea diving. The model used was schistosomiasis-associated chronic liver inflammation. Infected animals stayed 2 weeks in an hyperbaric chamber in a normal atmosphere supplemented with 0.7 MPa hydrogen. The treatment had significant protective effects towards liver injury, namely decreased fibrosis, improvement of hemodynamics, increased NOSII activity, increased antioxidant enzyme activity, decreased lipid peroxide levels and decreased circulating TNF-alpha levels. Under the same conditions, helium exerted also some protective effects, indicating that hydroxyl radical scavenging is not the only protective mechanism. These findings indicate that the proposed anti-inflammatory strategy deserves further attention. PMID:11510417

  5. Anti-inflammatory effects of Houttuynia cordata supercritical extract in carrageenan-air pouch inflammation model.

    PubMed

    Kim, Dajeong; Park, Dongsun; Kyung, Jangbeen; Yang, Yun-Hui; Choi, Ehn-Kyoung; Lee, Yoon-Bok; Kim, Hyun-Kyu; Hwang, Bang Yeon; Kim, Yun-Bae

    2012-06-01

    Anti-inflammatory effects of Houttuynia cordata supercritical extract (HSE) were investigated in rat carrageenan-air pouch model. Oral administration of HSE (50-200 mg/kg) suppressed carrageenan-induced exudation and albumin leakage, as well as inflammatory cell infiltration at a high dose (200 mg/kg). Intraperitoneal injection of dexamethasone (2 mg/kg) only decreased exudation and cell infiltration, while indomethacin (2 mg/kg, i.p.) reduced exudate volume and albumin content without influence on the cell number. HSE lowered tumor-necrosis factor-α (TNF-α) and nitric oxide (NO), as well as prostaglandin E(2) (PGE(2)). Dexamethasone only reduced TNF-α and NO, while indomethacin decreased PGE(2). The results indicate that HSE exhibits anti-inflammatory effects by inhibiting both TNF-α-NO and cyclooxygenase-2-PGE(2) pathways. PMID:22787488

  6. Screening of the topical anti-inflammatory activity of some Central American plants.

    PubMed

    Sosa, S; Balick, M J; Arvigo, R; Esposito, R G; Pizza, C; Altinier, G; Tubaro, Aurelia

    2002-07-01

    Hexane, chloroform and methanol extracts of seven herbal drugs used in the folk medicine of Central America against skin disorders (Aristolochia trilobata leaves and bark, Bursera simaruba bark, Hamelia patens leaves, Piper amalago leaves, and Syngonium podophyllum leaves and bark) were evaluated for their topical anti-inflammatory activity against the Croton oil-induced ear oedema in mice. Most of the extracts induced a dose-dependent oedema reduction. The chloroform extract of almost all the drugs exhibited interesting activities with ID(50) values ranging between 108 and 498 micro g/cm(2), comparable to that of indomethacin (93 micro g/cm(2)). Therefore, the tested plants are promising sources of principles with high anti-inflammatory activity. PMID:12065153

  7. Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites

    PubMed Central

    Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I.

    2010-01-01

    Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) to lipoxin A4 (LXA4) and 15-epi-LXA4. However it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE2, TXB2 and leukotriene B4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE2, but increased LTB4, LXA4 and 15-epi-LXA4 concentrations. Both doses attenuated the LPS effects on PGE2, and TXB2. The increments in LXA4 and 15-epi-LXA4 caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA4 and 15-epi-LXA4 and reduce pro-inflammatory PGE2 and TXB2 suggests considering aspirin further for treating clinical neuroinflammation. PMID:20981485

  8. Colitis caused by non-steroidal anti-inflammatory drugs.

    PubMed Central

    Ravi, S.; Keat, A. C.; Keat, E. C.

    1986-01-01

    Four cases of acute proctocolitis associated with non-steroidal anti-inflammatory drug therapy are presented. The drugs implicated were flufenamic acid, mefenamic acid, naproxen and ibuprofen. After resolution of symptoms and signs of proctocolitis three of the four patients were subsequently rechallenged with the implicated drug: in each there was a rapid relapse. PMID:3774712

  9. The Use of Nonsteroidal Anti-Inflammatory Drugs in Sports.

    ERIC Educational Resources Information Center

    Calabrese, Leonard H.; Rooney, Theodore W.

    1986-01-01

    Recent advances in the understanding of the mechanism of action and clinical pharmacology of the new nonsteroidal anti-inflammatory drugs (NSAIDs) can help practitioners decide which to use and how to administer them. Indications for and effects of NSAIDs are described. (MT)

  10. The present status of anti-inflammatory agents in dermatology.

    PubMed

    Stüttgen, G

    1988-01-01

    Many classes of drugs exert anti-inflammatory activity through mechanisms which affect all or part of the inflammatory process. Some of these agents are beneficial in the practice of dermatology, while others, such as penicillamine, mast cell blockers and serotonin antagonists, find little or no application. Corticosteroids, for example, are nonspecific in their anti-inflammatory effects and remain a mainstay of therapy, despite their side effect profile. Other drugs, such as the non-steroidal anti-inflammatory agents or gold, can be used in the treatment of diseases associated with rheumatic or autoimmune states. Moreover, antihistamines play an important role in the control of itching, but are mainly indicated in controlling non-dermatological allergic sequelae. Interestingly, chloroquine and dapsone, which were originally developed for use in malaria prophylaxis and leprosy, respectively, have value in treating a wide range of dermatological conditions via mechanisms which include the inhibition of P-450 isoenzymes. In diseases characterised by disturbed cornification (e.g. psoriasis pustulosa), retinoids are of particular value. These drugs are thought to act by inhibition of collagenases, proteases and granulocyte migration. Undoubtedly, further investigation of drug classes such as oxygen radical controllers and immunomodulators will clarify their mechanisms and establish their therapeutic usefulness among the anti-inflammatory agents now available for dermatological use. PMID:3076131

  11. Glycosaminoglycan analogs as a novel anti-inflammatory strategy

    PubMed Central

    Severin, India C.; Soares, Adriano; Hantson, Jennifer; Teixeira, Mauro; Sachs, Daniela; Valognes, Delphine; Scheer, Alexander; Schwarz, Matthias K.; Wells, Timothy N. C.; Proudfoot, Amanda E. I.; Shaw, Jeffrey

    2012-01-01

    Heparin, a glycosaminoglycan (GAG), has both anti-inflammatory and anti-coagulant properties. The clinical use of heparin against inflammation, however, has been limited by concerns about increased bleeding. While the anti-coagulant activity of heparin is well understood, its anti-inflammatory properties are less so. Heparin is known to bind to certain cytokines, including chemokines, small proteins which mediate inflammation through their control of leukocyte migration and activation. Molecules which can interrupt the chemokine-GAG interaction without inhibiting coagulation could therefore, represent a new class of anti-inflammatory agents. In the present study, two approaches were undertaken, both focusing on the heparin-chemokine relationship. In the first, a structure based strategy was used: after an initial screening of potential small molecule binders using protein NMR on a target chemokine, binding molecules were optimized through structure-based design. In the second approach, commercially available short oligosaccharides were polysulfated. In vitro, these molecules prevented chemokine-GAG binding and chemokine receptor activation without disrupting coagulation. However, in vivo, these compounds caused variable results in a murine peritoneal recruitment assay, with a general increase of cell recruitment. In more disease specific models, such as antigen-induced arthritis and delayed-type hypersensitivity, an overall decrease in inflammation was noted, suggesting that the primary anti-inflammatory effect may also involve factors beyond the chemokine system. PMID:23087686

  12. Viscum album Exerts Anti-Inflammatory Effect by Selectively Inhibiting Cytokine-Induced Expression of Cyclooxygenase-2

    PubMed Central

    Hegde, Pushpa; Maddur, Mohan S.; Friboulet, Alain; Bayry, Jagadeesh; Kaveri, Srini V.

    2011-01-01

    Viscum album (VA) preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2) and prostaglandin E2 (PGE2) play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells) as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez) for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2. PMID:22028854

  13. Fatty acid-binding protein 5 limits the anti-inflammatory response in murine macrophages.

    PubMed

    Moore, Sherri M; Holt, Vivian V; Malpass, Lillie R; Hines, Ian N; Wheeler, Michael D

    2015-10-01

    The beginning stages of liver damage induced by various etiologies (i.e. high fat diet, alcohol consumption, toxin exposure) are characterized by abnormal accumulation of lipid in liver. Alterations in intracellular lipid transport, storage, and metabolism accompanied by cellular insult within the liver play an important role in the pathogenesis of liver disease, often involving a sustained inflammatory response. The intracellular lipid transporter, fatty acid binding protein 5 (FABP5), is highly expressed in macrophages and may play an important role in the hepatic inflammatory response after endotoxin exposure in mice. This study tested the hypothesis that FABP5 regulates macrophage response to LPS in male C57bl/6 (wild type) and FABP5 knockout mice, both in vitro and in vivo. Treatment with LPS revealed that loss of FABP5 enhances the number of hepatic F4/80(+) macrophages in the liver despite limited liver injury. Conversely, FABP5 knock out mice display higher mRNA levels of anti-inflammatory cytokines IL-10, arginase, YM-1, and Fizz-1 in liver compared to wild type mice. Bone marrow derived macrophages stimulated with inflammatory (LPS and IFN-γ) or anti-inflammatory (IL-4) mediators also showed significantly higher expression of anti-inflammatory/regulatory factors. These findings reveal a regulatory role of FABP5 in the acute inflammatory response to LPS-induced liver injury, which is consistent with the principle finding that FABP5 is a regulator of macrophage phenotype. Specifically, these findings demonstrate that loss of FABP5 promotes a more anti-inflammatory response. PMID:26105806

  14. Evaluation of analgesic, antipyretic and anti-inflammatory activity on Cordia dichotoma G. Forst. Leaf

    PubMed Central

    Gupta, Richa; Kaur, Jagjit

    2015-01-01

    Background: Cordia dichotoma G. Forst. is an important medicinal plant of family Boraginaceae. Traditionally, its leaves are used to treat fever, headache, and joint pain but its medicinal activities have not been proven by research. Objective: To evaluate the analgesic, anti-inflammatory, and antipyretic activity of C. dichotoma G. Forst. leaf extract. Material and Methods: The various extracts of leaf powder were prepared by using soxhlet apparatus. The methanol extract was selected for pharmacological study. To evaluate analgesic activity, Eddy's hot plate method, to study anti-inflammatory activity, carageenan-induced rat paw edema method, and to study antipyretic activity, yeast-induced pyrexia method was used. SD female rats (180-200 g) were used for the study. Results: In all three tests, the methanol extract high dose (400 mg/kg) was found to be highly significant as compared to standard drug. Conclusion: This study proved the traditional uses of plant leaves and concluded the analgesic, anti-inflammatory, and antipyretic activity of the leaf methanol extract. PMID:25598647

  15. Anti-inflammatory drug delivery from hyaluronic acid hydrogels.

    PubMed

    Hahn, Sei K; Jelacic, Sandra; Maier, Ronald V; Stayton, Patrick S; Hoffman, Allan S

    2004-01-01

    Two different types of hyaluronic acid (HA) hydrogels were synthesized by crosslinking HA with divinyl sulfone (DVS) and poly(ethylene glycol)-divinyl sulfone (VS-PEG-VS). Vitamin E succinate (VES), an anti-inflammatory drug, and bovine serum albumin (BSA), a model of anti-inflammatory protein drugs, were loaded into the gels and their release kinetics were measured in vitro. VES and BSA released with a burst from both HA hydrogels during the first few hours, and release continued gradually for several days. The rate of release from HA-VS-PEG-VS-HA hydrogels was faster than that from HA-DVS-HA hydrogels, presumably due to the lower crosslink density in the former. The anti-inflammatory action of released VES was tested by incubating peripheral blood mononuclear cells (PBMC) on HA hydrogels with and without VES in the gel. The number of cells adhering on HA hydrogels was very low compared to that on tissue culture polystyrene (TCPS), which might be one of the important advantages of using HA hydrogels for implant coatings or tissue engineering applications. ELISA test results showed that the tumor necrosis factor-alpha (TNF-alpha) concentration was very low in the supernatant of the wells containing the HA hydrogel with VES in contact with the activated macrophages compared to that without VES. This is probably the effect of the released VES reducing the production of anti-inflammatory cytokine, TNF-alpha. HA hydrogels containing anti-inflammatory drugs may have potential for use in tissue engineering and also as biocompatible coatings of implants. PMID:15503629

  16. Anti-Inflammatory and Antioxidant Mechanism of Tangeretin in Activated Microglia.

    PubMed

    Lee, Yu Young; Lee, Eun-Jung; Park, Jin-Sun; Jang, Se-Eun; Kim, Dong-Hyun; Kim, Hee-Sun

    2016-06-01

    Tangeretin, a flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models, but further study is necessary for elucidating the detailed mechanisms of these effects. In this study, we examined the anti-inflammatory effect of tangeretin in lipopolysaccharide (LPS)-stimulated microglia. We first observed that tangeretin inhibited LPS-induced production of nitric oxide, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β, as well as LPS-induced mRNA expression of inducible nitric oxide synthases and cytokines. Additionally, we found that the activities, mRNA levels, and protein levels of matrix metalloproteinase (MMP)-3 and MMP-8 were inhibited, while the expression of tissue inhibitor of metalloproteinase-2 was enhanced by tangeretin in LPS-stimulated microglia. Further mechanistic study showed that tangeretin suppressed LPS-induced phosphorylation of mitogen-activated protein kinases and Akt. Also, tangeretin inhibited nuclear factor-κB by upregulating sirtuin 1 and 5'-adenosine monophosphate-activated protein kinase. We further demonstrated the antioxidant effect of tangeretin by showing that tangeretin inhibited reactive oxygen species production and p47(phox) phosphorylation, while enhancing the expression of heme oxygenase-1 and the DNA binding activity of nuclear factor-erythroid 2-related factor 2 to the antioxidant response element in LPS-stimulated microglia. Taken together, the results of the present study demonstrate that tangeretin possesses a potent anti-inflammatory and antioxidant effect in microglia. PMID:26899309

  17. Synthesis and anti-inflammatory properties of some aromatic and heterocyclic aromatic curcuminoids.

    PubMed

    Khan, M Akram; El-Khatib, Riyad; Rainsford, K D; Whitehouse, M W

    2012-02-01

    A variety of novel aromatic and heterocyclic aromatic curcuminoids were synthesised, characterised and their anti-inflammatory activities (AIA) determined in vivo. Some of these compounds also were tested for inflammatory mediator production. The AIA of the main representatives of these compounds were assessed by oral administration to female Wistar rats using (a) acute carrageenan-induced paw oedema, (b) chronic adjuvant arthritis (therapeutic mode), and (c) anti-pyretic activity assessed in the yeast pyrexia. Gastric ulceration was determined in pre-inflamed rats. Natural curcumin showed modest aspirin-like anti-inflammatory activity which was enhanced when co-administered with the PGE(1) analogue misoprostol as a synergist. In contrast, four novel curcuminoids (RK-97, RK-103, RK-104 and RK-106) in which the bis-methoxy-phenyl group of curcumin was replaced with bis-dimethoxybutenolidyl-(ascorbate), bis-naphthyl, and bis-furanyl derivatives, respectively, had potent activity in the anti-arthritic assay with little gastric or systemic toxicity, compared with the vehicle-treated controls. Of the curcuminoids the furan RK-106 was the only compound to inhibit production of TNFα and IL-1β in a monocytic cell-line THP-1 in vitro. The inactivity of RK-106 on the production of PGE(2) may be related to its absence of gastrotoxicity. None of the curcuminoids exhibited anti-pyretic activity and this may also be related to its insensitivity to PGE(2). Thus, these novel curcuminoids, such as RK-106, may warrant the development of new low gastro-toxic anti-inflammatory agents with selective inhibitory activity of cytokine inflammatory mediators. PMID:22172598

  18. Anti-oxidative and anti-inflammatory effects of Tagetes minuta essential oil in activated macrophages

    PubMed Central

    Karimian, Parastoo; Kavoosi, Gholamreza; Amirghofran, Zahra

    2014-01-01

    Objective To investigate antioxidant and anti-inflammatory effects of Tagetes minuta (T. minuta) essential oil. Methods In the present study T. minuta essential oil was obtained from leaves of T. minuta via hydro-distillation and then was analyzed by gas chromatography-mass spectrometry. The anti-oxidant capacity of T. minuta essential oil was examined by measuring reactive oxygen, reactive nitrogen species and hydrogen peroxide scavenging. The anti-inflammatory activity of T. minuta essential oil was determined through measuring NADH oxidase, inducible nitric oxide synthase and TNF-α mRNA expression in lipopolysacharide-stimulated murine macrophages using real-time PCR. Results Gas chromatography-mass spectrometry analysis indicated that the main components in the T. minuta essential oil were dihydrotagetone (33.86%), E-ocimene (19.92%), tagetone (16.15%), cis-β-ocimene (7.94%), Z-ocimene (5.27%), limonene (3.1%) and epoxyocimene (2.03%). The T. minuta essential oil had the ability to scavenge all reactive oxygen/reactive nitrogen species radicals with IC50 12-15 µg/mL, which indicated a potent radical scavenging activity. In addition, T. minuta essential oil significantly reduced NADH oxidase, inducible nitric oxide synthaseand TNF-α mRNA expression in the cells at concentrations of 50 µg/mL, indicating a capacity of this product to potentially modulate/diminish immune responses. Conclusions T. minuta essential oil has radical scavenging and anti-inflammatory activities and could potentially be used as a safe effective source of natural anti-oxidants in therapy against oxidative damage and stress associated with some inflammatory conditions. PMID:25182441

  19. Methanol extract of Xanthium strumarium L. possesses anti-inflammatory and anti-nociceptive activities.

    PubMed

    Kim, In-Tae; Park, Young-Mi; Won, Jong-Heon; Jung, Hyun-Ju; Park, Hee-Juhn; Choi, Jong-Won; Lee, Kyung-Tae

    2005-01-01

    As an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the effects of the methanol extract of the semen of Xanthium strumarium L. (MEXS) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) production in RAW 264.7 cells. Our data indicate that MEXS is a potent inhibitor of NO, PGE2 and TNF-alpha production. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2 and TNF-alpha mRNA were down-regulated in a concentration-dependent manner. Furthermore, MEXS inhibited nuclear factor kappa B (NF-kappaB) DNA binding activity and the translocation of NF-kappaB to the nucleus by blocking the degradation of inhibitor of kappa B-alpha (IkappaB-alpha). We further evaluated the anti-inflammatory and anti-nociceptive activities of MEXS in vivo. MEXS (100, 200 mg/kg/d, p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activities in an acetic acid-induced abdominal constriction test and a hot plate test in mice. Thus, our study suggests that the inhibitions of iNOS, COX-2 expression, and TNF-alpha release by the methanol extract of the semen of Xanthium strumarium L. are achieved by blocking NF-kappaB activation, and that this is also responsible for its anti-inflammatory effects. PMID:15635170

  20. Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases.

    PubMed

    Pham, Tho X; Park, Young-Ki; Lee, Ji-Young

    2016-01-01

    We previously demonstrated that the organic extract of Spirulina platensis (SPE), an edible blue-green alga, possesses potent anti-inflammatory effects. In this study, we investigated if the regulation of histone deacetylases (HDACs) play a role in the anti-inflammatory effect of SPE in macrophages. Treatment of macrophages with SPE rapidly and dose-dependently reduced HDAC2, 3, and 4 proteins which preceded decreases in their mRNA levels. Degradation of HDAC4 protein was attenuated in the presence of inhibitors of calpain proteases, lysosomal acidification, and Ca(2+)/calmodulin-dependent protein kinase II, respectively, but not a proteasome inhibitor. Acetylated histone H3 was increased in SPE-treated macrophages to a similar level as macrophages treated with a pan-HDAC inhibitor, with concomitant inhibition of inflammatory gene expression upon LPS stimulation. Knockdown of HDAC3 increased basal and LPS-induced pro-inflammatory gene expression, while HDAC4 knockdown increased basal expression of interleukin-1β (IL-1β), but attenuated LPS-induced inflammatory gene expression. Chromatin immunoprecipitation showed that SPE decreased p65 binding and H3K9/K14 acetylation at the Il-1β and tumor necrosis factor α (Tnfα) promoters. Our results suggest that SPE increased global histone H3 acetylation by facilitating HDAC protein degradation, but decreases histone H3K9/K14 acetylation and p65 binding at the promoters of Il-1β and Tnfα to exert its anti-inflammatory effect. PMID:27338466

  1. Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases

    PubMed Central

    Pham, Tho X.; Park, Young-Ki; Lee, Ji-Young

    2016-01-01

    We previously demonstrated that the organic extract of Spirulina platensis (SPE), an edible blue-green alga, possesses potent anti-inflammatory effects. In this study, we investigated if the regulation of histone deacetylases (HDACs) play a role in the anti-inflammatory effect of SPE in macrophages. Treatment of macrophages with SPE rapidly and dose-dependently reduced HDAC2, 3, and 4 proteins which preceded decreases in their mRNA levels. Degradation of HDAC4 protein was attenuated in the presence of inhibitors of calpain proteases, lysosomal acidification, and Ca2+/calmodulin-dependent protein kinase II, respectively, but not a proteasome inhibitor. Acetylated histone H3 was increased in SPE-treated macrophages to a similar level as macrophages treated with a pan-HDAC inhibitor, with concomitant inhibition of inflammatory gene expression upon LPS stimulation. Knockdown of HDAC3 increased basal and LPS-induced pro-inflammatory gene expression, while HDAC4 knockdown increased basal expression of interleukin-1β (IL-1β), but attenuated LPS-induced inflammatory gene expression. Chromatin immunoprecipitation showed that SPE decreased p65 binding and H3K9/K14 acetylation at the Il-1β and tumor necrosis factor α (Tnfα) promoters. Our results suggest that SPE increased global histone H3 acetylation by facilitating HDAC protein degradation, but decreases histone H3K9/K14 acetylation and p65 binding at the promoters of Il-1β and Tnfα to exert its anti-inflammatory effect. PMID:27338466

  2. The Combination of N-Acetyl Cysteine, Alpha-Lipoic Acid, and Bromelain Shows High Anti-Inflammatory Properties in Novel In Vivo and In Vitro Models of Endometriosis

    PubMed Central

    Agostinis, C.; Zorzet, S.; De Leo, R.; Zauli, G.; De Seta, F.; Bulla, R.

    2015-01-01

    To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory “marker” VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis. PMID:25960622

  3. The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis.

    PubMed

    Agostinis, C; Zorzet, S; De Leo, R; Zauli, G; De Seta, F; Bulla, R

    2015-01-01

    To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory "marker" VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis. PMID:25960622

  4. Anti-inflammatory action of high molecular weight Mytilus edulis hydrolysates fraction in LPS-induced RAW264.7 macrophage via NF-κB and MAPK pathways.

    PubMed

    Kim, Young-Sang; Ahn, Chang-Bum; Je, Jae-Young

    2016-07-01

    Anti-inflammatory Mytilus edulis hydrolysates (MEHs) were prepared by peptic hydrolysis and MEH was further fractionated into three fractions based on molecular weight, namely >5kDa, 1-5kDa, and <1kDa. The >5kDa peptide fraction exerted the highest nitric oxide (NO) inhibitory activity and inhibited prostaglandin E2 (PGE2) secretion in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Pretreatment with the >5kDa peptide fraction markedly inhibited LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and gene expressions. Stimulation by LPS induced the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1β (IL-1β), whereas co-treatment with the >5kDa peptide fraction suppressed pro-inflammatory cytokine production. The >5kDa peptide fraction inhibited the translocation of NF-κB (nuclear factor-kappa B) through the prevention of IκBα (inhibitory factor kappa B alpha) phosphorylation and degradation and also inhibited the MAPK signaling pathway in LPS-stimulated RAW264.7 macrophages. PMID:26920260

  5. Anti-inflammatory effect of conditioned medium from human uterine cervical stem cells in uveitis.

    PubMed

    Bermudez, Maria A; Sendon-Lago, Juan; Seoane, Samuel; Eiro, Noemi; Gonzalez, Francisco; Saa, Jorge; Vizoso, Francisco; Perez-Fernandez, Roman

    2016-08-01

    The aim of the present study was to evaluate the effect of conditioned medium from human uterine cervical stem cells (CM-hUCESCs) in uveitis. To do that, uveitis was induced in rats after footpad injection of Escherichia coli lipopolysaccaride (LPS). Human retinal pigment epithelial (ARPE-19) cells after LPS challenge were used to test anti-inflammatory effect of CM-hUCESCs 'ìn vitro'. Real-time PCR was used to evaluate mRNA expression levels of the pro-inflammatory cytokines interkeukin-6, interkeukin-8, macrophage inflammatory protein-1 alpha, tumor necrosis factor alpha, and the anti-inflammatory interkeukin-10. Leucocytes from aqueous humor (AqH) were quantified in a Neubauer chamber, and eye histopathological analysis was done with hematoxylin-eosin staining. Additionally, using a human cytokine antibody array we evaluated CM-hUCESCs to determine mediating proteins. Results showed that administration of CM-hUCESCs significantly reduced LPS-induced pro-inflammatory cytokines both 'in vitro' and 'in vivo', and decreased leucocytes in AqH and ocular tissues. High levels of cytokines with anti-inflammatory effects were found in CM-hUCESCs, suggesting a possible role of these factors in reducing intraocular inflammation. In summary, treatment with CM-hUCESCs significantly reduces inflammation in uveitis. Our data indicate that CM-hUCESCs could be regarded as a potential therapeutic agent for patients suffering from ocular inflammation. PMID:27381329

  6. Rutin-loaded chitosan microspheres: Characterization and evaluation of the anti-inflammatory activity.

    PubMed

    Cosco, Donato; Failla, Paola; Costa, Nicola; Pullano, Salvatore; Fiorillo, Antonino; Mollace, Vincenzo; Fresta, Massimo; Paolino, Donatella

    2016-11-01

    Rutin was microencapsulated in a chitosan matrix using the spray-drying technique and the resulting system was investigated. High amounts of rutin were efficiently entrapped within polymeric microspheres, and these microparticles were characterized by a smooth surface and afforded a controlled release of the active compound. The anti-inflammatory activity of rutin-loaded microspheres was investigated in in vitro models of NCTC 2544 and C-28 cells treated with LPS by determining the levels of IL-1β and IL-6. The rutin-loaded microspheres showed an increase of in vitro anti-inflammatory activity with respect to the free active compound. Confocal laser scanning microscopy demonstrated that massive intracellular uptake of the chitosan microspheres took place after a few hours of incubation and that the drug was localized in the cytosol compartment of the treated cells. The improved anti-inflammatory activity of the rutin-loaded microspheres was further confirmed by an in vivo model of carrageenan-induced paw edema. PMID:27516307

  7. Antioxidant, Analgesic, Anti-Inflammatory, and Hepatoprotective Effects of the Ethanol Extract of Mahonia oiwakensis Stem

    PubMed Central

    Chao, Jung; Liao, Jiunn-Wang; Peng, Wen-Huang; Lee, Meng-Shiou; Pao, Li-Heng; Cheng, Hao-Yuan

    2013-01-01

    The aim of this study was to evaluate pharmacological properties of ethanol extracted from Mahonia oiwakensis Hayata stems (MOSEtOH). The pharmacological properties included antioxidant, analgesic, anti-inflammatory and hepatoprotective effects. The protoberberine alkaloid content of the MOSEtOH was analyzed by high-performance liquid chromatography (HPLC). The results revealed that three alkaloids, berberine, palmatine and jatrorrhizine, could be identified. Moreover, the MOSEtOH exhibited antioxidative activity using the DPPH assay (IC50, 0.743 mg/mL). The DPPH radical scavenging activity of MOSEtOH was five times higher that that of vitamin C. MOSEtOH was also found to inhibit pain induced by acetic acid, formalin, and carrageenan inflammation. Treatment with MOSEtOH (100 and 500 mg/kg) or silymarin (200 mg/kg) decreased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the CCl4-treated group. Histological evaluation showed that MOSEtOH reduced the degree of liver injury, including vacuolization, inflammation and necrosis of hepatocytes. The anti-inflammatory and hepatoprotective effect of MOSEtOH were found to be related to the modulation of antioxidant enzyme activity in the liver and decreases in malondialdehyde (MDA) level and nitric oxide (NO) contents. Our findings suggest that MOSEtOH has analgesic, anti-inflammatory and hepatoprotective effects. These effects support the use of MOSEtOH for relieving pain and inflammation in folk medicine. PMID:23364614

  8. Mechanisms of Action of Ig Preparations: Immunomodulatory and Anti-Inflammatory Effects

    PubMed Central

    Matucci, Andrea; Maggi, Enrico; Vultaggio, Alessandra

    2015-01-01

    Primary immunodeficiency (PID) disorders that predispose patients to recurrent infections require immunoglobulin (Ig) replacement therapy. Ig replacement therapy has been stated as beneficial, although the optimal IgG trough level to be maintained over time in order to minimize infectious risk has not been established. The most common route of administration of Ig has been intravenously, although there are different options, one of them being the subcutaneous route. Ig replacement therapy has been a life-saving treatment for patients suffering from primary and secondary antibody immunodeficiency. The key role of regular Ig replacement in patients with antibody deficiencies is related to the ability to provide specific antibodies that could not be produced by these patients as demonstrated by the reduction of severe infections such as meningitis and pneumonia. The therapeutic benefits of Ig may also be due to an active role in various anti-inflammatory and immunomodulatory activities, which may complicate the clinical picture of PID. Anti-inflammatory activities are seen more generally when intravenous Ig is administered at high dose. The immunomodulatory and anti-inflammatory activities are important not only in the treatment of autoimmune diseases but also in patients suffering from immunodeficiency. PMID:25628625

  9. Anti-inflammatory action of γ-irradiated genistein in murine peritoneal macrophage

    NASA Astrophysics Data System (ADS)

    Sung, Nak-Yun; Byun, Eui-Baek; Song, Du-Sup; Jin, Yeung-Bae; Park, Jae-Nam; Kim, Jae-Kyung; Park, Jong-Heum; Song, Beom-Seok; Park, Sang-Hyun; Lee, Ju-Woon; Kim, Jae-Hun

    2014-12-01

    This present study was to examine the cytotoxicity and anti-inflammatory activity of gamma (γ)-irradiated genistein in murine peritoneal macrophage. Inflammation to macrophage was induced by adding the lipopolysaccharide (LPS). γ-Irradiated genistein significantly decreased the cytotoxicity to murine peritoneal macrophage in dose ranges from 5 to 10 μM than that of non-irradiated genistein. Anti-inflammatory activity within the doses less than 2 μM showed that γ-irradiated genistein treatment remarkably reduced the lipopolysaccharide-induced inflammation by decreasing the nitric oxide (NO) and cytokines (TNF-α, IL-6) production. In a structural analysis through the high pressure liquid chromatography (HPLC), γ-irradiated genistein showed a new peak production distinguished from main peak of genistein (non-irradiated). Therefore, increase of anti-inflammatory activity may closely mediate with structural changes induced by γ irradiation exposure. Based on the above result, γ-irradiation could be an effective tool for reduction of toxicity and increase of physiological activity of biomolecules.

  10. The role of pro- and anti-inflammatory responses in silica-induced lung fibrosis

    PubMed Central

    Barbarin, Virginie; Nihoul, Aurélie; Misson, Pierre; Arras, Mohammed; Delos, Monique; Leclercq, Isabelle; Lison, Dominique; Huaux, Francois

    2005-01-01

    Background It has been generally well accepted that chronic inflammation is a necessary component of lung fibrosis but this concept has recently been challenged. Methods Using biochemical, histological, immunohistochemistry, and cellular analyses, we compared the lung responses (inflammation and fibrosis) to fibrogenic silica particles (2.5 and 25 mg/g lung) in Sprague-Dawley rats and NMRI mice. Results Rats treated with silica particles developed chronic and progressive inflammation accompanied by an overproduction of TNF-α as well as an intense lung fibrosis. Dexamethasone or pioglitazone limited the amplitude of the lung fibrotic reaction to silica in rats, supporting the paradigm that inflammation drives lung fibrosis. In striking contrast, in mice, silica induced only a limited and transient inflammation without TNF-α overproduction. However, mice developed lung fibrosis of a similar intensity than rats. The fibrotic response in mice was accompanied by a high expression of the anti-inflammatory and fibrotic cytokine IL-10 by silica-activated lung macrophages. In mice, IL-10 was induced only by fibrotic particles and significantly expressed in the lung of silica-sensitive but not silica-resistant strains of mice. Anti-inflammatory treatments did not control lung fibrosis in mice. Conclusion These results indicate that, beside chronic lung inflammation, a pronounced anti-inflammatory reaction may also contribute to the extension of silica-induced lung fibrosis and represents an alternative pathway leading to lung fibrosis. PMID:16212659

  11. Effects of quinone derivatives, such as 1,4-naphthoquinone, on DNA polymerase inhibition and anti-inflammatory action.

