Sample records for highly potent anti-inflammatory

  1. Discovery of a highly potent anti-inflammatory epoxyisoprostane-derived lactone.

    PubMed

    Egger, Julian; Bretscher, Peter; Freigang, Stefan; Kopf, Manfred; Carreira, Erick M

    2014-12-17

    Epoxyisoprostanes EI (1) and EC (2) are effective inhibitors of the secretion of proinflammatory cytokines IL-6 and IL-12. In detailed studies toward the investigation of the molecular mode of action of these structures, a highly potent lactone (3) derived from 1 was identified. The known isoprostanoids 1 and 2 are most likely precursors of 3, the product of facile intramolecular reaction between the epoxide with the carboxylic acid in 2. PMID:25474746

  2. 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 ?M, 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

  3. 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 ?M) but showed cytotoxicity whereas compound 3 (IC50=6 ?M) which possess ?,?-unsaturated ?-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 ?,?-unsaturation is fruitful to show potent anti-inflammatory activity. PMID:25453809

  4. Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia.

    PubMed

    Costa, José Fernando Oliveira; Barbosa-Filho, José Maria; Maia, Gabriela Lemos de Azevedo; Guimarães, Elisalva Teixeira; Meira, Cássio Santana; Ribeiro-dos-Santos, Ricardo; de Carvalho, Lain Carlos Pontes; Soares, Milena Botelho Pereira

    2014-12-01

    Betulinic acid (BA) is a lupane-type triterpene with a number of biological activities already reported. While potent anti-HIV and antitumoral activities were attributed to BA, it is considered to have a moderate anti-inflammatory activity. Here we evaluated the effects of BA in a mouse model of endotoxic shock. Endotoxemia was induced through intraperitoneally LPS administration, nitric oxide (NO) and cytokines were assessed by Griess method and ELISA, respectively. Treatment of BALB/c mice with BA at 67 mg/kg caused a 100% survival against a lethal dose of lipopolysaccharide (LPS). BA treatment caused a reduction in TNF-? production induced by LPS but did not alter IL-6 production. Moreover, BA treatment increased significantly the serum levels of IL-10 compared to vehicle-treated, LPS-challenged mice. To investigate the role of IL-10 in BA-induced protection, wild-type and IL-10(-/-) mice were studied. In contrast to the observations in IL-10(+/+) mice, BA did not protect IL-10(-/-) mice against a lethal LPS challenge. Addition of BA inhibited the production of pro-inflammatory mediators by macrophages stimulated with LPS, while promoting a significant increase in IL-10 production. BA-treated peritoneal exudate macrophages produced lower concentrations of TNF-? and NO and higher concentrations of IL-10 upon LPS stimulation. Similarly, macrophages obtained from BA-treated mice produced less pro-inflammatory mediators and increased IL-10 when compared to non-stimulated macrophages obtained from vehicle-treated mice. In conclusion, we have shown that BA has a potent anti-inflammatory activity in vivo, protecting mice against LPS by modulating TNF-? production by macrophages in vivo through a mechanism dependent on IL-10. PMID:25281393

  5. Design of novel potent antihyperlipidemic agents with antioxidant/anti-inflammatory properties: exploiting phenothiazine's strong antioxidant activity.

    PubMed

    Matralis, Alexios N; Kourounakis, Angeliki P

    2014-03-27

    Because atherosclerosis is an inflammatory process involving a series of pathological events such as dyslipidemia, oxidative stress, and blood clotting mechanisms, we hereby report the synthesis and evaluation of novel compounds in which antioxidant, anti-inflammatory, and squalene synthase (SQS) inhibitory/hypolipidemic activities are combined in simple molecules through design. The coupling of two different pharmacophores afforded compounds 1-12, whose biological profile was markedly improved compared to those of parent lead structures (i.e., the hypolipidemic 2-hydroxy-2-aryl-(benzo)oxa(or thia)zine and the antioxidant phenothiazine). Most derivatives strongly inhibited in vitro microsomal lipid and LDL peroxidation, exhibiting potent free-radical scavenging activity. They further significantly inhibited SQS activity and showed remarkable antidyslipidemic activity in vivo in animal models of acute and high-fat-induced hyperlipidemia. Finally, several compounds showed anti-inflammatory activity in vitro, inhibiting cycloxygenase (COX-1/2) activity. The multimodal properties of the new compounds and especially their combined antioxidant/SQS/COX inhibitory activity render them interesting lead compounds for further evaluation against atherosclerosis. PMID:24568631

  6. Targeting the Hemoglobin Scavenger receptor CD163 in Macrophages Highly Increases the Anti-inflammatory Potency of Dexamethasone

    PubMed Central

    Graversen, Jonas H; Svendsen, Pia; Dagnæs-Hansen, Frederik; Dal, Jakob; Anton, Gabriele; Etzerodt, Anders; Petersen, Mikkel D; Christensen, Peter A; Møller, Holger J; Moestrup, Søren K

    2012-01-01

    Synthetic glucocorticoids are potent anti-inflammatory drugs but serious side effects such as bone mobilization, muscle mass loss, immunosuppression, and metabolic alterations make glucocorticoid therapy a difficult balance. The therapeutic anti-inflammatory effect of glucocorticoids relies largely on the suppressed release of tumor-necrosis factor-? and other cytokines by macrophages at the sites of inflammation. We have now developed a new biodegradable anti-CD163 antibody-drug conjugate that specifically targets the glucocorticoid, dexamethasone to the hemoglobin scavenger receptor CD163 in macrophages. The conjugate, that in average contains four dexamethasone molecules per antibody, exhibits retained high functional affinity for CD163. In vitro studies in rat macrophages and in vivo studies of Lewis rats showed a strong anti-inflammatory effect of the conjugate measured as reduced lipopolysaccharide-induced secretion of tumor-necrosis factor-?. The in vivo potency of conjugated dexamethasone was about 50-fold that of nonconjugated dexamethasone. In contrast to a strong systemic effect of nonconjugated dexamethasone, the equipotent dose of the conjugate had no such effect, measured as thymus lymphocytes apoptosis, body weight loss, and suppression of endogenous cortisol levels. In conclusion, the study shows antibody-drug conjugates as a future approach in anti-inflammatory macrophage-directed therapy. Furthermore, the data demonstrate CD163 as an excellent macrophage target for anti-inflammatory drug delivery. PMID:22643864

  7. A novel caffeoyl triterpene attenuates cerebral ischemic injury with potent anti-inflammatory and hypothermic effects.

    PubMed

    Ruan, Zhi; Wang, Hong Min; Huang, Xiao Tian; Fu, Yan; Wu, Jian; Ye, Chun Yan; Li, Jin Long; Wu, Lei; Gong, Qi; Zhao, Wei Min; Zhang, Hai Yan

    2015-04-01

    Despite the intense efforts in searching for stroke therapies, an urgent need still exists to explore novel neuroprotective agents for ischemic stroke that have high efficacy and wide therapeutic time-window. Here, we provide the first demonstration that 28-O-caffeoyl betulin (B-CA), a novel derivative of naturally occurring caffeoyl triterpene, could significantly alleviate brain infarction and neurological deficit when given as late as 6 h after transient middle cerebral artery occlusion in the rat. Moreover, post-ischemia B-CA administration exhibited long-term (14 days post stroke) protective effects on both brain infarction and functional (i.e., motor and sensory) deficits. Protective B-CA effects correlated with decreased inflammatory responses as indicated by inhibition of microglia and astrocyte activation [stained with ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) antibody, respectively], as well as suppression of tumor necrosis factor-?, interleukin-1?, and cyclooxygenase-2 overproduction in the ipsilateral cortex of ischemic rat. B-CA administration caused significant hypothermia in the focal cerebral ischemic rat, which may contribute to its ameliorative effects on brain damage and inflammation. In view of its potency in wide therapeutic time-window, robust anti-inflammatory and hypothermic effects, this novel caffeoyl triterpene derivative may lead toward the development of effective therapeutic strategies for the treatment of ischemic stroke. PMID:25626516

  8. Discovery of a novel COX-2 inhibitor as an orally potent anti-pyretic and anti-inflammatory drug: design, synthesis, and structure-activity relationship.

    PubMed

    Hayashi, Shigeo; Sumi, Yoko; Ueno, Naomi; Murase, Akio; Takada, Junji

    2011-10-01

    Cyclooxygenase (COX) has been considered as a significant pharmacological target because of its pivotal roles in the prostaglandin biosynthesis and following cascades that lead to various (patho)physiological effects. Non-steroidal anti-inflammatory drugs (NSAIDs) that suppress COX activities have been used clinically for the treatment of fever, inflammation, and pain; however, nonselective COX inhibitors exhibit serious side-effects such as gastrointestinal damage because of their inhibitory activities against COX-1. Thus, COX-1 is constitutive and expressed ubiquitously and serves a housekeeping role, while COX-2 is inducible or upregulated by inflammatory/injury stimuli such as interleukin-1?, tumor necrosis factor-?, and lipopolysaccharide in macrophage, monocyte, synovial, liver, and lung, and is associated with prostaglandin E? and prostacyclin production that evokes or sustains systemic/peripheral inflammatory symptoms. Also, hypersensitivity of aspirin is a significant concern clinically. Hence, design, synthesis, and structure-activity relationship of [2-{[(4-substituted)-pyridin-2-yl]carbonyl}-(6- or 5-substituted)-1H-indol-3-yl]acetic acid analogues were investigated to discover novel acid-type COX-2 inhibitor as an orally potent new-class anti-pyretic and anti-inflammatory drug. As significant findings, compounds 1-3 demonstrated potent COX-2 inhibitory activities with high selectivities for COX-2 over COX-1 in human cells or whole-blood in vitro, and demonstrated orally potent anti-pyretic activity against lipopolysaccharide-induced systemic-inflammatory fever model in F344 rats. Also compound 1 demonstrated orally potent anti-inflammatory activity against edema formation and a suppressive effect against PGE? production in carrageenan-induced peripheral-inflammation model on the paw of SD rats. These results suggest that compounds 1-3 are potential agents for the treatment of inflammatory disease and are useful for further pharmacological COX-2 inhibitor investigations. PMID:21741371

  9. High density lipoprotein mediates anti-inflammatory transcriptional reprogramming of macrophages via the transcriptional repressor ATF3

    PubMed Central

    De Nardo, Dominic; Labzin, Larisa I.; Kono, Hajime; Seki, Reiko; Schmidt, Susanne V.; Beyer, Marc; Xu, Dakang; Zimmer, Sebastian; Lahrmann, Catharina; Schildberg, Frank A.; Vogelhuber, Johanna; Kraut, Michael; Ulas, Thomas; Kerksiek, Anja; Krebs, Wolfgang; Bode, Niklas; Grebe, Alena; Fitzgerald, Michael L.; Hernandez, Nicholas J.; Williams, Bryan; Knolle, Percy; Kneilling, Manfred; Röcken, Martin; Lütjohann, Dieter; Wright, Samuel D.; Schultze, Joachim L.; Latz, Eicke