    PubMed

    Kobayashi, Kazuki; Nishiumi, Shin; Nishida, Masayuki; Hirai, Midori; Azuma, Takeshi; Yoshida, Hiromi; Mizushina, Yoshiyuki; Yoshida, Masaru

    2011-01-01

    Previously, we reported that vitamin K(3), which consists of a quinone component, inhibits the activity of human DNA polymerase γ (pol γ). In this study, we investigated the inhibitory effects of 4 quinone derivatives (1,4-benzoquinone (BQ), 1,4-naphthoquinone (NQ), 9,10-anthraquinone (AQ) and 5,12-naphthacenequinone (NCQ)) on the activity of mammalian pols. BQ and NQ potently inhibited the activity of all the pol species: pols α, β, γ, δ, ε and λ, and NQ was a stronger pol inhibitor than BQ. Because we previously found a positive relationship between pol l inhibition and anti-inflammatory action, we examined whether these quinone derivatives could inhibit inflammatory responses. BQ and NQ caused a marked reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ear, although AQ and NCQ did not. In a cell culture system using mouse macrophages, NQ displayed the strongest suppression in the production of tumor necrosis factor (TNF)-α induced by lipopolysaccharide (LPS) among the quinone derivatives tested. Moreover, NQ was found to inhibit the action of nuclear factor (NF)-κ. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of BQ and NQ to mice led to suppression of TNF-α production in serum. These anti-inflammatory responses of NQ were more potent than those of BQ. In conclusion, this study has identified several quinone derivatives, such as NQ, that are promising anti-inflammatory candidates. PMID:21235518

  12. Topical anti-inflammatory activity of 2alpha-hydroxy pentacyclic triterpene acids from the leaves of Ugni molinae.

    PubMed

    Aguirre, María C; Delporte, Carla; Backhouse, Nadine; Erazo, Silvia; Letelier, María Eugenia; Cassels, Bruce K; Silva, Ximena; Alegría, Sergio; Negrete, Rosa

    2006-08-15

    Leaf extracts of Ugni molinae Turcz. are used in the Chilean cosmetic industry on the assumption that they have decongestant, regenerative, and anti-aging properties. A bioassay-guided fractionation of this plant material showed that some extracts have potent anti-inflammatory activities. Further fractionation led to the isolation and identification of betulinic acid, a mixture of ursolic and oleanolic acids, and the 2alpha-hydroxy derivatives alphitolic, asiatic, and corosolic acids. The latter three were evaluated in vivo in the mouse ear assay for their topical anti-inflammatory activity, inducing inflammation with either arachidonic acid (AA) or 12-O-tetradecanoylphorbol-13 acetate (TPA). Only corosolic acid was active in the AA assay, with similar potency to nimesulide, but all three triterpene acids inhibited TPA-induced inflammation with potencies comparable to that of indomethacin. PMID:16697209

  13. Anti-inflammatory effect of Momordica charantia in sepsis mice.

    PubMed

    Chao, Che-Yi; Sung, Ping-Jyun; Wang, Wei-Hsien; Kuo, Yueh-Hsiung

    2014-01-01

    Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe), a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPARα and PPARγ. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%), moderate (2%), and high (10%) ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA) were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-α tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-κB, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis. PMID:25153878

  14. Anti-Inflammatory Effect of Taurine in Burned Patients

    PubMed Central

    Lak, Sima; Ostadrahimi, Alireza; Nagili, Behrooz; Asghari-Jafarabadi, Mohammad; Beigzali, Sanaz; Salehi, Feridoon; Djafarzadeh, Roxana

    2015-01-01

    Purpose: Burn induced inflammatory response can be mediated by reactive oxygen metabolites and accompanied by multiple organ dysfunction. Taurine has protective effects against various inflammatory conditions. The aim of this study was to determine the effect of Taurine supplement in thermal burn victims. Methods: Thirty patients with severe thermal burns were enrolled in this randomized double-blinded clinical trial. These patients were randomly divided into two equal groups (namely Control and Taurine groups), where both received isocaloric and isonitrogenous formula. One group was supplemented with 50 mg/kg of Taurine per day for a duration of 10 days. Blood samples were obtained to measure Interleukin-10 (IL-10), high-sensitivity C-reactive protein (hs-CRP), and Tumor Necrosis Factor alpha (TNF-α) levels at the beginning and the end of the study. Results: Change in serum level of IL-10 in Taurine group was more than Control group [-13.60(-31.40, -10.40) compared to -4.00(-20.00, -0.20) respectively; P = 0.030]. This change was significant in patients with more than 30% TBSA of burn [-14.20(-31.40, -10.40) compared to -2.40(-9.60, 0.40) respectively; P = 0.013]. As for the hs-CRP and TNF-α levels, the difference between the two groups were not significant. Conclusion: Based on the results obtained, Taurine supplement showed a positive outcome on anti-inflammatory cytokine IL-10 in all burn patients. This effect was even more significant in patients with higher percentage of burn area. Taurine had no significant effect on the inflammatory marker hs-CRP and the pro-inflammatory cytokine TNF-α level. For a more thorough verification, measurement of a wider range of inflammatory cytokines in more frequent time intervals are suggested. PMID:26819926

  15. Anti-inflammatory and cytotoxic activities of Bursera copallifera

    PubMed Central

    Columba-Palomares, M. F. María C.; Villareal, Dra. María L.; Acevedo Quiroz, M. C. Macdiel E.; Marquina Bahena, M. C. Silvia; Álvarez Berber, Dra. Laura P.; Rodríguez-López, Dra. Verónica

    2015-01-01

    Background: The plant species Bursera copallifera (DC) bullock is used in traditional medicine to treat inflammation. The leaves of this plant can be prepared as an infusion to treat migraines, bronchitis, and dental pain Objective: The purpose of this study was to determine the anti-inflammatory and cytotoxic activities of organic extracts from the stems, stem bark, and leaves of B. copallifera, which was selected based on the knowledge of its traditional use. Materials and Methods: We evaluated the ability of extracts to inhibit mouse ear inflammation in response to topical application of 12-O tetradecanoylphorbol-13-acetate. The extracts with anti-inflammatory activity were evaluated for their inhibition of pro-inflammatory enzymes. In addition, the in vitro cytotoxic activities of the organic extracts were evaluated using the sulforhodamine B assay. Results: The hydroalcoholic extract of the stems (HAS) exhibited an anti-inflammatory activity of 54.3% (0.5 mg/ear), whereas the anti-inflammatory activity of the dichloromethane-methanol extract from the leaves (DMeL) was 55.4% at a dose of 0.1 mg/ear. Methanol extract from the leaves (MeL) showed the highest anti-inflammatory activity (IC50 = 4.4 μg/mL), hydroalcoholic extract of leaves, and DMeL also reduce the enzyme activity, (IC50 = 6.5 μg/mL, IC50 = 5.7 μg/mL), respectively, from stems HAS exhibit activity at the evaluated concentrations (IC50 =6.4 μg/mL). The hydroalcoholic extract of the stems exhibited the highest cytotoxic activity against a breast adenocarcinoma cell line (MCF7, IC50 = 0.90 μg/mL), whereas DMeL exhibited an IC50 value of 19.9 μg/mL. Conclusion: In conclusion, extracts from leaves and stems inhibited cyclooxygenase-1, which is the target enzyme for nonsteroidal anti inflammatory drugs, and some of these extracts demonstrated substantial antiproliferative effects against the MCF7 cell line. These results validate the traditional use of B. copallifera. PMID:26664022

  16. Validated RP-HPLC and HPTLC methods for determination of anti-inflammatory bis-indole alkaloid in Desmodium gangeticum.

    PubMed

    Yadav, Akhilesh K; Gupta, Madan M

    2014-01-01

    Here, two simple and accurate methods, namely high-performance liquid chromatography and high-performance thin-layer chromatography for the detection of gangenoid, an anti-inflammatory alkaloid, in a well-known Indian medicinal plant Desmodium gangeticum, are described. The proposed methods were successfully used for the estimation of gangenoid in D. gangeticum root. PMID:24079376

  17. Anti-inflammatory and analgesic effects of cucurbitacins from Wilbrandia ebracteata.

    PubMed

    Peters, R R; Farias, M R; Ribeiro-do-Valle, R M

    1997-12-01

    The anti-inflammatory and antinociceptive actions of the CH2Cl2 extract and semipurified fraction (F-III) from roots of Wilbrandia ebracteata Cogn. have been investigated in rats and mice. The CH2Cl2 extract (1-10 mg/kg, i.p.; ID50 5 mg/kg) and (3-30 mg/kg, p.o.; ID50 15 mg/kg) inhibited, in a dose-related manner, carrageenan-induced paw edema in rats. The subfraction (F-III) from CH2Cl2 extract and compounds isolated as cucurbitacin B and E also inhibited carrageenan-induced edema. The CH2Cl2 extract and F-III also exhibited significant analgesic action in acetic acid-induced pain in mice. In the formalin test, the CH2Cl2 extract (0.3-10 mg/kg, i.p.) and (3-30 mg/kg, p.o.) caused inhibition of the neurogenic (first phase) and inflammatory phase (second phase) of formalin-induced pain. However, the CH2Cl2 extract was more effective in relation to the second phase than in inhibition of the formalin-induced edema. These findings suggest that CH2Cl2 extract has potent anti-inflammatory and analgesic action and that F-III and cucurbitacin B and E may account for these actions. PMID:9434604

  18. Anti-Inflammatory and Antinociceptive Activities of Anthraquinone-2-Carboxylic Acid

    PubMed Central

    Park, Jae Gwang; Kim, Seung Cheol; Kim, Yun Hwan; Yang, Woo Seok; Kim, Yong; Hong, Sungyoul; Kim, Kyung-Hee; Yoo, Byong Chul; Kim, Shi Hyung; Kim, Jong-Hoon; Cho, Jae Youl

    2016-01-01

    Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, the in vivo anti-inflammatory activity and molecular mechanisms of anthraquinones have not been fully elucidated. We investigated the activity of anthraquinones using acute inflammatory and nociceptive experimental conditions. Anthraquinone-2-carboxylic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA), one of the major anthraquinones identified from Brazilian taheebo, ameliorated various inflammatory and algesic symptoms in EtOH/HCl- and acetylsalicylic acid- (ASA-) induced gastritis, arachidonic acid-induced edema, and acetic acid-induced abdominal writhing without displaying toxic profiles in body and organ weight, gastric irritation, or serum parameters. In addition, AQCA suppressed the expression of inflammatory genes such as cyclooxygenase- (COX-) 2 in stomach tissues and lipopolysaccharide- (LPS-) treated RAW264.7 cells. According to reporter gene assay and immunoblotting analyses, AQCA inhibited activation of the nuclear factor- (NF-) κB and activator protein- (AP-) 1 pathways by suppression of upstream signaling involving interleukin-1 receptor-associated kinase 4 (IRAK1), p38, Src, and spleen tyrosine kinase (Syk). Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive components in vivo, thus contributing to the immune regulatory role of fruits and herbs. PMID:27057092

  19. Steroids with anti-inflammatory activity from Vernonia nigritiana Oliv. & Hiern.

    PubMed

    Vassallo, Antonio; De Tommasi, Nunziatina; Merfort, Irmgard; Sanogo, Rokia; Severino, Lorella; Pelin, Marco; Della Loggia, Roberto; Tubaro, Aurelia; Sosa, Silvio

    2013-12-01

    The leaves of Vernonia nigritiana Oliv. & Hiern. (Asteraceae) were investigated for their in vivo topical anti-inflammatory properties, following a bioassay-oriented fractionation approach. Petroleum ether, chloroform and chloroform-methanol extracts inhibited the Croton oil-induced ear dermatitis in mice. The chloroform extract was only about half as active as the non steroidal anti-inflammatory drug indomethacin (ID50=237 and 93 μg/cm(2), respectively). Phytochemical investigation of this extract led to the isolation of nine polyhydroxylated stigmasterol glycosides and six polyhydroxylated stigmasterols. Their structures were elucidated by NMR, MS and chemical methods. Each compound exerted a significant anti-oedema activity, the most active being 1 (3β-O-β-D-glucopyranosyloxy-5α-stigmasta-7,9(11),24(28)Z-triene-6β,16β,26,29-tetrol) and 3 (3β-O-β-D-glucopyranosyloxy-5α-stigmasta-7,9(11),24(28)Z-triene-6β,16β,29-triol), only two and five fold less potent than the steroidal drug hydrocortisone (ID50=0.10, 0.21 and 0.04 μmol/cm(2), respectively). Compound 1 (50 μM) also completely inhibited the transcription factor NF-κB in vitro. PMID:24074552

  20. Chemical composition and anti-inflammatory activities of the essential oils from Acacia mearnsii de Wild.

    PubMed

    Avoseh, Opeyemi N; Oyedeji, Ope-oluwa O; Aremu, Kayode; Nkeh-Chungag, Benedicta N; Songca, Sandile P; Oluwafemi, Samuel O; Oyedeji, Adebola O

    2015-01-01

    The volatile oils of the leaves and the stem bark of Acacia mearnsii de Wild obtained by hydro-distillation were analysed by gas chromatography-mass spectrometry. A total of 20, 38, 29 and 38 components accounted for 93.8%, 92.1%, 78.5% and 90.9% of the total oils of the fresh, dry leaves and fresh, dry stem bark, respectively. The major components of the oil were octadecyl alcohol (25.5%) and phytol (10.5%); cis-verbenol (29.5%); phytol (10.1%) and phytol (23.4%) for the fresh leaves, dried leaves, fresh stem, dry stem bark, respectively. Oral administration of essential oils at a dose of 2% showed significant (p < 0.05) anti-inflammatory properties in the albumin-induced test model in rats. Oils from the fresh leaves and dry stems inhibited inflammation beyond 4 h post treatment. The potent anti-inflammatory activity of essential oils of A. mearnsii hereby confirmed its traditional use in treating various inflammatory diseases. PMID:25422136

  1. Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature.

    PubMed

    Zhang, Linjie; Yang, Li

    2015-01-01

    Immune responses play an important role in the pathophysiology of atherosclerosis and ischemic stroke. Atherosclerosis is a common condition that increases the risk of stroke. Hyperlipidemia damages endothelial cells, thus initiating chemokine pathways and the release of inflammatory cytokines-this represents the first step in the inflammatory response to atherosclerosis. Blocking blood flow in the brain leads to ischemic stroke, and deprives neurons of oxygen and energy. Damaged neurons release danger-associated molecular patterns, which promote the activation of innate immune cells and the release of inflammatory cytokines. The nuclear factor κ-light-chain-enhancer of activated B cells κB (NF-κB) pathway plays a key role in the pathogenesis of atherosclerosis and ischemic stroke. Vinpocetine is believed to be a potent anti-inflammatory agent and has been used to treat cerebrovascular disorders. Vinpocetine improves neuronal plasticity and reduces the release of inflammatory cytokines and chemokines from endothelial cells, vascular smooth muscle cells, macrophages, and microglia, by inhibiting the inhibitor of the NF-κB pathway. This review clarifies the anti-inflammatory role of vinpocetine in atherosclerosis and ischemic stroke. PMID:25549058

  2. Anti-inflammatory activity of Yanshu spraying agent in animal models

    PubMed Central

    ZHANG, JIANQIAO; WANG, HONGSHENG; WANG, TIAN; CHONG, YATING; YU, PENGFEI; LU, CHENGWEN; XUE, YUNLI; FU, FENGHUA; ZHANG, LEIMING

    2013-01-01

    Acute pharyngitis is characterized by an inflammation of the mucous membranes in the pharynx. Yanshu spraying agent was prepared according to the traditional Chinese formulation for the treatment of acute pharyngitis. The present study aimed to investigate the anti-inflammatory effect of Yanshu in xylene-induced ear edema in mice and carrageenan-induced paw edema in rats by measuring the degree of edema in the animal models. The histopathology and the levels of prostaglandin E2 (PGE2) and cycloxygenase-2 (COX-2) in the hind paws of the carrageenan-treated rats were also analyzed. The results showed that Yanshu significantly reduced ear edema in the mice and paw edema in the rats. Furthermore, treatment with Yanshu also reduced the number of inflammatory cells in tissue and decreased the production of PGE2 and COX-2. These results suggest that Yanshu possesses potent anti-inflammatory activity mediated by the inhibition of COX-2 expression which, in turn, downregulates the inflammatory mediator PGE2. PMID:23251244

  3. Physicochemical, antimicrobial and anti-inflammatory evaluation of fixed oil from Boa constrictor.

    PubMed

    Falodun, Abiodun; Owolabi, Omonkhelin Josephine; Osahon, Obasuyi

    2008-01-01

    Boa constrictor is one of the snakes found in the riverine areas of Nigeria, especially in the Niger Delta regions. The fat obtained from the snake is used ethno-medicinally for the treatment of burns and inflammatory conditions. The purpose of this study was to validate the traditional use of this crude fat and oil. The fat obtained from the Boa snake was subjected to some physiochemical screening tests. A systematic chemical and antimicrobial investigation was carried out using some bacterial found in wound such as Staphylococcus aureus, B. subtilis and Streptococcus pyrogenes. The degree of zone of inhibition was a measure of the antimicrobial activity of the fat and oil. The maximal inhibitory dilution was determined for significant zone. The anti-inflammatory investigation was done using the croton oil induced ear edema. The results of the study revealed a potent anti-inflammatory and a significant antimicrobial activity of the fat from Boa constrictor against S. aureus and S. pyrogenes organisms, thus, justifying the traditional usage of the fat of Boa constrictor. PMID:19051590

  4. Anti-inflammatory potential of probiotic Lactobacillus spp. on carrageenan induced paw edema in Wistar rats.

    PubMed

    Archer, Ann Catherine; Muthukumar, S P; Halami, Prakash M

    2015-11-01

    The aim of the present study was to evaluate the anti-inflammatory ability of novel indigenous probiotic Lactobacillus fermentum MCC 2759, L. fermentum MCC 2760 and Lactobacillus delbrueckii MCC 2775 in a carrageenan induced acute inflammatory paw edema model. Probiotic cultures were administered to male Wistar rats via oral route. Carrageenan at a concentration of 1% was injected into hind paw of rats 30min after oral gavage on the 8th day of treatment regimen. Paw thickness (mm), stair climbing activity and motility score were the parameters used to score the inflammatory response. L. fermentum MCC 2759, L. fermentum MCC 2760 and L. delbrueckii MCC 2775 showed significant reduction in paw thickness (P<0.05) showing percentage inhibition of 15.67%, 14.72% and 14.84%, respectively, 24h after carrageenan induction. Probiotic treatment also markedly alleviated the stair climbing and motility score. Histological analysis of tissue sections revealed reduction in cellular infiltration of probiotic and drug treatment groups. Adhesion to resected rat intestinal tissue also showed significant adherence capability (>40%) of the probiotic cultures used. Therefore, L. fermentum MCC 2759, L. fermentum MCC 2760 and L. delbrueckii MCC 2775 may be used as potent anti-inflammatory agents with probiotic health benefits. PMID:26314910

  5. Anti-Diabetic and Anti-Inflammatory Effects of Green and Red Kohlrabi Cultivars (Brassica oleracea var. gongylodes)

    PubMed Central

    Jung, Hyun Ah; Karki, Subash; Ehom, Na-Yeon; Yoon, Mi-Hee; Kim, Eon Ji; Choi, Jae Sue

    2014-01-01

    The aim of the present study was to evaluate the anti-diabetic, anti-inflammatory, antioxidant potential, and total phenolic content (TPC) of green and red kohlrabi cultivars. Anti-diabetic and anti-inflammatory activities were evaluated via protein tyrosine phosphatase (PTP1B) and rat lens aldose reductase inhibitory assays and cell-based lipopolysaccharide (LPS)-induced nitric oxide (NO) inhibitory assays in RAW 264.7 murine macrophages. In addition, scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical, and peroxynitrite (ONOO−) were used to evaluate antioxidant potential and TPC was selected to assess phytochemical characteristics. Between the two kohlrabi cultivars, red kohlrabi (RK) had two times more TPC than green kohlrabi (GK) and showed significant antioxidant effects in DPPH, ABTS, and ONOO− scavenging assays. Likewise, methanol (MeOH) extracts of RK and GK inhibited LPS-induced NO production in a dose dependent manner that was further clarified by suppression of iNOS and COX-2 protein production. The MeOH extracts of RK and GK exhibited potent inhibitory activities against PTP1B with the corresponding IC50 values of 207±3.48 and 287±3.22 μg/mL, respectively. Interestingly, the RK MeOH extract exhibited significantly stronger anti-inflammatory, anti-diabetic, and antioxidant effects than that of GK MeOH extract. As a result, our study establishes that RK extract with a higher TPC might be useful as a potent anti-diabetic, antioxidant, and anti-inflammatory agent. PMID:25580392

  6. The non-aqueous titrimetric assay of the selected anti-inflammatory agents using tetra-n-butylammonium hydroxide as titrant.

    PubMed

    Cakirer, O; Kiliç, E; Atakol, O; Kenar, A

    1999-06-01

    A potentiometric titration method in non-aqueous media is proposed for the determination of some commonly used anti-inflammatory agents. The direct potentiometric titration of three anti-inflammatory agents, namely mefenamic acid, fenbufen and ibuprofen; and the indirect potentiometric titration of diclofenac sodium was carried out in acetonitrile solvent using tetra-n-butylammonium hydroxide as titrant, at 25 degrees C and under a nitrogen atmosphere. The method was found to be highly accurate and precise, having a relative standard deviation of <1.0% for all anti-inflammatory agents studied. Also, it was shown that the method could be successfully applied to the assay of commercial pharmaceuticals containing the above-mentioned anti-inflammatory agents. The validity of the method was tested by the recovery studies of standard addition to pharmaceuticals and the results were found to be satisfactory. The proposed method is simple, rapid and sufficiently precise for quality control purposes. PMID:10704006

  7. Liang-Ge-San, a classic traditional Chinese medicine formula, protects against lipopolysaccharide-induced inflammation through cholinergic anti-inflammatory pathway.

    PubMed

    Liu, Jun-Shan; Wei, Xi-Duan; Lu, Zi-Bin; Xie, Pei; Zhou, Hong-Ling; Chen, Yu-Yao; Ma, Jia-Mei; Yu, Lin-Zhong

    2016-04-19

    Liang-Ge-San (LGS) is a classic formula in traditional Chinese medicine, which is widely used to treat acute lung injury (ALI), pharyngitis and amygdalitis in clinic. However, the underlying mechanisms remain poorly defined. In this study, we discovered that LGS exerted potent anti-inflammatory effects in lipopolysaccharide (LPS)-induced inflammation. We found that LGS significantly depressed the production of IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophage cells. The degradation and phosphorylation of IκBα and the nuclear translocation of NF-κB p65 were also inhibited. Moreover, LGS activated α7 nicotinic cholinergic receptor (α7nAchR). The blockage of α7nAchR by selective inhibitor methyllycaconitine (MLA) or α7nAchR siRNA attenuated the inhibitory effects of LGS on IκBα, NF-κB p65, IL-6 and TNF-α. Critically, LGS significantly inhibited inflammation in LPS-induced ALI rats through the activation of NF-κB signaling pathway. However, these protective effects could be counteracted by the treatment of MLA. Taken together, we first demonstrated anti-inflammatory effects of LGS both in vitro and in vivo through cholinergic anti-inflammatory pathway. The study provides a rationale for the clinical application of LGS as an anti-inflammatory agent and supports the critical role of cholinergic anti-inflammatory pathway in inflammation. PMID:27034013

  8. Liang-Ge-San, a classic traditional Chinese medicine formula, protects against lipopolysaccharide-induced inflammation through cholinergic anti-inflammatory pathway

    PubMed Central

    Xie, Pei; Zhou, Hong-Ling; Chen, Yu-Yao; Ma, Jia-Mei; Yu, Lin-Zhong

    2016-01-01

    Liang-Ge-San (LGS) is a classic formula in traditional Chinese medicine, which is widely used to treat acute lung injury (ALI), pharyngitis and amygdalitis in clinic. However, the underlying mechanisms remain poorly defined. In this study, we discovered that LGS exerted potent anti-inflammatory effects in lipopolysaccharide (LPS)-induced inflammation. We found that LGS significantly depressed the production of IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophage cells. The degradation and phosphorylation of IκBα and the nuclear translocation of NF-κB p65 were also inhibited. Moreover, LGS activated α7 nicotinic cholinergic receptor (α7nAchR). The blockage of α7nAchR by selective inhibitor methyllycaconitine (MLA) or α7nAchR siRNA attenuated the inhibitory effects of LGS on IκBα, NF-κB p65, IL-6 and TNF-α. Critically, LGS significantly inhibited inflammation in LPS-induced ALI rats through the activation of NF-κB signaling pathway. However, these protective effects could be counteracted by the treatment of MLA. Taken together, we first demonstrated anti-inflammatory effects of LGS both in vitro and in vivo through cholinergic anti-inflammatory pathway. The study provides a rationale for the clinical application of LGS as an anti-inflammatory agent and supports the critical role of cholinergic anti-inflammatory pathway in inflammation. PMID:27034013

  9. Anti-Inflammatory Drug Design Using a Molecular Hybridization Approach

    PubMed Central

    Bosquesi, Priscila Longhin; Melo, Thais Regina Ferreira; Vizioli, Ednir Oliveira; dos Santos, Jean Leandro; Chung, Man Chin

    2011-01-01

    The design of new drugs with better physiochemical properties, adequate absorption, distribution, metabolism, and excretion, effective pharmacologic potency and lacking toxicity remains is a challenge. Inflammation is the initial trigger of several different diseases, such as Alzheimer's disease, asthma, atherosclerosis, colitis, rheumatoid arthritis, depression, cancer; and disorders such as obesity and sexual dysfunction. Although inflammation is not the direct cause of these disorders, inflammatory processes often increase related pain and suffering. New anti-inflammatory drugs developed using molecular hybridization techniques to obtain multiple-ligand drugs can act at one or multiple targets, allowing for synergic action and minimizing toxicity. This work is a review of new anti-inflammatory drugs developed using the molecular modification approach.

  10. Isoflavones: Anti-Inflammatory Benefit and Possible Caveats

    PubMed Central

    Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen

    2016-01-01

    Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks. PMID:27294954

  11. Anti-inflammatory and antipyretic effects of boldine.

    PubMed

    Backhouse, N; Delporte, C; Givernau, M; Cassels, B K; Valenzuela, A; Speisky, H

    1994-10-01

    Boldine, an antioxidant alkaloid isolated from Peumus boldus, exhibits a dose-dependent anti-inflammatory activity in the carrageenan-induced guinea pig paw edema test with an oral ED50 of 34 mg/kg. Boldine also reduces bacterial pyrogen-induced hyperthermia in rabbits to an extent which varied between 51% and 98% at a dose of 60 mg/kg p.o. In vitro studies carried out in rat aortal rings revealed that boldine is an effective inhibitor of prostaglandin biosynthesis, promoting 53% inhibition at 75 microM. The latter in vitro effect may be mechanistically linked to the anti-inflammatory and antipyretic effects of boldine exerted in vivo. PMID:7879695

  12. Constituents from Vigna vexillata and Their Anti-Inflammatory Activity

    PubMed Central

    Leu, Yann-Lii; Hwang, Tsong-Long; Kuo, Ping-Chung; Liou, Kun-Pei; Huang, Bow-Shin; Chen, Guo-Feng

    2012-01-01

    The seeds of Vigna genus are important food resources and there have already been many reports regarding their bioactivities. In our preliminary bioassay, the chloroform layer of methanol extracts of V. vexillata demonstrated significant anti-inflammatory bioactivity. Therefore, the present research is aimed to purify and identify the anti-inflammatory principles of V. vexillata. One new sterol (1) and two new isoflavones (2,3) were reported from the natural sources for the first time and their chemical structures were determined by the spectroscopic and mass spectrometric analyses. In addition, 37 known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. Among the isolates, daidzein (23), abscisic acid (25), and quercetin (40) displayed the most significant inhibition of superoxide anion generation and elastase release. PMID:22949828

  13. Anti-inflammatory effects of a Houttuynia cordata supercritical extract.

    PubMed

    Shin, Sunhee; Joo, Seong Soo; Jeon, Jeong Hee; Park, Dongsun; Jang, Min Jung; Kim, Tae Ook; Kim, Hyun Kyu; Hwang, Bang Yeon; Kim, Ki Yon; Kim, Yun Bae

    2010-09-01

    Anti-inflammatory effects of Houttuynia cordata supercritical extract (HSE) were investigated in a carrageenan-air pouch model. HSE (200 mg/kg, oral) suppressed exudation and albumin leakage, as well as inflammatory cell infiltration. Dexamethasone (2 mg/kg, i.p.) only decreased exudation and cell infiltration, while indomethacin (2 mg/kg, i.p.) reduced exudate volume and albumin content. HSE lowered tumor-necrosis factor (TNF)-alpha and nitric oxide (NO), as well as prostaglandin E(2) (PGE(2)). Dexamethasone only reduced TNF-alpha and NO, while indomethacin decreased TNF-alpha and PGE(2). The suppressive activity of HSE on NO and PGE(2) production was confirmed in RAW 264.7. These results demonstrate that HSE exerts anti-inflammatory effects by inhibiting both TNF-alpha-NO and cyclooxygenase II-PGE(2) pathways. PMID:20706037

  14. Isoflavones: Anti-Inflammatory Benefit and Possible Caveats.

    PubMed

    Yu, Jie; Bi, Xiaojuan; Yu, Bing; Chen, Daiwen

    2016-01-01

    Inflammation, a biological response of body tissues to harmful stimuli, is also known to be involved in a host of diseases, such as obesity, atherosclerosis, rheumatoid arthritis, and even cancer. Isoflavones are a class of flavonoids that exhibit antioxidant, anticancer, antimicrobial, and anti-inflammatory properties. Increasing evidence has highlighted the potential for isoflavones to prevent the chronic diseases in which inflammation plays a key role, though the underlying mechanisms remain unclear. Recently, some studies have raised concerns about isoflavones induced negative effects like carcinogenesis, thymic involution, and immunosuppression. Therefore, this review aims to summarize the anti-inflammatory effects of isoflavones, unravel the underlying mechanisms, and present the potential health risks. PMID:27294954

  15. Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

    PubMed Central

    Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

    2013-01-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

  16. Antibiotic and anti-inflammatory therapies for cystic fibrosis.

    PubMed

    Chmiel, James F; Konstan, Michael W; Elborn, J Stuart

    2013-10-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

  17. Pharmacology in rehabilitation: nonsteroidal anti-inflammatory agents.

    PubMed

    Biederman, Ross E

    2005-06-01

    Nonsteroidal anti-inflammatory agents (NSAIDs) are the most commonly encountered over-the-counter (OTC) and prescription medications in physical therapy practice. Worldwide, over 73000000 prescriptions for nonsteroidal agents are written yearly. NSAIDs produce a wide range of beneficial effects to the physical therapy patient, enhancing the outcome of treatment. Helpful effects of NSAIDs include analgesia, antipyretic, anti-inflammatory, and antithrombotic properties. However, NSAIDs are also associated with frequent and significant side effects that are deleterious to treatment outcome, including delay in soft tissue and bone healing, renal and liver toxicity, hemorrhagic events, gastric irritation and ulceration, and central nervous system effects. Understanding of the pharmacological properties of these drugs, exemplified by aspirin, and the individual pharmacokinetics of specific preparations will help the therapist to screen patients for potential side effects, develop more effective plans of care, and, where allowed, effectively and safely prescribe NSAIDs. PMID:16001907

  18. [Helicobacter pylori, nonsteroidal anti-inflammatory agents and gastroduodenal changes].

    PubMed

    Teixeira, A V

    1995-09-01

    The author discusses the possible interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (Hp) which may play an important role in the unleashing of gastroduodenal lesions. To our knowledge, AINEs have no influence on the prevalence of infection by Hp and the latter does not seem to influence the development and intensity of the lesions caused by NSAIDs. PMID:7484272

  19. The Anti-Inflammatory Actions of Exercise Training

    PubMed Central

    Flynn, Michael G.; McFarlin, Brian K.; Markofski, Melissa M.

    2014-01-01

    The list of diseases with a known inflammatory etiology is growing. Cardiovascular disease, osteoporosis, diabetes, geriatric cachexia, and Alzheimer’s disease have all been shown to be linked to or exacerbated by aberrantly regulated inflammatory processes. Nevertheless, there is mounting evidence that those who are physically active, or who become physically active, have a reduction in biomarkers associated with chronic inflammation. There was strong early consensus that exercise-induced reductions in inflammation were explained by body mass index or body fatness, but recent studies provide support for the contention that exercise has body fat–independent anti-inflammatory effects. With few exceptions, the anti-inflammatory effects of exercise appear to occur regardless of age or the presence of chronic diseases. What remains unclear are the mechanisms by which exercise training induces these anti-inflammatory effects, but there are several intriguing possibilities, including release of endogenous products, such as heat shock proteins; selective reduction of visceral adipose tissue mass or reducing infiltration of adipocytes by macrophages; shift in immune cell phenotype; cross-tolerizing effects; or exercise-induced shifts in accessory proteins of toll-like receptor signaling. However, future research endeavors are likely to uncover additional potential mechanisms, and it could be some time before functional mechanisms are made clear. In summary, the potential anti-inflammatory influences of exercise training may provide a low-cost, readily available, and effective treatment for low-grade systemic inflammation and could contribute significantly to the positive effects of exercise training on chronic disease. PMID:25431545

  20. Clinical Management of Nonsteroidal Anti-inflammatory Drug Hypersensitivity

    PubMed Central

    2008-01-01

    Hypersensitivity diseases caused by nonsteroidal anti-inflammatory agents are relatively common in the population. This article summarizes the present understanding on the various allergic and nonallergic clinical pictures produced through hypersensitivity to these drugs using the pathogenic classification of hypersensitivity reactions recently proposed by the Nomenclature Committee of the World Allergy Organization to guide clinicians in the diagnosis and management of patients with these conditions. PMID:23283307

  1. Mechanisms of nonsteroidal anti-inflammatory drugs in cancer prevention.

    PubMed

    Umar, Asad; Steele, Vernon E; Menter, David G; Hawk, Ernest T

    2016-02-01

    Various clinical and epidemiologic studies show that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase inhibitors (COXIBs) help prevent cancer. Since eicosanoid metabolism is the main inhibitory targets of these drugs the resulting molecular and biological impact is generally accepted. As our knowledge base and technology progress we are learning that additional targets may be involved. This review attempts to summarize these new developments in the field. PMID:26970125

  2. Anti-inflammatory activity of mycelial extracts from medicinal mushrooms.

    PubMed

    Geng, Yan; Zhu, Shuiling; Lu, Zhenming; Xu, Hongyu; Shi, Jin-Song; Xu, Zheng-Hong

    2014-01-01

    Medicinal mushrooms have been essential components of traditional Chinese herbal medicines for thousands of years, and they protect against diverse health-related conditions. The components responsible for their anti-inflammatory activity have yet to be fully studied. This study investigates the anti-inflammatory activity of n-hexane, chloroform, ethyl acetate, and methanol extracts of mycelia in submerged culture from 5 commercially available medicinal mushrooms, namely Cephalosporium sinensis, Cordyceps mortierella, Hericium erinaceus, Ganoderma lucidum, and Armillaria mellea. MTT colorimetric assay was applied to measure the cytotoxic effects of different extracts. Their anti-inflammatory activities were evaluated via inhibition against production of lipopolysaccharide (LPS)-induced nitric oxide (NO) in murine macrophage-like cell line RAW264.7 cells. Of the 20 extracts, n-hexane, chloroform, ethyl acetate, and methanol extracts from C. sinensis, C. mortierella, and G. lucidum; chloroform extracts from H. erinaceus and A. mellea; and ethyl acetate extracts from A. mellea at nontoxic concentrations (<300 μg/mL) dose-dependently inhibited LPS-induced NO production. Among them, the chloroform extract from G. lucidum was the most effective inhibitor, with the lowest half maximal inhibitory concentration (64.09 ± 6.29 μg/mL) of the LPS-induced NO production. These results indicate that extracts from medicinal mushrooms exhibited anti-inflammatory activity that might be attributable to the inhibition of NO generation and can therefore be considered a useful therapeutic and preventive approach to various inflammation-related diseases. PMID:25271860

  3. Analgesic, diuretic, and anti-inflammatory principle from Scoparia dulcis.

    PubMed

    Ahmed, M; Shikha, H A; Sadhu, S K; Rahman, M T; Datta, B K

    2001-08-01

    Scoparinol, a diterpene, isolated from Scoparia dulcis showed significant analgesic (p < 0.001) and anti-inflammatory activity (p < 0.01) in animals. A sedative action of scoparinol was demonstrated by a marked potentiation of pentobarbital-induced sedation with a significant effect on both onset and duration of sleep (p < 0.05). Measurement of urine volume after administration of scoparinol indicated its significant diuretic action. PMID:11534346

  4. Anti-inflammatory cyclohexenyl chalcone derivatives in Boesenbergia pandurata.

    PubMed

    Tuchinda, Patoomratana; Reutrakul, Vichai; Claeson, Per; Pongprayoon, Ubonwan; Sematong, Tuanta; Santisuk, Thawatchai; Taylor, Walter C

    2002-01-01

    The cyclohexenyl chalcone derivative [(-)-hydroxypanduratin A], together with the previously known panduratin A, sakuranetin, pinostrobin, pinocembrin, and dihydro-5,6-dehydrokawain were isolated from the chloroform extract of the red rhizome variety of Boesenbergia pandurata (Robx.) Schltr. [currently known as Boesenbergia rotunda (L.) Mansf., Kulturpfl.]. Their structures were assigned on the basis of their spectroscopic data. (-)-Hydroxypanduratin A and (-)-panduratin A showed significant topical anti-inflammatory activity in the assay of TPA-induced ear edema in rats. PMID:11809452

  5. Anti-inflammatory activity and composition of Senecio salignus Kunth.

    PubMed

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

    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

  6. 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

  7. UV Filters, Ingredients with a Recognized Anti-Inflammatory Effect

    PubMed Central

    Couteau, Céline; Chauvet, Catherine; Paparis, Eva; Coiffard, Laurence

    2012-01-01

    Background To explain observed differences during SPF determination using either an in vivo or in vitro method, we hypothesized on the presence of ingredients having anti-inflammatory properties. Methodology/Principal Findings To research our hypothesis, we studied the 21 UV filters both available on the market and authorized by European regulations and subjected these filters to the phorbol-myristate-acetate test using mice. We then catalogued the 13 filters demonstrating a significant anti-inflammatory effect with edema inhibition percentages of more than 70%. The filters are: diethylhexyl butamido triazone (92%), benzophenone-5 and titanium dioxide (90%), benzophenone-3 (83%), octocrylène and isoamyl p-methoxycinnamate (82%), PEG-25 PABA and homosalate (80%), octyl triazone and phenylbenzimidazole sulfonic acid (78%), octyl dimethyl PABA (75%), bis-ethylhexyloxyphenol methoxyphenyl triazine and diethylamino hydroxybenzoyl hexylbenzoate (70%). These filters were tested at various concentrations, including their maximum authorized dose. We detected a dose-response relationship. Conclusions/Significance The anti-inflammatory effect of a sunscreen ingredient may affect the in vivo SPF value. PMID:23284607

  8. Anti-inflammatory properties of pterocarpanquinone LQB-118 in mice.

    PubMed

    Riça, Ingred G; Netto, Chaquip D; Rennó, Magdalena N; Abreu, Paula A; Costa, Paulo R R; da Silva, Alcides J M; Cavalcante, Moisés C M

    2016-09-15

    Pterocarpanquinone (+/-)-LQB-118 presents antineoplastic and antiparasitic properties and also shows great inhibitory effect on TNF-α release in vitro. Here, its anti-inflammatory activity was evaluated in a lipopolysaccharide (LPS)-induced lung inflammation model in C57BL/6 mice. LPS inhalation induced a marked neutrophil infiltration to the lungs which was reduced by intraperitoneal treatment with (+/-)-LQB-118 in a similar manner to that of dexamethasone and even better than that of acetylsalicylic acid. Moreover, (+/-)-LQB-118 administration resulted in decrease of NF-κB activation and KC level in lungs, with a pronounced inhibitory effect on TNF-α release, measured in bronchoalveolar lavage fluid. Trying to understand the anti-inflammatory mechanism by which (+/-)-LQB-118 acts, we performed a molecular modeling analysis, including docking to estrogen receptors α and β. Results suggested that (+/-)-LQB-118 may bind to both receptors, with a similar orientation to 17-β-estradiol. Together, these results showed that (+/-)-LQB-118 exhibits an anti-inflammatory effect, most likely by inhibiting TNF-α release and NF-κB activation, which may be related to the estrogen receptor binding. PMID:27492193

  9. Genome Sequence of Lactobacillus delbrueckii subsp. lactis CNRZ327, a Dairy Bacterium with Anti-Inflammatory Properties

    PubMed Central

    El Kafsi, Hela; Binesse, Johan; Loux, Valentin; Buratti, Julien; Boudebbouze, Samira; Dervyn, Rozenn; Hammani, Amal; Maguin, Emmanuelle

    2014-01-01

    Lactobacillus delbrueckii subsp. lactis CNRZ327 is a dairy bacterium with anti-inflammatory properties both in vitro and in vivo. Here, we report the genome sequence of this bacterium, which appears to contain no less than 215 insertion sequence (IS) elements, an exceptionally high number regarding the small genome size of the strain. PMID:25035318

  10. Acai Juice Attenuates Atherosclerosis Through Antioxidant and Anti-Inflammatory Effects in ApoE Deficient Mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Acai fruit (Euterpe oleracea Mart.) has been shown to exhibit extremely high antioxidant capacity. Antioxidant capacities and anti-inflammatory effects of acai pulp or acai juices have been studied in human, animal and cell culture models. However, their potential effects on atheroscl...

  11. 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.

  12. Structure-based design, synthesis and preliminary anti-inflammatory activity of bolinaquinone analogues.

    PubMed

    Petronzi, Carmen; Filosa, Rosanna; Peduto, Antonella; Monti, Maria Chiara; Margarucci, Luigi; Massa, Antonio; Ercolino, Simona Francesca; Bizzarro, Valentina; Parente, Luca; Riccio, Raffaele; de Caprariis, Paolo

    2011-02-01

    As a part of our drug discovery efforts we developed a series of simplified derivatives of bolinaquinone (BLQ), a hydroxyquinone marine metabolite, showing potent anti-inflammatory activity. Thirteen new hydroxyquinone derivatives closely related to BLQ were synthesized and tested on mouse macrophage-like RAW 264.7 cell line in order to investigate their ability to modulate the production of Prostaglandin E2 (PGE2). This optimization process led to the identification of three strictly correlated compounds with comparable and higher inhibitory potency than BLQ on PGE2 production. To evaluate the affinity of BLQ and its analogues for hsPLA2, surface plasmon resonance (SPR) experiments were performed. PMID:21163556

  13. Repositioning of 2,4-dichlorophenoxy acetic acid as a potential anti-inflammatory agent: in silico and pharmaceutical formulation study.

    PubMed

    Khedr, Mohammed A; Shehata, Tamer M; Mohamed, Maged E

    2014-12-18

    2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known plant auxin which is widely used in plant tissue culture experiments as well as a weed killer and a herbicide. In this study, 2,4-D was rediscovered as a new anti-inflammatory agent through an in silico molecular modeling and docking studies along with drug formulation and in vivo anti-inflammatory inspection. The molecular modeling and docking studies indicated high affinity of 2,4-D toward COX-2 enzyme in a way similar to Ibuprofen, suggesting a higher anti-inflammatory activity. Molecular docking by both MOE 2013.08 and Leadit 2.1.2 revealed excellent binding pattern compared to some of well-known non-steroidal anti-inflammatory drugs. 2,4-D was formulated in different gel bases. In vitro drug release experiments were used to examine the best 2,4-D formula for in vivo studies. In vivo carrageenan-induced hind paw edema inflammatory model in rats was used to test the in silico finding. 2,4-D showed potential in vivo anti-inflammatory activity and significantly reduced the concentration of prostaglandin E2 in hind paw tissues in a way similar to Ibuprofen. These results may open the door to introduce a new anti-inflammatory molecule; especially that 2,4-D is a well-investigated regarding its toxicity and side effect. PMID:25245006

  14. Antiproliferative and anti-inflammatory polyhydroxylated spirostanol saponins from Tupistra chinensis

    PubMed Central

    Xiang, Limin; Yi, Xiaomin; Wang, Yihai; He, Xiangjiu

    2016-01-01

    Tupistra chinensis is widely distributed in southwestern China and its rhizome is a famous folk medicine for the treatment of carbuncles and pharyngitis. Its chemical identity of potent antiproliferative and anti-inflammatory constituents has been carried out in this study. Twenty-three polyhydroxylated spirostanol saponins, including nine novels, were isolated and identified. The new spirostanol saponins were elucidated as spirost-25(27)-en-1β,2β,3β,4β,5β-pentol-2-O-β-D-xylopyranoside (1), spirost-25(27)- en-1β,2β,3β,4β,5β-pentol-2-O-α-L-arabinopyranoside (2), spirost-25(27)-en- 1β,3α,5β-triol (12), spirost-25(27)-en-1β,3α,4β,5β,6β-pentol (13), spirost-25(27)-en- 1β,2β,3β,5β-tetraol-5-O-β-D-glucopyranoside (16), 5β-spirost-25(27)-en-1β,3β-diol- 3-O-β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranoside (17), (25R)-5β-spirostan- 1β,3β-diol-3-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (18), (25R)-5β- spirostan-1β,3β-diol-3-O-β-D-fructofuranosyl-(2 → 6)-β-D-glucopyranoside (19), 5β-spirost-25(27)-en-3β-ol-3-O-β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranoside (20). The antiproliferative effects against seven human cancer cell lines and inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in a macrophage cell line RAW 264.7 were assayed for all the isolated compounds. Compounds 17, 19 and 21 exhibited potential antiproliferative activities against all of human cancer cell lines tested. Compounds 21 showed significant inhibition on NO production with IC50 values of 11.5 μM. These results showed that the spirostanol saponins isolated from the dried rhizomes of T. chinensis have potent antiproliferative and anti-inflammatory activities and T. chinensis might be used as anticancer and.anti-inflammatory supplement. PMID:27530890

  15. Antiproliferative and anti-inflammatory polyhydroxylated spirostanol saponins from Tupistra chinensis.

    PubMed

    Xiang, Limin; Yi, Xiaomin; Wang, Yihai; He, Xiangjiu

    2016-01-01

    Tupistra chinensis is widely distributed in southwestern China and its rhizome is a famous folk medicine for the treatment of carbuncles and pharyngitis. Its chemical identity of potent antiproliferative and anti-inflammatory constituents has been carried out in this study. Twenty-three polyhydroxylated spirostanol saponins, including nine novels, were isolated and identified. The new spirostanol saponins were elucidated as spirost-25(27)-en-1β,2β,3β,4β,5β-pentol-2-O-β-D-xylopyranoside (1), spirost-25(27)- en-1β,2β,3β,4β,5β-pentol-2-O-α-L-arabinopyranoside (2), spirost-25(27)-en- 1β,3α,5β-triol (12), spirost-25(27)-en-1β,3α,4β,5β,6β-pentol (13), spirost-25(27)-en- 1β,2β,3β,5β-tetraol-5-O-β-D-glucopyranoside (16), 5β-spirost-25(27)-en-1β,3β-diol- 3-O-β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranoside (17), (25R)-5β-spirostan- 1β,3β-diol-3-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (18), (25R)-5β- spirostan-1β,3β-diol-3-O-β-D-fructofuranosyl-(2 → 6)-β-D-glucopyranoside (19), 5β-spirost-25(27)-en-3β-ol-3-O-β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranoside (20). The antiproliferative effects against seven human cancer cell lines and inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in a macrophage cell line RAW 264.7 were assayed for all the isolated compounds. Compounds 17, 19 and 21 exhibited potential antiproliferative activities against all of human cancer cell lines tested. Compounds 21 showed significant inhibition on NO production with IC50 values of 11.5 μM. These results showed that the spirostanol saponins isolated from the dried rhizomes of T. chinensis have potent antiproliferative and anti-inflammatory activities and T. chinensis might be used as anticancer and.anti-inflammatory supplement. PMID:27530890

  16. Role of lipoxins and resolvins as anti-inflammatory and proresolving mediators in colon cancer.

    PubMed

    Janakiram, Naveena B; Rao, Chinthalapally V

    2009-06-01

    Recently, lipoxins (LXs) and resolvins (Rvs) have become the topic of intense interest because of expanding views of their action, particularly in chronic disorders where unresolved inflammation is a key factor leading to colon carcinogenesis. Rvs are biosynthesized from omega-3 fatty acids eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) via cyclooxygenase-2/lipoxygenase (COX-2/LOX) pathways; Rvs are shown to dramatically reduce dermal inflammation, peritonitis, dendritic cell migration, and interleukin production. This explains that dietary supplementation of omega-3 fatty acids generates potent local endogenous mediators that control inflammation. LXs are biosynthesized from COX-2/LOX pathways. Metabolites of 15-LOX-1 and 2 are anti-tumorigenic; similarly, 15-epi-LXA(4) synthesized during COX-2 acetylation by low doses of aspirin too possesses anti-tumorigenic effects. Acetylating nonsteroidal anti-inflammatory drugs (NSAIDs), like aspirin, switches COX-2 from forming PGE(2) (promoting tumorigenesis) to 15-epi-LXA(4) (antitumorigenesis). LXs and Rvs are endogenously generated during the spontaneous resolution phase. These newly identified LXs and Rvs have proved to be potent regulators of both leukocytes and cytokine productions, thereby regulating the events of interest in inflammation and resolution. In light of existing knowledge on interconnected pathways of pro-inflammatory mediators (leukotrienes, chemokines (IL8, SDF-1 alpha, MIP-1 alpha, MCP-1,2 etc), and cytokines (IL3, IL6, IL12, IL-1 beta, GM-CSF, B94, TNF-alpha etc)), the anti-inflammatory properties of pro-resolving mediators in preventing chronic inflammation which leads to carcinogenesis needs further understanding. In this review, we explore the mechanisms that trigger formation of LXs and Rvs, to highlight the relative importance of LXs and Rvs in carcinogenesis in relation to pro-inflammatory mediators. PMID:19601807

  17. Analgesic and Anti-inflammatory Effects of Rosa damascena Hydroalcoholic Extract and its Essential Oil in Animal Models.

    PubMed

    Hajhashemi, Valiollah; Ghannadi, Alireza; Hajiloo, Mohammad

    2010-01-01

    Extracts obtained from the petals of Rosa damascena (Rosaceae) are used in Iranian folk medicine as remedies for the treatment of some inflammatory diseases. In this study the hydroalcoholic extract and essential oil of the plant were investigated for its possible anti-inflammatory and analgesic activities. The extract was administered at the doses (p.o.) of 250, 500 and 1000 mg/kg and the doses of essential oil were 100, 200 and 400 μL/kg. The acetic acid-induced writhing response, formalin-induced paw licking time in the early and late phases and light tail flick test were used in mice to assess analgesic activity. For evaluation of anti-inflammatory effect carrageenan-induced paw edema served as a valid animal model in rats. The extract significantly attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and also showed potent analgesic effect in both phases of formalin test but not in light tail flick test. In addition, the higher dose of the extract significantly (P < 0.05) reduced carrageenan-induced paw edema. Essential oil of the plant at all administered doses failed to show any analgesic or anti-inflammatory effect in above mentioned tests. These results provide support for the use of hydroalcoholic extract of Rosa damascena in relieving inflammatory pain, and insight into the development of new agents for treating inflammatory diseases. PMID:24363723

  18. Isolation and Identification of a Flavone Apigenin from Marine Red Alga Acanthophora spicifera with Antinociceptive and Anti-Inflammatory Activities

    PubMed Central

    El Shoubaky, Gihan A.; Abdel-Daim, Mohamed M.; Mansour, Mohamed H.; Salem, Essam A.

    2016-01-01

    Physicochemical investigation of the red alga Acanthophora spicifera (Vahl) Borgesen, collected from Al-Shoaiba coast, Red Sea, Saudi Arabia, led to the isolation of a flavone from the algal tissue with acetone. Preparative chromatography on silica gel thin-layer chromatography was used for the separation of the flavone and eluted with the methanol:chloroform:ethyl acetate (1:7:2) solvent system. The physicochemical analyses infrared, mass spectra, and ultraviolet spectra in addition to shift reagents (NaOMe, NaOAc, NaOAc + H3BO3, AlCl3, and AlCl3 + HCl) were used for the identification and elucidation of the structure of the flavone compound (4,5,7-trihydroxy flavonoids). The flavone compound was identified as apigenin bycomparing its physicochemical data with those in the literature. Analgesic and anti-inflammatory activities of apigenin were evaluated. Apigenin showed promising analgesic and anti-inflammatory activities in the hot plate test and writhing test in mice as well as tail-immersion tests and carrageenan-induced paw edema and cotton pellet-induced granuloma formation in rats. It is concluded that apigenin possesses potent analgesic, anti-inflammatory, and antiproliferative activities, which might be due to the inhibition of PGE2 as well as proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. PMID:26917974

  19. Antinociceptive and anti-inflammatory activities of the essential oil of Nepeta crispa Willd. in experimental rat models.

    PubMed

    Ali, Taskina; Javan, Mohammad; Sonboli, Ali; Semnanian, Saeed

    2012-01-01

    This study was conducted to evaluate the antinociceptive and anti-inflammatory activities of the essential oil of Nepeta crispa. The study was done using the tail-flick and formalin test pain models and the paw oedema model of inflammation. Male Wistar rats were used as the animal model. The essential oil dose-dependently produced analgesia in the acute pain models, including the tail-flick (p < 0.001) and the first phase of the formalin test (p < 0.01). In the late phase of the formalin test, as a model of chronic pain, the essential oil significantly reduced the pain-induced behaviour (p < 0.01). Nepeta crispa essential oil caused potent anti-inflammatory effects in the formalin-induced paw inflammation model and significantly reduced the paw oedema in all applied doses (p < 0.01). Its effects on pain in both the acute and chronic pain models and its anti-inflammatory effect suggest both central and peripheral mechanisms of action for the essential oil obtained from N. crispa. PMID:21981349

  20. Bioactivity-guided fractionation for anti-inflammatory and analgesic properties and constituents of Xanthium strumarium L.

    PubMed

    Han, T; Li, H-L; Zhang, Q-Y; Han, P; Zheng, H-C; Rahman, K; Qin, L-P

    2007-12-01

    The aim of this study was to fractionate an extract of Xanthium strumarium L. (EXS) and to investigate the anti-inflammatory and analgesic properties of the extract and its fractions. The ethanol extract of X. strumarium (EXS) was fractionated on the basis of polarity. Among the different fractions, the n-butanol fraction showed the highest anti-inflammatory activity in the croton-oil-induced ear edema test and furthermore reduced the number of writhings induced by acetic acid in mice in a dose-dependent manner. This indicates that the n-butanol fraction of X. strumarium possesses potent analgesic effects which are likely to be mediated by its anti-inflammatory activity. Bioassay-guided fractionation of EXS led to the isolation and identification of ten caffeoylquinic acids and three heterocyclics by HPLC-DAD-MS(n) from the active n-butanol fraction, implying that the active compounds are polar in nature. The isolated caffeoylquinic acids could partially explain the antinociceptive effect of X. strumarium polar extract. PMID:17350237

  1. Analgesic and Anti-Inflammatory Activities of the Methanolic Stem Bark Extract of Nyctanthes arbor-tristis Linn.

    PubMed Central

    Kakoti, Bibhuti Bhusan; Pradhan, Paresh; Borah, Sudarshana; Mahato, Kabita; Kumar, Mritunjay

    2013-01-01

    Stem bark of Nyctanthes arbor-tristis Linn. was extracted in methanol to evaluate their analgesic and anti-inflammatory activities. The analgesic activity was determined on Wistar albino rats by hot plate method, tail flick assay, and tail immersion method using Morphine sulphate as standard drug at a dose of 5 mg/kg of body weight and the results were expressed as mean increase in latency after drug administration ± SEM. The anti-inflammatory activity was assessed by Carrageenan-induced rat paw oedema using diclofenac sodium as standard drug at a dose of 100 mg/kg of body weight and expressed in terms of mean increase in paw volume ± SEM. Stem bark extract was given at a dose of 250 mg/kg and 500 mg/kg of body weight. Both standard drugs and extract were administered orally to the animals. Control received distilled water orally. Results showed that Nyctanthes arbor-tristis Linn. had potent analgesic and anti-inflammatory activities. PMID:23984409

  2. Antioxidant and anti-inflammatory activities of selected medicinal plants and fungi containing phenolic and flavonoid compounds

    PubMed Central

    2012-01-01

    Background This study aims to determine the relationship between the antioxidant and anti-inflammatory activities of the thirteen herbs and two fungi extracts, and their total phenolic and flavonoid contents. Methods Antioxidant activities were evaluated by four assays: an antioxidant activity assay using Saccharomyces cerevisiae, a DPPH ((2, 2-diphenyl-1-picrylhydrazyl) assay to assess free radical scavenging, an assay assessing ferrous ions or iron (II) chelating ability, and a ferric reducing antioxidant power (FRAP) assay. Total phenolic and flavonoid contents were determined using the Folin-Ciocalteu and aluminium chloride methods, respectively. Anti-inflammatory activities were determined by measuring the inhibition of nitric oxide and TNF-α production in lipopolysaccharide- and interferon-γ-activated J774A.1 macrophages. Their cytotoxicities against macrophages were determined by MTT assay. Results A positive linear correlation between antioxidant activities and the total phenolic and flavonoid content of the plant extracts was found. The plant extracts with high phenolic and flavonoid content also exhibited significant anti-inflammatory activity with good cell viability. Conclusion The selected herbs could be a rich source of antioxidants and free radical scavenging compounds. The levels of phenolic and flavonoid compounds were correlated with the antioxidant and anti-inflammatory activities of the extracts from the herbs. PMID:23176585

  3. Comparison of Anti-Oxidant and Anti-Inflammatory Effects between Fresh and Aged Black Garlic Extracts.

    PubMed

    Jeong, Yi Yeong; Ryu, Ji Hyeon; Shin, Jung-Hye; Kang, Min Jung; Kang, Jae Ran; Han, Jaehee; Kang, Dawon

    2016-01-01

    Numerous studies have demonstrated that aged black garlic (ABG) has strong anti-oxidant activity. Little is known however regarding the anti-inflammatory activity of ABG. This study was performed to identify and compare the anti-oxidant and anti-inflammatory effects of ABG extract (ABGE) with those of fresh raw garlic (FRG) extract (FRGE). In addition, we investigated which components are responsible for the observed effects. Hydrogen peroxide (H2O2) and lipopolysaccharide (LPS) were used as a pro-oxidant and pro-inflammatory stressor, respectively. ABGE showed high ABTS and DPPH radical scavenging activities and low ROS generation in RAW264.7 cells compared with FRGE. However, inhibition of cyclooxygenase-2 and 5-lipooxygenase activities by FRGE was stronger than that by ABGE. FRGE reduced PGE₂, NO, IL-6, IL-1β, LTD₄, and LTE₄ production in LPS-activated RAW264.7 cells more than did ABGE. The combination of FRGE and sugar (galactose, glucose, fructose, or sucrose), which is more abundant in ABGE than in FRGE, decreased the anti-inflammatory activity compared with FRGE. FRGE-induced inhibition of NF-κB activation and pro-inflammatory gene expression was blocked by combination with sugars. The lower anti-inflammatory activity in ABGE than FRGE could result from the presence of sugars. Our results suggest that ABGE might be helpful for the treatment of diseases mediated predominantly by ROS. PMID:27043510

  4. Management of nonsteroidal anti-inflammatory drug-related peptic ulcer bleeding.

    PubMed

    Sung, J J

    2001-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have superseded Helicobacter pylori infection as the most important cause of peptic ulcer bleeding. Eradication of H. pylori in NSAID users will not affect ulcer healing. In high-risk patients with a history of ulcer bleeding, curing H. pylori infection alone without acid suppression has substantially reduced the risk of rebleeding caused by low-dose aspirin but not nonaspirin NSAIDs. In a study comparing the safety profile of misoprostol in combination with NSAID against nabumetone in high-risk patients with a history of ulcer bleeding, both strategies were unable to confer significant protection against the risk of rebleeding. PMID:11165993

  5. Anti-inflammatory effects of OBA-09, a salicylic acid/pyruvate ester, in the postischemic brain.

    PubMed

    Lee, Hye-Kyung; Kim, Seung-Woo; Jin, Yinchuan; Kim, Il-Doo; Park, Ju-Young; Yoon, Sung-Hwa; Lee, Ja-Kyeong

    2013-08-28

    Cerebral ischemia leads to brain injury via a complex series of pathophysiological events, and therefore, multi-drug treatments or multi-targeting drug treatments provide attractive options with respect to limiting brain damage. Previously, we reported that a novel multi-functional compound oxopropanoyloxy benzoic acid (OBA-09, a simple ester of pyruvate and salicylic acid) affords robust neuroprotective effects in the postischemic rat brain. OBA-09 exhibited anti-oxidative effects that appeared to be executed by OBA-09 and by the salicylic acid afforded by hydrolysis. Here, we report the anti-inflammatory effects of OBA-09. Microglial activation observed at 2 days post-middle cerebral artery occlusion (MCAO, 90 min) and at 1 day after a LPS injection (0.5 mg/kg, intravenously) in the brains of Sprague-Dawley rats were markedly suppressed by the administration of OBA-09 (10 mg/kg). Inductions of proinflammatory markers (TNF-α, IL-1β, iNOS, and COX-2) were also suppressed by OBA-09 in both the LPS and MCAO models. Moreover, the anti-inflammatory effect of OBA-09 was accompanied by the suppression of infarct formation in the postischemic brain, but appeared to be independent of neuroprotection in LPS-treated rats. The inductions of proinflammatory markers were also inhibited by OBA-09 in LPS-treated BV2 cells (a microglia cell line) and in LPS-treated-primary neutrophils, possibly due to the suppression of NF-κB activity. Interestingly, the anti-inflammatory effect of OBA-09 was greater than that of equivalent co-treatment with pyruvate and salicylic acid. Together these results indicate that OBA-09 is a potent multi-modal neuroprotectant in the postischemic brain, and that its anti-inflammatory effect contributes to its neuroprotective function. PMID:23850644

  6. Anti-Inflammatory and Antioxidant Activity of Acalypha hispida Leaf and Analysis of its Major Bioactive Polyphenols by HPLC

    PubMed Central

    Siraj, Md. Afjalus; Shilpi, Jamil A.; Hossain, Md. Golam; Uddin, Shaikh Jamal; Islam, Md. Khirul; Jahan, Ismet Ara; Hossain, Hemayet

    2016-01-01

    Purpose: Inflammation and oxidative stress can lead to different chronic diseases including cancer and atherosclerosis. Many medicinal plants have the potential to show as anti-inflammatory activity. Present investigation was performed to investigate anti-inflammatory, antioxidant activity, and quantification of selected bioactive plant polyphenols of the ethanol (EAH) and aqueous (AAH) extracts of Acalypha hispida (Euphorbiaceae) leaves. Methods: Anti-inflammatory activity was evaluated by carragenan and histamine induced rat paw edema models while antioxidant capacity was evaluated by DPPH free radical scavenging, Fe+2 chelating ability, reducing power, NO scavenging, total phenolic and total flavonoid content assay. Identification and quantification of bioactive polyphenols was done by HPLC. Results: At the doses of 200 and 400 mg/kg, both EAH and AAH showed statistically significant inhibition of paw volume in the anti-inflammatory activity test. Both the extracts showed DPPH scavenging (IC50: 14 and 17 µg/ml, respectively), Fe+2 ion chelating (IC50: 40 and 46 µg/ml, respectively), NO scavenging activity (65.49 and 60.66% inhibition at 100 µg/ml), and concentration dependent reducing power ability. For EAH and AAH, flavonoid content was 126.30 and 149.72 mg QE/g dry extract, while phenolic content was 130.51 and 173.80 mg GAE/g dry extract, respectively. HPLC analysis of EAH and AAH indicated the presence of high content of ellagic acid along with other phenolic constituents. Conclusion: High content of ellagic acid along with other phenolic constituents might have played an important role in the observed anti-inflammatory and antioxidant activity. PMID:27478793

  7. Anti-inflammatory, Anti-estrogenic, and Anti-implantation Activity of Bergia suffruticosa (Delile) Fenzl

    PubMed Central

    Bind, Sandeep Kumar; Jivrajani, Mehul; Anandjiwala, Sheetal; Nivsarkar, Manish

    2015-01-01

    Background: Bergia suffruticosa (Delile) Fenzl (Syn. Bergia odorata Edgew) (Elatinaceae family) is used traditionally to repair bones and is applied as a poultice on sores. It is also used for stomach troubles and as an antidote to scorpion stings. So far, very little scientific work has been reported to validate its ethnomedical uses in the alleviation of pain, bone repair, etc., Objective: This study was designed to explore the anti-inflammatory and anti-implantation potential of n-hexane extract of B. suffruticosa whole plant in mice along with identification of its chemical constituents. Materials and Methods: n-Hexane extract of B. suffruticosa whole plant was screened for acute and chronic anti-inflammatory activity followed by an anti-estrogenic activity. Eventually, n-hexane extract was tested for anti-implantation activity by exploiting markers of uterine receptivity, lipid peroxidation, and superoxide enzyme activity. The extract was administered orally at a dose of 100 mg/kg body weight in each study. Results: Thin layer chromatography fingerprint profile of n-hexane extract revealed the presence of lupeol and β-sitosterol. The n-hexane extract reduced the edema by 80% in acute inflammation, whereas it reduced edema to 75% on the 5th day in chronic inflammation. The n-hexane extract reduced elevated malonaldehyde level from 6 to 2.5 nmol/g × 10−5 and increased superoxide dismutase enzyme activity from 0 to 350 units/g in treated animals on the 5th day of pregnancy. Moreover, extract decreased uterine weight from 0.33 to 0.2 g in estradiol treated animals. Conclusion: These results indicate that n-hexane extract of B. suffruticosa is having potent anti-inflammatory, anti-estrogenic, and anti-implantation activity. This is the first report of all the pharmacological activities of B. suffruticosa mentioned above. SUMMARY TLC fingerprint profile of n-hexane extract of Bergia suffruticosa whole plant revealed the presence of lupeol and

  8. Anti-inflammatory, anti-bacterial, and cytotoxic activity of fibrous clays.

    PubMed

    Cervini-Silva, Javiera; Nieto-Camacho, Antonio-; Ramírez-Apan, María Teresa; Gómez-Vidales, Virginia; Palacios, Eduardo; Montoya, Ascención; Ronquillo de Jesús, Elba

    2015-05-01

    Produced worldwide at 1.2m tons per year, fibrous clays are used in the production of pet litter, animal feed stuff to roof parcels, construction and rheological additives, and other applications needing to replace long-fiber length asbestos. To the authors' knowledge, however, information on the beneficial effects of fibrous clays on health remains scarce. This paper reports on the anti-inflammatory, anti-bacterial, and cytotoxic activity by sepiolite (Vallecas, Spain) and palygorskite (Torrejon El Rubio, Spain). The anti-inflammatory activity was determined using the 12-O-tetradecanoylphorbol-13-acetate (TPA) and myeloperoxidase (MPO) methods. Histological cuts were obtained for quantifying leukocytes found in the epidermis. Palygorkite and sepiolite caused edema inhibition and migration of neutrophils ca. 68.64 and 45.54%, and 80 and 65%, respectively. Fibrous clays yielded high rates of infiltration, explained by cleavage of polysomes and exposure of silanol groups. Also, fibrous clays showed high inhibition of myeloperoxidase contents shortly after exposure, but decreased sharply afterwards. In contrast, tubular clays caused an increasing inhibition of myeloperoxidase with time. Thus, clay structure restricted the kinetics and mechanism of myeloperoxidase inhibition. Fibrous clays were screened in vitro against human cancer cell lines. Cytotoxicity was determined using the protein-binding dye sulforhodamine B (SRB). Exposing cancer human cells to sepiolite or palygorskite showed growth inhibition varying with cell line. This study shows that fibrous clays served as an effective anti-inflammatory, limited by chemical transfer and cellular-level signals responding exclusively to an early exposure to clay, and cell viability decreasing significantly only after exposure to high concentrations of sepiolite. PMID:25819359

  9. Biogenic synthesis, purification, and chemical characterization of anti-inflammatory resolvins derived from docosapentaenoic acid (DPAn-6).

    PubMed

    Dangi, Bindi; Obeng, Marcus; Nauroth, Julie M; Teymourlouei, Mah; Needham, Micah; Raman, Krishna; Arterburn, Linda M

    2009-05-29

    Enzymatically oxygenated derivatives of the omega-3 fatty acids cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) and cis-5,8,11,14,17-eicosapentaenoic acid, known as resolvins, have potent inflammation resolution activity (Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N., and Gronert, K. (2000) J. Exp. Med. 192, 1197-1204; Hong, S., Gronert, K., Devchand, P. R., Moussignac, R., and Serhan, C. N. (2003) J. Biol. Chem. 278, 14677-14687). Our objective was to determine whether similar derivatives are enzymatically synthesized from other C-22 fatty acids and whether these molecules possess inflammation resolution properties. The reaction of DHA, DPAn-3, and DPAn-6 with 5-, 12-, and 15-lipoxygenases produced oxylipins, which were identified and characterized by liquid chromatography coupled with tandem mass-spectrometry. DPAn-6 and DPAn-3 proved to be good substrates for 15-lipoxygenase. 15-Lipoxygenase proved to be the most efficient enzyme of the three tested for conversion of long chain polyunsaturated fatty acids to corresponding oxylipins. Since DPAn-6 is a major component of Martek DHA-S oil, we focused our attention on reaction products obtained from the DPAn-6 and 15-lipoxygenase reaction. (17S)-hydroxy-DPAn-6 and (10,17S)-dihydroxy-DPAn-6 were the main products of this reaction. These compounds were purified by preparatory high performance liquid chromatography techniques and further characterized by NMR, UV spectrophotometry, and tandem mass spectrometry. We tested both compounds in two animal models of acute inflammation and demonstrated that both compounds are potent anti-inflammatory agents that are active on local intravenous as well as oral administration. These oxygenated DPAn-6 compounds can thus be categorized as a new class of DPAn-6-derived resolvins. PMID:19324874

  10. Biogenic Synthesis, Purification, and Chemical Characterization of Anti-inflammatory Resolvins Derived from Docosapentaenoic Acid (DPAn-6)

    PubMed Central

    Dangi, Bindi; Obeng, Marcus; Nauroth, Julie M.; Teymourlouei, Mah; Needham, Micah; Raman, Krishna; Arterburn, Linda M.

    2009-01-01

    Enzymatically oxygenated derivatives of the ω-3 fatty acids cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) and cis-5,8,11,14,17-eicosapentaenoic acid, known as resolvins, have potent inflammation resolution activity (Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N., and Gronert, K. (2000) J. Exp. Med. 192, 1197–1204; Hong, S., Gronert, K., Devchand, P. R., Moussignac, R., and Serhan, C. N. (2003) J. Biol. Chem. 278, 14677–14687). Our objective was to determine whether similar derivatives are enzymatically synthesized from other C-22 fatty acids and whether these molecules possess inflammation resolution properties. The reaction of DHA, DPAn-3, and DPAn-6 with 5-, 12-, and 15-lipoxygenases produced oxylipins, which were identified and characterized by liquid chromatography coupled with tandem mass-spectrometry. DPAn-6 and DPAn-3 proved to be good substrates for 15-lipoxygenase. 15-Lipoxygenase proved to be the most efficient enzyme of the three tested for conversion of long chain polyunsaturated fatty acids to corresponding oxylipins. Since DPAn-6 is a major component of Martek DHA-S™ oil, we focused our attention on reaction products obtained from the DPAn-6 and 15-lipoxygenase reaction. (17S)-hydroxy-DPAn-6 and (10,17S)-dihydroxy-DPAn-6 were the main products of this reaction. These compounds were purified by preparatory high performance liquid chromatography techniques and further characterized by NMR, UV spectrophotometry, and tandem mass spectrometry. We tested both compounds in two animal models of acute inflammation and demonstrated that both compounds are potent anti-inflammatory agents that are active on local intravenous as well as oral administration. These oxygenated DPAn-6 compounds can thus be categorized as a new class of DPAn-6-derived resolvins. PMID:19324874

  11. Salivary gland derived peptides as a new class of anti-inflammatory agents: review of preclinical pharmacology of C-terminal peptides of SMR1 protein

    PubMed Central

    2010-01-01

    The limitations of steroidal and non steroidal anti-inflammatory drugs have prompted investigation into other biologically based therapeutics, and identification of immune selective anti-inflammatory agents of salivary origin. The traditional view of salivary glands as accessory digestive structures is changing as their importance as sources of systemically active immunoregulatory and anti-inflammatory factors is recognized. Salivary gland involvement in maintenance of whole body homeostasis is regulated by the nervous system and thus constitutes a "neuroendocrine axis". The potent anti-inflammatory activities, both in vivo and in vitro, of the tripeptide Phe-Glu-Gly (FEG) are reviewed. FEG is a carboxyl terminal peptide of the prohormone SMR1 identified in the rat submandibular salivary gland, The D-isomeric form (feG) mimics the activity of its L-isomer FEG. Macropharmacologically, feG attenuates the cardiovascular and inflammatory effects of endotoxemia and anaphylaxis, by inhibition of hypotension, leukocyte migration, vascular leak, and disruption of pulmonary function and intestinal motility. Mechanistically, feG affects activated inflammatory cells, especially neutrophils, by regulating integrins and inhibiting intracellular production of reactive oxygen species. Pharmacodynamically, feG is active at low doses (100 μg/kg) and has a long (9-12 hour) biological half life. As a therapeutic agent, feG shows promise in diseases characterized by over exuberant inflammatory responses such as systemic inflammatory response syndrome and other acute inflammatory diseases. Arthritis, sepsis, acute pancreatitis, asthma, acute respiratory inflammation, inflammatory bowel disease, and equine laminitis are potential targets for this promising therapeutic peptide. The term "Immune Selective Anti-Inflammatory Derivatives" (ImSAIDs) is proposed for salivary-derived peptides to distinguish this class of agents from corticosteroids and nonsteroidal anti-inflammatory drugs

  12. Antinociceptive and anti-inflammatory potential of Rhododendron arboreum bark.

    PubMed

    Nisar, Muhammad; Ali, Sajid; Muhammad, Naveed; Gillani, Syed N; Shah, Muhmmad R; Khan, Haroon; Maione, Francesco

    2016-07-01

    Rhododendron arboreum Smith. (Ericaceae), an evergreen small tree, is one of the 1000 species that belongs to genus Rhododendron distributed worldwide. In folk medicine, as various parts of this plant exhibit medicinal properties, it is used in the treatment of different ailments.The present study was designed to evaluate the potential anti-inflammatory and antinociceptive effects of methanolic extract of R. arboreum bark, followed by activity-guided fractionation of n-hexane, n-butanol, chloroform, ethyl acetate and aqueous fractions.The ethyl acetate fraction (200 mg/kg i.p.) showed the maximum analgesic effect (82%) in acetic acid-induced writhing, followed, to a less extent, by crude extract and chloroform fraction both at a dose of 200 mg/kg i.p. (65.09% and 67.89%, respectively). In carrageenan-induced mouse paw oedema, the crude extract and its related fractions displayed in a dose-dependent manner (50-200 mg/kg i.p.) an anti-inflammatory activity for all time-courses (1-5 hrs). For the active extract/fractions (200 mg/kg i.p.), the maximum effect was observed 5 h after carrageenan injection. These evidences were also supported by in vitro lipoxygenase inhibitory properties. In conclusion, R. arboreum crude methanolic extract and its fractions exhibited anti-inflammatory and antinociceptive effects. For these reasons, this plant could be a promising source of new compounds for the management of pain and inflammatory diseases. PMID:25501256

  13. Anti-inflammatory activity of Euphorbia aegyptiaca extract in rats

    PubMed Central

    Abo-dola, Marium A.; Lutfi, Mohamed F.