    2014-01-01

    High Density Lipoprotein (HDL) mediates reverse cholesterol transport and it is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional repressor ATF3, as an HDL-inducible target gene in macrophages that down-regulates the expression of Toll-like receptor (TLR)-induced pro-inflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of novel HDL-based therapies. PMID:24317040

  10. Indole-3-ethylsulfamoylphenylacrylamides: potent histone deacetylase inhibitors with anti-inflammatory activity.

    PubMed

    Mehndiratta, Samir; Hsieh, Yi-Ling; Liu, Yi-Min; Wang, Amber Weiching; Lee, Hsueh-Yun; Liang, Lung-Yu; Kumar, Sunil; Teng, Che-Ming; Yang, Chia-Ron; Liou, Jing-Ping

    2014-10-01

    A series of 2-methyl-1H-indol-3-ethylsulfamoylphenylacrylamides based on LBH589-PXD101 core have been synthesized and evaluated for their histone deacetylase (HDAC) inhibitory and anti-inflammatory activity. In vitro, compounds 9-12 show 2.6-fold better HDAC inhibition and 3-fold better IL-6 suppression compared to LBH589·HCl (1·HCl). Furthermore, these compounds did not show apparent cell viability suppression on macrophages while in contrast, treatment with 1·HCl resulted in significant reduction in cell viability as demonstrated by an MTT assay. Repressed expression of iNOS, COX-2 and reduced phosphorylation of p65 revealed the inhibitory effect of these analogues on inflammatory mediator release which is related to inhibited NF-?B signals. (N-Hydroxy-3-{3-[2-(2-methyl-1H-indol-3-yl)-ethylsulfamoyl]-phenyl}-acrylamide) (9), exhibited ability superior to that of 1·HCl, was able to reduce carrageenan-induced acute inflammation in an animal model. Compounds 9-12 have potential anti-inflammatory activity and compound 9 can serve as lead compound for further development. PMID:25113875

  11. 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 ?-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 NF?B activation, HIV replication in T cells, releases of IL-1?, IL-6, IL-8, and TNF-?, 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

  12. Arzanol, a potent mPGES-1 inhibitor: novel anti-inflammatory agent.

    PubMed

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

    2013-01-01

    Arzanol is a novel phloroglucinol ? -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 NF ?B activation, HIV replication in T cells, releases of IL-1 ? , IL-6, IL-8, and TNF-? , and biosynthesis of PGE? 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

  13. 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

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

    PubMed

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

    2013-01-15

    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 activities in an NF-?B luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves 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 greater than or equal to 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of stinging nettle may be more effective than traditional tinctures (water, methanol, ethanol) in clinical evaluations for the treatment of inflammatory disorders especially arthritis. A chemical investigation into the lipophilic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted. PMID:23092723

  15. Synthesis and biological evaluation of novel pyrazoline derivatives as potent anti-inflammatory agents.

    PubMed

    He, Jiqiang; Ma, Liang; Wei, Zhe; Zhu, Jun; Peng, Fei; Shao, Mingfeng; Lei, Lei; He, Lin; Tang, Minghai; He, Linhong; Wu, Yuzhe; Chen, Lijuan

    2015-06-01

    Twenty-eight pyrazoline derivatives, which originated from pyranochalcones, have been synthesized and evaluated for their inhibitory potency on the production of inflammatory mediator nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. Among them, three compounds (1c, 11c, and 15c) exhibited potent inhibitory effects on NO production and iNOS activity superior to positive control Indomethacin, with 1c being most efficacious. Furthermore, 1c could suppress the progress of carrageenan-induced hind paw edema at a dosage of 50mg/kg/day and dose-dependently ameliorate the development of adjuvant-induced arthritis (AIA). Docking study confirmed that 1c was an iNOS inhibitor with good binding into the active site of murine iNOS. PMID:25881822

  16. 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

    2015-03-11

    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-? activated RAW 264.7 macrophages, most of the anti-inflammatory activity, measured by down-regulation of nitric oxide and TNF-? 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 ?M (7.3 ± 1.2 ?g mL(-1)) and 35 ± 9 ?M (5.7 ± 1.5 ?g mL(-1)), respectively; and IC50 values for TNF-? of 63 ± 9 ?M (8.3 ± 1.2 ?g mL(-1)) and 78 ± 16 ?M (12.6 ± 2.6 ?g 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

  17. Synthesis of novel celecoxib analogues by bioisosteric replacement of sulfonamide as potent anti-inflammatory agents and cyclooxygenase inhibitors.

    PubMed

    Chandna, Nisha; Kumar, Satish; Kaushik, Pawan; Kaushik, Dhirender; Roy, Somendu K; Gupta, Girish K; Jachak, Sanjay M; Kapoor, Jitander K; Sharma, Pawan K

    2013-08-01

    Two series of celecoxib analogues having 1,5-diaryl relationship were synthesized. The key strategy of the molecular design was oriented towards exploring bioisosteric modifications of the sulfonamide moiety of celecoxib. First series (2a-2i) of celecoxib analogues bearing cyano functionality in place of sulfonamide moiety was synthesized by the reaction of appropriate trifluoromethyl-?-diketones (5a-5i) with 4-hydrazinylbenzonitrile hydrochloride (4) in ethanol. Cyano moiety of pyrazoles 2 was then converted into corresponding carbothioamides 3 by bubbling H2S gas in the presence of triethylamine. All the synthesized compounds (2a-2i and 3a-3i) were screened for their in vivo anti-inflammatory (AI) activity using carrageenan-induced rat paw edema assay. COX-1 and COX-2 inhibitory potency was evaluated through in vitro cyclooxygenase (COX) assays. Compounds 2a, 2b, 2c, 2e and 3c showed promising AI activity at 3-4h after the carrageenan injection that was comparable to that of the standard drug indomethacin. Although compounds 3d, 3e and 3f exhibited more pronounced COX-2 inhibition but they also inhibit COX-1 effectively thus being less selective against COX-2. Three compounds 2a, 2f and 3a were found to have a COX profile comparable to the reference drug indomethacin. However 2e, 3b, 3c and 3i compounds were the most potent selective COX-2 inhibitors of this study with 3b showing the best COX-2 profile. In order to better rationalize the action and the binding mode of these compounds, docking studies were carried out. These studies were in agreement with the biological data. PMID:23769654

  18. Identification of plumericin as a potent new inhibitor of the NF-?B 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-?B 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-?B 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-?B luciferase reporter gene assay was used to identify NF-?B pathway inhibitors from H.?sucuuba extracts. Monitoring of TNF-?-induced expression of the adhesion molecules VCAM-1, ICAM-1 and E-selectin by flow cytometry was used to confirm NF-?B 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-?B-mediated transactivation of a luciferase reporter gene (IC50 1??M), abolished TNF-?-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-?B pathway inhibitory effect by blocking I?B phosphorylation and degradation. Plumericin also inhibited NF-?B activation induced by transfection with the constitutively active catalytic subunit of the I?B kinase (IKK-?), suggesting IKK involvement in the inhibitory action of this natural product. CONCLUSION AND IMPLICATIONS Plumericin is a potent inhibitor of NF-?B pathways with a new chemical scaffold. It could be further explored as a novel anti-inflammatory lead compound. PMID:24329519

  19. 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 ?g/mL and 10 ?g/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 ?g/mL Magnolia officinalis L. extract with 1 ?g/mL of each of the other extracts maintained the anti-inflammatory effect of Magnolia officinalis L. extract. Combination of 5 ?g/mL Magnolia officinalis L. extract with 5 ?g/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

  20. Potent inhibition of human 5-lipoxygenase and microsomal prostaglandin E? synthase-1 by the anti-carcinogenic and anti-inflammatory agent embelin.

    PubMed

    Schaible, Anja M; Traber, Heidi; Temml, Veronika; Noha, Stefan M; Filosa, Rosanna; Peduto, Antonella; Weinigel, Christina; Barz, Dagmar; Schuster, Daniela; Werz, Oliver

    2013-08-15

    Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) possesses anti-inflammatory and anti-carcinogenic properties in vivo, and these features have been related to interference with multiple targets including XIAPs, NF?B, STAT-3, Akt and mTOR. However, interference with these proteins requires relatively high concentrations of embelin (IC??>4 ?M) and cannot fully explain its bioactivity observed in several functional studies. Here we reveal human 5-lipoxygenase (5-LO) and microsomal prostaglandin E? synthase (mPGES)-1 as direct molecular targets of embelin. Thus, embelin potently suppressed the biosynthesis of eicosanoids by selective inhibition of 5-LO and mPGES-1 with IC??=0.06 and 0.2 ?M, respectively. In intact human polymorphonuclear leukocytes and monocytes, embelin consistently blocked the biosynthesis of various 5-LO products regardless of the stimulus (fMLP or A23187) with IC??=0.8-2 ?M. Neither the related human 12- and 15-LO nor the cyclooxygenases-1 and -2 or cytosolic phospholipase A? were significantly affected by 10 ?M embelin. Inhibition of 5-LO and mPGES-1 by embelin was (I) essentially reversible after wash-out, (II) not impaired at higher substrate concentrations, (III) unaffected by inclusion of Triton X-100, and (IV) did not correlate to its proposed antioxidant properties. Docking simulations suggest concrete binding poses in the active sites of both 5-LO and mPGES-1. Because 5-LO- and mPGES-1-derived eicosanoids play roles in inflammation and cancer, the interference of embelin with these enzymes may contribute to its biological effects and suggests embelin as novel chemotype for development of dual 5-LO/mPGES-1 inhibitors. PMID:23623753

  1. 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 ?mol/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

  2. NT-702 (parogrelil hydrochloride, NM-702), a novel and potent phosphodiesterase 3 inhibitor, suppress the asthmatic response in guinea pigs, with both bronchodilating and anti-inflammatory effects.