    2016-01-01

    Background There were no studies on the anti-inflammatory activity of Euphorbia aegyptiaca, though it is commonly used by Sudanese herbalists in the treatment of rheumatoid arthritis. Objectives To determine phytochemical constituents of Euphorbia aegyptiaca To investigate the anti-inflammatory activity of Euphorbia aegyptiaca in rats. Methodology Plant material was extracted by ethanol and phytochemical screening was done according to standard methods. The thickness of Albino rats’ paws were measured before injection of 0.1 ml of 1% formalin in the sub planter region and then, 1, 2, 3, 4 and 24 hours after oral dose of ethanolic extract of Euphorbia aegyptiaca at a rate of 400mg/kg, 800mg/kg, indomethacin (5mg/kg) and normal saline (5ml/kg). Edema inhibition percentage (EI%) and mean paw thickness (MPT) were measured in the different groups and compared using appropriate statistical methods. Results The phytochemical screening revealed the presence of saponins, cumarins, flavonoids, tannins, sterols, triterpenes, and absence of alkaloids, anthraquinones glycosides and cyanogenic glycosides. The mean of EI% of rats treated with indomethacin at a dose of 5 mg/kg over different time intervals (64.0%) was significantly lower compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (75.0%, P< 0.001), but higher compared to rats treated at higher dose of 400 mg/kg (57.4%, P< 0.001). In contrast, MPT of rats treated with indomethacin at a dose of 5 mg/kg (6.5±1.1 mm) was significantly higher compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (6.1±.7 mm, P< 0.001) as well as 400 mg/kg (5.9±.5, P< 0.001). Conclusion Euphorbia aegyptiaca ethanolic extract has a sustained dose-dependent anti-inflammatory activity. PMID:27004059

  14. General unknown screening, antioxidant and anti-inflammatory potential of Dendrobium macrostachyum Lindl.

    PubMed Central

    Sukumaran, Nimisha Pulikkal; Yadav, R. Hiranmai

    2016-01-01

    Context: D. macrostachyum is an epiphytic orchid abundant in Southern India and is reported for pain relief in folklore. Aims: The objective of the present study was to determine in vitro free radical scavenging and anti-inflammatory activity of D. macrostachyum and to perform LCMS based metabolic profiling of the plant. Settings and Design: Sequential stem and leaf extracts were assessed for its antioxidant and anti-inflammatory activity by in vitro methods. Materials and Methods: The antioxidant activity determined by assays based on the decolourization of the radical monocation of DPPH, ABTS and reducing power. Total amount of phenolics for quantitative analysis of antioxidative components was estimated. In vitro anti-inflammatory activity was evaluated using protein denaturation assay, membrane stabilization assay and proteinase inhibitory activity. Methanolic extract of plant was subjected to LCMS. Results: The stem ethanolic extracts exhibited significant IC50 value of 10.21, 31.54 and 142.97 μg/ml respectively for DPPH, ABTS radical scavenging and reducing power activity. The ethanol and water extract was highly effective as albumin denaturation inhibitors (IC50 = 114.13 and 135.818 μg/ml respectively) and proteinase inhibitors (IC50 = 72.49 and 129.681 μg/ml respectively). Membrane stabilization was also noticeably inhibited by the stem ethanolic extract among other extracts (IC50 = 89.33 μg/ml) but comparatively lower to aspirin standard (IC50 = 83.926 μg/ml). The highest total phenol content was exhibited by ethanolic stem and leaf extracts respectively at 20 and 16 mg of gallic acid equivalents of dry extract. On LCMS analysis 20 constituents were identified and it included chemotaxonomic marker for Dendrobium species. Conclusions: The results showed a relatively high concentration of phenolics, high scavenger activity and high anti-inflammatory activity of the stem extract compared to the leaf extract. The results indicate that the plant can be a

  15. Oenothein B's contribution to the anti-inflammatory and antioxidant activity of Epilobium sp.

    PubMed

    Kiss, Anna K; Bazylko, Agnieszka; Filipek, Agnieszka; Granica, Sebastian; Jaszewska, Edyta; Kiarszys, Urszula; Kośmider, Anita; Piwowarski, Jakub

    2011-05-15

    Willow herb tea or preparation are available and relatively popular in the European market, and claimed to be effective inter alia because of their anti-inflammatory activity. The present study is therefore aimed at comparing the anti-inflammatory and antioxidant activity of extracts of the three most popular Epilobium species (E. angustifolium, E. hirsutum and E. parviflorum) and at juxtaposing this activity against the dominating compounds from the following extracts: oenothein B (OeB), quercetin-3-O-glucuronide and myricetin-3-O-rhamnoside. The phytochemical analysis of the extracts has shown that OeB quantities vary between 20% and 35%, while flavonoids content does not exceed 2%. All extracts have inhibited the activity of hyaluronidase and lipoxygenase with IC₅₀ around 5 μg/ml and 25 μg/ml. The inhibition of hyaluronidase is related with the presence of OeB, a strong inhibitor of this enzyme (IC₅₀) 1.1 μM). Additionally, the extracts inhibited myeloperoxidase (MPO) release from stimulated neutrophils. OeB inhibited MPO release similarly to the anti-inflammatory drug indomethacin with IC₅₀ 7.7 μM and 15.4 μM, respectively. Tested extracts significantly reduced the production of reactive oxygen species (ROS) from f-MLP and PMA induced neutrophils with IC₅₀ 5 μg/ml and 25 μg/ml, respectively. The flavonoids content seems to exert little influence on extracts' activity, contrary to OeB, whose high concentration explains the activity of extract obtained from Epilobium. Tested currently marketed Epilobium preparations are often wrongly assigned, but we should stress that the level of OeB in all tested herbs was high and always exceeded 2% in raw material. PMID:21112753

  16. Magnetoliposomes Loaded with Poly-Unsaturated Fatty Acids as Novel Theranostic Anti-Inflammatory Formulations

    PubMed Central

    Calle, Daniel; Negri, Viviana; Ballesteros, Paloma; Cerdán, Sebastián

    2015-01-01

    We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning 1H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved 1H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may become

  17. Magnetoliposomes loaded with poly-unsaturated fatty acids as novel theranostic anti-inflammatory formulations.

    PubMed

    Calle, Daniel; Negri, Viviana; Ballesteros, Paloma; Cerdán, Sebastián

    2015-01-01

    We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents. Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters. This resulted in uniform preparations of liposomes of approximately 200 nm diameter. Extraliposomal contents were removed from the preparation by gel filtration chromatography. High Resolution Magic Angle Spinning (1)H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved (1)H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration. The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development. Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development. Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may

  18. Assessment of the Polyphenolic Content, Free Radical Scavenging, Anti-inflammatory, and Antimicrobial Activities of Acetone and Aqueous Extracts of Lippia javanica (Burm.F.) Spreng

    PubMed Central

    Asowata-Ayodele, Abiola M.; Otunola, Gloria A.; Afolayan, Anthony J.

    2016-01-01

    Background: Lippia javanica (Burm.F.) Spreng is one of the spice plants commonly found in almost every part of South Africa. Apart from its culinary uses, it is also traditionally used as an insect repellant and infusion for fever, flu, kidney stone treatment, cough, common cold, and chest pain. Materials and Methods: The antioxidant activities of the aqueous and acetone extracts were determined by measuring their effects against 1,1-Diphenyl-2-picryl-hydrazyl, 2,2’azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), nitric oxide, phosphomolybdate, lipid peroxidation, hydrogen peroxide, and reducing power. The antimicrobial activities were evaluated against four bacterial (two Gram-positive, two Gram-negative) strains and 9 fungal pathogens using the agar well diffusion and microdilution methods. Anti-inflammatory activity was assessed by determining the inhibition against protein denaturation and membrane stabilizing effects. Objective: The polyphenolic content, free radical scavenging, anti-inflammatory, and antimicrobial activities of the aqueous and acetone extracts of the plant were evaluated. Results: A significantly high total phenolic content and free radical scavenging activities were observed in the acetone extracts of the plants. The study also revealed a concentration-dependent inhibition of protein denaturation and membrane stabilization effects by both the aqueous and acetone extracts at the concentrations studied. The ability of L. javanica extracts to inhibit protein denaturation and maintain membrane stability could be responsible for its folkloric use. The overall antimicrobial activity indicates that both extracts were active against the bacterial strains but the acetone extract exhibited the most potent antifungal activity higher than even the reference drugs. Conclusion: Overall, the acetone extract of L. javanica exhibited a more pronounced antioxidant, anti-inflammatory, and antimicrobial effects than the aqueous extract. SUMMARY The

  19. Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents.

    PubMed

    Zeng, Kui; Thompson, Karin Emmons; Yates, Charles R; Miller, Duane D

    2009-09-15

    Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. cat's claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappaB). Herein, we describe the synthesis and biological testing of novel QA derivatives. Inhibition of NF-kappaB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-kappaB response element. A549-NF-kappaB cells were stimulated with TNF-alpha (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at the carboxylic acid position yielded potent inhibitors of NF-kappaB. A variety of modifications to the amide substitution were tolerated with the N-propyl amide derivative being the most potent. Further examination of the SAR demonstrated that acetylation of the hydroxyl groups reduced NF-kappaB inhibitory activity. QA amide derivatives lacked anti-oxidant activity and were found to be neither anti-proliferative nor cytotoxic at concentrations up to 100 microM. In conclusion, we have discovered a novel series of non-toxic QA amides that potently inhibit NF-kappaB, despite their lack of anti-oxidant activity. Mechanistic studies and pre-clinical efficacy studies in various inflammatory animal models are on-going. PMID:19674895

  20. Extracts from Lentinula edodes (Shiitake) Edible Mushrooms Enriched with Vitamin D Exert an Anti-Inflammatory Hepatoprotective Effect.

    PubMed

    Drori, Ariel; Shabat, Yehudit; Ben Ya'acov, Ami; Danay, Ofer; Levanon, Dan; Zolotarov, Lidya; Ilan, Yaron

    2016-04-01

    Vitamin D has been known for its anti-inflammatory properties. Extracts derived from Lentinula edodes (Shiitake) edible mushroom exert an anti-inflammatory effect. These extracts contain high levels of ergosterol, which converts into ergocalciferol (vitamin D2) following exposure to ultraviolet light, followed by absorption and hydroxylation into the active form 25-hydroxyvitamin D [25(OH)D]. To determine the anti-inflammatory effect of overexpression of vitamin D in edible mushrooms, L. edodes mushrooms were exposed to ultraviolet-B light, freeze-dried, followed by measurement of vitamin D2 contents, in their dry weight. C57B1/6 mice were orally treated with vitamin D2-enriched or nonenriched mushroom extract prior and during concanavalin A-immune-mediated liver injury. Exposure to ultraviolet light increased vitamin D2 content in Shiitake edible mushrooms. Following feeding of vitamin D-enriched mushroom extracts to mice with immune-mediated hepatitis, a significant decrease in liver damage was noted. This was shown by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels, a decrease in proportion of mice with severe liver injury, and by improvement in liver histology. These effects were associated with a decrease in serum interferon gamma levels. A synergistic effect was noted between the anti-inflammatory effect of the mushroom extracts and that of vitamin D. Oral administration of vitamin D-enriched L. edodes edible mushroom exerts a synergistic anti-inflammatory effect in the immune-mediated hepatitis. The data support its potential use as safe immunomodulatory adjuvant for the treatment of HCV and nonalcoholic steatohepatitis. PMID:27027234

  1. Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway.

    PubMed

    Liu, Xiaojie; Mei, Zhigang; Qian, Jingping; Zeng, Yongbao; Wang, Mingzhi

    2013-12-01

    Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) reduced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-α in brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-κB) inhibition. These observations were inhibited by the alpha7 nicotinic acetylcholine receptor (α7nAchR) antagonist α-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory response. Our results also indicated that the anti-inflammatory effect of puerarin may partly be mediated through the activation of the cholinergic anti-inflammatory pathway. PMID:25206641

  2. Anti-inflammatory activity of Abutilon indicum extract.

    PubMed

    Tripathi, Priyanka; Chauhan, N S; Patel, J R

    2012-01-01

    Abutilon indicum Linn. had been broadly used for its reported biological activities in indigenous system of medicine. The ethanolic extract of the whole plant of A. indicum Linn. was evaluated for its anti-inflammatory activity at doses 250, 500 and 750 mg kg⁻¹ using the carrageenan-induced paw oedema in healthy Wistar albino rats. Results of in vivo activity led to the conclusion that the ethanolic extract of A. indicum showed predominantly significant activity in a dose-dependent manner, which is comparable to the reference standard ibuprofen. The results prove the traditional use of plant in the treatment of inflammation. PMID:21999427

  3. Natural anti-inflammatory agents for pain relief

    PubMed Central

    Maroon, Joseph C.; Bost, Jeffrey W.; Maroon, Adara

    2010-01-01

    The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions. This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements. Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use. PMID:21206541

  4. Multiple cutaneous sensitization to nonsteroidal anti-inflammatory drugs.

    PubMed

    Gonzalo, M A; Revenga, F

    1996-01-01

    The use of topical nonsteroidal anti-inflammatory drugs is widespread (particularly in countries bordering the Mediterranean). Compared to their wide use, the incidence of published adverse cutaneous effects appears minimal, although they are increasing. Most of them are a form of allergic contact dermatitis (ACD). Multiple sensitization and/or cross-reactions are rarely reported. Interestingly, our patient presented ACD with diclofenac and etofenamate (both from different chemical groups) and, furthermore, patch tests were positive with bencydamine and indomethacin (both indolacetic acid derivatives), piroxicam and fepradinol. We think that our results could not be explained due to cross-reactivity, and that multiple sensitization was more likely. PMID:8864624

  5. Synthesis and anti-inflammatory activity of indole glucosinolates.

    PubMed

    Vo, Quan V; Trenerry, Craige; Rochfort, Simone; Wadeson, Jenny; Leyton, Carolina; Hughes, Andrew B

    2014-01-15

    The nitronate and nitrovinyl methods to synthesize indole glucosinolates (GLs) have been investigated. The results were applied to generally the most prevalent natural indole glucosinolates to synthesize 4-methoxyglucobrassicin (MGB) and neo-glucobrassicin (NGB) in moderate overall yield for the first time. The anti-inflammatory activity of the synthetic indole GLs was determined by inhibition of TNF-α secretion in LPS-stimulated THP-1 cells. The data showed that glucobrassicin (GB) exhibited higher activity than other synthetic indolyl GLs. PMID:24360830

  6. Anti-inflammatory and immunosuppressive drugs and reproduction

    PubMed Central

    Østensen, Monika; Khamashta, Munther; Lockshin, Michael; Parke, Ann; Brucato, Antonio; Carp, Howard; Doria, Andrea; Rai, Raj; Meroni, Pierluigi; Cetin, Irene; Derksen, Ronald; Branch, Ware; Motta, Mario; Gordon, Caroline; Ruiz-Irastorza, Guillermo; Spinillo, Arsenio; Friedman, Deborah; Cimaz, Rolando; Czeizel, Andrew; Piette, Jean Charles; Cervera, Ricard; Levy, Roger A; Clementi, Maurizio; De Carolis, Sara; Petri, Michelle; Shoenfeld, Yehuda; Faden, David; Valesini, Guido; Tincani, Angela

    2006-01-01

    Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given. PMID:16712713

  7. Anti-inflammatory guaiane-type sesquiterpenes from the fruits of Pittosporum undulatum.

    PubMed

    Mendes, Sofia A C; Mansoor, Tayyab A; Rodrigues, Ana; Armas, Jácome Bruges; Ferreira, Maria-José U

    2013-11-01

    Two unprecedented guaiane-type sesquiterpene glycosides (undulatumosides A and B) were isolated by bioassay-guided fractionation from the MeOH extract of Pittosporum undulatum fruits, along with six known compounds, including the guaiane isomers 5-guaien-11-ol and 4-guaien-11-ol. The structures of the compounds were established as 4-guaiene-11-O-β-d-(3'-angeloxy-6'-deoxy)-glucopyranoside and 1(5)-guaiene-11-O-β-d-(3'-angeloxy-6'-deoxy)-glucopyranoside by spectroscopic methods, including 1D and 2D homo- and heteronuclear NMR experiments (COSY, HSQC, HMBC and NOESY), and HR-mass spectrometry. P. undulatum is a highly invasive weed that often outcompetes other plants, yet its fruits have become a traditional anti-inflammatory medicine in Azores. Therefore, aiming to investigate the claimed properties, the in vitro anti-inflammatory activity of guaiane-type sesquiterpenes was evaluated by analyzing their inhibitory effects on chemical mediators released by the LPS activated RAW 264.7 murine macrophages cell line. In addition, the cytotoxicity of these compounds was also evaluated in this cell line. Undulatumoside A, 5-guaien-11-ol and 4-guaien-11-ol displayed anti-inflammatory activity with IC50 values of 16.4, 8.1 and 7.2μM, respectively, comparable to that of the positive control, indomethacin (IC50=18.2 μM), with no cytotoxic effects (IC50 ≥ 198 μM). Furthermore, the same set of compounds was also assessed for anti-proliferative activity in lung large cell carcinoma COR-L23 and amelanotic melanoma C32 cells. PMID:23899690

  8. Binary graft modification of polypropylene for anti-inflammatory drug-device combo products.

    PubMed

    Melendez-Ortiz, Hector Ivan; Díaz-Rodríguez, Patricia; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Bucio, Emilio

    2014-04-01

    Temperature- and pH-responsive copolymers were γ-ray grafted onto polypropylene (PP) to provide its surface with capability to load and to control the release of nonsteroidal anti-inflammatory drugs (NSAIDs) with the aim of being useful as component of drug-eluting medical devices. Poly(N,N'-dimethylaminoethylmethacrylate) (PDMAEMA) or poly(4-vinylpyridine) (P4VP) were grafted onto PP films via a direct method, and then poly(N-isopropylacrylamide) (PNIPAAm) was grafted applying a preirradiation method. The binary graft copolymers showed hemocompatibility and certain capability to adsorb albumin. (PP-g-DMAEMA)-g-NIPAAm exhibited higher affinity for ibuprofen and, particularly, diclofenac than (PP-g-4VP)-g-NIPAAm. Sustained release was observed under physiological conditions. Cytotoxicity and anti-inflammatory activity of NSAID-eluting (PP-g-DMAEMA)-g-NIPAAm films were evaluated on RAW 264.7 macrophage cells. First, dose dependence of anti-inflammatory activity and cytotoxicity of ibuprofen and diclofenac on RAW 264.7 cells were investigated to elucidate the ranges of drug concentration that the graft copolymers should provide. Optimal concentrations of diclofenac and ibuprofen at which they reduce inflammation while maintaining cell viability were determined to be 200 μg/mL and above 400 μg/mL in culture medium. Sequential grafting of DMAEMA and NIPAAm made PP surface to exhibit remarkably high affinity to diclofenac, being able to load and to regulate drug release fulfilling in vitro requirements to avoid inflammatory response. PMID:24615379

  9. Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii

    DOE PAGESBeta

    Miquel, Sylvie; Leclerc, Marion; Martin, Rebeca; Chain, Florian; Lenoir, Marion; Raguideau, Sébastien; Hudault, Sylvie; Bridonneau, Chantal; Northen, Trent; Bowen, Benjamin; et al

    2015-04-21

    Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable andmore » stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood.« less

  10. Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease

    PubMed Central

    Lee, In-Ah; Kamba, Alan; Low, Daren; Mizoguchi, Emiko

    2014-01-01

    Family 18 chitinases have a binding capacity with chitin, a polymer of N-acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1 (CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major members of family 18 chitinases, play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD), bronchial asthma and several other inflammatory disorders. Based on the data from high-throughput screening, it has been found that three methylxanthine derivatives, caffeine, theophylline, and pentoxifylline, have competitive inhibitory effects against a fungal family 18 chitinase by specifically interacting with conserved tryptophans in the active site of this protein. Methylxanthine derivatives are also known as adenosine receptor antagonists, phosphodiesterase inhibitors and histone deacetylase inducers. Anti-inflammatory effects of methylxanthine derivatives have been well-documented in the literature. For example, a beneficial link between coffee or caffeine consumption and type 2 diabetes as well as liver cirrhosis has been reported. Furthermore, theophylline has a long history of being used as a bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating effect for peripheral vascular disease. However, it is still largely unknown whether these methylxanthine derivative-mediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells. In this review article we will examine the above possibility and summarize the biological significance of methylxanthine derivatives in intestinal epithelial cells. We hope that this study will provide a rationale for the development of methylxanthine derivatives, in particular caffeine, -based anti-inflammatory therapeutics in the field of IBD and IBD-associated carcinogenesis. PMID:24574789

  11. Identification of Metabolic Signatures Linked to Anti-Inflammatory Effects of Faecalibacterium prausnitzii

    PubMed Central

    Miquel, Sylvie; Leclerc, Marion; Martin, Rebeca; Chain, Florian; Lenoir, Marion; Raguideau, Sébastien; Hudault, Sylvie; Bridonneau, Chantal; Northen, Trent; Bowen, Benjamin; Bermúdez-Humarán, Luis G.; Sokol, Harry; Thomas, Muriel

    2015-01-01

    ABSTRACT Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable and stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (α-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood. PMID:25900655

  12. The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: an overview.

    PubMed

    Wu, Qinghua; Liu, Lian; Miron, Anca; Klímová, Blanka; Wan, Dan; Kuča, Kamil

    2016-08-01

    Spirulina is a species of filamentous cyanobacteria that has long been used as a food supplement. In particular, Spirulina platensis and Spirulina maxima are the most important. Thanks to a high protein and vitamin content, Spirulina is used as a nutraceutical food supplement, although its other potential health benefits have attracted much attention. Oxidative stress and dysfunctional immunity cause many diseases in humans, including atherosclerosis, cardiac hypertrophy, heart failure, and hypertension. Thus, the antioxidant, immunomodulatory, and anti-inflammatory activities of these microalgae may play an important role in human health. Here, we discuss the antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina in both animals and humans, along with the underlying mechanisms. In addition, its commercial and regulatory status in different countries is discussed as well. Spirulina activates cellular antioxidant enzymes, inhibits lipid peroxidation and DNA damage, scavenges free radicals, and increases the activity of superoxide dismutase and catalase. Notably, there appears to be a threshold level above which Spirulina will taper off the antioxidant activity. Clinical trials show that Spirulina prevents skeletal muscle damage under conditions of exercise-induced oxidative stress and can stimulate the production of antibodies and up- or downregulate the expression of cytokine-encoding genes to induce immunomodulatory and anti-inflammatory responses. The molecular mechanism(s) by which Spirulina induces these activities is unclear, but phycocyanin and β-carotene are important molecules. Moreover, Spirulina effectively regulates the ERK1/2, JNK, p38, and IκB pathways. This review provides new insight into the potential therapeutic applications of Spirulina and may provide new ideas for future studies. PMID:27259333

  13. Biochemical effects, hypolipidemic and anti-inflammatory activities of Artemisia vulgaris extract in hypercholesterolemic rats.

    PubMed

    El-Tantawy, Walid Hamdy

    2015-07-01

    The purpose of the present study was to investigate hypolipidemic and anti-inflammatory effects of Artemisia vulgaris extract in hypercholesterolemic rats. Hypercholesterolemia was induced by feeding of rats with high fat diet containing 3% cholesterol in olein oil, for 8 weeks. Feeding of rats with high fat diet for 8 weeks, leading to a significant increase in serum triglycerides, total cholesterol, low density lipoprotein cholesterol, malondialdehyde and nitric oxide, tumor necrosis factor-α levels and a significant decrease in serum high density lipoprotein cholesterol level, liver hydroxymethylglutaryl-CoA reductase activity and paraoxonase-1 activities as compared to the normal control group. Treatment of high fat diet rats with Artemisia vulgaris extract for 4 weeks at a dose of 100 mg/kg per day, resulted in normalized serum lipid profile, a significant increase in paraoxonase-1 activity and decrease in serum malondialdehyde, nitric oxide and tumor necrosis factor-α level as compared to high fat diet-treated animals. Also the extract caused a significant decrease in hydroxymethylglutaryl-CoA reductase activity as compared with both high fat diet-treated animals and control ones. In conclusion, Artemisia vulgaris extract has hypolipidemic, anti-inflammatory, antioxidant properties; it may serve as a source for the prevention of atherosclerosis and cardiovascular diseases. PMID:26236098

  14. [The mode of anti-inflammatory action of a topical non-steroidal anti-inflammatory drug, etofenamate].

    PubMed

    Nakamura, H; Motoyoshi, S; Ishii, K; Seto, Y; Shimoda, A; Kadokawa, T

    1987-01-01

    In order to ascertain the mode of anti-inflammatory action of a topical non-steroidal anti-inflammatory drug, etofenamate which is a diethylene glycol ester of flufenamic acid, the in vitro test for the mechanism of the action were carried out. Etofenamate (3 microM) was hydrolysed to flufenamic acid at a rate of 39.5% and 57.0% of the dose during 30 and 60 min incubation, respectively, when incubated with rat peritoneal macrophages stimulated with starch and bacto peptone in phosphate-buffered saline. PGE2 generation by these cells in MEM medium was dose-relatedly inhibited with etofenamate as well as flufenamic acid at the dosage range of 1 to 30 microM. This suggests that unchanged etofenamate is active, since the highest conversion rate of etofenamate to flufenamic acid was 15% of the dose during the incubation. Etofenamate produced a dose-related inhibition against lipoxygenase prepared from peritoneal polymorphonuclear leucocytes of guinea pigs, and its activity (IC50 = 5.3 X 10(-5) M) was stronger than that of caffeic acid; flufenamic acid was inactive. Inhibitory activity of etofenamate was one-third or less that of flufenamic acid against the hypotonic-hyperthermic lysis of rat erythrocytes and heat-denaturation of bovine serum albumin. From these results, it was suggested that topically applied etofenamate produces its anti-inflammatory action through prostaglandin synthesis inhibition by flufenamic acid produced in the inflammatory tissue and inhibition of prostaglandin synthesis by macrophages and lipoxygenase inhibition by unchanged etofenamate. PMID:2883093

  15. Actions and toxicity of nonsteroidal anti-inflammatory drugs.

    PubMed

    Simon, L S

    1996-05-01

    Use of nonsteroidal anti-inflammatory drugs (NSAIDs) continues to be an important therapeutic intervention throughout the world for patients with pain and inflammation. The six major classes of NSAIDs (including the salicylates) bear the common property of inhibiting cyclooxygenase, the enzyme that catalyzes the synthesis of cyclic endoperoxides from arachidonic acid to yield prostaglandins. Anecdotal evidence has accumulated that the nonacetylated salicylates are as efficacious as the other NSAIDs, but there have been few controlled trials demonstrating that they are reasonable anti-inflammatory agents. This paper discusses the newest of the available clinical observations that nonacetylated salicylates are as efficacious as one of the newer NSAIDs in patients with rheumatoid arthritis. Because the nonacetylated salicylates are weak prostaglandin inhibitors, several other non-prostaglandin mediated mechanisms of action for the NSAIDs have been postulated and are described in this paper. In addition to papers describing NSAID effects on cartilage, this year several interesting papers described further effects of tenidap, a novel NSAID presently in development. Other papers reviewed attempts to develop NSAIDs with less severe gastrointestinal effects. Some reports discuss the use of topical NSAIDs, which are not clearly better than oral preparations. Data are also reviewed demonstrating that misoprostol effectively decreased significant poor gastrointestinal outcomes in patients who were treated with this NSAID for 6 months. New treatment regimens for decreasing misoprostol-induced toxicity are also reviewed. Finally, the effects of NSAID prophylaxis in preventing heterotopic bone formation in patients with osteoarthritis who undergo hip replacement surgery are noted. PMID:8796974

  16. Anticancer and anti-inflammatory activities of some dietary cucurbits.

    PubMed

    Sharma, Dhara; Rawat, Indu; Goel, H C

    2015-04-01

    In this study, we investigated few dietary cucurbits for anticancer activity by monitoring cytotoxic (MTT and LDH assays), apoptotic (caspase-3 and annexin-V assays), and also their anti-inflammatory effects by IL-8 cytokine assay. Aqua-alcoholic (50:50) whole extracts of cucurbits [Lagenaria siceraria (Ls), Luffa cylindrica (Lc) and Cucurbita pepo (Cp)] were evaluated in colon cancer cells (HT-29 and HCT-15) and were compared with isolated biomolecule, cucurbitacin-B (Cbit-B). MTT and LDH assays revealed that the cucurbit extracts and Cbit-B, in a concentration dependent manner, decreased the viability of HT-29 and HCT-15 cells substantially. The viability of lymphocytes was, however, only marginally decreased, yielding a potential advantage over the tumor cells. Caspase-3 assay revealed maximum apoptosis with Ls while annexin V assay demonstrated maximum efficacy of Lc in this context. These cucurbits have also shown decreased secretion of IL-8, thereby revealing their anti-inflammatory capability. The results have demonstrated the therapeutic potential of dietary cucurbits in inhibiting cancer and inflammatory cytokine. PMID:26011982

  17. Anti-inflammatory Cerebrosides from Cultivated Cordyceps militaris.

    PubMed

    Chiu, Ching-Peng; Liu, Shan-Chi; Tang, Chih-Hsin; Chan, You; El-Shazly, Mohamed; Lee, Chia-Lin; Du, Ying-Chi; Wu, Tung-Ying; Chang, Fang-Rong; Wu, Yang-Chang

    2016-02-24

    Cordyceps militaris (bei-chong-chaw, northern worm grass) is a precious and edible entomopathogenic fungus, which is widely used in traditional Chinese medicine (TCM) as a general booster for the nervous system, metabolism, and immunity. Saccharides, nucleosides, mannitol, and sterols were isolated from this fungus. The biological activity of C. militaris was attributed to the saccharide and nucleoside contents. In this study, the aqueous methanolic fraction of C. militaris fruiting bodies exhibited a significant anti-inflammatory activity. Bioactivity-guided fractionation of the active fraction led to the isolation of eight compounds, including one new and two known cerebrosides (ceramide derivatives), two nucleosides, and three sterols. Cordycerebroside A (1), the new cerebroside, along with soyacerebroside I (2) and glucocerebroside (3) inhibited the accumulation of pro-inflammatory iNOS protein and reduced the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophages. This is the first study on the isolation of cerebrosides with anti-inflammatory activity from this TCM. PMID:26853111

  18. Immunosuppressive and anti-inflammatory properties of engineered nanomaterials

    PubMed Central

    Ilinskaya, A N; Dobrovolskaia, M A

    2014-01-01

    Nanoparticle interactions with various components of the immune system are determined by their physicochemical properties such as size, charge, hydrophobicity and shape. Nanoparticles can be engineered to either specifically target the immune system or to avoid immune recognition. Nevertheless, identifying their unintended impacts on the immune system and understanding the mechanisms of such accidental effects are essential for establishing a nanoparticle's safety profile. While immunostimulatory properties have been reviewed before, little attention in the literature has been given to immunosuppressive and anti-inflammatory properties. The purpose of this review is to fill this gap. We will discuss intended immunosuppression achieved by either nanoparticle engineering, or the use of nanoparticles to carry immunosuppressive or anti-inflammatory drugs. We will also review unintended immunosuppressive properties of nanoparticles per se and consider how such properties could be either beneficial or adverse. Linked Articles This article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-17 PMID:24724793

  19. Anti-inflammatory strategies in the treatment of schizophrenia.

    PubMed

    Andrade, Chittaranjan

    2016-01-01

    Schizophrenia is a major mental illness with a lifetime prevalence of about 1%. Antipsychotic drugs, with a primary mechanism of action that involves dopamine receptor blockade, are the mainstay in the treatment of the disorder. However, despite optimum antipsychotic treatment, few patients return to pre-morbid levels; the treatment deficit includes refractory positive symptoms, negative symptoms, mood impairments, cognitive impairments, social impairments, and/or a variety of medication-related adverse effects, including extrapyramidal symptoms, metabolic disturbances, hyperprolactinemia, and others. To address these, antipsychotic treatment has been augmented with psychosocial interventions, cognitive rehabilitation, different kinds of electrical and magnetic brain stimulation, and a large range of drugs from the neuropsychiatric as well as, surprise, the general medical pharmacopeia. The pleomorphic pathophysiology of schizophrenia includes abnormalities in immunological and inflammatory pathways, and so it is not surprising that anti-inflammatory drugs have also been trialed as augmentation agents in schizophrenia. This article critically examines the outcomes after augmentation with conventional anti-inflammatory interventions; results from randomized controlled trials do not encourage the use of either aspirin (1000 mg/day) or celecoxib (400 mg/day), both of which have been studied for this indication during the past decade and a half. PMID:26427750

  20. Anti-inflammatory, antiapoptotic, and antioxidant activity of fluoxetine.

    PubMed

    Caiaffo, Vitor; Oliveira, Belisa D R; de Sá, Fabrício B; Evêncio Neto, Joaquim

    2016-06-01

    Fluoxetine is a selective serotonin uptake inhibitor that has been widely used to determine the neurotransmission of serotonin in the central nervous system. This substance has emerged as the drug of choice for the treatment of depression due to is safer profile, fewer side effects, and greater tolerability. Studies have found the following important functions of fluoxetine related to the central nervous system: neuroprotection; anti-inflammatory properties similar to standard drugs for the treatment of inflammatory conditions; antioxidant properties, contributing to its therapeutic action and an important intracellular mechanism underlying the protective pharmacological effects seen in clinical practice in the treatment of different stress-related adverse health conditions; and antiapoptotic properties, with greater neuron survival and a reduction in apoptosis mediators as well as oxidative substances, such as superoxide dismutase and hydrogen peroxide. The aim of this study was to perform a review of the literature on the important role of fluoxetine in anti-inflammatory, cell survival, and neuron trophicity mechanisms (antiapoptotic properties) as well as its role regarding enzymes of the antioxidant defense system. PMID:27433341

  1. Analgesic, anti-inflammatory, and antipyretic effects of Ixora coccinea.

    PubMed

    Ali Adnan, Md Syed; Al-Amin, Md Mamun; Nasir Uddin, Mir Muhammad; Shohel, M; Bhattacharjee, Rajib; Hannan, J M A; Das, Biplab Kumar

    2014-01-27

    Abstract Background: The present study was carried out to explore the potential of the ethanol extract of Ixora coccinea L. (IC) leaves as analgesic, anti-inflammatory and antipyretic agents using the hot-plate, acetic acid-induced writhing, carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests in rodents. Methods: The extract was prepared by soaking the dried powdered leaves of IC in ethanol for 2 days. The filtrate thus obtained by filtration and evaporation was considered as a stock solution and was used in all experimental models. Results: Oral administration of IC (250 and 500 mg/kg) significantly (p<0.05) increased the reaction time in the hot-plate test. Ixora coccinea (250 and 500 mg/kg) produced 56.14% and 63.16% inhibition (p<0.05) in acetic acid-induced writhing. It also (250 and 500 mg/kg) produced significant (p<0.05) inhibition of paw edema pronounced at 6 h after carrageenan injection. Intraperitoneal administration of IC (250 and 500 mg/kg) lowered the body temperature in brewer's yeast-induced hyperthermia. Conclusions: Based on the findings, it may be concluded that the IC leaves possessed analgesic, anti-inflammatory, and antipyretic activities. Phytochemical constituents of IC leaves such as flavonoids, tannins, and triterpenes in ethanol extract could be correlated with its observed biological activities. PMID:24468614

  2. Human milk anti-inflammatory component contents during acute mastitis.

    PubMed

    Buescher, E S; Hair, P S

    2001-06-15

    Mastitis is a common complication of human lactation. We examined milk specimens from eight women with clinical mastitis to determine their content of anti-inflammatory components. Antioxidant activity (spontaneous cytochrome c reducing activity), selected pro-inflammatory cytokines (IL-6, IL-1beta), selected endogenous cytokine control molecules (sIL-6R, sIL-1RII, and sTNFRI), lactoferrin, Na(+):K(+) ratios, and milk bioactivities that cause shedding of sIL-1RII from human polymorphonuclear leukocytes (PMN), suppress PMN aggregation, and suppress PMN adherence responses were not increased compared to normal milks. Neither the bioactivities that deplete PMN intracellular Ca(2+) stores nor those that block Ca(2+) influx into fMLP-stimulated PMN were significantly increased in mastitis milks. In contrast, levels of TNFalpha, sTNFRII, and IL-1RA and bioactivities that cause shedding of sTNFRI from human PMN were significantly increased compared to normal milks. Mastitis milk has the same anti-inflammatory components and characteristics of normal milk, with elevations in selected components/activities that may help protect the nursing infant from developing clinical illness due to feeding on mastitis milk. PMID:11520075

  3. Anti-inflammatory effects of fangchinoline and tetrandrine.

    PubMed

    Choi, H S; Kim, H S; Min, K R; Kim, Y; Lim, H K; Chang, Y K; Chung, M W

    2000-02-01

    Fangchinoline and tetrandrine are the major alkaloids from Stephania tetrandrae S. Moore which has been used traditionally for the treatment of inflammatory diseases in oriental countries including Korea. Both fangchinoline and tetrandrine showed anti-inflammatory effects on mouse ear edema induced by croton oil. In addition, the effects of fangchinoline and tetrandrine on cyclooxygenase, murine interleukin-5 (mIL-5) and human interleukin-6 (hIL-6) were examined in vitro to investigate the anti-inflammatory action mechanisms. One hundred micromolar of fangchinoline showed 35% of inhibition on cyclooxygenase, but the same concentration of tetrandrine did not show any inhibition. On the other hand, 12.5 microM of tetrandrine exhibited 95% of inhibition on mIL-5 activity, while fangchinoline did not show any effects. However, 4 microM of fangchinoline and 6 microM of tetrandrine showed 63 and 86% of inhibitions on hIL-6 activity, respectively. These results suggest that biochemical mechanisms of fangchinoline and tetrandrine on anti-inflammation are significantly different even though they are similar in chemical structure. PMID:10687873

  4. Selenium Supplementation of Amaranth Sprouts Influences Betacyanin Content and Improves Anti-Inflammatory Properties via NFκB in Murine RAW 264.7 Macrophages.

    PubMed

    Tyszka-Czochara, Malgorzata; Pasko, Pawel; Zagrodzki, Pawel; Gajdzik, Ewelina; Wietecha-Posluszny, Renata; Gorinstein, Shela

    2016-02-01

    Sprouts contain potent compounds which while influencing crucial transduction pathways in cell reveal anti-inflammatory and anticancer activities. In this study, we report the biological activity for seeds and colourful sprouts of four types of edible amaranth, as amaranth has recently attracted interest due to its appreciable nutritional value. MTT assay conducted for the amaranth seeds and sprouts did not show any adverse effect on the viability of murine RAW 264.7 cells. As amaranth accumulates selenium, the sprouts were supplemented with this trace element (10 mg/L; 15 mg/L Se as sodium selenite) while growing. Selenium concentration in sprouts was observed to be significantly correlated with betacyanins content of the tested species. The amounts of Se and betacyanins in sprouts varied for various Amaranth species. In the present study, Amaranthus cruentus sprouts with the highest betacyanins (19.30 ± 0.57-28.85 ± 2.23 mg of amaranthin/100 g of fresh weight) and high total selenium (22.51 ± 1.57-1044.75 ± 73.08 μg/L in methanol extracts) content prevented NFκB translocation to the cell nucleus and subsequently exerted an anti-inflammatory effect by significant decreasing inflammatory interleukin 6 production (587.3 ± 34.2-710.0 ± 88.1 pg/mL) in the cell culture of activated RAW 264.7 macrophages (vs LPS control 1520 ± 114 pg/mL). PMID:26162623

  5. Lactobacillus crispatus strain SJ-3C-US induces human dendritic cells (DCs) maturation and confers an anti-inflammatory phenotype to DCs.

    PubMed

    Eslami, Solat; Hadjati, Jamshid; Motevaseli, Elahe; Mirzaei, Reza; Farashi Bonab, Samad; Ansaripour, Bita; Khoramizadeh, Mohammad Reza

    2016-08-01

    Lactobacillus crispatus is one of the most predominant species in the healthy vagina microbiota. Nevertheless, the interactions between this commensal bacterium and the immune system are largely unknown. Given the importance of the dendritic cells (DCs) in the regulation of the immunity, this study was performed to elucidate the influence of vaginal isolated L. crispatus SJ-3C-US from healthy Iranian women on DCs, either directly by exposure of DCs to ultraviolet-inactivated (UVI) and heat-killed (HK) L. crispatus SJ-3C-US or indirectly to its cell-free supernatant (CFS), and the outcomes of immune response. In this work we showed that L. crispatus SJ-3C-US induced strong dose-dependent activation of dendritic cells and production of high levels of IL-10, whereas IL-12p70 production was induced at low level in an inverse dose-dependent manner. This stimulation skewed T cells polarization toward CD4(+) CD25(+) FOXP3(+) Treg cells and production of IL-10 in a dose-dependent manner in mixed leukocyte reaction (MLR) test. The mode of bacterial inactivation did not affect the DCs activation pattern, upon encounter with L. crispatus SJ-3C-US. Moreover, while DCs stimulated with CFS showed moderate phenotypic maturation and IL-10 production, it failed to skew T cells polarization toward CD4(+) CD25(+) FOXP3(+) regulatory T cells (Treg) and production of IL-10. This study showed that L. crispatus SJ-3C-US confers an anti-inflammatory phenotype to DCs through up-regulation of anti-inflammatory/regulatory IL-10 cytokine production and induction of CD4(+) CD25(+) FOXP3(+) T cells at optimal dosage. Our findings suggest that L. crispatus SJ-3C-US could be a potent candidate as protective probiotic against human immune-mediated pathologies, such as chronic inflammation, vaginitis or pelvic inflammatory disease (PID). PMID:27245496

  6. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage

    PubMed Central

    Sasso, Oscar; Migliore, Marco; Habrant, Damien; Armirotti, Andrea; Albani, Clara; Summa, Maria; Moreno-Sanz, Guillermo; Scarpelli, Rita; Piomelli, Daniele

    2015-01-01

    The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit cyclooxygenase (Cox)-1 and Cox-2 underlies the therapeutic efficacy of these drugs, as well as their propensity to damage the gastrointestinal (GI) epithelium. This toxic action greatly limits the use of NSAIDs in inflammatory bowel disease (IBD) and other chronic pathologies. Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide, which attenuates inflammation and promotes GI healing. Here, we describe the first class of systemically active agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and selectivity. The class prototype 4 (ARN2508) is potent at inhibiting FAAH, Cox-1, and Cox-2 (median inhibitory concentration: FAAH, 0.031 ± 0.002 µM; Cox-1, 0.012 ± 0.002 µM; and Cox-2, 0.43 ± 0.025 µM) but does not significantly interact with a panel of >100 off targets. After oral administration in mice, ARN2508 engages its intended targets and exerts profound therapeutic effects in models of intestinal inflammation. Unlike NSAIDs, ARN2508 causes no gastric damage and indeed protects the GI from NSAID-induced damage through a mechanism that requires FAAH inhibition. Multitarget FAAH/Cox blockade may provide a transformative approach to IBD and other pathologies in which FAAH and Cox are overactive.—Sasso, O., Migliore, M., Habrant, D., Armirotti, A., Albani, C., Summa, M., Moreno-Sanz, G., Scarpelli, R., Piomelli, D. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage. PMID:25757568

  7. Convergence of Nitric Oxide and Lipid Signaling: Anti-Inflammatory Nitro-Fatty Acids

    PubMed Central

    Baker, Paul R.S.; Schopfer, Francisco J.; O’Donnell, Valerie B.; Freeman, Bruce A.

    2009-01-01

    The signaling mediators nitric oxide (·NO) and oxidized lipids, once viewed to transduce metabolic and inflammatory information via discrete and independent pathways, are now appreciated as interdependent regulators of immune response and metabolic homeostasis. The interactions between these two classes of mediators result in reciprocal control of mediator sythesis that is strongly influenced by the local chemical environment. The relationship between the two pathways extends beyond co-regulation of ·NO and eicosanoid formation to converge via the nitration of unsaturated fatty acids to yield nitro derivatives (NO2-FA). These pluripotent signaling molecules are generated in vivo as an adaptive response to oxidative inflammatory conditions and manifest predominantly anti-inflammatory signaling reactions. These actions of NO2-FA are diverse, with these species serving as a potential chemical reserve of ·NO, reacting with cellular nucleophiles to post-translationally modify protein structure, function and localization. In this regard these species act as potent endogenous ligands for peroxisome proliferator activated receptor γ. Functional consequences of these signaling mechanisms have been shown in multiple model systems, including the inhibition of platelet and neutrophil functions, induction of heme oxygenase-1, inhibition of LPS-induced cytokine release in monocytes, increased insulin sensitivity and glucose uptake in adipocytes and relaxation of pre-constricted rat aortic segments. These observations have propelled further in vitro and in vivo studies of mechanisms of NO2-FA signaling and metabolism, highlighting the therapeutic potential of this class of molecules as anti-inflammatory drug candidates. PMID:19200454

  8. Anti-inflammatory activity of patchouli alcohol isolated from Pogostemonis Herba in animal models.

    PubMed

    Li, Yu-Cui; Xian, Yan-Fang; Ip, Siu-Po; Su, Zi-Ren; Su, Ji-Yan; He, Jing-Jin; Xie, Qing-Feng; Lai, Xiao-Ping; Lin, Zhi-Xiu

    2011-12-01

    Pogostemonis Herba has long been used in traditional Chinese medicine for the treatment of inflammatory disorders. Patchouli alcohol (PA), a tricyclic sesquiterpene isolated from Pogostemonis Herba, is known to possess a variety of pharmacological activities. The present study aimed to investigate the in vivo anti-inflammatory effect of PA using two common inflammatory animal models i.e., xylene-induced ear edema in mice and carrageenan-induced paw edema in rats. The degree of edema in both inflammatory animals, as well as the protein and mRNA expression of some inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E₂ (PGE₂) and nitric oxide (NO) in the hind paw of carrageenan-treated rats were measured. Results showed that PA (10-40 mg/kg) significantly inhibited the ear edema induced by xylene in mice and the paw edema induced by carrageenan in rats. In addition, treatment with PA (10-40 mg/kg) also dose-dependently decreased the production of TNF-α, IL-1β, PGE₂ and NO in the hind paw of carrageenan-treated rats. Furthermore, PA treatment also suppressed the mRNA expression of TNF-α, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the hind paw of carrageenan-treated rats. These results suggest that PA possesses potent anti-inflammatory activity, which may be mediated, at least in part, by down-regulating the mRNA expression of a panel of inflammatory mediators including TNF-α, IL-1β, iNOS and COX-2. PMID:21958968

  9. Degradable magnesium-based implant materials with anti-inflammatory activity.

    PubMed

    Peng, Qiuming; Li, Kun; Han, Zengsheng; Wang, Erde; Xu, Zhigang; Liu, Riping; Tian, Yongjun

    2013-07-01

    The objective of this study was to prepare a new biodegradable Mg-based biomaterial, which provides good mechanical integrity in combination with anti-inflammatory function during the degradation process. The silver element was used, because it improved the mechanical properties as an effective grain refiner and it is also treated as a potential anti-inflammatory core. The new degradable Mg-Zn-Ag biomaterial was prepared by zone solidification technology and extrusion. The mechanical properties were mostly enhanced by fine grain strengthening. In addition, the alloys exhibited good cytocompatibility. The anti-inflammatory function of degradation products was identified by both interleukin-1α and nitric oxide modes. The anti-inflammatory impact was significantly associated with the concentration of silver ion. It was demonstrated that Mg-Zn-Ag system was a potential metallic stent with anti-inflammatory function, which can reduce the long-term dependence of anti-inflammatory drug after coronary stent implantation. PMID:23203562

  10. Hugan Qingzhi Exerts Anti-Inflammatory Effects in a Rat Model of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Tang, WaiJiao; Zeng, Lu; Yin, JinJin; Yao, YuFa; Feng, LiJuan; Yao, XiaoRui; Sun, XiaoMin; Zhou, BenJie

    2015-01-01

    Ethnopharmacological Relevance. The Hugan Qingzhi tablet (HQT) is a traditional Chinese medicine used for treating NAFLD (nonalcoholic fatty liver disease). The present study evaluated the anti-inflammatory effects of HQT in rats with NAFLD. Materials and Methods. HQT was administered daily to the NAFLD experimental groups. Biochemical markers, histopathological data, and oxidative stress/antioxidant biomarkers were determined. Proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were detected by enzyme-linked immunoassay. Expressions of silent information regulator 1 (SIRT1) and acetylated-nuclear-factor kappaB-p65 (Ac-NF-κB-p65) were performed by western blotting. Results. At high and moderate doses, HQT was highly effective in decreasing serum alanine aminotransferase (P < 0.01), aspartate aminotransferase (P < 0.01), hepatic total cholesterol (P < 0.01), triglycerides (P < 0.01), and free fatty acid levels (P < 0.01). Moreover, high and moderate doses of HQT reduced hepatic levels of the proinflammatory cytokines TNF-α (P < 0.01), IL-1β (P < 0.01), and IL-6 (P < 0.01), enhanced SIRT1 expression, and depressed Ac-NF-κB-p65 expression at protein level. Conclusions. In our NAFLD rat model, HQT exerted substantial anti-inflammatory and antioxidant activities, possibly involving the regulation of SIRT1 and Ac-NF-κB-p65 expression. PMID:26146507

  11. Analogue-based design, synthesis and molecular docking analysis of 2,3-diaryl quinazolinones as non-ulcerogenic anti-inflammatory agents.

    PubMed

    Manivannan, E; Chaturvedi, S C

    2011-08-01

    In our effort to identify potent gastric sparing anti-inflammatory agents, a series of methyl sulfanyl/methyl sulfonyl substituted 2,3-diaryl quinazolinones were designed by analogue-based design strategy and synthesized for biological evaluation. Subsequently, the compounds were evaluated for both cyclooxygenase inhibitions by ovine COX assay and carrageenan-induced rat paw edema assay. All the methyl sulfonyl substituted quinazolinones were exhibited promising anti-inflammatory activity. In particular, 6-bromo-3-(4-methanesulfonyl-phenyl)-2-phenyl-3H-quinazolin-4-one, 7-chloro-3-(4-methanesulfonyl-phenyl)-2-phenyl-3H-quinazolin-4-one, 3-(4-methanesulfonyl-phenyl)-2-(4-methoxy-phenyl)-3H-quinazolin-4-one and 6-bromo-3-(4-methanesulfonyl-phenyl)-2-(4-methoxy-phenyl)-3H-quinazolin-4-one emerged as the most active compounds in the series. The results of ulcerogenic activity assay suggest that these compounds are gastric safe compared to indomethacin. The molecular docking analysis was performed to understand the binding interactions of these compounds to COX-2 enzyme. The results from the present investigation suggests that 2,3-diaryl quinazolinones as a promising template for the design of new gastric safe anti-inflammatory agents, which can be further explored for potential anti-inflammatory activity. PMID:21724403

  12. Evaluation of anti-inflammatory activity of Solanum xanthocarpum Schrad and Wendl (Kaṇṭakāri) extract in laboratory animals

    PubMed Central

    More, Shraddha K.; Lande, Anirudha A.; Jagdale, Priti G.; Adkar, Prafulla P.; Ambavade, Shirishkumar D.

    2013-01-01

    Context: Solanum xanthocarpum Schrad and Wendl (Kaṇṭakāri) is a diffuse herb with prickly stem, traditionally used for the treatment of inflammation and one in the group of daśamūla (group of ten herbs) herbs commonly used drug in Ayurveda. Aims: In continuation of search for potent natural anti-inflammatory agents, the present research work was planned to evaluate the anti-inflammatory activity of ethanol extract of S. xanthocarpum whole plant. Settings and Design: The ethanol extract was evaluated at dose 10, 30 and 100 mg/kg p.o. in rats. Materials and Methods: Using pharmacological screening models carrageenan induced rat paw edema, histamine induced rat paw edema and cotton pellet granuloma in rats. Statistical Analysis Used: Data obtained was analyzed statistically using analysis of variance followed by post-hoc Dunnett test, P < 0.05 is considered as statistically significant. Results: Acute treatment didn’t show anti-inflammatory activity against carrageenan and histamine induced paw edema. However, administration of 100 mg/kg p.o for 7 day reduced the granuloma formation in cotton pellet granuloma model. Conclusions: Present results support the traditional use of plant for anti-inflammatory activity. In brief, the results provide scientific pharmacological basis for the therapeutic use of S. xanthocarpum. PMID:24991071

  13. Synthesis, characterization and biological evaluation of novel 4'-fluoro-2'-hydroxy-chalcone derivatives as antioxidant, anti-inflammatory and analgesic agents.

    PubMed

    Abdellatif, Khaled R A; Elshemy, Heba A H; Salama, Samir A; Omar, Hany A

    2015-06-01

    In an effort to develop safe and potent anti-inflammatory agents, a series of novel 4'-fluoro-2'-hydroxychalcones 5a-d and their dihydropyrazole derivatives 6a-d was prepared. It was synthesized via aldol condensation of 4'-fluoro-2'-hydroxyacetophenone with appropriately substituted aldehydes followed by cyclization with hydrazine hydrate. All the synthesized compounds were evaluated for their antioxidant, anti-inflammatory, cyclooxygenase inhibition selectivity and analgesic activities. The dimethoxychalcone 5a and its dihydropyrazole derivative 6a showed the highest antioxidant activity, while the monomethoxychalcone 5d and its dihydropyrazole derivative 6d showed the highest analgesic and anti-inflammatory activities. It was also found that there is a close correlation between 4'-fluoro-2'-hydroxychalcones 5a-d and their dihydropyrazole derivatives 6a-d in the screened biological activities. To explain the correlation between the synthesized chalcones and their dihydropyrazole derivatives, especially for the anti-inflammatory activity, docking studies were performed. PMID:25198887

  14. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status

    PubMed Central

    Cameron, Amy R.; Morrison, Vicky L.; Levin, Daniel; Mohan, Mohapradeep; Forteath, Calum; Beall, Craig; McNeilly, Alison D.; Balfour, David J.K.; Savinko, Terhi; Wong, Aaron K.F.; Viollet, Benoit; Sakamoto, Kei; Fagerholm, Susanna C.; Foretz, Marc

    2016-01-01

    Rationale: The diabetes mellitus drug metformin is under investigation in cardiovascular disease, but the molecular mechanisms underlying possible benefits are poorly understood. Objective: Here, we have studied anti-inflammatory effects of the drug and their relationship to antihyperglycemic properties. Methods and Results: In primary hepatocytes from healthy animals, metformin and the IKKβ (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-α–dependent IκB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1β, and CXCL1/2 (C-X-C motif ligand 1/2). Metformin suppressed IKKα/β activation, an effect that could be separated from some metabolic actions, in that BI605906 did not mimic effects of metformin on lipogenic gene expression, glucose production, and AMP-activated protein kinase activation. Equally AMP-activated protein kinase was not required either for mitochondrial suppression of IκB degradation. Consistent with discrete anti-inflammatory actions, in macrophages, metformin specifically blunted secretion of proinflammatory cytokines, without inhibiting M1/M2 differentiation or activation. In a large treatment naive diabetes mellitus population cohort, we observed differences in the systemic inflammation marker, neutrophil to lymphocyte ratio, after incident treatment with either metformin or sulfonylurea monotherapy. Compared with sulfonylurea exposure, metformin reduced the mean log-transformed neutrophil to lymphocyte ratio after 8 to 16 months by 0.09 U (95% confidence interval, 0.02–0.17; P=0.013) and increased the likelihood that neutrophil to lymphocyte ratio would be lower than baseline after 8 to 16 months (odds ratio, 1.83; 95% confidence interval, 1.22–2.75; P=0.00364). Following up these findings in a double-blind placebo controlled trial in nondiabetic heart failure (trial registration: NCT00473876), metformin suppressed plasma cytokines including the aging

  15. Anti-inflammatory and antifibrotic effects of methyl palmitate

    SciTech Connect

    El-Demerdash, Ebtehal

    2011-08-01

    Methyl palmitate (MP) has been shown earlier to inhibit Kupffer cells and rat peritoneal macrophages. To evaluate the potential of MP to inhibit the activation of other macrophages, RAW cells (macrophages of alveolar origin) were treated with varying concentrations of MP (0.25, 0.5, 1 mM). Assessment of cytotoxicity using MTT assay revealed that 0.25 and 0.5 mM are not toxic to RAW cells. MP was able to inhibit the phagocytic function of RAW cells. Treatment of cells with MP 24 hours prior to LPS stimulation significantly decreased nitric oxide release and altered the pattern of cytokines release; there was a significant decrease in TNF-{alpha} and a significant increase in IL-10 compared to the controls. However, there is a non-significant change in IL-6 level. Furthermore, phosphorylation of inhibitory kappa B (I{kappa}B{alpha}) protein was significantly decreased in RAW cells treated with 0.5 mM MP after LPS stimulation. Based upon the in-vitro results, it was examined whether MP treatment will be effective in preventing bleomycin-induced lung inflammation and fibrosis in-vivo. Bleomycin given by itself caused destruction of the lung architecture characterized by pulmonary fibrosis with collapse of air alveoli and emphysematous. Bleomycin induced a significant increase in hydroxyproline level and activated NF-{kappa}B, p65 expression in the lung. MP co-treatment significantly ameliorated bleomycin effects. These results suggest that MP has a potential of inhibiting macrophages in general. The present study demonstrated for the first time that MP has anti-inflammatory and antifibrotic effect that could be through NF-kB inhibition. Thus MP like molecule could be a promising anti-inflammatory and antifibrotic drug. - Research Highlights: >Methyl palmitate is a universal macrophage inhibitor. >It could be a promising nucleus of anti-inflammatory and antifibrotic drugs. >The underlying mechanism of these effects could be through NF-kB inhibition.

  16. Neuroactive and Anti-inflammatory Frankincense Cembranes: A Structure-Activity Study.

    PubMed

    Pollastro, Federica; Golin, Samantha; Chianese, Giuseppina; Putra, Masteria Yunovilsa; Schiano Moriello, Aniello; De Petrocellis, Luciano; García, Victor; Munoz, Eduardo; Taglialatela-Scafati, Orazio; Appendino, Giovanni

    2016-07-22

    An expeditious isolation method for the cembrane diterpene alcohols incensol (1a) and serratol (2) has been developed from respectively African and Indian frankincense. The two native alcohols and a series of semisynthetic derivatives of incensol were evaluated for transient receptor potential vanilloid 3 (TRPV3) activation and the inhibition of NF-κB, the putative molecular targets underlying the psychotropic and anti-inflammatory activities of incensol acetate (IA, 1b). Serratol (2) was the most potent TRPV3 activator, outperforming by 2 orders of magnitude the reference agonist thymol and by 1 order of magnitude incensol acetate (1b). Acylation, epimerization, and oxidation did not significantly improve the affinity of incensol for TRPV3, while NF-κB inhibition, marginal for both natural alcohols, could be improved by esterification of incensol (1a) with lipophilic acids. Interestingly, incensol (1a) but not IA (1b) was a potent inhibitor of STAT3, raising the possibility that hydrolysis to incensol (1a) might be involved in the in vivo biological activity of IA (1b). Serratol was not amenable to chemical modification, but some marine cembranoids related to the frankincense diterpenoids showed a certain degree of TRPV3-activating properties, qualifying the aliphatic macrocyclic cembrane skeleton as a selective chemotype to explore the pharmacology of TRPV3, a thermo-TRP otherwise resistant to modulation by small molecules. PMID:27352042

  17. Studies on the antiplatelet and antithrombotic profile of anti-inflammatory coumarin derivatives.

    PubMed

    Kontogiorgis, Christos; Nicolotti, Orazio; Mangiatordi, Giuseppe Felice; Tognolini, Massimiliano; Karalaki, Foteini; Giorgio, Carmine; Patsilinakos, Alexandros; Carotti, Angelo; Hadjipavlou-Litina, Dimitra; Barocelli, Elisabetta

    2015-12-01

    The interest towards coumarin-based structures stems from their polypharmacological profile. Herein, we present a series of Mannich bases and 7-azomethine-linked coumarin derivatives exhibiting antiplatelet and antithrombotic activities, in addition to the already known anti-inflammatory and antioxidant activities. Among others, compounds 15 and 16 were found to be the most potent and selective inhibitors of platelet aggregation whereas compound 3 also proved to be the most potent in the clot retraction assay. Structure-activity relationship studies were conducted to elucidate the molecular determinants responsible for the herein observed activities. The chance of inhibiting cyclooxygenase-1 was also investigated for evaluating the platelet aggregation induced by arachidonic acid. Taken together, these results suggest that the investigation of other targets connected to the antiplatelet activity, such as phosphodiesterase-3 (PDE3), could be a viable strategy to shed light on the polypharmacological profile of coumarin-based compounds. Docking simulations towards PDE3 were also carried out. PMID:25807297

  18. Eicosapentaenoic acid is converted via ω-3 epoxygenation to the anti-inflammatory metabolite 12-hydroxy-17,18-epoxyeicosatetraenoic acid.

    PubMed

    Kubota, Tadafumi; Arita, Makoto; Isobe, Yosuke; Iwamoto, Ryo; Goto, Tomomi; Yoshioka, Takeshi; Urabe, Daisuke; Inoue, Masayuki; Arai, Hiroyuki

    2014-02-01

    Eicosapentaenoic acid (EPA) has beneficial effects in many inflammatory disorders. In this study, dietary EPA was converted to 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) by ω-3 epoxygenation in the mouse peritoneal cavity. Mediator lipidomics revealed a series of novel oxygenated metabolites of 17,18-EpETE, and one of the major metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE), displayed a potent anti-inflammatory action by limiting neutrophil infiltration in murine zymosan-induced peritonitis. 12-OH-17,18-EpETE inhibited leukotriene B4-induced neutrophil chemotaxis and polarization in vitro in a low nanomolar range (EC50 0.6 nM). The complete structures of two natural isomers were assigned as 12S-OH-17R,18S-EpETE and 12S-OH-17S,18R-EpETE, using chemically synthesized stereoisomers. These natural isomers displayed potent anti-inflammatory action, whereas the unnatural stereoisomers were essentially devoid of activity. These results demonstrate that 17,18-EpETE derived from dietary EPA is converted to a potent bioactive metabolite 12-OH-17,18-EpETE, which may generate an endogenous anti-inflammatory metabolic pathway. PMID:24128889

  19. Tocotrienol-rich fraction of palm oil exhibits anti-inflammatory property by suppressing the expression of inflammatory mediators in human monocytic cells.

    PubMed

    Wu, Shu-Jing; Liu, Po-Len; Ng, Lean-Teik

    2008-08-01

    Tocotrienol-rich fraction (TRF) of palm oil has been shown to possess potent antioxidant, anticancer, and cholesterol lowering activities. In this study, our aim was to examine the effects of TRF on LPS-induced inflammatory response through measuring the production of inflammatory mediators, namely nitric oxide (NO), prostaglandin E(2) (PGE(2)), inducible nitric oxide synthase (iNOS), cytokines (TNF-alpha, IL-4, and IL-8), cyclooxygenase-1 and -2 (COX-1 and COX-2), and nuclear factor-kappaB (NF-kappaB) in human monocytic (THP-1) cells. At concentrations 0.5-5.0 microg/mL, TRF dose-dependently protected against LPS-induced cell death. At same concentrations, TRF also showed potent anti-inflammatory activity as demonstrated by a dose-dependent inhibition of LPS (1 microg/mL)-induced release of NO and PGE(2), and a significant decrease in the transcription of proinflammatory cytokines. TRF at 1.0 microg/mL significantly blocked the LPS induction of iNOS and COX-2 expression, but not COX-1. This anti-inflammatory activity was further supported by the inhibition of NF-kappaB expression. These results conclude that TRF possesses potent anti-inflammatory activity, and its mechanism of action could be through the inhibition of iNOS and COX-2 production, as well as NF-kappaB expression. PMID:18481320

  20. Anti-oxidant and anti-inflammatory activities of Inonotus obliquus and germinated brown rice extracts.

    PubMed

    Debnath, Trishna; Park, Sa Ra; Kim, Da Hye; Jo, Jeong Eun; Lim, Beong Ou

    2013-01-01

    Inonotus obliquus (IO) is parasitic mushroom that grows on birch and other trees in Russia, Korea, Europe and United States. However, IO is not readily available for consumption due to its high cost and difficult growth. In this regard, IO was inoculated on germinated brown rice (GBR) in the present study and the antioxidant and anti-inflammatory activities of the IO grown on germinated brown rice (IOGBR) extracts were evaluated extensively and compared with those for IO and GBR. IOGBR showed highest antioxidant activities with scavenging total intracellular ROS and MDA levels as well as increasing the antioxidant enzymes activity in the H₂O₂-stimulated mice liver. It also exhibited best inflammatory activities by suppressing the proinflammatory mediators such as NO, PGE₂, iNOS, COX-2, TNF-α, IL-1β, and IL-6 in an LPS-stimulated RAW 264.7 cell line. This study provides a comparative approach to find out an excellent natural source of antioxidants and anti-inflammatory agent as a dietary supplement. PMID:23917116

  1. Purification and anti-inflammatory action of tripeptide from salmon pectoral fin byproduct protein hydrolysate.

    PubMed

    Ahn, Chang-Bum; Cho, Young-Sook; Je, Jae-Young

    2015-02-01

    In this study, the anti-inflammatory peptide from salmon pectoral fin byproduct protein hydrolysate by pepsin hydrolysis, was purified and identified using Sephadex G-25 gel permeation chromatography, high performance liquid chromatography and time-of-flight liquid chromatography/tandem mass spectrometry (TOF LC/MS/MS). The purified anti-inflammatory peptide was identified to be a tripeptide (PAY). Lipopolysaccharide treatment significantly (p<0.05) stimulated the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW264.7 cells. However, PAY treatment significantly (p<0.05) inhibited the production of NO by 63.80% and PGE2 by 45.33%. Western blotting analysis revealed that PAY significantly (p<0.05) suppressed the protein expression of inducible nitric oxide synthase and cyclooxygenase-2, which are responsible for the production of NO and PGE2. Additionally, PAY treatment also significantly (p<0.05) attenuated the production of pro-inflammatory cytokines, including tumour necrosis factor-α, interleukin-6 and -1β. PMID:25172694

  2. Antinociceptive and Anti-Inflammatory Activities of Leaf Methanol Extract of Cotyledon orbiculata L. (Crassulaceae)

    PubMed Central

    Amabeoku, George J.; Kabatende, Joseph

    2012-01-01

    Leaf methanol extract of C. orbiculata L. was investigated for antinociceptive and anti-inflammatory activities using acetic acid writhing and hot-plate tests and carrageenan-induced oedema test in mice and rats, respectively. C. orbiculata (100–400 mg/kg, i.p.) significantly inhibited acetic acid-induced writhing and significantly delayed the reaction time of mice to the hot-plate-induced thermal stimulation. Paracetamol (300 mg/kg, i.p.) significantly inhibited the acetic acid-induced writhing in mice. Morphine (10 mg/kg, i.p.) significantly delayed the reaction time of mice to the thermal stimulation produced with hot plate. Leaf methanol extract of C. orbiculata (50–400 mg/kg, i.p.) significantly attenuated the carrageenan-induced rat paw oedema. Indomethacin (10 mg/kg, p.o.) also significantly attenuated the carrageenan-induced rat paw oedema. The LD50 value obtained for the plant species was greater than 4000 mg/kg (p.o.). The data obtained indicate that C. orbiculata has antinociceptive and anti-inflammatory activities, justifying the folklore use of the plant species by traditional medicine practitioners in the treatment of painful and inflammatory conditions. The relatively high LD50 obtained shows that C. orbiculata may be safe in or nontoxic to mice. PMID:22235200

  3. Heparin-based hydrogels with tunable sulfation & degradation for anti-inflammatory small molecule delivery.

    PubMed

    Peng, Yifeng; Tellier, Liane E; Temenoff, Johnna S

    2016-08-16

    Sustained release of anti-inflammatory agents remains challenging for small molecule drugs due to their low molecular weight and hydrophobicity. Therefore, the goal of this study was to control the release of a small molecule anti-inflammatory agent, crystal violet (CV), from hydrogels fabricated with heparin, a highly sulfated glycosaminoglycan capable of binding positively-charged molecules such as CV. In this system, both electrostatic interactions between heparin and CV and hydrogel degradation were tuned simultaneously by varying the level of heparin sulfation and varying the amount of dithiothreitol within hydrogels, respectively. It was found that heparin sulfation significantly affected CV release, whereby more sulfated heparin hydrogels (Hep and Hep(-N)) released CV with near zero-order release kinetics (R-squared values between 0.96-0.99). Furthermore, CV was released more quickly from fast-degrading hydrogels than slow-degrading hydrogels, providing a method to tune total CV release between 5-15 days while maintaining linear release kinetics. In particular, N-desulfated heparin hydrogels exhibited efficient CV loading (∼90% of originally included CV), near zero-order CV release kinetics, and maintenance of CV bioactivity after release, making this hydrogel formulation a promising CV delivery vehicle for a wide range of inflammatory diseases. PMID:27447003

  4. Recent Breakthroughs in the Antioxidant and Anti-Inflammatory Effects of Morella and Myrica Species.

    PubMed

    Silva, Bruno J C; Seca, Ana M L; Barreto, Maria do Carmo; Pinto, Diana C G A

    2015-01-01

    Oxidative stress is one of the risk factors for the development of several chronic diseases, such as diabetes, cancer, cardiovascular and neurodegenerative diseases. Antioxidants are therefore highly sought and can be seen as a type of preventive medicine against several diseases. Myrica and Morella genus (Myricaceae) are taxonomically very close and their species are trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine, for instance in Chinese or Japanese folk medicine they are used to treat diarrhea, digestive problems, headache, burns and skin diseases. Nearly 36 compounds were isolated from different morphological parts of Myrica and/or Morella species and their antioxidant and anti-inflammatory activities evaluated. Thirteen of these compounds exhibit greater effects than the positive controls used. Adenodimerin A was the most active compound reported (in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay EC50= 7.9 ± 0.3 µM). These results are just one aspect of the antioxidant and anti-inflammatory evaluations reported regarding Myrica and Morella species, so a comprehensive overview on the current status, highlighting the antioxidant health promoting effect of these species, their key antioxidant compounds as well as the compounds with protective effects against oxidative stress related diseases such as inflammation, is relevant. PMID:26308834

  5. Substrate-anchored and degradation-sensitive anti-inflammatory coatings for implant materials

    NASA Astrophysics Data System (ADS)

    Wu, Duo; Chen, Xingyu; Chen, Tianchan; Ding, Chunmei; Wu, Wei; Li, Jianshu

    2015-06-01

    Implant materials need to be highly biocompatible to avoid inflammation in clinical practice. Although biodegradable polymeric implants can eliminate the need for a second surgical intervention to remove the implant materials, they may produce acidic degradation products in vivo and cause non-bacterial inflammation. Here we show the strategy of “substrate-anchored and degradation-sensitive coatings” for biodegradable implants. Using poly(lactic acid)/hydroxyapatite as an implant material model, we constructed a layer-by-layer coating using pH-sensitive star polymers and dendrimers loaded with an anti-inflammatory drug, which was immobilised through a hydroxyapatite-anchored layer. The multifunctional coating can effectively suppress the local inflammation caused by the degradation of implant materials for at least 8 weeks in vivo. Moreover, the substrate-anchored coating is able to modulate the degradation of the substrate in a more homogeneous manner. The “substrate-anchored and degradation-sensitive coating” strategy therefore exhibits potential for the design of various self-anti-inflammatory biodegradable implant materials.