    PubMed

    Hori, Miyuki; Iwama, Takehisa; Asakura, Yumiko; Kawanishi, Masafumi; Kamon, Junji; Hoshino, Akihiko; Takahashi, Shuya; Takahashi, Kenzo; Nakaike, Shiro; Tsuruzoe, Nobutomo

    2009-09-15

    We evaluated the effects of NT-702 (parogrelil hydrochloride, NM-702, 4-bromo-6-[3-(4-chlorophenyl) propoxy]-5-[(pyridine-3-ylmethyl) amino] pyridazin-3(2H)-one hydrochloride), a selective phosphodiesterase 3 inhibitor, on the asthmatic response in guinea pigs. NT-702 at a concentration of 1 x 10(-7)M elevated the cyclic adenosine monophosphate content in prostaglandin E(2)-treated guinea pig tracheal smooth muscle cells. Leukotriene (LT) D(4)- and histamine-induced contraction of isolated guinea pig tracheal strips was inhibited by NT-702, with EC(50) values of 3.2 x 10(-7) and 2.5 x 10(-7)M, respectively. In an in vivo study, NT-702 suppressed LTD(4)-induced bronchoconstriction and the ovalbumin-induced immediate asthmatic response in guinea pigs through its bronchodilating effect. Furthermore, NT-702 also suppressed the ovalbumin-induced late asthmatic response, airway hyperresponsiveness, and the accumulation of inflammatory cells in the bronchoalveolar lavage fluid. These results suggest that NT-702 has an anti-inflammatory effect as well as a bronchodilating effect and might be useful as a novel potent therapeutic agent for the treatment of bronchial asthma, a new type of agent with both a bronchodilating and an anti-inflammatory effect. PMID:19616537

  3. 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 ?-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

  4. Prevention effects of ND-07, a novel drug candidate with a potent antioxidative action and anti-inflammatory action, in animal models of severe acute pancreatitis.

    PubMed

    Lee, Jin Hwan; An, Chun San; Yun, Bok Sun; Kang, Kum Suk; Lee, Young Ae; Won, Sun Mi; Gwag, Byoung Joo; Cho, Sung Ig; Hahm, Ki-Baik

    2012-07-15

    Oxidative stress and inflammation both play major roles in the development of the acute pancreatitis. Currently, a pancreatic enzyme inhibitor with limited efficacy is only clinically available in a few countries, and antioxidants or non-steroidal anti-inflammatory drugs (NSAIDs) provide only partial tissue protection in acute pancreatitis animal models. Here, we introduce a new drug candidate for treating acute pancreatitis named ND-07 [chemical name: 2-acetoxy-5-(2-4-(trifluoromethyl)-phenethylamino)-benzoic acid] that exhibits both potent antioxidative and anti-inflammatory activities. In an electron spin resonance (ESR) study, ND-07 almost blocked hydroxyl radical generation as low as 0.05 ?M and significantly suppressed DNA oxidation and cell death in a lipopolysaccharide (LPS)-stimulated pancreatic cell line. In a cerulein plus LPS-induced acute pancreatitis model, ND-07 pretreatment showed significant tissue protective effects, with reductions of serum amylase and lipase levels and pancreatic wet weights. ND-07 not only diminished the plasma levels of malondialdehyde (MDA) and nitric oxide but also significantly decreased prostaglandin E? (PGE?) and expression of tumor necrotizing factor-alpha (TNF-?) in the pancreatic tissue. In a severe acute necrotizing pancreatitis model induced by a choline deficient, ethionine-supplemented (CDE) diet, ND-07 dramatically protected the mortality even without any death, providing attenuation of pancreas, lung, and liver damages as well as the reductions in serum levels of lactate dehydrogenase (LDH), amylase and lipase, MDA levels in the plasma and pancreatic tissues, plasma levels of TNF-?, and interleukin-1 (IL-1?). These findings suggest that current dual synergistic action mechanisms of ND-07 might provide a superior protection for acute pancreatitis than conventional drug treatments. PMID:22575522

  5. Synthesis of N-benzenesulfonamide-1H-pyrazoles bearing arylsulfonyl moiety: novel celecoxib analogs as potent anti-inflammatory agents.

    PubMed

    Abdel-Aziz, Hatem A; Al-Rashood, Khalid A; ElTahir, Kamal Eldin H; Suddek, Ghada M

    2014-06-10

    The reaction of arylsulfones 11a-d with hydrazonoyl chloride derivative 13 furnished celecoxib analogs 4-(3-acetyl-5-aryl-4-(arylsulfonyl)-1H-pyrazol-1-yl)benzenesulfonamides 15a-d, respectively. Oximes 16a, b and hydrazones 17a, b were prepared by reacting sulfones 11a, b with hydroxyl amine and phenyl hydrazine, respectively. The anti-inflammatory activity of the synthesized compounds showed that, 5-(4-bromophenyl)-4-(phenylsulfonyl)pyrazole 15c and 5-(4-bromophenyl)-4-(4-tolylsulfonyl)pyrazole 15d exhibited excellent anti-inflammatory activity with ED50 = 68 ± 2.2 and 51 ± 0.7 ?M/kg, respectively, higher than that of celecoxib (ED50 = 86 ± 1.1 ?M/kg) after 3 h with acceptable ulcer index. In addition, the LD50 of 15c and 15d is 7.1 mM/kg for each, and 9.8 mM/kg for celecoxib. Compound 15d appeared selectivity index (COX-2/COX-1) almost the half of celecoxib while 15c is non-selective for COX-2. Compound 15c with ED50 = 80 ± 2.8 ?M/kg showed a significant analgesic activity when compared with celecoxib (ED50 = 70 ± 3.9 ?M/kg) after 2 h whereas 15b (ED50 = 50 ± 1.2 ?M/kg) and 15d (ED50 = 69 ± 2.7 ?M/kg) seemed to be more potent than celecoxib (ED50 = 156 ± 4.8 ?M/kg) but with a shorter duration (0.5 h). PMID:24794773

  6. New triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resins, and their potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of mice

    Microsoft Academic Search

    Ikuko Kimura; Masayuki Yoshikawa; Shinjiro Kobayashi; Yoshitaka Sugihara; Miho Suzuki; Hideo Oominami; Toshiyuki Murakami; Hisashi Matsuda; Vijay V Doiphode

    2001-01-01

    Myrrhanol A, a new triterpene isolated from guggul (Balsamodendron or Commiphora mukul Hook.)-gum resin, displays a potent anti-inflammatory effect on exudative pouch fluid, angiogenesis, and granuloma weights in adjuvant-induced air-pouch granuloma of mice. Its effects were more marked than those of hydrocortisone and the 50% aqueous methanolic extract of the crude drug. Myrrhanol A is a plausible candidate for a

  7. A novel, potent dual inhibitor of the leukocyte proteases cathepsin G and chymase: molecular mechanisms and anti-inflammatory activity in vivo.

    PubMed

    de Garavilla, Lawrence; Greco, Michael N; Sukumar, Narayanasami; Chen, Zhi-Wei; Pineda, Agustin O; Mathews, F Scott; Di Cera, Enrico; Giardino, Edward C; Wells, Grace I; Haertlein, Barbara J; Kauffman, Jack A; Corcoran, Thomas W; Derian, Claudia K; Eckardt, Annette J; Damiano, Bruce P; Andrade-Gordon, Patricia; Maryanoff, Bruce E

    2005-05-01

    Certain leukocytes release serine proteases that sustain inflammatory processes and cause disease conditions, such as asthma and chronic obstructive pulmonary disease. We identified beta-ketophosphonate 1 (JNJ-10311795; RWJ-355871) as a novel, potent dual inhibitor of neutrophil cathepsin G (K(i) = 38 nm) and mast cell chymase (K(i) = 2.3 nm). The x-ray crystal structures of 1 complexed with human cathepsin G (1.85 A) and human chymase (1.90 A) reveal the molecular basis of the dual inhibition. Ligand 1 occupies the S(1) and S(2) subsites of cathepsin G and chymase similarly, with the 2-naphthyl in S(1), the 1-naphthyl in S(2), and the phosphonate group in a complex network of hydrogen bonds. Surprisingly, however, the carboxamido-N-(naphthalene-2-carboxyl)piperidine group is found to bind in two distinct conformations. In cathepsin G, this group occupies the hydrophobic S(3)/S(4) subsites, whereas in chymase, it does not; rather, it folds onto the 1-naphthyl group of the inhibitor itself. Compound 1 exhibited noteworthy anti-inflammatory activity in rats for glycogen-induced peritonitis and lipopolysaccharide-induced airway inflammation. In addition to a marked reduction in neutrophil influx, 1 reversed increases in inflammatory mediators interleukin-1alpha, interleukin-1beta, tissue necrosis factor-alpha, and monocyte chemotactic protein-1 in the glycogen model and reversed increases in airway nitric oxide levels in the lipopolysaccharide model. These findings demonstrate that it is possible to inhibit both cathepsin G and chymase with a single molecule and suggest an exciting opportunity in the treatment of asthma and chronic obstructive pulmonary disease. PMID:15741158

  8. [Pharmacological analysis of anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation].

    PubMed

    Gapeev, A B; Lushnikov, K V; Shumilina, Iu V; Chemeris, N K

    2006-01-01

    The anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm2) was compared with the action of the known anti-inflammatory drug sodium diclofenac and the antihistamine clemastine on acute inflammatory reaction in NMRI mice. The local inflammatory reaction was induced by intraplantar injection of zymosan into the left hind paw. Sodium diclofenac in doses of 2, 3, 5, 10, and 20 mg/kg or clemastine in doses of 0.02, 0.1, 0.2, 0.4, and 0.6 mg/kg were injected intraperitoneally 30 min after the initiation of inflammation. The animals were whole-body exposed to EHF EMR for 20 min at 1 h after the initiation of inflammation. The inflammatory reaction was assessed over 3 - 8 h after the initiation by measuring the footpad edema and hyperthermia of the inflamed paw. Sodium diclofenac in doses of 5 - 20 mg/kg reduced the exudative edema on the average by 26% as compared to the control. Hyperthermia of the inflamed paw decreased to 60% as the dose of was increased diclofenac up to 20 mg/kg. EHF EMR reduced both the footpad edema and hyperthermia by about 20%, which was comparable with the effect of a single therapeutic dose of diclofenac (3 - 5 mg/kg). The combined action of diclofenac and the exposure to the EHF EMR caused a partial additive effect. Clemastine in doses of 0.02-0.4 mg/kg it did not cause any significant effects on the exudative edema, but in a dose of 0.6 mg/kg it reduced edema by 14 - 22% by 5 - 8 h after zymosan injection. Clemastine caused a dose-dependent increase in hyperthermia of inflamed paw at doses of 0.02-0.2 mg/kg and did not affect the hyperthermia at doses of 0.4 and 0.6 mg/kg. The combined action of clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that both arachidonic acid metabolites and histamine are involved in the realization of anti-inflammatory effects of low-intensity PMID:17175917

  9. Extraction Optimization for Obtaining Artemisia capillaris Extract with High Anti-Inflammatory Activity in RAW 264.7 Macrophage Cells