  6. Triblock polymeric micelles as carriers for anti-inflammatory drug delivery.

    PubMed

    Yoncheva, Krassimira; Petrov, Petar; Pencheva, Ivanka; Konstantinov, Spiro

    2015-01-01

    This study evaluated the properties of poly(ethylene oxide)-b-poly(n-butyl acrylate)-b-poly(acrylic acid) (PEO-PnBA-PAA) polymeric micelles as carriers for anti-inflammatory drugs (prednisolone and budesonide). The micelles comprising a hydrophobic PnBA core and a PEO/PAA corona showed average diameter less than 40 nm. The size of the drug-loaded micelles did not change during eight hours into media that mimic physiological fluids indicating high colloidal stability. The calculation of Flory-Huggins parameter showed greater compatibility between budesonide and micellar core suggesting its location in the micellar core, whereas prednisolone was located also into the interface layer. This observation correlated further with slower release of budesonide, especially in acid medium (pH = 1.2). The inclusion of budesonide into micelles showed significant protective effect against the cytotoxic damage induced by the co-cultivation of differentiated human EOL-1 and HT-29 cells. This study revealed the capacity of PEO-PnBA-PAA terpolymer as carrier of nanosized micelles suitable for oral delivery of anti-inflammatory drugs. PMID:25539075

  7. Substrate-anchored and degradation-sensitive anti-inflammatory coatings for implant materials

    PubMed Central

    Wu, Duo; Chen, Xingyu; Chen, Tianchan; Ding, Chunmei; Wu, Wei; Li, Jianshu

    2015-01-01

    Implant materials need to be highly biocompatible to avoid inflammation in clinical practice. Although biodegradable polymeric implants can eliminate the need for a second surgical intervention to remove the implant materials, they may produce acidic degradation products in vivo and cause non-bacterial inflammation. Here we show the strategy of “substrate-anchored and degradation-sensitive coatings” for biodegradable implants. Using poly(lactic acid)/hydroxyapatite as an implant material model, we constructed a layer-by-layer coating using pH-sensitive star polymers and dendrimers loaded with an anti-inflammatory drug, which was immobilised through a hydroxyapatite-anchored layer. The multifunctional coating can effectively suppress the local inflammation caused by the degradation of implant materials for at least 8 weeks in vivo. Moreover, the substrate-anchored coating is able to modulate the degradation of the substrate in a more homogeneous manner. The “substrate-anchored and degradation-sensitive coating” strategy therefore exhibits potential for the design of various self-anti-inflammatory biodegradable implant materials. PMID:26077243

  8. Recent Breakthroughs in the Antioxidant and Anti-Inflammatory Effects of Morella and Myrica Species

    PubMed Central

    Silva, Bruno J. C.; Seca, Ana M. L.; Barreto, Maria do Carmo; Pinto, Diana C. G. A.

    2015-01-01

    Oxidative stress is one of the risk factors for the development of several chronic diseases, such as diabetes, cancer, cardiovascular and neurodegenerative diseases. Antioxidants are therefore highly sought and can be seen as a type of preventive medicine against several diseases. Myrica and Morella genus (Myricaceae) are taxonomically very close and their species are trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine, for instance in Chinese or Japanese folk medicine they are used to treat diarrhea, digestive problems, headache, burns and skin diseases. Nearly 36 compounds were isolated from different morphological parts of Myrica and/or Morella species and their antioxidant and anti-inflammatory activities evaluated. Thirteen of these compounds exhibit greater effects than the positive controls used. Adenodimerin A was the most active compound reported (in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay EC50= 7.9 ± 0.3 µM). These results are just one aspect of the antioxidant and anti-inflammatory evaluations reported regarding Myrica and Morella species, so a comprehensive overview on the current status, highlighting the antioxidant health promoting effect of these species, their key antioxidant compounds as well as the compounds with protective effects against oxidative stress related diseases such as inflammation, is relevant.

  9. Isolation and characterization of anti-inflammatory peptides derived from whey protein.

    PubMed

    Ma, Ye; Liu, Jie; Shi, Haiming; Yu, Liangli Lucy

    2016-09-01

    The present study was conducted to isolate and characterize anti-inflammatory peptides from whey protein hydrolysates using alcalase. Nine subfractions were obtained after sequential purification by ultrafiltration, Sephadex G-25 gel (GE Healthcare, Uppsala, Sweden) filtration chromatography, and preparative HPLC. Among them, subfraction F4e showed the strongest inhibitory activity on interleukin-1β (IL-1β), cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) mRNA expression in lipopolysaccharide-induced RAW 264.7 mouse macrophages. Eight peptides, including 2 new peptides-Asp-Tyr-Lys-Lys-Tyr (DYKKY) and Asp-Gln-Trp-Leu (DQWL)-were identified from subfractions F4c and F4e, respectively, using ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Peptide DQWL showed the strongest inhibitory ability on IL-1β, cyclooxygenase-2, and TNF-α mRNA expression and production of IL-1β and TNF-α proteins at concentrations of 10 and 100μg/mL, respectively. Additionally, DQWL treatment significantly inhibited nuclear factor-κB activation by suppressing nuclear translocation of nuclear factor-κB p65 and blocking inhibitor κB kinase phosphorylation and inhibitor κB degradation together with p38 mitogen-activated protein kinase activation. Our study suggests that peptide DQWL has anti-inflammatory potential; further confirmation using an in vivo model is needed. PMID:27394940

  10. Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases

    PubMed Central

    Aggarwal, Bharat B.; Prasad, Sahdeo; Reuter, Simone; Kannappan, Ramaswamy; Yadev, Vivek R.; Park, Byoungduck; Kim, Ji Hye; Gupta, Subash C.; Phromnoi, Kanokkarn; Sundaram, Chitra; Prasad, Seema; Chaturvedi, Madan M.; Sung, Bokyung

    2011-01-01

    Inflammation, although first characterized by Cornelius Celsus, a physician in first Century Rome, it was Rudolf Virchow, a German physician in nineteenth century who suggested a link between inflammation and cancer, cardiovascular diseases, diabetes, pulmonary diseases, neurological diseases and other chronic diseases. Extensive research within last three decades has confirmed these observations and identified the molecular basis for most chronic diseases and for the associated inflammation. The transcription factor, Nuclear Factor-kappaB (NF-κB) that controls over 500 different gene products, has emerged as major mediator of inflammation. Thus agents that can inhibit NF-κB and diminish chronic inflammation have potential to prevent or delay the onset of the chronic diseases and further even treat them. In an attempt to identify novel anti-inflammatory agents which are safe and effective, in contrast to high throughput screen, we have turned to “reverse pharmacology” or “bed to benchside” approach. We found that Ayurveda, a science of long life, almost 6000 years old, can serve as a “goldmine” for novel anti-inflammatory agents used for centuries to treat chronic diseases. The current review is an attempt to provide description of various Ayurvedic plants currently used for treatment, their active chemical components, and the inflammatory pathways that they inhibit. PMID:21561421

  11. Anti-inflammatory effects of anthocyanins-rich extract from bilberry (Vaccinium myrtillus L.) on croton oil-induced ear edema and Propionibacterium acnes plus LPS-induced liver damage in mice.

    PubMed

    Luo, Hui; Lv, Xiao-Dan; Wang, Guo-En; Li, Yi-Fang; Kurihara, Hiroshi; He, Rong-Rong

    2014-08-01

    Bilberry (Vaccinium myrtillus L.) has been known to play a protective role in human health due to its high anthocyanin content. This study investigated the anti-inflammatory effects of bilberry extract (BE, containing 42.04% anthocyanin) on Propionibacterium acnes (P. acnes) plus lipopolysaccharide (LPS) induced liver injury and croton oil-induced ear edema in mice. Results showed that BE could effectively inhibit croton oil-induced ear edema and liver inflammation provoked by P. acnes plus LPS, as reflected by the reduced plasma alanine aminotransferase and aspartate aminotransferase activities. These findings were confirmed by hepatic pathological examination. Moreover, BE administration markedly suppressed the increase of liver mRNA levels of iNOS, TNF-α, IL-1β and IL-6, and the protein levels of iNOS, TNF-α and NF-κB. In addition, liver malondialdehyde and NO contents were significantly reduced by BE treatment. These results indicated that BE has potent protective effects on acute and immunological inflammation, which might contribute to the study of the anti-inflammatory effects of natural products and healthy food. PMID:24548119

  12. 15-Lipoxygenase metabolites of α-linolenic acid, [13-(S)-HPOTrE and 13-(S)-HOTrE], mediate anti-inflammatory effects by inactivating NLRP3 inflammasome

    PubMed Central

    Kumar, Naresh; Gupta, Geetika; Anilkumar, Kotha; Fatima, Naireen; Karnati, Roy; Reddy, Gorla Venkateswara; Giri, Priyanka Voori; Reddanna, Pallu

    2016-01-01

    The ratio of ω-6 to ω-3 polyunsaturated fatty acids (PUFAs) appears to be critical in the regulation of various pathophysiological processes and to maintain cellular homeostasis. While a high proportion of dietary intake of ω-6 PUFAs is associated with various inflammatory disorders, higher intake of ω-3 PUFAs is known to offer protection. It is now well established that beneficial effects of ω-3 PUFAs are mediated in part by their oxygenated metabolites mainly via the lipoxygenase (LOX) and cyclooxygenase (COX) pathways. However, the down-stream signaling pathways that are involved in these anti-inflammatory effects of ω-3 PUFAs have not been elucidated. The present study evaluates the effects of 15-LOX metabolites of α-linolenic acid (ALA, ω-3 PUFA) on lipopolysaccharide (LPS) induced inflammation in RAW 264.7 cells and peritoneal macrophages. Further, the effect of these metabolites on the survival of BALB/c mice in LPS mediated septic shock and also polymicrobial sepsis in Cecal Ligation and Puncture (CLP) mouse model was studied. These studies reveal the anti-inflammatory effects of 13-(S)-hydroperoxyoctadecatrienoic acid [13-(S)-HPOTrE] and 13-(S)-hydroxyoctadecatrienoic acid [13-(S)-HOTrE] by inactivating NLRP3 inflammasome complex through the PPAR-γ pathway. Additionally, both metabolites also deactivated autophagy and induced apoptosis. In mediating all these effects 13-(S)-HPOTrE was more potent than 13-(S)-HOTrE. PMID:27535180

  13. Anti-inflammatory effects of hydroxycinnamic acid derivatives

    SciTech Connect

    Nagasaka, Reiko; Chotimarkorn, Chatchawan; Shafiqul, Islam Md.; Hori, Masatoshi; Ozaki, Hiroshi; Ushio, Hideki . E-mail: hushio@kaiyodai.ac.jp

    2007-06-29

    NF-{kappa}B family of transcription factors are involved in numerous cellular processes, including differentiation, proliferation, and inflammation. It was reported that hydroxycinnamic acid derivatives (HADs) are inhibitors of NF-{kappa}B activation. Rice bran oil contains a lot of phytosteryl ferulates, one of HADs. We have investigated effects of phytosteryl ferulates on NF-{kappa}B activation in macrophage. Cycloartenyl ferulate (CAF), one of phytosteryl ferulates, significantly reduced lipopolysaccharide (LPS)-induced NO production and mRNA expression of inducible NO synthase and cyclooxygenese-2 but upregulated SOD activity. Electrophoresis mobility shift assay revealed that CAF inhibited DNA-binding of NF-{kappa}B. CAF and phytosteryl ferulates probably have potentially anti-inflammatory properties.

  14. Risk of stroke associated with nonsteroidal anti-inflammatory drugs

    PubMed Central

    Park, Ki; Bavry, Anthony A

    2014-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs), both cyclooxygenase (COX)-2-selective and nonselective agents, have been associated with the increased risk of adverse cardiovascular events. The majority of studies have focused on myocardial infarction as the primary cardiovascular outcome. However, the association between NSAIDs and the risk of stroke events is not as clear, although an understanding of this association is important since stroke continues to be a significant cause of morbidity and mortality. Various factors may contribute to an association between NSAIDs and stroke, including hypertension and thrombosis. Additionally, the risk may vary with different NSAID types. In this review, we discuss the relevant literature assessing the possible association between NSAID use and stroke events, along with the potential mechanisms and the possible directions for future study. PMID:24421643

  15. Hormetic and anti-inflammatory properties of oxidized phospholipids.

    PubMed

    Mauerhofer, Christina; Philippova, Maria; Oskolkova, Olga V; Bochkov, Valery N

    2016-06-01

    Oxidized phospholipids are generally recognized as deleterious factors involved in disease pathogenesis. This review summarizes the data suggesting that under certain biological conditions the opposite is correct, namely that OxPLs can also induce protective effects. Examples that are discussed in the review include upregulation of antioxidant genes, inhibition of inflammatory signaling pathways through Nrf2-dependent and -independent mechanisms, antagonism of Toll-like receptors, immuno-modulating and immuno-suppressive action of OxPLs in adaptive immunity and autoimmune disease, activation of PPARs known for their anti-inflammatory action, as well as protective action against lung edema in acute lung inflammation. The data support the notion that oxidation of phospholipids provides a negative feedback preventing damage to host tissues due to uncontrolled inflammation and oxidative stress. PMID:26948981

  16. Go Green: The Anti-Inflammatory Effects of Biliverdin Reductase

    PubMed Central

    Wegiel, Barbara; Otterbein, Leo E.

    2012-01-01

    Biliverdin (BV) has emerged as a cytoprotective and important anti-inflammatory molecule. Conversion of BV to bilirubin (BR) is catalyzed by biliverdin reductase (BVR) and is required for the downstream signaling and nuclear localization of BVR. Recent data by others and us make clear that BVR is a critical regulator of innate immune responses resulting from acute insult and injury and moreover, that a lack of BVR results in an enhanced proinflammatory phenotype. In macrophages, BVR is regulated by its substrate BV which leads to activation of the PI3K–Akt-IL-10 axis and inhibition of TLR4 expression via direct binding of BVR to the TLR4 promoter. In this review, we will summarize recent findings on the role of BVR and the bile pigments in inflammation in context with its activity as an enzyme, receptor, and transcriptional regulator. PMID:22438844

  17. Anti-inflammatory activity of the bark of Hippocratea excelsa.

    PubMed

    Perez, R M; Perez, S; Zavala, M A; Salazar, M

    1995-07-01

    The ethanol extract of the plant Hippocratea excelsa was examined for its anti-inflammatory effects using several animal models. It produced significant inhibition of carrageenan-induced paw edema and reduced the weight of cotton pellet-induced granuloma at doses of 25-100 mg/kg. The extract was found to exert a protective effect on heat-induced erythrocyte lysis at concentrations of 25, 50 and 100 micrograms/ml. In chronic models of formaldehyde and adjuvant arthritis, its anti-arthritic activity was found to be less than that of phenylbutazone (PNB). It may be inferred that the ethanol extract is effective against both exudative-proliferative and chronic phases of inflammation. PMID:7500640

  18. Nonsteroidal Anti-Inflammatory Drugs and the Kidney

    PubMed Central

    Hörl, Walter H.

    2010-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion) vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will rarely experience adverse renal effects with the use of NSAIDs, elderly patients and those with co-morbibity (e.g., congestive heart failure, liver cirrhosis or chronic kidney disease) and drug combinations (e.g., renin-angiotensin blockers, diuretics plus NSAIDs) may develop acute renal failure. This review summarizes our present knowledge how traditional NSAIDs and selective COX-2 inhibitors may affect the kidney under various experimental and clinical conditions, and how these drugs may influence renal inflammation, water transport, sodium and potassium balance and how renal dysfunction or hypertension may result.

  19. [Anti-inflammatory effects of tea-flavonoids].

    PubMed

    Hoensch, H; Oertel, R

    2012-12-01

    Tea flavonoids belong to the large group of polyphenols and display antioxidative, anti-inflammatory and anti-neoplastic activities. These phytochemicals are xenobiotics and are synthesized by tea plants such as Camellia sinensis and Camomilla recucita. These botanicals exhibit in vivo activities similar to that of biologicals which are widely used for chronic inflammatory diseases (rheumatoid arthritis, chronic inflammatory bowel disease). Epigallocathechin gallate and apigenin from these plants inhibit cytokines, chemokines and activated immune cells in vivo and in vitro. Clinical disorders with induced inflammatory pathways could benefit from flavonoid treatment. Dietary supplementation with specific tea-flavonoids could be used for Crohn's disease, ulcerative colitis and irritable bowel syndrome. Suppression of cytokine production could ultimately lead to inhibition of carcinogenesis. This mechanism could explain why flavonoids are effective in the prevention of intestinal neoplasia. This innovative new form of therapy should be tested in controlled, randomized clinical studies. PMID:23233307

  20. Antioxidant and Anti-Inflammatory Activities of Barettin

    PubMed Central

    Lind, Karianne F.; Hansen, Espen; Østerud, Bjarne; Eilertsen, Karl-Erik; Bayer, Annette; Engqvist, Magnus; Leszczak, Kinga; Jørgensen, Trond Ø.; Andersen, Jeanette H.

    2013-01-01

    In this paper, we present novel bioactivity for barettin isolated from the marine sponge Geodia barretti. We found that barettin showed strong antioxidant activity in biochemical assays as well as in a lipid peroxidation cell assay. A de-brominated synthetic analogue of barettin did not show the same activity in the antioxidant cell assay, indicating that bromine is important for cellular activity. Barettin was also able to inhibit the secretion of the inflammatory cytokines IL-1β and TNFα from LPS-stimulated THP-1 cells. This combination of anti-inflammatory and antioxidant activities could indicate that barettin has an atheroprotective effect and may therefore be an interesting product to prevent development of atherosclerosis. PMID:23880935

  1. Anti-inflammatory agents from plants: progress and potential.

    PubMed

    Recio, M C; Andujar, I; Rios, J L

    2012-01-01

    The identification of substances that can promote the resolution of inflammation in a way that is homeostatic, modulatory, efficient, and well-tolerated by the body is of fundamental importance. Traditional medicines have long provided front-line pharmacotherapy for many millions of people worldwide. Medicinal extracts are a rich source of therapeutic leads for the pharmaceutical industry. The use of medicinal plant therapies to treat chronic illness, including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), is thus widespread and on the rise.The aim of this review is to present recent progress in clinical anti-inflammatory studies of plant extracts and compound leads such as green tea polyphenols, curcumin, resveratrol, boswellic acid, and cucurbitacins, among others, against chronic inflammatory diseases, mainly RA and IBD. In this context, the present paper also highlights the most promising experimental data on those plant extracts and pure compounds active in animal models of the aforementioned diseases. PMID:22414101

  2. Further studies on the anti-inflammatory effect of insulin.

    PubMed

    Ottlecz, A; Koltai, M; Gecse, A

    1977-10-01

    Experiments performed on rats showed that insulin, when applied i.v. or s.c., inhibited the foot edema induced by carrageenin, thermic effect of 45.7 degrees C, compound 48/80 and 5-HT, but moderately increased the paw swelling evoked by kallikrein, a kinin-forming enzyme. The increased vascular permeability elicited by intradermal injection of histamine, 5-HT, bradykinin, PGE1, carrageenin and compound 48/80 was also suppressed. The anti-inflammatory effect was not significantly altered by propranolol and adrenalectomy on the thermal and carrageenin edema, it was variably inhibited on the skin test, and was completely abolished on the paw swelling induced by 5-HT and compound 48/80. Since insulin had little or no effect on the vascular response when given topically together with the vasoactive agents, its complex effect on the acute inflammation appears to be brought about via indirect mechanisms. PMID:930760

  3. Anti-inflammatory polyphenol constituents derived from Cissus pteroclada Hayata.

    PubMed

    Li, Yi-Jie; Xu, Cheng-Ting; Lin, Dan-Dan; Qin, Jiang-Ke; Ye, Gao-Jie; Deng, Qing-Hua

    2016-08-01

    A new bergenin derivative, bergenin-11-O-α-d-galactopyranoside (compound 1), together with seven known polyphenolic compounds, were isolated from the stem of Cissus pteroclada Hayata. The structures of the 8 compounds were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Moreover, the in vitro anti-inflammatory effects of compounds (1-8) in LPS-stimulated murine macrophage RAW 264.7 cells were also investigated. Our results revealed that compound 1 inhibited the production of pro-inflammatory mediators NO and PGE2 and the expression of NF-κB, TNF-α, IL-1β, iNOS and COX-2. PMID:27374242

  4. Discovery of a highly potent glucocorticoid for asthma treatment

    PubMed Central

    He, Yuanzheng; Shi, Jingjing; Yi, Wei; Ren, Xin; Gao, Xiang; Li, Jianshuang; Wu, Nanyan; Weaver, Kevin; Xie, Qian; Khoo, Sok Kean; Yang, Tao; Huang, Xiaozhu; Melcher, Karsten; Xu, H Eric

    2015-01-01

    Glucocorticoids are the most effective treatment for asthma. However, their clinical applications are limited by low efficacy in severe asthma and by undesired side effects associated with high dose or prolonged use. The most successful approach to overcome these limitations has been the development of highly potent glucocorticoids that can be delivered to the lungs by inhalation to achieve local efficacy with minimal systemic effects. On the basis of our previous structural studies, we designed and developed a highly potent glucocorticoid, VSGC12, which showed an improved anti-inflammation activity in both cell-based reporter assays and cytokine inhibition experiments, as well as in a gene expression profiling of mouse macrophage RAW264.7 cells. In a mouse asthma model, VSGC12 delivered a higher efficacy than fluticasone furoate, a leading clinical compound, in many categories including histology and the number of differentiated immune cells. VSGC12 also showed a higher potency than fluticasone furoate in repressing most asthma symptoms. Finally, VSGC12 showed a better side effect profile than fluticasone furoate at their respective effective doses, including better insulin response and less bone loss in an animal model. The excellent therapeutic and side effect properties of VSGC12 provide a promising perspective for developing this potent glucocorticoid as a new effective drug for asthma. PMID:27066265

  5. Urinary PGE-M levels are associated with risk of colorectal adenomas and chemopreventive response to anti-inflammatory drugs.

    PubMed

    Bezawada, Navya; Song, Mingyang; Wu, Kana; Mehta, Raaj S; Milne, Ginger L; Ogino, Shuji; Fuchs, Charles S; Giovannucci, Edward L; Chan, Andrew T

    2014-07-01

    Prostaglandin E2 (PGE2) promotes colorectal carcinogenesis. Overall, systemic PGE2 production can be assessed by measuring its major metabolite, PGE-M, in urine. We examined the potential role of PGE-M as a biomarker for colorectal adenoma risk and chemopreventive response to anti-inflammatory drugs. We conducted a prospective case-control study nested within the Nurses' Health Study. Among women who previously provided a urine sample, we identified 420 cases diagnosed with colorectal adenoma during follow-up and matched them to 420 endoscopy-negative controls. We measured urinary PGE-M using an LC/MS assay. Compared with women in the lowest quartile of urinary PGE-M, women in the highest quartile had a multivariate OR of 1.40 (95% confidence interval (CI), 0.92-2.14) for any adenoma; 0.91 (95% CI, 0.48-1.72) for low-risk adenoma (solitary adenoma <1 cm in greatest diameter with tubular/unspecified histology); and 1.66 (95% CI, 1.04-2.67) for high-risk adenoma (adenoma ≥1 cm in greatest diameter and/or tubulovillous, villous or high-grade dysplasia histology or multiple adenomas of any size or histology). Regular use of anti-inflammatory drugs (≥2 standard tablets of aspirin/NSAIDs per week) was associated with a significant reduction in adenoma risk (multivariate OR, 0.61; 95% CI, 0.43-0.87) in women with high baseline PGE-M (quartiles 2-4), but not low PGE-M (quartile 1).Urinary PGE-M is associated with an increased risk of high-risk adenoma. Anti-inflammatory drugs seem to reduce adenoma risk among women with high, but not low PGE-M. Urinary PGE-M may serve as a biomarker to define subsets of the population who may obtain differential chemopreventive benefit from anti-inflammatory drugs. PMID:24824037

  6. A Potent Systemically Active N-Acylethanolamine Acid Amidase Inhibitor that Suppresses Inflammation and Human Macrophage Activation.

    PubMed

    Ribeiro, Alison; Pontis, Silvia; Mengatto, Luisa; Armirotti, Andrea; Chiurchiù, Valerio; Capurro, Valeria; Fiasella, Annalisa; Nuzzi, Andrea; Romeo, Elisa; Moreno-Sanz, Guillermo; Maccarrone, Mauro; Reggiani, Angelo; Tarzia, Giorgio; Mor, Marco; Bertozzi, Fabio; Bandiera, Tiziano; Piomelli, Daniele

    2015-08-21

    Fatty acid ethanolamides such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are lipid-derived mediators that potently inhibit pain and inflammation by ligating type-α peroxisome proliferator-activated receptors (PPAR-α). These bioactive substances are preferentially degraded by the cysteine hydrolase, N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages. Here, we describe a new class of β-lactam derivatives that are potent, selective, and systemically active inhibitors of intracellular NAAA activity. The prototype of this class deactivates NAAA by covalently binding the enzyme's catalytic cysteine and exerts profound anti-inflammatory effects in both mouse models and human macrophages. This agent may be used to probe the functions of NAAA in health and disease and as a starting point to discover better anti-inflammatory drugs. PMID:25874594

  7. Injecting engineered anti-inflammatory macrophages therapeutically induces white adipose tissue browning and improves diet-induced insulin resistance.

    PubMed

    Liu, Pu-Ste; Lin, Yi-Wei; Burton, Frank H; Wei, Li-Na

    2015-01-01

    We recently exploited a transgenic approach to coerce macrophage anti-inflammatory M2 polarization in vivo by lowering Receptor Interacting Protein 140 (RIP140) level in macrophages (mφRIP140KD), which induced browning of white adipose tissue (WAT). In vitro, conditioned medium from cultured adipose tissue macrophages (ATMs) of mφRIP140KD mice could trigger preadipocytes' differentiation into beige cells. Here we describe a cell therapy for treating high fat diet (HFD)-induced insulin resistance (IR). Injecting M2 ATMs retrieved from the WAT of mφRIP140KD mice into HFD-fed obese adult wild-type mice effectively triggers their WAT browning, reduces their pro-inflammatory responses, and improves their insulin sensitivity. These data provide a proof-of-concept that delivering engineered anti-inflammatory macrophages can trigger white fat browning, stimulate whole-body thermogenesis, and reduce obesity-associated IR. PMID:26167415

  8. A fraction from Dojuksan 30% ethanol extract exerts its anti-inflammatory effects through Nrf2-dependent heme oxygenase-1 expression.

    PubMed

    Lee, Dong-Sung; Kim, Kyoung-Su; Ko, Wonmin; Bae, Gi-Sang; Park, Sung-Joo; Jang, Jun-Hyeog; Oh, Hyuncheol; Kim, Youn-Chul

    2016-02-01

    Dojuksan is a traditional herbal medicine used in Korea and China to treat urinary diseases. In the present study, we aimed to examine the anti-inflammatory effects of an ethanol solvent extract of Dojuksan and a fraction (by bioassay-guided fractionation) derived from this extract, and to elucidate the specific mechanisms involved. The Dojuksan 30% ethanol extract (DEE) had a more significant and potent anti-inflammatory effect than the Dojuksan water extract (DWE). DEE markedly inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), as well as nuclear factor-κB (NF-κB) binding activity. We found that the anti-inflammatory effects of DEE were mediated by the induction of nuclear factor E2-related factor 2 (Nrf2)-dependent heme oxygenase-1 (HO-1). To further explore the anti-inflammatory effects of DEE, we generated 6 different fractions of DEE. Of these, DEE-5 decreased the production of NO more significantly than the other fractions. DEE-5 also significantly decreased the expression of iNOS and COX-2, and the production of NO, PGE2, TNF-α and IL-1β. In addition, DEE-5 also significantly increased HO-1 levels; HO-1 significanlty contributed to the inhibitory effects of DEE-5 on the production of pro-inflammatory mediators. In this study, we determined whether the choice of extraction solvent affects the biological activity of Dojuksan, a traditional herbal formula. Our findings demonstrate that DEE and a fraction derived from this extract exerts anti-inflammatory effects through Nrf2‑dependent HO-1 expression, and that DEE may thus have greater potential therapeutic application than DWE. PMID:26647788

  9. In-vitro anti- inflammatory activity of aqueous extract of leaves of Plectranthus amboinicus (Lour.) Spreng

    PubMed Central

    Ravikumar, V.R.; Dhanamani, M.; Sudhamani, T.

    2009-01-01

    Aqueous extract of leaves of Plectranthus amboinicus (lour.) Spreng, which is traditionally used in the treatment of cough and cold was screened for its anti- inflammatory activity by HRBC membrane stabilisation model. Aqueous extract (500 mcg/ml) showed significant anti-inflammatory activity as compared to that of hydrocortisone sodium. PMID:22557324

  10. In-vitro anti- inflammatory activity of aqueous extract of leaves of Plectranthus amboinicus (Lour.) Spreng.

    PubMed

    Ravikumar, V R; Dhanamani, M; Sudhamani, T

    2009-04-01

    Aqueous extract of leaves of Plectranthus amboinicus (lour.) Spreng, which is traditionally used in the treatment of cough and cold was screened for its anti- inflammatory activity by HRBC membrane stabilisation model. Aqueous extract (500 mcg/ml) showed significant anti-inflammatory activity as compared to that of hydrocortisone sodium. PMID:22557324

  11. Hypericum in Infection: Identification of Anti-viral and Anti-inflammatory Constituents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Iowa Center for Research on Botanical Dietary Supplements seeks to optimize Echinacea, Hypericum and Prunella supplements for human-health benefit, focusing on anti-viral, anti-inflammatory and anti-pain effects. This paper reports on ongoing anti-viral and anti-inflammatory studies on Hypericu...

  12. Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methylthioadenosine (MTA) is a precursor of the methionine salvage pathway and has been shown to have anti-inflammatory properties in various models of acute and chronic inflammation. However, the anti-inflammatory properties of MTA in models of intestinal inflammation are not defined. We hypothesiz...

  13. Phytochemical Compositions and Antioxidant and Anti-Inflammatory Activities of Crude Extracts from Ficus pandurata H. (Moraceae)

    PubMed Central

    Lv, Huiqing; Zhang, Xiaoping; Chen, XueZhi; Xie, Zhijun; Wen, Chengping; Jiang, Kezhi

    2013-01-01

    Background. Ficus pandurata H. (Moraceae) is widely used in traditional Chinese medicine as a healthy food condiment or a medicine for treatment of various diseases including inflammation. Objective. The purpose of the present study is to investigate the phytochemical compositions and antioxidant and anti-inflammatory activities of crude water (FPW) and ethanolic extracts (FPE) from Ficus pandurata H. Methods. Phytochemical compositions were identified by a high-performance liquid chromatography-electrospray ionization-mass spectrometry method (HPLC-ESI-MS). The antioxidant activities were evaluated by diphenylpicrylhydrazyl (DPPH) and hydroxyl radical assays, and the anti-inflammatory activities were evaluated by paw edema and levels of inflammatory mediator TNF-α and PGE2 in monosodium urate (MSU) crystal-induced rats. Results. Six compounds were identified by HPLC-MS method, and abundance of phenolics was found in FPE. The FPE showed concentration-dependent-significant scavenging of DPPH and hydroxyl radicals with IC50 values 118.4 and 192.9 μg/mL, respectively. The FPE treatment significantly inhibited the paw edema and the production of TNF-α and PGE2 in MSU crystal-induced rats. Conclusion. The FPE exerted stronger antioxidant and anti-inflammatory activities which may be attributed to its high phenolic content. PMID:24191163

  14. Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages

    SciTech Connect

    He, Xiao-dong; Tobo, Masayuki; Mogi, Chihiro; Nakakura, Takashi; Komachi, Mayumi; Murata, Naoya; Takano, Mutsumi; Tomura, Hideaki; Sato, Koichi; Okajima, Fumikazu

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Glucocorticoid (GC) induced the expression of proton-sensing TDAG8 in macrophages. Black-Right-Pointing-Pointer GC enhanced acidic pH-induced cAMP accumulation and inhibition of TNF-{alpha} production. Black-Right-Pointing-Pointer The enhancement of the GC-induced actions was lost by TDAG8 deficiency. Black-Right-Pointing-Pointer GC-induced anti-inflammatory actions are partly mediated by TDAG8 expression. -- Abstract: Dexamethasone (DEX), a potent glucocorticoid, increased the expression of T-cell death associated gene 8 (TDAG8), a proton-sensing G protein-coupled receptor, which is associated with the enhancement of acidic pH-induced cAMP accumulation, in peritoneal macrophages. We explored the role of increased TDAG8 expression in the anti-inflammatory actions of DEX. The treatment of macrophages with either DEX or acidic pH induced the cell death of macrophages; however, the cell death was not affected by TDAG8 deficiency. While DEX inhibited lipopolysaccharide-induced production of tumor necrosis factor-{alpha}, an inflammatory cytokine, which was independent of TDAG8, at neutral pH, the glucocorticoid enhanced the acidic pH-induced inhibition of tumor necrosis factor-{alpha} production in a manner dependent on TDAG8. In conclusion, the DEX-induced increase in TDAG8 expression is in part involved in the glucocorticoid-induced anti-inflammatory actions through the inhibition of inflammatory cytokine production under the acidic pH environment. On the other hand, the role of TDAG8 in the DEX-induced cell death is questionable.