    PubMed Central

    Jang, Mi; Jeong, Seung-Weon; Kim, Bum-Keun; Kim, Jong-Chan

    2015-01-01

    Plant extracts have been used as herbal medicines to treat a wide variety of human diseases. We used response surface methodology (RSM) to optimize the Artemisia capillaris Thunb. extraction parameters (extraction temperature, extraction time, and ethanol concentration) for obtaining an extract with high anti-inflammatory activity at the cellular level. The optimum ranges for the extraction parameters were predicted by superimposing 4-dimensional response surface plots of the lipopolysaccharide- (LPS-) induced PGE2 and NO production and by cytotoxicity of A. capillaris Thunb. extracts. The ranges of extraction conditions used for determining the optimal conditions were extraction temperatures of 57–65°C, ethanol concentrations of 45–57%, and extraction times of 5.5–6.8?h. On the basis of the results, a model with a central composite design was considered to be accurate and reliable for predicting the anti-inflammation activity of extracts at the cellular level. These approaches can provide a logical starting point for developing novel anti-inflammatory substances from natural products and will be helpful for the full utilization of A. capillaris Thunb. The crude extract obtained can be used in some A. capillaris Thunb.-related health care products. PMID:26075271

  10. Potent anti-inflammatory\\/analgesic effects of lornoxicam in comparison to other nsaids: A c-fos study in the rat

    Microsoft Academic Search

    J. Buritova; J. M. Besson

    1997-01-01

    This study evaluates the anti-inflammatory\\/analgesic effects of lornoxicam, a new non-steroidal anti-inflammatory drug, using\\u000a the method of c-Fos protein immunoreactivity in the carrageenan model of inflammatory nociception in the rat. The immunohistochemical\\u000a revelation of inflammatory\\/nociceptive stimulation evoked c-Fos expression in spinal neurons was used as an indirect marker\\u000a of neurons involved in spinal nociceptive transmission. Lornoxicam (0.1, 0.3, 1, 3

  11. 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 NF?B-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

  12. Antihyperglycemic and Anti-Inflammatory Effects of Standardized Curcuma xanthorrhiza Roxb. Extract and Its Active Compound Xanthorrhizol in High-Fat Diet-Induced Obese Mice

    PubMed Central

    2014-01-01

    Xanthorrhizol, a natural compound isolated from Curcuma xanthorrhiza Roxb. (Java turmeric), has been reported to possess antioxidant and anticancer properties; however, its effects on metabolic disorders remain unknown. The aim of the present study was to evaluate the effects of xanthorrhizol (XAN) and C. xanthorrhiza extract (CXE) with standardized XAN on hyperglycemia and inflammatory markers in high-fat diet- (HFD-) induced obese mice. Treatment with XAN (10 or 25?mg/kg/day) or CXE (50 or 100?mg/kg/day) significantly decreased fasting and postprandial blood glucose levels in HFD-induced obese mice. XAN and CXE treatments also lowered insulin, glucose, free fatty acid (FFA), and triglyceride (TG) levels in serum. Epididymal fat pad and adipocyte size were decreased by high doses of XAN (26.6% and 20.1%) and CXE (25.8% and 22.5%), respectively. XAN and CXE treatment also suppressed the development of fatty liver by decreasing liver fat accumulation. Moreover, XAN and CXE significantly inhibited production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-?), interleukin-6 (IL-6), interleukin-1? (IL-1?), and C-reactive protein (CRP) in adipose tissue (27.8–82.7%), liver (43.9–84.7%), and muscle (65.2–92.5%). Overall, these results suggest that XAN and CXE, with their antihyperglycemic and anti-inflammatory activities, might be used as potent antidiabetic agents for the treatment of type 2 diabetes. PMID:25053966

  13. Antihyperglycemic and Anti-Inflammatory Effects of Standardized Curcuma xanthorrhiza Roxb. Extract and Its Active Compound Xanthorrhizol in High-Fat Diet-Induced Obese Mice.

    PubMed

    Kim, Mi-Bo; Kim, Changhee; Song, Youngwoo; Hwang, Jae-Kwan

    2014-01-01

    Xanthorrhizol, a natural compound isolated from Curcuma xanthorrhiza Roxb. (Java turmeric), has been reported to possess antioxidant and anticancer properties; however, its effects on metabolic disorders remain unknown. The aim of the present study was to evaluate the effects of xanthorrhizol (XAN) and C. xanthorrhiza extract (CXE) with standardized XAN on hyperglycemia and inflammatory markers in high-fat diet- (HFD-) induced obese mice. Treatment with XAN (10 or 25?mg/kg/day) or CXE (50 or 100?mg/kg/day) significantly decreased fasting and postprandial blood glucose levels in HFD-induced obese mice. XAN and CXE treatments also lowered insulin, glucose, free fatty acid (FFA), and triglyceride (TG) levels in serum. Epididymal fat pad and adipocyte size were decreased by high doses of XAN (26.6% and 20.1%) and CXE (25.8% and 22.5%), respectively. XAN and CXE treatment also suppressed the development of fatty liver by decreasing liver fat accumulation. Moreover, XAN and CXE significantly inhibited production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-?), interleukin-6 (IL-6), interleukin-1? (IL-1?), and C-reactive protein (CRP) in adipose tissue (27.8-82.7%), liver (43.9-84.7%), and muscle (65.2-92.5%). Overall, these results suggest that XAN and CXE, with their antihyperglycemic and anti-inflammatory activities, might be used as potent antidiabetic agents for the treatment of type 2 diabetes. PMID:25053966

  14. Liposomal delivery system enhances anti-inflammatory properties of curcumin.

    PubMed

    Basnet, Purusotam; Hussain, Haider; Tho, Ingunn; Skalko-Basnet, Natasa

    2012-02-01

    Curcumin is a well-established natural antioxidant and anti-inflammatory agent. Up till now its potential in treatment of vaginal inflammation has not been evaluated. We are aiming at developing liposomal delivery system for curcumin targeting vaginal administration. Liposomes as nanosized phospholipid-based vesicles are expected to solubilize curcumin and enhance its activity, thus serving as an advanced topical formulation in the treatment of vaginal inflammation. Curcumin and curcuminoids were analyzed by the high-performance liquid chromatography method. Liposomes containing curcumin/curcuminoids of various sizes were prepared and characterized. Antioxidant activities of curcumin and liposomal curcumin were compared based on 1,1-diphenyl-2-picrylhydrazyl radical scavenging and superoxide dismutase activities. The anti-inflammatory activities were determined by measuring the inhibition of lipopolysaccharide -induced nitric oxide, interleukin-1?, and tumor necrosis factor-? production in macrophage RAW 264.7 cells. Curcumin/curcuminoids were encapsulated in phosphatidylcholine vesicles with high yields. Vesicles in the size range around 200 nm were selected for stability and cell experiments. Liposomal curcumin were found to be twofold to sixfold more potent than corresponding curcuminoids. Moreover, the mixture of curcuminoids was found to be more potent than pure curcumin in regard to the antioxidant and anti-inflammatory activities. Liposomal delivery systems for curcumin are promising formulations for the treatment of vaginal inflammation. PMID:21989712

  15. Evaluation of Anti-Inflammatory Effects of Cassia fistula (Leguminosae) Leaf Extract on Rats

    Microsoft Academic Search

    Tejendra Bhakta; Pulok K. Mukherjee; Kakali Saha; M. Pal; B. P. Saha; Subhash C. Mandal

    2000-01-01

    Cassia fistula Linn. is used by the people of Tripura, India as an anti-inflammatory, but the mode of activity is unknown. In this study, Cassia fistula leaves were tested for anti-inflammatory effects, as compared with phenylbutazone, using carrageenin, histamine, and dextran induced paw edema in rats. Potent anti-inflammatory activity against all phlogistic agents was noted.

  16. The anti-inflammatory effects of a high-frequency oligodeoxynucleotide from the genomic DNA of Lactobacillus casei.

    PubMed

    Hiramatsu, Yukihiro; Satho, Tomomitsu; Hyakutake, Mika; Irie, Keiichi; Mishima, Kenichi; Miake, Fumio; Kashige, Nobuhiro

    2014-11-01

    Genomic DNA has been identified as an anti-inflammatory component of Lactobacillus species, the effects of which are mediated through toll-like receptor (TLR) 9. In this study, we identified 14 novel anti-inflammatory oligodeoxynucleotide (ODN) from the genomic DNA of Lactobacillus casei by measuring their effects on the secretion of interleukin (IL)-8 (CXCL8) in the human epithelial colorectal adenocarcinoma cell line Caco-2 cells. The ODN TTTTGCCG strongly decreased IL-8 secretion. In the genomic DNA of Lactobacillus species, the frequency of TTTTGCCG was highest in the genomic DNA of L. casei and similar among strains of L. casei. Decreases in inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions in macrophage-like differentiated THP-1 cells confirmed the anti-inflammatory effect of TTTTGCCG. Furthermore, oral administration of TTTTGCCG ameliorated dextran sodium sulfate (DSS)-induced murine colitis and DSS-induced increased expression of inflammatory factor mRNAs, such as macrophage inflammatory protein (MIP)-2 (CXCL2), iNOS, and COX-2. The anti-inflammatory effect of TTTTGCCG was mainly regulated by an increase in heat shock protein (Hsp) 70 expression in the epithelium. TLR9 and Hsp90 may primarily mediate the anti-inflammatory effect of TTTTGCCG on Hsp70 signaling. PMID:25193776

  17. 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 ?g/mL reduced LPS-stimulated TNF-? production in THP-1 monocytes by 72% relative to the stimulated vehicle control. Isolated sesquiterpene lactones, neurolenins B, C+D, lobatin B and 9?-hydroxy-8?-isovalerianyloxy-calyculatolide were more active (IC50=0.17-2.32 ?M) than the positive control parthenolide (IC50=4.79 ?M). The results provide a pharmacological and phytochemical basis for the traditional use of this leaf for inflammatory conditions. PMID:23747054

  18. Heart failure is associated with impaired anti-inflammatory and antioxidant properties of high-density lipoproteins.

    PubMed

    Kim, Juyong Brian; Hama, Susan; Hough, Greg; Navab, Mohamad; Fogelman, Alan M; Maclellan, W Robb; Horwich, Tamara B; Fonarow, Gregg C

    2013-12-01

    Oxidative stress and inflammation are hallmarks of the heart failure (HF) disease state. In the present study, we investigated the inflammatory/anti-inflammatory characteristics of high-density lipoproteins (HDL) in patients with HF. Ninety-six consecutive patients with systolic HF were followed in an advanced HF center, and 21 healthy subjects were recruited. Plasma was tested for HDL inflammatory index (HII) using a monocyte chemotactic activity assay, with HII >1.0 indicating proinflammatory HDL. We found significantly increased inflammatory properties of HDL in patients with HF (median HII 1.56 vs 0.59 in controls; p <0.0001). Serum amyloid A level was markedly elevated and the activity of paraoxonase-1, an HDL antioxidant enzyme, was significantly reduced in patients versus controls. HDL and albumin from patients with HF contained markedly elevated levels of oxidized products of arachidonic and linoleic acids. HDL function improved when plasma was treated in vitro with 4F, an apolipoprotein A-I mimetic peptide (40% reduction in HII, p <0.0001). There was no correlation found between HII level and ejection fraction or New York Heart Association functional class. In conclusion, HDL function is significantly impaired and oxidation products of arachidonic and linoleic acids are markedly elevated in patients with HF compared with non-HF controls. PMID:24050409

  19. 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

  20. Gut health immunomodulatory and anti-inflammatory functions of gut enzyme digested high protein micro-nutrient dietary supplement-Enprocal

    Microsoft Academic Search

    Jagat R Kanwar; Rupinder K Kanwar

    2009-01-01

    BACKGROUND: Enprocal is a high-protein micro-nutrient rich formulated supplementary food designed to meet the nutritional needs of the frail elderly and be delivered to them in every day foods. We studied the potential of Enprocal to improve gut and immune health using simple and robust bioassays for gut cell proliferation, intestinal integrity\\/permeability, immunomodulatory, anti-inflammatory and anti-oxidative activities. Effects of Enprocal

  1. Anti-inflammatory effect of water-soluble complex of 1'-acetoxychavicol acetate with highly branched ?-1,3-glucan on contact dermatitis.