  15. The flavonoid content and antiproliferative, hypoglycaemic, anti-inflammatory and free radical scavenging activities of Annona dioica St. Hill

    PubMed Central

    2013-01-01

    Background Annona dioica St. Hill (Annonacaeae) is a Brazilian plant used in folk medicine for the treatment of several types of rheumatisms and diarrhoea. The focus of this work was to evaluate the in vitro antiproliferative and antioxidant activity and the in vivo hypoglycaemic and anti-inflammatory activity of A. dioica and identify the principal constituents of this plant. Methods The crude methanol extract (EAD) and hexane (HF), chloroform (CF), ethyl acetate (EAF) and hydromethanol fractions (HMF) were evaluated for free radical scavenging activity using the DPPH assay. The EAD and EAF were assayed for hypoglycaemic activity in rats. The EAD was tested in an antiproliferation assay and for anti-inflammatory effects in paw oedema, in addition to myeloperoxidase activity induced by carrageenan (Cg) in mice. The EAF was assayed using chromatographic methods. Results The fractionation of the EAF through chromatographic methods identified derivatives of the flavonoids quercetin and kaempferol. Among all the tested fractions, the ethyl acetate and hydromethanol fractions were the most potent, exhibiting an IC50 of 8.53 and 10.57 μg/mL, respectively, which is comparable to that of the commercial antioxidant butylated hydroxytoluene (BHT). The oral administration of the EAD (100 mg/kg) and EAF (15 mg/kg) inhibited the increase of glucose levels, resulting in a hypoglycaemic effect. The EAD (30 to 300 mg/kg) exhibited an anti-oedematogenic effect in Cg-induced paw oedema in a time- and dose-dependent manner. The results showed a reduction of MPO activity by A. dioica 6 h after the induction of paw oedema at all doses tested with maximal inhibition at 300 mg/kg. Conclusions Our results reveal for the first time that compounds contained in the A. dioica leaves exert anti-inflammatory, hypoglycaemic, antiproliferative, and antioxidant effects. The antioxidant activity may be associated with the presence of flavonoids. PMID:23311341

  16. Antioxidant and anti-inflammatory potential of hesperetin metabolites obtained from hesperetin-administered rat serum: an ex vivo approach.

    PubMed

    Yang, Hsin-Ling; Chen, Ssu-Ching; Senthil Kumar, K J; Yu, Kang-Ni; Lee Chao, Pei-Dawn; Tsai, Shang-Yuan; Hou, Yu-Chi; Hseu, You-Cheng

    2012-01-11

    In recent years much attention has been focused on the pharmaceutical relevance of bioflavonoids, especially hesperidin and its aglycon hesperetin in terms of their antioxidant and anti-inflammatory actions. However, the bioactivity of their metabolites, the real molecules in vivo hesperetin glucuronides/sulfates produced after ingestion, has been poorly understood. Thus, the study using an ex vivo approach is aimed to compare the antioxidant and anti-inflammatory activities of hesperidin/hesperetin or hesperetin metabolites derived from hesperetin-administered rat serum. We found that hesperetin metabolites (2.5-20 μM) showed higher antioxidant activity against various oxidative systems, including superoxide anion scavenging, reducing power, and metal chelating effects, than that of hesperidin or hesperetin. The data also showed that pretreatment of hesperetin metabolites (1-10 μM) within the range of physiological concentrations, compared to hesperetin, significantly inhibited nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production, as evidenced by the inhibition of their precursors, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels without appreciable cytotoxicity on LPS-activated RAW264.7 macrophages or A7r5 smooth muscle cells. Concomitantly, hesperetin metabolites dose-dependently inhibited LPS-induced intracellular reactive oxygen species (ROS). Furthermore, hesperetin metabolites significantly downregulate LPS-induced nuclear factor-κB (NF-κB) activation followed by the suppression of inhibitor-κB (I-κB) degradation and phosphorylation of c-Jun N-terminal kinase1/2 (JNK1/2) and p38 MAPKs after challenge with LPS. Hesperetin metabolites ex vivo showed potent antioxidant and anti-inflammatory activity in comparison with hesperidin/hesperetin. PMID:22098419

  17. Comparative study on anti-oxidant and anti-inflammatory activities of Caesalpinia crista and Centella asiatica leaf extracts

    PubMed Central

    Ramesh, B. N.; Girish, T. K.; Raghavendra, R. H.; Naidu, K. Akhilender; Rao, U. J. S. Prasada; Rao, K. S.

    2014-01-01

    Background: Amyloidosis, oxidative stress and inflammation have been strongly implicated in neurodegenerative disorders like Alzheimer's disease. Traditionally, Caesalpinia crista and Centella asiatica leaf extracts are used to treat brain related diseases in India. C. crista is used as a mental relaxant drink as well as to treat inflammatory diseases, whereas C. asiatica is reported to be used to enhance memory and to treat dementia. Objective: The present study is aimed to understand the anti-oxidant and anti-inflammatory potential of C. asiatica and C. crista leaf extracts. Materials and Methods: Phenolic acid composition of the aqueous extracts of C. crista and C. asiatica were separated on a reverse phase C18 column (4.6 x 250 mm) using HPLC system. Antioxidant properties of the leaf extracts were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and the reducing potential assay. The anti-inflammatory activities of aqueous extracts of C. crista and C. asiatica were studied using 5-lipoxygenase assay. Polymorphonuclear leukocytes (PMNLs) were isolated from blood by Ficoll-Histopaque density gradient followed by hypotonic lysis of erythrocytes. Results: Gallic, protocatechuic, gentisic, chlorogenic, caffeic, p-coumaric and ferulic acids were the phenolic acids identified in C. crista and C. asiatica leaf aqueous extracts. However, gallic acid and ferulic acid contents were much higher in C. crista compared to C. asiatica. Leaf extracts of C. asiatica and C. crista exhibited antioxidant properties and inhibited 5-lipoxygenase (anti-inflammatory) in a dose dependent manner. However, leaf extracts of C. crista had better antioxidant and anti-inflammatory activity compared to that of C. asiatica. The better activity of C. crista is attributed to high gallic acid and ferulic acid compared to C. asiatica. Conclusions: Thus, the leaf extract of C. crista can be a potential therapeutic role for Alzheimer's disease. PMID:24741275

  18. Antioxidant and anti-inflammatory activities of selected Chinese medicinal plants and their relation with antioxidant content

    PubMed Central

    2012-01-01

    Background The main aim of this study is to evaluate the antioxidant and anti-inflammatory properties of forty four traditional Chinese medicinal herbal extracts and to examine these activities in relation to their antioxidant content. Methods The antioxidant activities were investigated using DPPH radical scavenging method and yeast model. The anti-inflammatory properties of the herbal extracts were evaluated by measuring their ability to inhibit the production of nitric oxide and TNF-α in RAW 264.7 macrophages activated by LPS and IFN- γ, respectively. The cytotoxic effects of the herbal extracts were determined by Alomar Blue assay by measuring cell viability. In order to understand the variation of antioxidant activities of herbal extracts with their antioxidant contents, the total phenolics, total flavonoids and trace metal (Mg, Mn, Cu, Zn, Se and Mo) quantities were estimated and a correlation analysis was carried out. Results Results of this study show that significant levels of phenolics, flavonoids and trace metal contents were found in Ligustrum lucidum, Paeonia suffuticosa, Salvia miltiorrhiza, Sanguisorba officinalis, Spatholobus suberectus, Tussilago farfara and Uncaria rhyncophylla, which correlated well with their antioxidant and anti-inflammatory activities. Some of the plants displayed high antioxidant and anti-inflammatory activities but contained low levels of phenolics and flavonoids. Interestingly, these plants contained significant levels of trace metals (such as Zn, Mg and Se) which are likely to be responsible for their activities. Conclusions The results indicate that the phenolics, flavonoids and trace metals play an important role in the antioxidant activities of medicinal plants. Many of the plants studied here have been identified as potential sources of new antioxidant compounds. PMID:23038995

  19. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation

    PubMed Central

    Macedo, E.M.A.; Santos, W.C.; Sousa, B.P.; Lopes, E.M.; Piauilino, C.A.; Cunha, F.V.M.; Sousa, D.P.; Oliveira, F.A.; Almeida, F.R.C.

    2016-01-01

    Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association

  20. Atypical Activin A and IL-10 Production Impairs Human CD16+ Monocyte Differentiation into Anti-Inflammatory Macrophages.

    PubMed

    González-Domínguez, Érika; Domínguez-Soto, Ángeles; Nieto, Concha; Flores-Sevilla, José Luis; Pacheco-Blanco, Mariana; Campos-Peña, Victoria; Meraz-Ríos, Marco A; Vega, Miguel A; Corbí, Ángel L; Sánchez-Torres, Carmen

    2016-02-01

    Human CD14(++)CD16(-) and CD14(+/lo)CD16(+) monocyte subsets comprise 85 and 15% of blood monocytes, respectively, and are thought to represent distinct stages in the monocyte differentiation pathway. However, the differentiation fates of both monocyte subsets along the macrophage (Mϕ) lineage have not yet been elucidated. We have now evaluated the potential of CD14(++) CD16(-) and CD16(+) monocytes to differentiate and to be primed toward pro- or anti-inflammatory Mϕs upon culture with GM-CSF or M-CSF, respectively (subsequently referred to as GM14, M14, GM16, or M16). Whereas GM16 and GM14 were phenotypic and functionally analogous, M16 displayed a more proinflammatory profile than did M14. Transcriptomic analyses evidenced that genes associated with M-CSF-driven Mϕ differentiation (including FOLR2, IL10, IGF1, and SERPINB2) are underrepresented in M16 with respect to M14. The preferential proinflammatory skewing of M16 relative to M14 was found to be mediated by the secretion of activin A and the low levels of IL-10 produced by M16. In fact, activin A receptor blockade during the M-CSF-driven differentiation of CD16(+) monocytes, or addition of IL-10-containing M14-conditioned medium, significantly enhanced their expression of anti-inflammatory-associated molecules while impairing their acquisition of proinflammatory-related markers. Thus, we propose that M-CSF drives CD14(++)CD16- monocyte differentiation into bona fide anti-inflammatory Mϕs in a self-autonomous manner, whereas M-CSF-treated CD16(+) monocytes generate Mϕs with a skewed proinflammatory profile by virtue of their high activin A expression unless additional anti-inflammatory stimuli such as IL-10 are provided. PMID:26729812

  1. The microalga Spirulina platensis presents anti-inflammatory action as well as hypoglycemic and hypolipidemic properties in diabetic rats.

    PubMed

    Joventino, Ivan P; Alves, Henrique G R; Neves, Lia C; Pinheiro-Joventino, Francisca; Leal, Luzia Kalyne A M; Neves, Samya A; Ferreira, Francisco Valdeci; Brito, Gerly Anne C; Viana, Glauce B

    2012-01-01

    Spirulina platensis (Spi) is a microalga presenting high contents of proteins, γ-linolenic acid, vitamins and minerals, and showing many biological activities. It is a promising drug for the treatment of diseases including diabetes. The objectives of this work were to study Spi effects on alloxan-induced diabetic rats, and associate this to its anti-inflammatory activity. The treatment with Spi (25, 50 or 100 mg/kg, p.o.) started 48 h after the alloxan injection, continuing for 5 or 10 days. Biochemical parameters were measured in sera of treated and untreated animals. The anti-inflammatory activity of Spi was assessed by the formalin test and carrageenan-induced paw edema in mice. Immunostainings for TNF-alpha were carried out in the carrageenan-induced paw edema in rats, before and after the Spi treatment, and its effect on the release of myeloperoxidase from human neutrophils was also determined. Spi decreased glycemia as well as triglyceride and total cholesterol levels of diabetic rats. Levels of urea and creatinine were also reduced, while liver transaminases were unaltered. Spi also decreased dose-dependently the 1st (neurogenic) and mainly the 2nd phase (inflammatory) of the formalin test, as well as the carrageenan-induced paw edema in mice. The anti-inflammatory effect of Spi was further confirmed by decreases in TNF-alpha immunostaining in the inflamed paw and in the myeloperoxidase release from human neutrophils. The results showed that the anti-diabetic effect of S. platensis is already manifested after a 5-day treatment. Additionally, considering the relationship between diabetes and inflammation, the microalga anti-inflammatory action may also be involved. PMID:22944720

  2. Characterization, Anti-Inflammatory and Antiproliferative Activities of Natural and Sulfonated Exo-Polysaccharides from Streptococcus thermophilus ASCC 1275.

    PubMed

    Li, Siqian; Shah, Nagendra P

    2016-05-01

    Exo-polysaccharides (EPS) isolated from Streptococcus thermophilus ASCC 1275 were sulfated (31%). High-performance liquid chromatography identified that EPS was composed of mannose (30.19%), galactose (20.10%), glucose (18.05%), glucosamine (16.04%), galactosamine (9.06%), glucuronic acid (3.55%), and ribose (3.01%). Pro-/anti-inflammatory cytokine secretion ratios (IL-1β/IL-10, IL-6/IL-10, and TNF-α/IL-10) of lipopolysaccharide stimulated RAW 264.7 macrophages were significantly decreased by EPS and S.EPS treatments in a dose dependent manner. Furthermore, anti-inflammatory activities of S.EPS improved 49.3% and 24.0% than those of EPS before or after LPS treatment. The reactive oxygen species were inhibited by EPS and S.EPS by 49.6% and 55.1% at 50 μg/mL, respectively. Inhibition activities of S.EPS on nitric oxide production were 12.9% and 55.4% higher than those of EPS at 10 and 50 μg/mL. Additionally, S.EPS exhibited stronger antiproliferative activity on Caco-2 and HepG2 cells. Our results indicated that anti-inflammatory and antiproliferative activities of EPS were significantly (P < 0.01) improved by sulfonation. PMID:27010963

  3. Antioxidant, Antibacterial, Cytotoxic, and Anti-Inflammatory Potential of the Leaves of Solanum lycocarpum A. St. Hil. (Solanaceae)

    PubMed Central

    da Costa, Guilherme Augusto Ferreira; Morais, Melissa Grazielle; Saldanha, Aline Aparecida; Assis Silva, Izabela Caputo; Aleixo, Álan Alex; Ferreira, Jaqueline Maria Siqueira; Soares, Adriana Cristina; Duarte-Almeida, Joaquim Maurício; Lima, Luciana Alves Rodrigues dos Santos

    2015-01-01

    Ethanol extract and fractions obtained from leaves of Solanum lycocarpum were examined in order to determine their phenolic composition, antioxidant, antibacterial, anti-inflammatory, and cytotoxic potential. High performance liquid chromatography coupled with DAD analysis indicated that the flavonoids apigenin and kaempferol were the main phenolic compounds present in dichloromethane and ethyl acetate fractions, respectively. The antioxidant activity was significantly more pronounced for dichloromethane, ethyl acetate, and hydroethanol fractions than that of the commercial antioxidant 2,6-di-tert-butyl-4-methylphenol. The hexane and dichloromethane fractions were more active against the tested bacteria. The hydroethanol fraction exhibited significant anti-inflammatory activity at the dose of 75 and 150 mg/kg in the later phase of inflammation. However, the antiedematogenic effect of the higher dose of the ethyl acetate fraction (150 mg/kg) was more pronounced. The ethyl acetate fraction also presented a less cytotoxic effect than the ethanol extract and other fractions. These activities found in S. lycocarpum leaves can be attributed, at least in part, to the presence of phenolic constituents such as flavonoids. This work provided the knowledge of phenolic composition in the extract and fractions and the antioxidant, antibacterial, anti-inflammatory, and cytotoxic activities of leaves of S. lycocarpum. PMID:26064159

  4. Anti-Inflammatory and Anticancer Activities of Taiwanese Purple-Fleshed Sweet Potatoes (Ipomoea batatas L. Lam) Extracts.

    PubMed

    Sugata, Marcelia; Lin, Chien-Yih; Shih, Yang-Chia

    2015-01-01

    Purple-fleshed sweet potato (PFSP) (Ipomoea batatas L. Lam) has been known to possess high amount of anthocyanins which contribute to its antioxidant activity. However, a few reports are available concerning its anti-inflammatory and anticancer properties. In this study, PFSP "Tainung 73," which is locally grown in Taiwan, was steamed and extracted using acidified ethanol pH 3.5 under 80°C. Two kinds of crude anthocyanins extracts were obtained, namely, SP (Steamed, Peeled) and SNP (Steamed, No Peeled). Then, anti-inflammatory and anticancer activities of these extracts were investigated. Cell viability assay (MTT) showed that SP and SNP extracts were not toxic to RAW 264.7 cells. They even exhibited anti-inflammatory activities by suppressing the production of NO and proinflammatory cytokines, such as NF-κβ, TNF-α, and IL-6, in LPS-induced macrophage cells. Anticancer activities of these extracts were displayed through their ability to inhibit the growth of cancer cell lines, such as MCF-7 (breast cancer), SNU-1 (gastric cancer), and WiDr (colon adenocarcinoma), in concentration- and time-dependent manner. Further studies also revealed that SP extracts could induce apoptosis in MCF-7 and SNU-1 cancer cells through extrinsic and intrinsic pathway. In the future, PSFP extracts may have potential to be applied in nutraceutical, pharmaceutical, and food industries. PMID:26509161

  5. Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L.) in Human Gastric Epithelial Cells: A Comparative Study.

    PubMed

    Di Lorenzo, Chiara; Sangiovanni, Enrico; Fumagalli, Marco; Colombo, Elisa; Frigerio, Gianfranco; Colombo, Francesca; Peres de Sousa, Luis; Altindişli, Ahmet; Restani, Patrizia; Dell'Agli, Mario

    2016-01-01

    Raisins (Vitis vinifera L.) are dried grapes largely consumed as important source of nutrients and polyphenols. Several studies report health benefits of raisins, including anti-inflammatory and antioxidant properties, whereas the anti-inflammatory activity at gastric level of the hydro-alcoholic extracts, which are mostly used for food supplements preparation, was not reported until now. The aim of this study was to compare the anti-inflammatory activity of five raisin extracts focusing on Interleukin (IL)-8 and Nuclear Factor (NF)-κB pathway. Raisin extracts were characterized by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis and screened for their ability to inhibit Tumor necrosis factor (TNF)α-induced IL-8 release and promoter activity in human gastric epithelial cells. Turkish variety significantly inhibited TNFα-induced IL-8 release, and the effect was due to the impairment of the corresponding promoter activity. Macroscopic evaluation showed the presence of seeds, absent in the other varieties; thus, hydro-alcoholic extracts from fruits and seeds were individually tested on IL-8 and NF-κB pathway. Seed extract inhibited IL-8 and NF-κB pathway, showing higher potency with respect to the fruit. Although the main effect was due to the presence of seeds, the fruit showed significant activity as well. Our data suggest that consumption of selected varieties of raisins could confer a beneficial effect against gastric inflammatory diseases. PMID:27447609

  6. Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives

    PubMed Central

    Beg, Sarwar; Swain, Suryakanta; Hasan, Hameed; Barkat, M Abul; Hussain, Md Sarfaraz

    2011-01-01

    Many synthetic drugs reported to be used for the treatment of inflammatory disorders are of least interest now a days due to their potential side effects and serious adverse effects and as they are found to be highly unsafe for human assistance. Since the last few decades, herbal drugs have regained their popularity in treatment against several human ailments. Herbals containing anti-inflammatory activity (AIA) are topics of immense interest due to the absence of several problems in them, which are associated with synthetic preparations. The primary objective of this review is to provide a deep overview of the recently explored anti-inflammatory agents belonging to various classes of phytoconstituents like alkaloids, glycosides, terpenoids, steroids, polyphenolic compounds, and also the compounds isolated from plants of marine origin, algae and fungi. Also, it enlists a distended view on potential interactions between herbals and synthetic preparations, related adverse effects and clinical trials done on herbals for exploring their AIA. The basic aim of this review is to give updated knowledge regarding plants which will be valuable for the scientists working in the field of anti-inflammatory natural chemistry. PMID:22279370

  7. A Novel Nanoparticle Drug Delivery System: The Anti-inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes

    PubMed Central

    Sun, Dongmei; Zhuang, Xiaoying; Xiang, Xiaoyu; Liu, Yuelong; Zhang, Shuangyin; Liu, Cunren; Barnes, Stephen; Grizzle, William; Miller, Donald; Zhang, Huang-Ge

    2010-01-01

    Monocyte-derived myeloid cells play vital roles in inflammation-related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off-target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumin delivered by exosomes is more stable and more highly concentrated in the blood. We show that the target specificity is determined by exosomes, and the improvement of curcumin activity is achieved by directing curcumin to inflammatory cells associated with therapeutic, but not toxic, effects. Furthermore, we validate the therapeutic relevance of this technique in a lipopolysaccharide (LPS)-induced septic shock mouse model. We further show that exosomes, but not lipid alone, are required for the enhanced anti-inflammatory activity of curcumin. The specificity of using exosomes as a drug carrier creates opportunities for treatments of many inflammation-related diseases without significant side effects due to innocent bystander or off-target effects. PMID:20571541

  8. Synthesis and biological evaluation of novel indole-2-one and 7-aza-2-oxindole derivatives as anti-inflammatory agents

    PubMed Central

    Chen, Gaozhi; Jiang, Lili; Dong, Lili; Wang, Zhe; Xu, Fengli; Ding, Ting; Fu, Lili; Fang, Qilu; Liu, Zhiguo; Shan, Xiaoou; Liang, Guang

    2014-01-01

    Sepsis, a typically acute inflammatory disease, is the biggest cause of death in ICU (intensive care unit). Novel anti-inflammatory alternatives are still in urgent need. In this study, we designed and synthesized 30 indole-2-one and 7-aza-2-oxindole derivatives based on the skeleton of tenidap, and their anti-inflammatory activity was determined by evaluating the inhibitory potency against lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)-α and interleukin (IL)-6 release in RAW264.7 macrophages. Quantitative SAR (structure–activity relationship) analysis revealed that a high molecular polarizability and low lipid/water partition coefficient (ALogP) in indole-2-one are beneficial for anti-inflammatory activity. Moreover, compounds 7i and 8e inhibited the expression of TNF-α, IL-6, COX-2, PGES, and iNOS in LPS-stimulated macrophages, and 7i exhibited a significant protection from LPS-induced septic death in mouse models. These data present a series of new indole-2-one compounds with potential therapeutic effects in acute inflammatory diseases. PMID:25378906

  9. Anti-Inflammatory and Anticancer Activities of Taiwanese Purple-Fleshed Sweet Potatoes (Ipomoea batatas L. Lam) Extracts

    PubMed Central

    Sugata, Marcelia; Lin, Chien-Yih; Shih, Yang-Chia

    2015-01-01

    Purple-fleshed sweet potato (PFSP) (Ipomoea batatas L. Lam) has been known to possess high amount of anthocyanins which contribute to its antioxidant activity. However, a few reports are available concerning its anti-inflammatory and anticancer properties. In this study, PFSP “Tainung 73,” which is locally grown in Taiwan, was steamed and extracted using acidified ethanol pH 3.5 under 80°C. Two kinds of crude anthocyanins extracts were obtained, namely, SP (Steamed, Peeled) and SNP (Steamed, No Peeled). Then, anti-inflammatory and anticancer activities of these extracts were investigated. Cell viability assay (MTT) showed that SP and SNP extracts were not toxic to RAW 264.7 cells. They even exhibited anti-inflammatory activities by suppressing the production of NO and proinflammatory cytokines, such as NF-κβ, TNF-α, and IL-6, in LPS-induced macrophage cells. Anticancer activities of these extracts were displayed through their ability to inhibit the growth of cancer cell lines, such as MCF-7 (breast cancer), SNU-1 (gastric cancer), and WiDr (colon adenocarcinoma), in concentration- and time-dependent manner. Further studies also revealed that SP extracts could induce apoptosis in MCF-7 and SNU-1 cancer cells through extrinsic and intrinsic pathway. In the future, PSFP extracts may have potential to be applied in nutraceutical, pharmaceutical, and food industries. PMID:26509161

  10. Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L.) in Human Gastric Epithelial Cells: A Comparative Study

    PubMed Central

    Di Lorenzo, Chiara; Sangiovanni, Enrico; Fumagalli, Marco; Colombo, Elisa; Frigerio, Gianfranco; Colombo, Francesca; Peres de Sousa, Luis; Altindişli, Ahmet; Restani, Patrizia; Dell’Agli, Mario

    2016-01-01

    Raisins (Vitis vinifera L.) are dried grapes largely consumed as important source of nutrients and polyphenols. Several studies report health benefits of raisins, including anti-inflammatory and antioxidant properties, whereas the anti-inflammatory activity at gastric level of the hydro-alcoholic extracts, which are mostly used for food supplements preparation, was not reported until now. The aim of this study was to compare the anti-inflammatory activity of five raisin extracts focusing on Interleukin (IL)-8 and Nuclear Factor (NF)-κB pathway. Raisin extracts were characterized by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis and screened for their ability to inhibit Tumor necrosis factor (TNF)α-induced IL-8 release and promoter activity in human gastric epithelial cells. Turkish variety significantly inhibited TNFα-induced IL-8 release, and the effect was due to the impairment of the corresponding promoter activity. Macroscopic evaluation showed the presence of seeds, absent in the other varieties; thus, hydro-alcoholic extracts from fruits and seeds were individually tested on IL-8 and NF-κB pathway. Seed extract inhibited IL-8 and NF-κB pathway, showing higher potency with respect to the fruit. Although the main effect was due to the presence of seeds, the fruit showed significant activity as well. Our data suggest that consumption of selected varieties of raisins could confer a beneficial effect against gastric inflammatory diseases. PMID:27447609

  11. Anti-inflammatory effects of sucrose-derived oligosaccharides produced by a constitutive mutant L. mesenteroides B-512FMCM dextransucrase in high fat diet-fed mice.

    PubMed

    Kang, Min-Gyung; Lee, Hee Jae; Cho, Jae-Young; Kim, Kanghwa; Yang, Soo Jin; Kim, Doman

    2016-08-26

    Oligosaccharide (OS) is used as a sugar replacement as well as an ingredient in functional foods because of its beneficial effects, mainly on reducing calorie content and promoting intestinal health. By contrast, the effects of OS on inflammation are less well investigated. The purpose of this study was to investigate the effects of sucrose-derived OS on glucose control and inflammation in high fat (HF) diet-fed mice. Male C57BL6 mice were randomly assigned to six treatment groups (n = 10-14 mice per group): 1) lean control (CON), 2) HF control, 3) HF-low sucrose (LS, 100 mg/kg/day), 4) HF-high sucrose (HS, 1000 mg/kg/day), 5) HF-low OS (LOS, 100 mg/kg/day), and 6) HF-high OS (HOS, 1000 mg/kg/day). PBS (vehicle), sucrose, and OS were administered by stomach gavage. Body weight, food intake, and markers of liver function (activities of aspartate aminotransferase and alanine aminotransferase) were not affected by the treatments. HOS treatment decreased levels of serum glucose, insulin, and homeostasis model assessment-insulin resistance compared with sucrose treatment. However, serum adiponectin levels of the HOS group were higher than those of the sucrose groups. Serum levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and fetuin-A were lower in the HOS group than in the sucrose groups. Hepatic gene expression levels of pro-inflammatory cytokines and related factors (fetuin-A, NF-κB, TLR4, TNF-alpha, and IL-6) were decreased and the levels of insulin signaling-related molecules (sirtuin 1, insulin receptor, and Akt) were increased in HOS-treated mice as compared with sucrose-treated mice. These results demonstrate that OS treatment is effective in improving glucose control and inflammation in high fat diet-fed mice. PMID:27342664

  12. Anti-inflammatory effects of a polyphenols-rich extract from tea (Camellia sinensis) flowers in acute and chronic mice models.

    PubMed

    Chen, Bang-Tian; Li, Wei-Xi; He, Rong-Rong; Li, Yi-Fang; Tsoi, Bun; Zhai, Yu-Jia; Kurihara, Hiroshi

    2012-01-01

    While beneficial health properties of tea leaves have been extensively studied, less attention is paid to the flowers of tea. In this study, the anti-inflammatory effects of hot water extract of tea (Camellia sinensis) flowers were investigated. Pharmacological studies found that administration of tea flowers extract (TFE) could effectively inhibit croton oil-induced ear edema and carrageenin-induced paw edema. Furthermore, administration of TFE also protected against Propionibacterium acnes (P. ances) plus lipopolysaccharide-(LPS-) induced liver inflammation by reversing the histologic damage and plasma alanine aminotransferase (ALT) increase. Moreover, the levels of nitric oxide (NO), tumor necrosis factor-(TNF)-α and interleukin-(IL-) 1β mRNA in mouse liver were markedly suppressed after treatment with TFE in mice with immunological liver inflammation. These results indicated that tea flowers had potent anti-inflammatory effects on acute and immunological inflammation in vivo, and may be used as a functional natural food. PMID:22900128

  13. Evaluation of the anti-inflammatory and liver-protective effects of anoectochilus formosanus, ganoderma lucidum and gynostemma pentaphyllum in rats.

    PubMed

    Lin, J M; Lin, C C; Chiu, H F; Yang, J J; Lee, S G

    1993-01-01

    The pharmacological effects of Anoectochilus formosanus, Ganoderma lucidum and Gynostemma pentaphyllum were studied against carrageenan-induced paw edema and CC1(4)-induced hepatotoxicity in rats. The water extracts of G. pentaphyllum and G. lucidum were found to possess significant anti-inflammatory activity against carrageenan induced edema. The administration of Gynostemma pentaphyllum displayed an activity even more potent than indomethacin. In contrast, Anoectochilus formosanus showed a delayed onset of anti-inflammatory activity starting from 4 hrs post carrageenan administration. However, A. formosanus significantly decreased the acute increase in serum GOT and GPT level caused by CC1(4). Histological changes such as necrosis, fatty change, ballooning degeneration, inflammatory infiltration of lymphocytes and Kupffer cells around the central vein were simultaneously improved by the treatment of A. formosanus. PMID:8328423

  14. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity

    PubMed Central

    Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; khan, Amjad A

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect. PMID:24753740

  15. PAFR in adipose tissue macrophages is associated with anti-inflammatory phenotype and metabolic homoeostasis.

    PubMed

    Filgueiras, Luciano Ribeiro; Koga, Marianna Mainardi; Quaresma, Paula G; Ishizuka, Edson Kiyotaka; Montes, Marlise B A; Prada, Patricia O; Saad, Mario J; Jancar, Sonia; Rios, Francisco J

    2016-04-01

    Metabolic dysfunction is associated with adipose tissue inflammation and macrophage infiltration. PAFR (platelet-activating factor receptor) is expressed in several cell types and binds to PAF (platelet-activating factor) and oxidized phospholipids. Engagement of PAFR in macrophages drives them towards the anti-inflammatory phenotype. In the present study, we investigated whether genetic deficiency of PAFR affects the phenotype of ATMs (adipose tissue macrophages) and its effect on glucose and insulin metabolism. PARFKO (PAFR-knockout) and WT (wild-type) mice were fed on an SD (standard diet) or an HFD (high-fat diet). Glucose and insulin tolerance tests were performed by blood monitoring. ATMs were evaluated by FACS for phenotypic markers. Gene and protein expression was investigated by real-time reverse transcription-quantitative PCR and Western blotting respectively. Results showed that the epididymal adipose tissue of PAFRKO mice had increased gene expression of Ccr7, Nos2, Il6 and Il12, associated with pro-inflammatory mediators, and reduced expression of the anti-inflammatory Il10. Moreover, the adipose tissue of PAFRKO mice presented more pro-inflammatory macrophages, characterized by an increased frequency of F4/80(+)CD11c(+) cells. Blood monocytes of PAFRKO mice also exhibited a pro-inflammatory phenotype (increased frequency of Ly6C(+) cells) and PAFR ligands were detected in the serum of both PAFRKO and WT mice. Regarding metabolic parameters, compared with WT, PAFRKO mice had: (i) higher weight gain and serum glucose concentration levels; (ii) decreased insulin-stimulated glucose disappearance; (iii) insulin resistance in the liver; (iv) increased expression of Ldlr in the liver. In mice fed on an HFD, some of these changes were potentiated, particularly in the liver. Thus it seems that endogenous ligands of PAFR are responsible for maintaining the anti-inflammatory profile of blood monocytes and ATMs under physiological conditions. In the absence of

  16. 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

  17. Lipoxins exert antiangiogenic and anti-inflammatory effects on Kaposi's sarcoma cells.

    PubMed

    Marginean, Alexandru; Sharma-Walia, Neelam

    2015-08-01

    Lipoxin A4 (LXA4) is an endogenously produced host molecule with anti-inflammatory resolution effects. Previous studies demonstrated it to be involved in anti-vascular endothelial growth factor (VEGF)-mediated angiogenesis and in a possible anticancer role via interaction with its receptor, lipoxin A 4 receptor (ALXR). Here, we examined the effects of LXA4 and its epimer 15-epi-LXA4 in inhibiting proinflammatory and angiogenic functions in a human Kaposi's sarcoma tumor-derived cell line (KS-IMM). KS-IMM cells expressed increased levels of inflammatory cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LO) pathway enzymes when compared with human microvascular dermal endothelial cells (HMVEC-d). KS-IMM cells secreted high levels of prostaglandin E2 (PGE2) and chemotactic leukotriene B4 (LTB4). Treatment with LXA4 or 15-epi-LXA4 effectively reduced the levels of COX-2, 5-LO proteins, and secretion of PGE2 and LTB4 in KS-IMM cells. LXA4 or 15-epi-LXA4 treatment also decreased secretion of proinflammatory interleukin 6 (IL-6) and IL-8 cytokines but induced the secretion of anti-inflammatory IL-10. LXA4 treatment reduced the phosphorylation of VEGF receptor (VEGFR) and ephrin family receptor tyrosine kinases. LXA4 treatment effectively induced dephosphorylation of multiple cellular kinases such as Focal Adhesion Kinase, Protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells, and Extracellular signal-regulated kinases (ERK)1/2, and reduced angiogenic factor VEGF-C secretion in KS cells. LX treatment drastically induced the Src-homology 2 domain-containing phosphatase tyrosine (Y542) phosphatase and reduced VEGFR-2 phosphorylation at sites Y1059, Y1175, and Y1212. Treatment of KS-IMM cells with LXA4 resulted in selective localization of VEGFR-2 in nonlipid raft (non-LR) and ALXR to LR fractions. These results demonstrated that LXA4 or 15-epi-LXA4 induce anti-inflammatory and antiangiogenic effects in KS cells and suggest that treatment with LXs is

  18. Anti-Inflammatory Activities of a Chinese Herbal Formula IBS-20 In Vitro and In Vivo

    PubMed Central

    Yang, Zhonghan; Grinchuk, Viktoriya; Ip, Siu Po; Che, Chun-Tao; Fong, Harry H. S.; Lao, Lixing; Wu, Justin C.; Sung, Joseph J.; Berman, Brian; Shea-Donohue, Terez; Zhao, Aiping

    2012-01-01

    Irritable bowel syndrome (IBS) is a functional bowel disorder and the etiology is not well understood. Currently there is no cure for IBS and no existing medication induces symptom relief in all patients. IBS-20 is a 20-herb Chinese medicinal formula that offers beneficial effects in patients with IBS; however, the underlying mechanisms are largely unknown. This study showed that IBS-20 potently inhibited LPS- or IFNΓ-stimulated expression of pro-inflammatory cytokines, as well as classically activated macrophage marker nitric oxide synthase 2. Similarly, IBS-20 or the component herb Coptis chinensis decreased LPS-stimulated pro-inflammatory cytokine secretion from JAWS II dendritic cells. IBS-20 or the component herbs also blocked or attenuated the IFNΓ-induced drop in transepithelial electric resistance, an index of permeability, in fully differentiated Caco-2 monolayer. Finally, the up-regulation of key inflammatory cytokines in inflamed colon from TNBS-treated mice was suppressed significantly by orally administrated IBS-20, including IFNΓ and IL-12p40. These data indicate that the anti-inflammatory activities of IBS-20 may contribute to the beneficial effects of the herbal extract in patients with IBS, providing a potential mechanism of action for IBS-20. In addition, IBS-20 may be a potential therapeutic agent against other Th1-dominant gut pathologies such as inflammatory bowel disease. PMID:22461841

  19. Antioxidant, anti-inflammatory and antiproliferative activities of Kalanchoe gracilis (L.) DC stem.

    PubMed

    Lai, Zhen-Rung; Ho, Yu-Ling; Huang, Shun-Chieh; Huang, Tai-Hung; Lai, Shang-Chih; Tsai, Jen-Chieh; Wang, Ching-Ying; Huang, Guan-Jhong; Chang, Yuan-Shiun

    2011-01-01

    Oxidative stress and inflammation are related to several chronic diseases including cancer and atherosclerosis. Kalanchoe gracilis (L.) DC is a special folk medicinal plant in Taiwan. The aim of this study was to evaluate the antioxidant, anti-inflammatory and antiproliferative activities of the methanolic extract and fractions of the stem of K. gracilis. TEAC, total phenolic compound content, total flavonoid content, DPPH radical scavenging activity, reducing power, inhibition of NO production in LPS-induced RAW264.7 cells, and inhibition of cancer cell proliferation were analyzed. Among all fractions, the chloroform fraction showed the highest TEAC and DPPH radical scavenging activities. The chloroform fraction also had the highest content of polyphenols and flavonoids. Chloroform fractions also decreased LPS-induced NO production and expressions of iNOS and COX-2 in RAW264.7 cells. The antiproliferative activities of the methanolic extract and fractions were studied in vitro using HepG2 cells, and the results were consistent with their antioxidant capacities. Chloroform fractions had the highest antiproliferative activity with an IC(50) of 136.85 ± 2.32 μg/ml. Eupafolin also had good pharmacological activity in the antioxidant, anti-inflammation and antiproliferative. Eupafolin might be an important bioactive compound in the stem of K. gracilis. The above experimental data indicated that the stem of K. gracilis is a potent antioxidant medicinal plant, and such efficacy may be mainly attributed to its polyphenolic compounds. PMID:22083996

  20. Anti-inflammatory activities of cecropin A and its mechanism of action.

    PubMed

    Lee, Eunjung; Shin, Areum; Kim, Yangmee

    2015-01-01

    Cecropin A is a novel 37-residue cecropin-like antimicrobial peptide isolated from the cecropia moth, Hyalophora cecropia. We have demonstrated that cecropin A is an antibacterial agent and have investigated its mode of action. In this study, we show that cecropin A has potent antimicrobial activity against 2 multidrug resistant organisms-Acinetobacter baumanii and-Pseudomonas aeruginosa. Interactions between cecropin A and membrane phospholipids were studied using tryptophan blue shift experiments. Cecropin A has a strong interaction with bacterial cell mimetic membranes. These results imply that cecropin A has selectivity for bacterial cells. To address the potential the rapeutic efficacy of cecropin A, its anti-inflammatory activities and mode of action in mouse macrophage-derived RAW264.7 cells stimulated with lipopolysaccharide (LPS) were examined. Cecropin A suppressed nitrite production, mTNF-α, mIL-1β, mMIP-1, and mMIP-2 cytokine release in LPS-stimulated RAW264.7 cells. Furthermore, cecropin A inhibited intracellular cell signaling via the ERK, JNK, and p38 MAPK pathway, leading to the prevention of COX-2 expression in LPS-stimulated RAW264.7 cells. These results strongly suggest that cecropin A should be investigated as a potential agent for the prevention and treatment of inflammatory diseases. PMID:25319409

  1. Chemical composition, antioxidant and anti-inflammatory properties of pistachio hull extracts.

    PubMed

    Grace, Mary H; Esposito, Debora; Timmers, Michael A; Xiong, Jia; Yousef, Gad; Komarnytsky, Slavko; Lila, Mary Ann

    2016-11-01

    Phytochemical and bioactivity analyses of pistachio hulls revealed the presence of anacardic acids (3198mg/100g), fatty acids (1500mg/100g), and phytosterols (192mg/100g) as major components. Carotenoids (4.93mg/100g), chlorophylls (10.27mg/100g), tocopherols (8.83mg/100g), and three triterpene acids (mangiferolic, isomangiferolic and mangiferonic acids) were characterized. A polar (P) extract contained quercetin-3-O-glucoside (6.27mg/g), together with smaller concentrations of quercetin, myricetin and luteolin flavonoids, accounting for 5.53mg/g. Gallotannins and other phenolic compounds esterified with a gallic acid moiety characterized the P extract. P extract potently inhibited the release of nitric oxide (NO) and reactive oxygen species (ROS) in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. The mRNA expression levels of the anti-inflammatory cytokine COX-2 were significantly inhibited by fractions P2-P5, while IL-6 was only inhibited by fraction P3. Moreover, the P extract significantly decreased the non-mitochondrial oxidative burst associated with inflammatory response in macrophages. PMID:27211624

  2. Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.