    PubMed

    Li, Jiawei; Aizawa, Yui; Hiramoto, Keiichi; Kasahara, Emiko; Tsuruta, Daisuke; Suzuki, Toshio; Ikeda, Atsushi; Azuma, Hideki; Nagasaki, Takeshi

    2015-02-01

    The anti-inflammatory effect on contact dermatitis of the water solubilized 1'-Acetoxychavicol Acetate (ACA) by complexation with ?-1,3-glucan isolated form Aureobasidium pullulans black yeast is reported. It is well-known that ACA possesses a function to inhibit the activation of NF-?B by which genes encoding proinflammatory cytokines, chemokines, and growth factors are regulated. However, because ACA is quite insoluble in water, its usefulness has been extremely limited. On the other hand, a triple-helical polysaccharide ?-1,3-glucan can include hydrophobic compounds into intrastrand hydrophobic cavity and solubilize poorly water-soluble compounds. In this study, solubilization of ACA by complexation with highly branched ?-1,3-glucan was achieved. The effect of anti-inflammatory response of water-soluble ACA complex with ?-1,3-glucan was confirmed in vitro and in vivo. PMID:25661358

  2. The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits

    PubMed Central

    2013-01-01

    Background Atherosclerosis has been widely accepted as an inflammatory disease of vascular, adhesion molecules play an important role in the early progression of it. The aim of the present study was to evaluate the effect of kaempferol on the inflammatory molecules such as E-selectin (E-sel), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesionmolecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in high cholesterol induced atherosclerosis rabbit models. Methods Thirty male New Zealand white (NZW) rabbits were randomly divided into five groups, control group, model group, fenofibrate (12mg/kg) group and kaempferol groups (150 mg/kg and 30 mg/kg). The rabbits were fed with a normal diet or a high cholesterol diet for 10 weeks. Levels of blood lipids, serum tumour-necrosis factor-alpha (TNF-?) and serum interleukin-1beta (IL-1?) were detected at the end of the sixth and tenth week. Malonaldehyde (MDA) level and superoxide dismutase (SOD) activity in serum were also determined. Lesion areas of the aorta were measured with morphometry analysis after ten weeks. Gene expression of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas was determined by RT-PCR (reverse transcription-polymerase chain reaction). Immunohistochemical staining was employed to measure protein expression of E-sel, ICAM-1, VCAM-1 and MCP-1. Results Model rabbits fed with ten weeks of high-cholesterol diet developed significant progression of atherosclerosis. Compared with the control, levels of blood lipids, TNF-?, IL-1? and MDA increased markedly in serum of model rabbits, while SOD levels decreased. Gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in atherosclerotic aortas increased remarkably in model group. However, comparing to the model rabbits, levels of TNF-?, IL-1? and MDA decreased significantly and serum SOD activity increased, gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas decreased significantly with the treatment of kaempferol. Conclusion Kaempferol shows anti-atherosclerotic effect by modulating the gene and protein expression of inflammatory molecules. PMID:23895132

  3. 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

  4. ANTIINFLAMMATORY ACTIVITY OF VOLATILE OIL OF PSIDIUM GUAJAVA

    PubMed Central

    Kavimani, S.; Ilango, R.; Vertichelvan, T.

    1998-01-01

    Volatile oil of Psidium guajava leaves obtained by steam distillation was given orally to study its effects on the exudation and proliferative phases of the inflammatory reaction, using technique of carragenin induced paw edema and cotton pellets in male albino rats. The anti inflammatory activity as compared with ketorolac tromethamine. In carragenin induced edemas,. 0.8ml/kg of the volatile oil ad anti-inflammatory activity as that of ketorolac tromethamine. The oil was also found to be potent in cotton pellet granuom studies. Preliminary investigation revealed that the volatile oil fraction consist sesqueterpene which may be responsible for its anti inflammatory activity. PMID:22556859

  5. Anti - inflammatory activity of volatile oil of psidium guajava.

    PubMed

    Kavimani, S; Ilango, R; Vertichelvan, T

    1998-04-01

    Volatile oil of Psidium guajava leaves obtained by steam distillation was given orally to study its effects on the exudation and proliferative phases of the inflammatory reaction, using technique of carragenin induced paw edema and cotton pellets in male albino rats. The anti inflammatory activity as compared with ketorolac tromethamine. In carragenin induced edemas,. 0.8ml/kg of the volatile oil ad anti-inflammatory activity as that of ketorolac tromethamine. The oil was also found to be potent in cotton pellet granuom studies. Preliminary investigation revealed that the volatile oil fraction consist sesqueterpene which may be responsible for its anti inflammatory activity. PMID:22556859

  6. Anti-inflammatory activity of Gentiana striata Maxim.

    PubMed

    Cao, Feihua; Shao, Hao; Li, Qiang; Li, Jinrong; Li, Wenqun; Li, Chong

    2012-01-01

    The anti-inflammatory activity and the mechanism of action of Gentiana striata Maxim. has been investigated. The most active phase, the ethyl acetate extract of Gentiana striata Maxim. (EGS), displayed potent inhibitory activity on feet oedema of rheumatoid arthritis (RA) inflicted rats. This anti-inflammatory activity might be partly based on the notable reduction of prostaglandin E2 (PGE?) and nitric oxide (NO) levels. Six further compounds isolated from EGS have previously been reported as having anti-inflammatory activity. PMID:21985356

  7. Molecular mechanisms of inflammation. Anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal.

    PubMed

    Lucas, Lisa; Russell, Aaron; Keast, Russell

    2011-01-01

    Chronic inflammation is a critical factor in the pathogenesis of many inflammatory disease states including cardiovascular disease, cancer, diabetes, degenerative joint diseases and neurodegenerative diseases. Chronic inflammatory states are poorly understood, however it is known that dietary habits can evoke or attenuate inflammatory responses. Popular methods to deal with inflammation and its associated symptoms involve the use of non steroidal anti-inflammatory drugs, however the use of these drugs are associated with severe side effects. Therefore, investigations concerned with natural methods of inflammatory control are warranted. A traditional Mediterranean diet has been shown to confer some protection against the pathology of chronic diseases through the attenuation of pro-inflammatory mediators and this has been partially attributed to the high intake of virgin olive oil accompanying this dietary regime. Virgin olive oil contains numerous phenolic compounds that exert potent anti-inflammatory actions. Of interest to this paper is the recently discovered phenolic compound oleocanthal. Oleocanthal is contained in virgin olive oil and possesses similar anti-inflammatory properties to ibuprofen. This pharmacological similarity has provoked interest in oleocanthal and the few studies conducted thus far have verified its anti-inflammatory and potential therapeutic actions. A review of the health benefits of the Mediterranean diet and anti-inflammatory properties of virgin olive oil is presented with the additional emphasis on the pharmacological and anti-inflammatory properties of the phenolic compound oleocanthal. PMID:21443487

  8. Effects of anti-inflammatory drugs on convulsant activity of quinolones: a comparative study of drug interaction between quinolones and anti-inflammatory drugs

    Microsoft Academic Search

    Seiji Hori; Junko Kizu; Masahiro Kawamura

    2003-01-01

    Quinolones have been reported to possess potent convulsant activity, which is enhanced when they are administered concurrently with anti-inflammatory drugs. To define the individual drug interactions of quinolones with anti-inflammatory drugs, we studied the convulsant activity of six quinolones with or without 13 anti-inflammatory drugs and 3 analgesic\\/antipyretic drugs in mice. Intraventricular injections of norfloxacin (NFLX), enoxacin (ENX), ciprofloxacin, lomefloxacin

  9. Non-steroidal Anti-inflammatory Drugs

    PubMed Central

    Cardario, Barbara; McKinnon, Allan A.

    1991-01-01

    Gastrointestinal, renal, hepatic, and hematological adverse effects are all associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). Some patients are particularly at risk for such problems. Preventive measures and recommendations for managing and monitoring high-risk patients are presented. Patients receiving long-term NSAID therapy should be carefully monitored. PMID:21234090

  10. Anti-inflammatory and immune-regulatory mechanisms prevent contact hypersensitivity to Arnica montana L.

    PubMed

    Lass, Christian; Vocanson, Marc; Wagner, Steffen; Schempp, Christoph M; Nicolas, Jean-Francois; Merfort, Irmgard; Martin, Stefan F

    2008-10-01

    Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-kappaB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice. PMID:18341569

  11. 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-1? complex indicated that vCCI uses negatively charged residues in ?-sheet II to interact with positively charged residues in the MIP-1?N-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-1?complex, 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-1? 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.

  12. Structural Insights into the Interaction between a Potent Anti-inflammatory Protein, Viral CC Chemokine Inhibitor (vCCI), and the Human CC Chemokine, Eotaxin-1*

    PubMed Central

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

    2014-01-01

    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 poxvirus-encoded protein viral CC chemokine inhibitor (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-1? (macrophage inflammatory protein-1?) complex indicated that vCCI uses negatively charged residues in ?-sheet II to interact with positively charged residues in the MIP-1? N terminus, 20s region and 40s 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), a 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-1? complex 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-1. In addition, the binding affinity between vCCI and other wild type CC chemokines, MCP-1 (monocyte chemoattractant protein-1), MIP-1?, and RANTES (regulated on activation normal T cell expressed and secreted), were determined as 1.1, 1.2, and 0.22 nm, respectively. To our knowledge, this is the first work quantitatively measuring the binding affinity between vCCI and multiple CC chemokines. PMID:24482230

  13. Synthesis and Anti-inflammatory Effect of Chalcones and Related Compounds

    Microsoft Academic Search

    Hsin-Kaw Hsieh; Tai-Hua Lee; Jih-Pyang Wang; Jeh-Jeng Wang; Chun-Nan Lin

    1998-01-01

    Purpose. Mast cell and neutrophil degradations are the important players in inflammatory disorders. Combined with potent inhibition of chemical mediators released from mast cells and neutrophil degranulations, it could be a promising anti-inflammatory agent. 2',5'-Dihydroxychalcone has been reported as a potent chemical mediator and cyclooxygenase inhibitor. In an effort to continually develop potent anti-inflammatory agents, a novel series of chalcone,

  14. [Simultaneous analysis of 4 non-steroidal anti-inflammatory drug residues in mutton muscle using high performance liquid chromatography assisted by ultrasonic-microwave extraction].