    PubMed

    Hodkinson, Duncan J; Khawaja, Nadine; OʼDaly, Owen; Thacker, Michael A; Zelaya, Fernando O; Wooldridge, Caroline L; Renton, Tara F; Williams, Steven C R; Howard, Matthew A

    2015-07-01

    Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the antihyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in presurgical and postsurgical states and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction, and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow under pain-free conditions (presurgery). However, in the postsurgical state, we observed increased activation of top-down modulatory circuits, which was accompanied by decreases in the areas engaged because of ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management. PMID:25851460

  3. Non-steroidal Anti-inflammatory Drugs in Raptors

    USGS Publications Warehouse

    Oaks, J. Lindsay; Meteyer, Carol U.

    2012-01-01

    The use of analgesia has become standard, and appropriate, practice in avian medicine. As in mammals, pain control in avian patients is usually accomplished with opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) used singly or in combination for a multimodal approach. Despite their usefulness, widespread use, and relative safety in clinical use, few controlled studies in birds have been conducted on efficacy, safety, and dosing. The guidelines for the use of NSAIDs in raptors and other birds have mainly been empirical. More recently, NSAIDs in free-living raptors have emerged as a major conservation issue with the discovery that diclofenac sodium was responsible for the population crash of three species of Gyps vultures in southern Asia. In this context, residues of veterinary NSAIDs in domestic animals are now considered environmental contaminants that can be significantly toxic to vultures and possibly other avian scavengers. Ironically, the disaster with Asian vultures has led to a considerable body of research on NSAIDs in raptors to the benefit of clinicians who now have scientific information available to help assess dosing, safety, toxicity, and pharmacokinetics of NSAIDs in their raptor patients.

  4. Anti-inflammatory phenanthrene derivatives from stems of Dendrobium denneanum.

    PubMed

    Lin, Yuan; Wang, Fei; Yang, Li-Juan; Chun, Ze; Bao, Jin-Ku; Zhang, Guo-Lin

    2013-11-01

    Cultivated Dendrobium denneanum has been substituted for other endangered Dendrobium species in recent years, but there have been few studies regarding either its chemical constituents or pharmacological effects. In this study, three phenanthrene glycosides, three 9,10-dihydrophenanthrenes, two 9,10-dihydrophenanthrenes glycosides, and four known phenanthrene derivatives, were isolated from the stems of D. denneanum. Their structures were elucidated on the basis of MS and NMR spectroscopic data. Ten compounds were found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells with IC50 values of 0.7-41.5 μM, and exhibited no cytotoxicity in RAW264.7, HeLa, or HepG2 cells. Additionally, it was found that 2,5-dihydroxy-4-methoxy-phenanthrene 2-O-β-d-glucopyranoside, and 5-methoxy-2,4,7,9S-tetrahydroxy-9,10-dihydrophenanthrene suppressed LPS-induced expression of inducible NO synthase (iNOS) inhibited phosphorylation of p38, JNK as well as mitogen-activated protein kinase (MAPK), and inhibitory kappa B-α (IκBα). This indicated that both compounds exert anti-inflammatory effects by inhibiting MAPKs and nuclear factor κB (NF-κB) pathways. PMID:24042064

  5. Incorporation of anti-inflammatory agent into mesoporous silica.

    PubMed

    Braz, Wilson Rodrigues; Rocha, Natállia Lamec; de Faria, Emerson H; Silva, Márcio L A E; Ciuffi, Katia J; Tavares, Denise C; Furtado, Ricardo Andrade; Rocha, Lucas A; Nassar, Eduardo J

    2016-09-23

    The unique properties of macroporous, mesoporous, and microporous systems, including their ability to accommodate molecules of different sizes inside their pores and to act as drug delivery systems, have been the object of extensive studies. In this work, mesoporous silica with hexagonal structure was obtained by template synthesis via the sol-gel process. The resulting material was used as support to accommodate the anti-inflammatory agent indomethacin. The alkaline route was used to prepare the mesoporous silica; cetyltrimethylammonium bromide was employed as porogenic agent. The silica particles were functionalized with 3-aminopropyltriethoxysilane alkoxide (APTES) by the sol-gel post-synthesis method. Indomethacin was incorporated into the silica functionalized with APTES and into non-functionalized silica. The resulting systems were characterized by x-ray diffraction (XRD), specific area, infrared spectroscopy, and thermal analyses (TGA). XRD attested to formation of mesoporous silica with hexagonal structure. This structure remained after silica functionalization with APTES and incorporation of indomethacin. Typical infrared spectroscopy vibrations and organic material decomposition during TGA confirmed silica functionalization and drug incorporation. The specific surface area and pore volume of the functionalized material incorporated with indomethacin decreased as compared with the specific surface area and pore volume of the non-functionalized silica containing no drug, suggesting both the functionalizing agent and the drug were present in the silica. Cytotoxicity tests conducted on normal fibroblasts (GM0479A) cells attested that the silica matrix containing indomethacin was less toxic than the free drug. PMID:27533108

  6. 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

  7. Anti-inflammatory effects of glaucocalyxin B in microglia cells.

    PubMed

    Gan, Ping; Zhang, Li; Chen, Yanke; Zhang, Yu; Zhang, Fali; Zhou, Xiang; Zhang, Xiaohu; Gao, Bo; Zhen, Xuechu; Zhang, Jian; Zheng, Long Tai

    2015-05-01

    Over-activated microglia is involved in various kinds of neurodegenerative process including Parkinson, Alzheimer and HIV dementia. Suppression of microglial over activation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory and neuroprotective effects of the ent-kauranoid diterpenoids, which were isolated from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, were investigated in cultured microglia cells. Glaucocalyxin B (GLB), one of five ent-kauranoid diterpenoids, significantly decreased the generation of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-activated microglia cells. In addition, GLB inhibited activation of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) in LPS-activated microglia cells. Furthermore, GLB strongly induced the expression of heme oxygenase (HO)-1 in BV-2 microglia cells. Finally, GLB exhibited neuroprotective effect by preventing over-activated microglia induced neurotoxicity in a microglia/neuron co-culture model. Taken together, the present study demonstrated that the GLB possesses anti-nueroinflammatory activity, and might serve as a potential therapeutic agent for treating neuroinflammatory diseases. PMID:26003084

  8. Immunomodulatory and anti-inflammatory effects of chondroitin sulphate

    PubMed Central

    du Souich, Patrick; García, Antonio G; Vergés, Josep; Montell, Eulàlia

    2009-01-01

    Chondroitin sulphate (CS) is a natural glycosaminoglycan present in the extracellular matrix and is formed by the 1–3 linkage of D-glucuronic acid to N-acetylgalactosamine. In chondrocytes, CS diminishes interleukin-1 p (IL-1p)-induced increases in p38 mitogen-activated protein kinase (p38MAPK) and signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and decreases nuclear factor-KB (NF-kB) nuclear translocation and as a consequence, reduces the formation of pro-inflammatory cytokines, IL-1 p and TNF-a, and pro-inflammatory enzymes, such as phospholipase A2 (PLA2), cyclooxygenase 2 (COX-2) and nitric oxide synthase-2 (NOS-2). The mechanism of action of CS explains its beneficial effect on the cartilage, synovial membrane and subchondral bone. On the other hand, in vivo, CS given orally prevents hepatic NF-κB nuclear translocation, suggesting that systemic CS may elicit an anti-inflammatory effect in many tissues besides the articulation. There is preliminary evidence showing that in human beings, CS may be of benefit in other diseases where inflammation is an essential marker, such as psoriasis and atherosclerosis. The review of the literature suggest that CS might also be of interest for the treatment of other diseases with an inflammatory and/or autoimmune character, such as inflammatory bowel disease, degenerative diseases of the central nervous system and stroke, multiple sclerosis and other autoimmune diseases. PMID:19522843

  9. Effects of nonsteroidal anti-inflammatory drugs on microvascular dynamics.

    PubMed

    Slater, C; House, S D

    1993-03-01

    Techniques of intravital microscopy were used to assess the effect of the nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and ibuprofen, on the microcirculation. Hemodynamics in venules of the rat mesentery were studied in terms of vessel diameter, red blood cell velocity, and leukocyte-endothelium interactions: leukocyte-endothelium adhesion (LEA), white blood cell (WBC) marginating flux, and WBC velocity. Measurements were made during (1) control conditions (topical suffusion with ringer-gelatin drip), (2) topically suffused indomethacin or ibuprofen, (3) an induced inflammatory response (suffusion with the chemoattractant N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP)), and (4) concomitant suffusion with FMLP and NSAID. Short term topical suffusion (90 sec) with indomethacin and ibuprofen had little or no effect on control hemodynamics. Five-minute suffusions with indomethacin (5 x 10(-5) to 5 x 10(-4) M) significantly increased LEA while ibuprofen (5 x 10(-3) M) significantly decreased LEA. Topical suffusion with the chemotactic agent FMLP induced inflammation and significantly increased LEA in venules. Treatment with indomethacin during induced inflammation had no effect on the inflammatory reaction in terms of the microvascular hemodynamics measured in this study. Treatment with ibuprofen during induced inflammation significantly reduced LEA and increased red blood cell velocity. In conclusion, although both of the NSAIDs studied here are known to block the cyclooxygenase pathway of arachidonic acid metabolism, the actions of indomethacin and ibuprofen on the inflammatory process are very different with an important effect of ibuprofen being to decrease LEA. PMID:8361400

  10. Proteomic analysis of the anti-inflammatory action of minocycline

    PubMed Central

    Dunston, Christopher R; Griffiths, Helen R; Lambert, Peter A; Staddon, Susan; Vernallis, Ann B

    2011-01-01

    Minocycline possesses anti-inflammatory properties independently of its antibiotic activity although the underlying molecular mechanisms are unclear. Lipopolysaccharide (LPS)-induced cytokines and pro-inflammatory protein expression are reduced by minocycline in cultured macrophages. Here, we tested a range of clinically important tetracycline compounds (oxytetracycline, doxycycline, minocycline and tigecycline) and showed that they all inhibited LPS-induced nitric oxide production. We made the novel finding that tigecycline inhibited LPS-induced nitric oxide production to a greater extent than the other tetracycline compounds tested. To identify potential targets for minocycline, we assessed alterations in the macrophage proteome induced by LPS in the presence or absence of a minocycline pre-treatment using 2-DE and nanoLC-MS. We found a number of proteins, mainly involved in cellular metabolism (ATP synthase β-subunit and aldose reductase) or stress response (heat shock proteins), which were altered in expression in response to LPS, some of which were restored, at least in part, by minocycline. This is the first study to document proteomic changes induced by minocycline. The observation that minocycline inhibits some, but not all, of the LPS-induced proteomic changes shows that minocycline specifically affects some signalling pathways and does not completely inhibit macrophage activation. PMID:21182193

  11. Proteasome inhibition: a new anti-inflammatory strategy.

    PubMed

    Elliott, Peter J; Zollner, Thomas Matthias; Boehncke, Wolf-Henning

    2003-04-01

    The ubiquitin-proteasome pathway has a central role in the selective degradation of intracellular proteins. Among the key proteins modulated by the proteasome are those involved in the control of inflammatory processes, cell cycle regulation, and gene expression. Consequently proteasome inhibition is a potential treatment option for cancer and inflammatory conditions. Thus far, proof of principle has been obtained from studies in numerous animal models for a variety of human diseases including cancer, reperfusion injury, and inflammatory conditions such as rheumatoid arthritis, asthma, multiple sclerosis, and psoriasis. Two proteasome inhibitors, each representing a unique chemical class, are currently under clinical evaluation. Velcade (PS-341) is currently being evaluated in multiple phase II clinical trials for several solid tumor indications and has just entered a phase III trial for multiple myeloma. PS-519, representing another class of inhibitors, focuses on the inflammatory events following ischemia and reperfusion injury. Since proteasome inhibitors exhibit anti-inflammatory and antiproliferative effects, diseases characterized by both of these processes simultaneously, as is the case in rheumatoid arthritis or psoriasis, might also represent clinical opportunities for such drugs. PMID:12700891

  12. Pharmaceutical aspects of anti-inflammatory TNF-blocking drugs.

    PubMed

    Jinesh, Sandhya

    2015-06-01

    Tumor necrosis factor (TNF) is a key regulator of inflammatory processes in several immune-mediated inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. Inactivating TNF has been found to be a plausible approach in treating these conditions. Two major strategies have been adopted by scientists to inactivate TNF: one is to use monoclonal antibodies (mAbs) that bind to TNF, and the other is to use fusion proteins that bind to TNF, both inactivate TNF and help to prevent TNF-mediated inflammatory processes. Monoclonal antibodies (mAbs) are biological products that selectively bind to specific antigen molecules, and fusion proteins are soluble receptors that bind to TNF. These types of drugs are generally known as biologics and there has been an explosion in the development and testing of biologics since the 1994 US approval and launch of abciximab, a mAb that binds to GPIIb/IIIa on platelets. Anti-TNF drugs that are currently approved by FDA for treating inflammatory conditions include adalimumab, certolizumab pegol, golimumab, infliximab and etanercept. Since these agents are complex protein molecules, the pharmacodynamics and pharmacokinetics of these drugs are different from small-molecule anti-inflammatory agents. This review focuses on the pharmaceutical aspects of these drugs such as mechanism of action, adverse effects, pharmacokinetics and drug interactions. An effort was also taken to compare the pharmacodynamics and pharmacokinetic properties of these drugs, with the available data at this time. PMID:25687751

  13. Anti-inflammatory Hydrolyzable Tannins from Myricaria bracteata.

    PubMed

    Liu, Jia-Bao; Ding, Ya-Si; Zhang, Ying; Chen, Jia-Bao; Cui, Bao-Song; Bai, Jin-Ye; Lin, Ming-Bao; Hou, Qi; Zhang, Pei-Cheng; Li, Shuai

    2015-05-22

    Twelve hydrolyzable tannins were obtained from the twigs of Myricaria bracteata, including two new hellinoyl-type dimers, bracteatinins D1 (1) and D2 (2); a new hellinoyl-type trimer, bracteatinin T1 (3); two known monomers, nilotinin M4 (4) and 1,3-di-O-galloyl-4,6-O-(aS)-hexahydroxydiphenoyl-β-d-glucose (5); six known dimers, tamarixinin A (6), nilotinin D8 (7), hirtellins A (10), B (9), and E (8), and isohirtellin C (11); and a known trimer, hirtellin T3 (12). The structures of the tannins were elucidated by spectroscopic data analysis and comparisons to known tannins. All compounds were evaluated as free radical scavengers using 1,1-diphenyl-2-picrylhydrazyl and hydroxy radicals and compared to the activity of BHT and Trolox. Compound 6 showed a significant anti-inflammatory effect on croton oil-induced ear edema in mice (200 mg/kg, inhibition rate 69.8%) and on collagen-induced arthritis in DBA/1 mice (20 mg/kg, inhibition rate 46.0% at day 57). PMID:25918997

  14. Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

    PubMed Central

    Roth, Sanford H

    2011-01-01

    Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis. PMID:21753867

  15. Cannabinoid-like anti-inflammatory compounds from flax fiber.

    PubMed

    Styrczewska, Monika; Kulma, Anna; Ratajczak, Katarzyna; Amarowicz, Ryszard; Szopa, Jan

    2012-09-01

    Flax is a valuable source of fibers, linseed and oil. The compounds of the latter two products have already been widely examined and have been proven to possess many health-beneficial properties. In the course of analysis of fibers extract from previously generated transgenic plants overproducing phenylpropanoids a new terpenoid compound was discovered.The UV spectra and the retention time in UPLC analysis of this new compound reveal similarity to a cannabinoid-like compound, probably cannabidiol (CBD). This was confirmed by finding two ions at m/z 174.1 and 231.2 in mass spectra analysis. Further confirmation of the nature of the compound was based on a biological activity assay. It was found that the compound affects the expression of genes involved in inflammatory processes in mouse and human fibroblasts and likely the CBD from Cannabis sativa activates the specific peripheral cannabinoid receptor 2 (CB2) gene expression. Besides fibers, the compound was also found in all other flax tissues. It should be pointed out that the industrial process of fabric production does not affect CBD activity.The presented data suggest for the first time that flax products can be a source of biologically active cannabinoid-like compounds that are able to influence the cell immunological response. These findings might open up many new applications for medical flax products, especially for the fabric as a material for wound dressing with anti-inflammatory properties. PMID:22706678

  16. Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children

    PubMed Central

    2007-01-01

    Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA)-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX)-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children. PMID:20525116

  17. Activation of Endogenous Anti-Inflammatory Mediator Cyclic AMP Attenuates Acute Pyelonephritis in Mice Induced by Uropathogenic Escherichia coli

    PubMed Central

    Wei, Yang; Li, Ke; Wang, Na; Cai, Gui-Dong; Zhang, Ting; Lin, Yan; Gui, Bao-Song; Liu, En-Qi; Li, Zong-Fang; Zhou, Wuding

    2015-01-01

    The pathogenesis of pyelonephritis caused by uropathogenic Escherichia coli (UPEC) is not well understood. Here, we show that besides UPEC virulence, the severity of the host innate immune response and invasion of renal epithelial cells are important pathogenic factors. Activation of endogenous anti-inflammatory mediator cAMP significantly attenuated acute pyelonephritis in mice induced by UPEC. Administration of forskolin (a potent elevator of intracellular cAMP) reduced kidney infection (ie, bacterial load, tissue destruction); this was associated with attenuated local inflammation, as evidenced by the reduction of renal production of proinflammatory mediators, renal infiltration of inflammatory cells, and renal myeloperoxidase activity. In primary cell culture systems, forskolin not only down-regulated UPEC-stimulated production of proinflammatory mediators by renal tubular epithelial cells and inflammatory cells (eg, monocyte/macrophages) but also reduced bacterial internalization by renal tubular epithelial cells. Our findings clearly indicate that activation of endogenous anti-inflammatory mediator cAMP is beneficial for controlling UPEC-mediated acute pyelonephritis in mice. The beneficial effect can be explained at least in part by limiting excessive inflammatory responses through acting on both renal tubular epithelial cells and inflammatory cells and by inhibiting bacteria invasion of renal tubular epithelial cells. PMID:25478807

  18. Inhibitory effect of quinolone antimicrobial and nonsteroidal anti-inflammatory drugs on a medium chain acyl-CoA synthetase.

    PubMed

    Kasuya, F; Hiasa, M; Kawai, Y; Igarashi, K; Fukui, M

    2001-08-01

    The inhibitory effects of quinolone antimicrobial agents and nonsteroidal anti-inflammatory drugs on purified mouse liver mitochondrial medium chain acyl-CoA synthetase catalyzing the first reaction of glycine conjugation were examined, using hexanoic acid as a substrate. Enoxacin, ofloxacin, nalidixic acid, diflunisal, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxydodecanoic acid, which do not act as substrates, were potent inhibitors. Diflunisal, nalidixic acid, salicylic acid, 2-hydroxynaphthoic acid, and 2-hydroxydodecanoic acid inhibited competitively this medium chain acyl-CoA synthetase with K(i) values of 0.6, 12.4, 19.6, 13.4, and 15.0 microM, respectively. Enoxacin and ofloxacin inhibited this medium chain acyl-CoA synthetase in a mixed-type manner with K(i) values of 23.7 and 38.2 microM, respectively. Felbinac, which is a substrate, inhibited the activity of this medium chain acyl-CoA synthetase for hexanoic acid (IC50 = 25 microM). The concomitant presence of enoxacin and felbinac strongly inhibited this medium chain acyl-CoA synthetase. These findings indicate that medium chain acyl-CoA synthetases may be influenced by quinolone antimicrobial and nonsteroidal anti-inflammatory drugs. PMID:11434910

  19. Anti-Inflammatory and PPAR Transactivational Effects of Oleanane-Type Triterpenoid Saponins from the Roots of Pulsatilla koreana

    PubMed Central

    Li, Wei; Yan, Xi Tao; Sun, Ya Nan; Ngan, Thi Thanh; Shim, Sang Hee; Kim, Young Ho

    2014-01-01

    In this study, 23 oleanane-type triterpenoid saponins were isolated from a methanol extract of the roots of Pulsatilla koreana. The NF-κB inhibitory activity of the isolated compounds was measured in TNFα-treated HepG2 cells using a luciferase reporter system. Compounds 19–23 inhibited TNFα-stimulated NF-κB activation in a dose-dependent manner, with IC50 values ranging from 0.75–8.30 μM. Compounds 19 and 20 also inhibited the TNFα-induced expression of iNOS and ICAM-1 mRNA. Moreover, effect of the isolated compounds on PPARs transcriptional activity was assessed. Compounds 7–11 and 19–23 activated PPARs the transcriptional activity significantly in a dose-dependent manner, with EC50 values ranging from 0.9–10.8 μM. These results suggest the presence of potent anti-inflammatory components in P. koreana, and will facilitate the development of novel anti-inflammatory agents. PMID:25143813

  20. Determination of the binding mode for anti-inflammatory natural product xanthohumol with myeloid differentiation protein 2

    PubMed Central

    Fu, Weitao; Chen, Lingfeng; Wang, Zhe; Zhao, Chengwei; Chen, Gaozhi; Liu, Xing; Dai, Yuanrong; Cai, Yuepiao; Li, Chenglong; Zhou, Jianmin; Liang, Guang

    2016-01-01

    It is recognized that myeloid differentiation protein 2 (MD-2), a coreceptor of toll-like receptor 4 (TLR4) for innate immunity, plays an essential role in activation of the lipopolysaccharide signaling pathway. MD-2 is known as a neoteric and suitable therapeutical target. Therefore, there is great interest in the development of a potent MD-2 inhibitor for anti-inflammatory therapeutics. Several studies have reported that xanthohumol (XN), an anti-inflammatory natural product from hops and beer, can block the TLR4 signaling by binding to MD-2 directly. However, the interaction between MD-2 and XN remains unknown. Herein, our work aims at characterizing interactions between MD-2 and XN. Using a combination of experimental and theoretical modeling analysis, we found that XN can embed into the hydrophobic pocket of MD-2 and form two stable hydrogen bonds with residues ARG-90 and TYR-102 of MD-2. Moreover, we confirmed that ARG-90 and TYR-102 were two necessary residues during the recognition process of XN binding to MD-2. Results from this study identified the atomic interactions between the MD-2 and XN, which will contribute to future structural design of novel MD-2-targeting molecules for the treatment of inflammatory diseases. PMID:26869767

  1. Anti-Inflammatory, Antioxidant, Anti-Angiogenic and Skin Whitening Activities of Phryma leptostachya var. asiatica Hara Extract

    PubMed Central

    Jung, Hyun-Joo; Cho, Young-Wook; Lim, Hye-Won; Choi, Hojin; Ji, Dam-Jung; Lim, Chang-Jin

    2013-01-01

    This work aimed to assess some pharmacological activities of P. leptostachya var. asiatica Hara. The dried roots of P. leptostachya var. asiatica Hara were extracted with 70% ethanol to generate the powdered extract, named PLE. Anti-angiogenic activity was detected using chick chorioallantoic membrane (CAM) assay. In vitro anti-inflammatory activity was evaluated via analyzing nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and reactive oxygen species (ROS) level in the stimulated macrophage cells. Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) activities in the culture media were detected using zymography. PLE exhibits an anti-angiogenic activity in the CAM assay, and displays an inhibitory action on the generation of NO in the LPS-stimulated macrophage cells. In the stimulated macrophage cells, it is able to diminish the enhanced ROS level. It can potently scavenge the stable DPPH free radical. It suppresses the induction of iNOS and COX-2 and the enhanced MMP-9 activity in the stimulated macrophage cells. Both monooxygenase and oxidase activities of tyrosinase were strongly inhibited by PLE. Taken together, the dried roots of P. leptostachya var. asiatica Hara possess anti-angiogenic, anti-inflammatory, antioxidant and skin whitening activities, which might partly provide its therapeutic efficacy in traditional medicine. PMID:24009862

  2. Anti-inflammatory Effects of Novel Polysaccharide Sacran Extracted from Cyanobacterium Aphanothece sacrum in Various Inflammatory Animal Models.

    PubMed

    Motoyama, Keiichi; Tanida, Yuki; Hata, Kyona; Hayashi, Tomoya; Hashim, Irhan Ibrahim Abu; Higashi, Taishi; Ishitsuka, Yoichi; Kondo, Yuki; Irie, Tetsumi; Kaneko, Shinichiro; Arima, Hidetoshi

    2016-07-01

    The goal of this study was to investigate the topical anti-inflammatory effects of the megamolecular polysaccharide sacran extracted from cyanobacterium Aphanothece sacrum using various inflammatory animal models. Sacran showed potent anti-inflammatory effects with optimum effective concentrations at 0.01 and 0.05% (w/v). Sacran markedly inhibited paw swelling and neutrophil infiltration in carrageenan-induced rat paw edema. Additionally, 6,7-dimethoxy-1-methyl-2(1H)-quinoxalinone-3-propionyl-carboxylic acid (DMEQ)-labeled sacran had the ability to penetrate carrageenan-induced rat paw skin rather than normal skin. Also, sacran significantly suppressed kaolin-induced and dextran-induced rat paw edema throughout the duration of the study. Furthermore, sacran significantly suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and mRNA expression levels of cyclooxygenase (COX)-2 as well as pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Safety of sacran solution was verified by negligible cytotoxicity in HaCaT cells. These results suggest that sacran may be useful as a therapeutic agent against inflammatory skin diseases with no life-threatening adverse effects. PMID:27170516

  3. Activation of endogenous anti-inflammatory mediator cyclic AMP attenuates acute pyelonephritis in mice induced by uropathogenic Escherichia coli.

    PubMed

    Wei, Yang; Li, Ke; Wang, Na; Cai, Gui-Dong; Zhang, Ting; Lin, Yan; Gui, Bao-Song; Liu, En-Qi; Li, Zong-Fang; Zhou, Wuding

    2015-02-01

    The pathogenesis of pyelonephritis caused by uropathogenic Escherichia coli (UPEC) is not well understood. Here, we show that besides UPEC virulence, the severity of the host innate immune response and invasion of renal epithelial cells are important pathogenic factors. Activation of endogenous anti-inflammatory mediator cAMP significantly attenuated acute pyelonephritis in mice induced by UPEC. Administration of forskolin (a potent elevator of intracellular cAMP) reduced kidney infection (ie, bacterial load, tissue destruction); this was associated with attenuated local inflammation, as evidenced by the reduction of renal production of proinflammatory mediators, renal infiltration of inflammatory cells, and renal myeloperoxidase activity. In primary cell culture systems, forskolin not only down-regulated UPEC-stimulated production of proinflammatory mediators by renal tubular epithelial cells and inflammatory cells (eg, monocyte/macrophages) but also reduced bacterial internalization by renal tubular epithelial cells. Our findings clearly indicate that activation of endogenous anti-inflammatory mediator cAMP is beneficial for controlling UPEC-mediated acute pyelonephritis in mice. The beneficial effect can be explained at least in part by limiting excessive inflammatory responses through acting on both renal tubular epithelial cells and inflammatory cells and by inhibiting bacteria invasion of renal tubular epithelial cells. PMID:25478807

  4. Induction of cytochrome P-450 BM-3 (CYP 102) by non-steroidal anti-inflammatory drugs in Bacillus megaterium.

    PubMed Central

    English, N; Hughes, V; Wolf, C R

    1996-01-01

    Bacillus megaterium contains a cytochrome P-450 fatty acid mono-oxygenase which is inducible with barbiturate drugs. We have demonstrated that this enzyme system is inducible with peroxisome proliferators. In mammals, peroxisome proliferators also induce mono-oxygenases in the CYP4A gene family. In this paper we demonstrate that the non-steroidal anti-inflammatory drugs ibuprofen, ketoprofen and indomethacin are potent inducers of fatty acid mono-oxygenase activity as well as of P-450BM-3 protein in B. megaterium. The levels of induction of P-450 protein were 11.8-, 3.9- and 3.0-fold respectively. In addition, we demonstrate that these inducing agents interact with a transcriptional repressor, Bm3R1, which leads to its dissociation from its operator sequence. This provides a rational mechanism for the induction process. This is the first report which demonstrates that non-steroidal anti-inflammatory drugs can interact directly with a transcription factor to initiate gene expression, and further substantiates the structure-activity relationships that identify inducers of cytochrome P-450BM-3 and compounds that have the potential to act as peroxisome proliferators and induce CYP4A expression in mammals. PMID:8645218

  5. [Anti-inflammatory activity of benzo(c) phenanthridine derivatives and possible mechanisms of action (author's transl)].

    PubMed

    Iwata, H; Yamamoto, I; Masukawa, T; Komoriya, K; Iwaki, H

    1977-07-01

    Of five newly synthesized benzo[c]phenanthridine derivatives tested, the two compounds, BPD-I and BPD-II were found to have potent anti-edematous activity with intraperitoneal administration to S.D. rats. BPD-I showed a marked inhibitory effect against acute inflammation such as induced rat paw edema and leucocyte emigration and protein exudation by means of CMC pouch method and capillary permeability enhancement induced by various phlogists. This compound also inhibited subacute and chronic inflammatory responses such as granuloma formation induced by croton oil or cotton pellet. The anti-inflammatory activities of this compound resembled those of hydrocortisone. The inhibitory effects of carragenan edema and capillary permeability enhancement by ATP were strikingly reduced in adrenalectomized rats suggesting involvement of the hypophysis-adrenal systems. Rat serum corticosterone level and hepatic tyrosine aminotransferase activity (TAT) were then measured after BPD-I injection. The serum corticosterone level was increased and shortly after the elevation of corticosterone, hepatic TAT levels also increased. Thus it is concluded that the corticosterone release from adrenal gland plays a role in the anti-inflammatory action of BPD-I. PMID:21834

  6. Synthesis of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide as anticancer and anti-inflammatory agents.

    PubMed

    Bashir, Rafia; Ovais, Syed; Yaseen, Shafiya; Hamid, Hinna; Alam, M S; Samim, Mohammad; Singh, Surender; Javed, Kalim

    2011-07-15

    Thirteen new 2-pyrazoline derivatives bearing benzenesulfonamide moiety (2a-m) were synthesized by condensing appropriate chalcones with 4-hydrazinonbenzenesulfonamide hydrochloride and tested for anticancer and anti-inflammatory actions. According to the protocol of the National Cancer Institute (NCI) in vitro disease-oriented human cells screening panel assay compounds 2b, 2c, 2e, 2f and 2g exhibited considerable antitumor activities against the entire tested tumor cell lines and showed effective growth inhibition GI(50) (MG-MID) values of 2.63, 2.57, 6.61, 3.31 and 2.57μM, respectively, beside a cyclostatic activity TGI (MG-MID) 9.54, 8.51, 24.0, 19.9 and 8.71μM, respectively. Two compounds 2g and 2k showed more potent anti-inflammatory activity than celecoxib at 5h in carrageenan-induced rat paw edema bioassay. These compounds (2g and 2k) proved to have superior gastrointestinal safety profiles as compared to celecoxib, when tested for their ulcerogenic effects. Compounds 2g and 2k showed no inhibition against the enzymatic activity of bovine COX-2 (in vitro). PMID:21664130