    PubMed

    Kang, Yongfeng; Zou, Shiwen; Duan, Wuping; Li, Yan; Sun, Tao

    2010-11-01

    A method for the simultaneous determination of 4 non-steroidal anti-inflammatory drug (NSAID) residues, including flunixin meglumine, meloxicam, diclofenac sodium and ketoprofen, in mutton muscle was developed using high performance liquid chromatography assisted by ultrasonic-microwave extraction. The NSAIDs were extracted with acidified ethanol and purified by a diatomite column. The subsequent analysis of NSAIDs was achieved on a Hypersil C18 column (250 mm x 4.6 mm, 5 microm) with the mobile phase of acetonitrile-0.2% triethylamine (40 : 60, v/v, pH 3.5 adjusted by phosphoric acid) at a flow rate of 0.8 mL/min at 30 degrees C. The detection wavelength was set at 255 nm. The 4 NSAIDs were well separated within 20 min. The correlation coefficients for 4 NSAIDs were from 0.999 3 to 0.999 8 with the limits of detection (LOD, S/N = 3) of 5-10 microg/kg and the limits of quantification (LOQ, S/N = 10) of 15-30 microg/kg. The recoveries were in the range of 65.3% - 99.6% with the relative standard deviations (RSDs) less than 15%. This method is simple, rapid and highly sensitive, and can meet the requirement for the qualitative and quantitative analysis. PMID:21381422

  15. 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-?/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

  16. 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 ?M corresponding to 0.42 ?g/ml) was much more effective compared to Trolox (EC(50) 12 ?g/ml) and N-acetylcysteine (EC(50) 847 ?g/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

  17. De Novo Design and Synthesis of Ultra-Short Peptidomimetic Antibiotics Having Dual Antimicrobial and Anti-Inflammatory Activities

    PubMed Central

    Ahn, Mija; Hwang, Eunha; Sohn, Hoik; Park, Hyo-Nam; Lee, Eunjung; Seo, Ji-Hyung; Cheong, Chaejoon; Nam, Ky-Youb; Hyun, Jae-Kyung; Jeong, Ki-Woong; Kim, Yangmee; Shin, Song Yub; Bang, Jeong Kyu

    2013-01-01

    Background Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability. Methodology/Principal Findings In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(?)- and N(?)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti–methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. Conclusion/Significance The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics. PMID:24302996

  18. High-risk use of over-the-counter non-steroidal anti-inflammatory drugs: a population-based cross-sectional study

    PubMed Central

    Koffeman, Aafke R; Valkhoff, Vera E; Çelik, Sevde; Jong, Geert W ’t; Sturkenboom, Miriam CJM; Bindels, Patrick JE; van der Lei, Johan; Luijsterburg, Pim AJ; Bierma-Zeinstra, Sita MA

    2014-01-01

    Background The use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with serious adverse drug events (ADEs). Aim To determine the prevalence of over-the-counter (OTC) NSAID use in the general population and in patients with a high risk of developing a serious NSAID-related ADE. Design and setting Cross-sectional study in four general practices in the Netherlands. Method Two patient samples were selected: a random sample of adults (general population sample); and adult patients with a high risk of developing a serious ADE in case of NSAID use (high-risk sample). All included patients were sent a questionnaire regarding their use of OTC NSAIDs in the 4 weeks prior to participation. Results In the general population sample, 118 of 456 (26%) invited patients completed the questionnaire. Of these, 35 (30%) had used an OTC NSAID. In the high-risk sample, 264 of 713 (37%) invited patients completed the questionnaire, and of these high-risk patients 33 (13%) had used an OTC NSAID. Over 20% of OTC NSAID users in the general population sample and over 30% in the high-risk sample had used the OTC NSAID for >7 days. OTC NSAIDs were used in a dosage exceeding the recommended daily maximum by 9% and 3% of OTC NSAID users in the general population and the high-risk sample respectively. Conclusion OTC NSAIDs are used by almost one-third of the general population. In the high-risk patients selected, one in eight patients used an OTC NSAID. Continued efforts by health authorities and healthcare professionals to inform patients of the risks of these drugs are warranted. PMID:24686883

  19. Anti-inflammatory Agents: Present and Future

    PubMed Central

    Dinarello, Charles A.

    2012-01-01

    Inflammation involving the innate and adaptive immune systems is a normal response to infection. However, when allowed to continue unchecked, inflammation may result in autoimmune or autoinflammatory disorders, neurodegenerative disease, or cancer. A variety of safe and effective anti-inflammatory agents are available, including aspirin and other nonsteroidal anti-inflammatories, with many more drugs under development. In particular, the new era of anti-inflammatory agents includes “biologicals” such as anticytokine therapies and small molecules that block the activity of kinases. Other anti-inflammatories currently in use or under development include statins, histone deacetylase inhibitors, PPAR agonists, and small RNAs. This Review discusses the current status of anti-inflammatory drug research and the development of new anti-inflammatory therapeutics. PMID:20303881

  20. Anti-Inflammatory Effect of Hepatocyte Growth Factor in Chronic Kidney Disease: Targeting the Inflamed Vascular Endothelium

    Microsoft Academic Search

    Rujun Gong; Abdalla Rifai; Lance D. Dworkin

    2006-01-01

    Recent studies show that hepatocyte growth factor (HGF) has potent anti-inflammatory effects in multiple animal models of disease in various organ systems, including the kidney, suggesting that HGF may suppress a common proinflammatory process. The aim of this study was to examine the molecular mechanism of HGF's anti-inflammatory actions in a model of chronic kidney disease. Beginning 2 wk after

  1. Anti-Inflammatory Effects of ?-Melanocyte-Stimulating Hormone in Celiac Intestinal Mucosa

    Microsoft Academic Search

    Gualtiero Colombo; Roberto Buffa; Maria Teresa Bardella; Letizia Garofalo; Andrea Carlin; James M. Lipton; Anna Catania

    2002-01-01

    Objectives: The peptide ?-melanocyte-stimulating hormone (?-MSH) possesses potent anti-inflammatory activities and has been previously implicated in the endogenous control of inflammatory reactions. The aim of the present research was to determine whether ?-MSH and its receptors participate in a localized anti-inflammatory response in the duodenal mucosa of celiac patients. Methods: Three series of experiments were performed, using duodenal biopsy pairs

  2. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice

    Microsoft Academic Search

    Tzong-Shyuan Lee; Lee-Young Chau

    2002-01-01

    The mechanisms underlying the action of the potent anti-inflammatory interleukin-10 (IL-10) are poorly understood. Here we show that, in murine macrophages, IL-10 induces expression of heme oxygenase-1 (HO-1), a stress-inducible protein with potential anti-inflammatory effect, via a p38 mitogen-activated protein kinase-dependent pathway. Inhibition of HO-1 protein synthesis or activity significantly reversed the inhibitory effect of IL-10 on production of tumor

  3. 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 promote Lilium bulbs as a therapeutic functional food worldwide. PMID:25702713

  4. Synthesis and assignment of absolute configuration of (-)-oleocanthal: a potent, naturally occurring non-steroidal anti-inflammatory and anti-oxidant agent derived from extra virgin olive oils.

    PubMed

    Smith, Amos B; Han, Qiang; Breslin, Paul A S; Beauchamp, Gary K

    2005-10-27

    [structure: see text] Effective total syntheses and the assignment of absolute configurations of both the (+)- and (-)-enantiomers of oleocanthal 1 (a.k.a. deacetoxy ligstroside aglycon), the latter derived from extra virgin olive oils and known to be responsible for the back of the throat irritant properties of olive oils, have been achieved. The absolute and relative stereochemistry of the naturally occurring enantiomer (-)-1 proved to be 3S,4E. Both syntheses begin with d-(-)-ribose, proceed in 12 steps, and are achieved with an overall yield of 7%. Both enantiomers proved to be non-steroidal anti-inflammatory and anti-oxidant agents. PMID:16235961

  5. Gut health immunomodulatory and anti-inflammatory functions of gut enzyme digested high protein micro-nutrient dietary supplement-Enprocal

    PubMed Central

    Kanwar, Jagat R; Kanwar, Rupinder K

    2009-01-01

    Background Enprocal is a high-protein micro-nutrient rich formulated supplementary food designed to meet the nutritional needs of the frail elderly and be delivered to them in every day foods. We studied the potential of Enprocal to improve gut and immune health using simple and robust bioassays for gut cell proliferation, intestinal integrity/permeability, immunomodulatory, anti-inflammatory and anti-oxidative activities. Effects of Enprocal were compared with whey protein concentrate 80 (WPC), heat treated skim milk powder, and other commercially available milk derived products. Results Enprocal (undigested) and digested (Enprocal D) selectively enhanced cell proliferation in normal human intestinal epithelial cells (FHs74-Int) and showed no cytotoxicity. In a dose dependent manner Enprocal induced cell death in Caco-2 cells (human colon adencarcinoma epithelial cells). Digested Enprocal (Enprocal D: gut enzyme cocktail treated) maintained the intestinal integrity in transepithelial resistance (TEER) assay, increased the permeability of horseradish peroxidase (HRP) and did not induce oxidative stress to the gut epithelial cells. Enprocal D upregulated the surface expression of co-stimulatory (CD40, CD86, CD80), MHC I and MHC II molecules on PMA differentiated THP-1 macrophages in coculture transwell model, and inhibited the monocyte/lymphocyte (THP-1/Jurkat E6-1 cells)-epithelial cell adhesion. In cytokine secretion analyses, Enprocal D down-regulated the secretion of proinflammatory cytokines (IL-1? and TNF-?) and up-regulated IFN-?, IL-2 and IL-10. Conclusion Our results indicate that Enprocal creates neither oxidative injury nor cytotoxicity, stimulates normal gut cell proliferation, up regulates immune cell activation markers and may aid in the production of antibodies. Furthermore, through downregulation of proinflammatory cytokines, Enprocal appears to be beneficial in reducing the effects of chronic gut inflammatory diseases such as inflammatory bowel disease (IBD). Stimulation of normal human fetal intestinal cell proliferation without cell cytotoxicity indicates it may also be given as infant food particularly for premature babies. PMID:19183498

  6. 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 ?B (NF-?B) 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-?B-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-?B activation, and modulating the expression of genes for NF-?B-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-?B activity, and NF-?B-related inflammatory genes. PMID:21332402

  7. Nonsteroidal Anti-Inflammatory Drugs

    Microsoft Academic Search

    Leslie J. Crofford

    \\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a ?Nonsteriodal anti-inflammatory drugs (NSAIDs) relieve inflammation and pain by inhibiting the production of prostaglandins.\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a ?Prostaglandin (PG) biosynthesis occurs via a three-enzyme cascade. Current NSAIDs inhibit the enzyme cyclooxygenase (COX),\\u000a accounting for their efficacy and toxicity.\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a ?Pharmacologic properties of the different NSAIDs, including specificity for COX-1 or -2 and drug half-life, influence the\\u000a toxicity profile.\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a ?The most

  8. 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

  9. Evaluation of AntiInflammatory Activity of Eclipta alba in rats

    PubMed Central

    Kumar, S. Suresh; Sivakumar, T.; Chandrasekar, M.J.N.; Suresh, B.

    2005-01-01

    The anti-inflammatory effect of the plant of Eclipta alba (Family – Asteraceae) was evaluated using carrageenin, mediators such as histamine and serotonin induced paw oedema, and cotton pellet induced granuloma tests for their effect on acute and chronic phase inflammation models in rats. Maximum inhibition (55.85%) was noted at the dose of 500 mg/kg after 3 hr of drug treatment in carrageenin induced paw oedema, whereas the Indomethacin (standard drug ) produced 61.30% of inhibition. In the chronic model (cotton pellet induced granuloma) the CEEA and standard drug showed decreased formation of granuloma tissue by 49.7,41.5,22.1% and 53.48 % respectively. The results indicate the potent anti-inflammatory effect and therapeutic efficacy of Eclipta alba extract on animal models, which is compared with Indomethacin. PMID:22557164

  10. Anti-inflammatory potential of allyl-isothiocyanate – role of Nrf2, NF-?B and microRNA-155

    PubMed Central

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

    2012-01-01

    Abstract 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 ? mRNA levels and its secretion in LPS stimulated RAW264.7 macrophages. Furthermore, gene expression of other pro-inflammatory markers including interleukin-1? and inducible nitric oxide synthase were down-regulated following AITC treatment. AITC decreased nuclear p65 protein levels, a subunit of the transcription factor NF-?B. 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-1? 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

  11. Anti-inflammatory potential of allyl-isothiocyanate--role of Nrf2, NF-(?) 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 ? mRNA levels and its secretion in LPS stimulated RAW264.7 macrophages. Furthermore, gene expression of other pro-inflammatory markers including interleukin-1? and inducible nitric oxide synthase were down-regulated following AITC treatment. AITC decreased nuclear p65 protein levels, a subunit of the transcription factor NF-?B. 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-1? 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

  12. Structures and mechanism for the design of highly potent glucocorticoids

    PubMed Central

    He, Yuanzheng; Yi, Wei; Suino-Powell, Kelly; Zhou, X Edward; Tolbert, W David; Tang, Xiaobo; Yang, Jing; Yang, Huaiyu; Shi, Jingjing; Hou, Li; Jiang, Hualiang; Melcher, Karsten; Xu, H Eric

    2014-01-01

    The evolution of glucocorticoid drugs was driven by the demand of lowering the unwanted side effects, while keeping the beneficial anti-inflammatory effects. Potency is an important aspect of this evolution as many undesirable side effects are associated with use of high-dose glucocorticoids. The side effects can be minimized by highly potent glucocorticoids that achieve the same treatment effects at lower doses. This demand propelled the continuous development of synthetic glucocorticoids with increased potencies, but the structural basis of their potencies is poorly understood. To determine the mechanisms underlying potency, we solved the X-ray structures of the glucocorticoid receptor (GR) ligand-binding domain (LBD) bound to its endogenous ligand, cortisol, which has relatively low potency, and a highly potent synthetic glucocorticoid, mometasone furoate (MF). The cortisol-bound GR LBD revealed that the flexibility of the C1-C2 single bond in the steroid A ring is primarily responsible for the low affinity of cortisol to GR. In contrast, we demonstrate that the very high potency of MF is achieved by its C-17? furoate group completely filling the ligand-binding pocket, thus providing additional anchor contacts for high-affinity binding. A single amino acid in the ligand-binding pocket, Q642, plays a discriminating role in ligand potency between MF and cortisol. Structure-based design led to synthesis of several novel glucocorticoids with much improved potency and efficacy. Together, these results reveal key structural mechanisms of glucocorticoid potency and provide a rational basis for developing novel highly potent glucocorticoids. PMID:24763108

  13. Structures and mechanism for the design of highly potent glucocorticoids.

    PubMed

    He, Yuanzheng; Yi, Wei; Suino-Powell, Kelly; Zhou, X Edward; Tolbert, W David; Tang, Xiaobo; Yang, Jing; Yang, Huaiyu; Shi, Jingjing; Hou, Li; Jiang, Hualiang; Melcher, Karsten; Xu, H Eric

    2014-06-01

    The evolution of glucocorticoid drugs was driven by the demand of lowering the unwanted side effects, while keeping the beneficial anti-inflammatory effects. Potency is an important aspect of this evolution as many undesirable side effects are associated with use of high-dose glucocorticoids. The side effects can be minimized by highly potent glucocorticoids that achieve the same treatment effects at lower doses. This demand propelled the continuous development of synthetic glucocorticoids with increased potencies, but the structural basis of their potencies is poorly understood. To determine the mechanisms underlying potency, we solved the X-ray structures of the glucocorticoid receptor (GR) ligand-binding domain (LBD) bound to its endogenous ligand, cortisol, which has relatively low potency, and a highly potent synthetic glucocorticoid, mometasone furoate (MF). The cortisol-bound GR LBD revealed that the flexibility of the C1-C2 single bond in the steroid A ring is primarily responsible for the low affinity of cortisol to GR. In contrast, we demonstrate that the very high potency of MF is achieved by its C-17? furoate group completely filling the ligand-binding pocket, thus providing additional anchor contacts for high-affinity binding. A single amino acid in the ligand-binding pocket, Q642, plays a discriminating role in ligand potency between MF and cortisol. Structure-based design led to synthesis of several novel glucocorticoids with much improved potency and efficacy. Together, these results reveal key structural mechanisms of glucocorticoid potency and provide a rational basis for developing novel highly potent glucocorticoids. PMID:24763108

  14. Anti-Inflammatory Agents for Cancer Therapy

    PubMed Central

    Rayburn, Elizabeth R.; Ezell, Scharri J.; Zhang, Ruiwen

    2010-01-01

    Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents. PMID:20333321

  15. 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

  16. 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

  17. Evaluation of Anti-nociceptive and Anti-inflammatory Activities of Novel Chalcone Derivatives

    PubMed Central

    Razmi, Ali; Zarghi, Afshin; Arfaee, Sara; Naderi, Nima; Faizi, Mehrdad

    2013-01-01

    Chalcone (1,3-diarylprop-2-en-1-one) derivatives have been introduced as selective cyclooxygenase-2 inhibitors. In the present study, anti-nociceptive and anti-inflammatory effects of eight novel compounds were evaluated in male mice and Wistar rats by using the writhing and formalin-induced paw edema tests respectively. The activities of the compounds were compared with celecoxib as a reference drug. Then, novel compounds were divided into two regioisomeric groups based on the position of the methylsulfonyl substitution. Compounds with substituents such as: 1) H, 2) Me, 3) F and 4) Cl at para position of the phenyl ring of (E)-3-(4-Methanesulfonylphenyl)-1-phenylprop-2 en-1-one were selected in the first group. The regioisomer compounds with 5) H, 6) Me, 7) F and 8) OMe substitutions at C-4 of phenyl ring of (E)-1-(4-Methanesulfonylphenyl)-3-phenylprop-2-en-1-one were chosen as second group. All compounds showed dose-dependent anti-nociceptive activity in writhing test. Interestingly, the potency of anti-nociceptive effect of compounds 1, 2, 5 and 6 were significantly higher than celecoxib. The regioisomeric compounds 1 and 5 with high anti-nociceptive effects, showed a significant dose-dependent anti inflammatory activity in the paw edema test as well. The results showed that compounds with no substituent or small size substituents at para position of the phenyl ring are the most potent compound in writhing test. Our results revealed that the introduction of a bulky group such as methoxy or chlorine at the vicinal aromatic chain of the derivatives decreases the anti-inflammatory/ anti-nociceptive effects. The comparison of estimated ED50 of each pair of the regioisomeric compounds indicates that the relative position of SO2Me to carbonyl moiety did not affect the potency. PMID:24250683

  18. 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 ?g/mL), similar to baicalein. Bioactivity-guided fractionation led to the isolation of 2-hydroxybenzoic acid and ?-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

  19. 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

  20. 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

  1. 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 ?-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

  2. Anti-inflammatory effects of five commercially available mushroom species determined in lipopolysaccharide and interferon-? 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-? (IFN-?) activated murine RAW 264.7 macrophages. Potent anti-inflammatory activity (IC??<0.1 mg/ml), measured as inhibition of NO production, could be detected in all raw mushroom preparations, but only raw Oyster (IC??=0.035 mg/ml), Shiitake (IC??=0.047 mg/ml) and Enoki mushrooms (IC??=0.099 mg/ml) showed also potent inhibition of TNF-? 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

  3. 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 ?-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 ?-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

  4. Anti-Inflammatory Effect of Selected Dihydroxyflavones

    PubMed Central

    Sangeetha, K.S.Sridevi

    2015-01-01

    Background The mechanism of inflammation is attributed, to release of reactive oxygen species from activated neutrophils and macrophages. Over production of reactive oxygen species may result in tissue injury by damaging macromolecules. Flavones are the polyphenolic compounds with antioxidant property. This antioxidant property of flavones may have beneficial effect against inflammation. Aim To study the anti-inflammatory effect of selected dihydroxyflavones (DHF) in albino rats. The prime objective of the present study is to identify safe and effective agents to treat inflammation from among the selected DHF group of compounds. Materials and Methods The present study was designed to investigate the anti-inflammatory action of four selected dihydroxyflavone derivatives; 2’,3’- dihydroxyflavone and 2’, 4’ -dihydroxyflavones, 5, 3’- dihydroxyflavone and 7, 3’ dihydroxyflavone. The anti-inflammatory activity of selected DHF was studied in rats by carrageenan induced hind paw oedema method. Results All the selected dihydroxyflavone derivatives showed dose and time dependent inhibition of carrageenan induced paw oedema.

  5. Anti-Inflammatory Effects of Statins: Clinical Evidence and Basic Mechanisms

    Microsoft Academic Search

    Mukesh K. Jain; Paul M. Ridker

    2005-01-01

    Chronic inflammation is a key feature of vascular disease states such as atherosclerosis. Multiple clinical studies have shown that a class of medications termed statins lower cardiovascular morbidity and mortality. Originally developed to lower serum cholesterol, increasing evidence suggests that these medications have potent anti-inflammatory effects that contribute to their beneficial effects in patients. Here, we discuss the clinical and

  6. The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats

    Microsoft Academic Search

    Young Bae Kwon; Hye Jung Lee; Ho Jae Han; Woung Chon Mar; Sung Keel Kang; Ok Byung Yoon; Alvin J. Beitz; Jang Hern Lee

    2002-01-01

    We recently demonstrated that bee venom (BV) injection into the Zusanli acupoint produced a significantly more potent anti-inflammatory and antinociceptive effect than injection into a non-acupoint in a Freund's adjuvant induced rheumatoid arthritis (RA) model. However, the precise BV constituents responsible for these antinociceptive and\\/or anti-inflammatory effects are not fully understood. In order to investigate the possible role of the

  7. Topical anti-inflammatory activity of Solenostemma argel leaves.

    PubMed

    Innocenti, G; Dall'acqua, S; Sosa, S; Altinier, G; Della Loggia, R

    2005-11-14

    The topical anti-inflammatory activity of Solenostemma argel Hayne leaves was evaluated using the Croton oil ear test in mice. A bioassay-guided fractionation procedure led to a highly active chloroform extract: at 300 microg/cm(2), it induced 73% oedema reduction, while the reference drug indomethacin (100 microg/cm(2)) induced 56% reduction. The extract contained a new pregnene glycoside (1, solenoside A) and the known 14 beta,15 alpha-dihydroxy-Delta(4)pregnene-3,20 dione (2), kaempferol-3-O-glucoside (3) and kaempferol-3-O-rutinoside (4). Their structures were determined by ID and 2D NMR experiments as well as HRMS. Compounds 2 and 4 showed anti-inflammatory activity comparable to that of indomethacin. PMID:16061338

  8. Investigation of the anti-inflammatory properties of hydroxypyridinones.

    PubMed Central

    Hewitt, S D; Hider, R C; Sarpong, P; Morris, C J; Blake, D R

    1989-01-01

    Synovial iron deposition associated with rheumatoid disease may result in the production of highly reactive oxygen free radicals, leading to tissue damage. This chain of events can be interrupted by iron chelation. Families of strong iron (III) chelators have been tested for their iron scavenging properties in vitro and their effects assessed in vivo using a rat model of inflammation. All the chelators competed successfully for iron with apotransferrin, and some removed up to 34% of iron from ferritin. The best anti-inflammatory effects were achieved with the most hydrophilic chelators and those which chelated iron most avidly. Activity was dependent on dose. The route of administration was also an important factor with lower affinity chelators. This work introduces a range of simple bidentate iron chelators, which under certain conditions exceed desferrioxamine in their iron scavenging abilities, and some of which, in this simple animal model, approach indomethacin in their anti-inflammatory capabilities. PMID:2730166

  9. Synthesis of some novel chalcones, flavanones and flavones and evaluation of their anti-inflammatory activity.

    PubMed

    Bano, Sameena; Javed, Kalim; Ahmad, Shamim; Rathish, I G; Singh, Surender; Chaitanya, M; Arunasree, K M; Alam, M S

    2013-07-01

    A novel series of synthetic 2'-hydroxychalcones (1a-h), 2'-methoxychalcones (2a-l), flavanones (3a-k) and flavones (4a-f) have been synthesized and evaluated for their anti-inflammatory activity in carrageenan induced rat paw oedema model. Compounds 1a, 1e-g, 2e-g, 3j, and 4f showed potent anti-inflammatory activity comparable to the reference drug indomethacin with insignificant ulceration. Compound 1f showed mild inhibition against the enzymatic activity of ovine COX-1 and COX-2 (in-vitro). Compound 1f also exhibited inhibitory activity in LPS induced TNF-? production. PMID:23693150

  10. Structure and function of papiliocin with antimicrobial and anti-inflammatory activities isolated from the swallowtail butterfly, Papilio xuthus.

    PubMed

    Kim, Jin-Kyoung; Lee, Eunjung; Shin, Soyoung; Jeong, Ki-woong; Lee, Jee-Young; Bae, Su-Young; Kim, Soo-Hyun; Lee, Juneyoung; Kim, Seong Ryul; Lee, Dong Gun; Hwang, Jae-Sam; Kim, Yangmee

    2011-12-01

    Papiliocin is a novel 37-residue cecropin-like peptide isolated recently from the swallowtail butterfly, Papilio xuthus. With the aim of identifying a potent antimicrobial peptide, we tested papiliocin in a variety of biological and biophysical assays, demonstrating that the peptide possesses very low cytotoxicity against mammalian cells and high bacterial cell selectivity, particularly against Gram-negative bacteria as well as high anti-inflammatory activity. Using LPS-stimulated macrophage RAW264.7 cells, we found that papiliocin exerted its anti-inflammatory activities by inhibiting nitric oxide (NO) production and secretion of tumor necrosis factor (TNF)-? and macrophage inflammatory protein (MIP)-2, producing effects comparable with those of the antimicrobial peptide LL-37. We also showed that the innate defense response mechanisms engaged by papiliocin involve Toll-like receptor pathways that culminate in the nuclear translocation of NF-?B. Fluorescent dye leakage experiments showed that papiliocin targets the bacterial cell membrane. To understand structure-activity relationships, we determined the three-dimensional structure of papiliocin in 300 mm dodecylphosphocholine micelles by NMR spectroscopy, showing that papiliocin has an ?-helical structure from Lys(3) to Lys(21) and from Ala(25) to Val(36), linked by a hinge region. Interactions between the papiliocin and LPS studied using tryptophan blue-shift data, and saturation transfer difference-NMR experiments revealed that Trp(2) and Phe(5) at the N-terminal helix play an important role in attracting papiliocin to the cell membrane of Gram-negative bacteria. In conclusion, we have demonstrated that papiliocin is a potent peptide antibiotic with both anti-inflammatory and antibacterial activities, and we have laid the groundwork for future studies of its mechanism of action. PMID:21965682

  11. Determination of Residual Nonsteroidal Anti-Inflammatory Drugs in Aqueous Sample Using Magnetic Nanoparticles Modified with Cetyltrimethylammonium Bromide by High Performance Liquid Chromatography

    PubMed Central

    Khoeini Sharifabadi, Malihe; Saber-Tehrani, Mohammad; Waqif Husain, Syed; Mehdinia, Ali; Aberoomand-Azar, Parviz

    2014-01-01

    A simple and sensitive solid-phase extraction method for separation and preconcentration of trace amount of four nonsteroidal anti-inflammatory drugs (naproxen, indomethacin, diclofenac, and ibuprofen) using Fe3O4 magnetic nanoparticles modified with cetyltrimethylammonium bromide has been developed. For this purpose, the surface of MNPs was modified with cetyltrimethylammonium bromide (CTAB) as a cationic surfactant. Effects of different parameters influencing the extraction efficiency of drugs including the pH, amount of salt, shaking time, eluent type, the volume of solvent, amount of adsorbent, sample volume, and the time of desorption were investigated and optimized. Methanol has been used as desorption solvent and the extracts were analysed on a reversed-phase octadecyl silica column using 0.02 M phosphate-buffer (pH = 6.02) acetonitrile (65?:?35?v/v) as the mobile phase and the effluents were measured at 202?nm with ultraviolet detector. The relative standard deviation (RSD%) of the method was investigated at three concentrations (25, 50, and 200?ng/mL) and was in the range of 3.98–9.83% (n = 6) for 50?ng/mL. The calibration curves obtained for studied drugs show reasonable linearity (R2 > 0.99) and the limit of detection (LODs) ranged between 2 and 7?ng/mL. Finally, the proposed method has been effectively employed in extraction and determination of the drugs in biological and environmental samples. PMID:24982923

  12. Anti-inflammatory effect of (+)-pinitol

    Microsoft Academic Search

    R. K. Singh; B. L. Pandey; M. Tripathi; V. B. Pandey

    2001-01-01

    In the carrageenin-induced paw oedema in rats, (+)-pinitol (2.5–10 mg\\/kg, i.p.), isolated from Abies pindrow leaves, showed a significant anti-inflammatory effect, the highest dose being comparable to phenylbutazone (100 mg\\/kg, i.p.).

  13. Determination of four acidic nonsteroidal anti-inflammatory drugs in wastewater samples by dispersive liquid-liquid microextraction based on solidification of floating organic droplet and high-performance liquid chromatography.

    PubMed

    Beldean-Galea, Mihail Simion; Coman, Virginia; Thiébaut, Didier; Vial, Jérome

    2015-02-01

    A simple, environmentally friendly, and sensitive dispersive liquid-liquid microextraction based on solidification of floating organic droplet for the extraction of four acidic nonsteroidal anti-inflammatory drugs (ketoprofen, naproxen, ibuprofen, and diclofenac) from wastewater samples subsequent by high-performance liquid chromatography analysis was developed. The influence of extraction parameters such as pH, the effect of solution ionic strength, type of extraction solvent, disperser solvent, and extraction solvent volume were studied. High enrichment factors (283-302) were obtained through the developed method. The method provides good linearity (r > 0.999) in a concentration range of 1-100 ?g/L, good intra- and inter-day precision (relative standard deviation < 7%) and low limits of quantification. The relative recoveries of the selected compounds were situated over 80% both in synthetic and real water samples. The developed method has been successfully applied for the analysis of the selected compounds in wastewater samples. PMID:25487631

  14. Anti-inflammatory and antimicrobial activities of triterpenoids from Strobilanthes callosus nees.

    PubMed

    Singh, B; Sahu, P M; Sharma, M K

    2002-05-01

    The anti-inflammatory and antimicrobial activities of the 95% ethanol extract, benzene fraction and isolated triterpenoids of Strobilanthes callosus were investigated. In the carrageenan-induced paw edema inflammation model, the taraxerol showed a high reduction of edema, but the antimicrobial effect observed was lower at the two doses employed. These results confirm the use of this plant in folk medicine as an anti-inflammatory and antimicrobial herbal drug. PMID:12120818

  15. Synthesis and biological evaluation of curcumin derivatives containing NSAIDs for their anti-inflammatory activity.

    PubMed

    Liu, Wenfeng; Li, Yonlian; Yue, Yuan; Zhang, Kun; Chen, Qian; Wang, Huaqian; Lu, Yujing; Huang, Mou-Tuan; Zheng, Xi; Du, Zhiyun

    2015-08-01

    Oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) was frequently associated with serious adverse effects. Inspired by curcumin-a naturally traditional Chinese medicine, a series of curcumin derivatives containing NSAIDs, used for transdermal application, were synthesized and screened for their anti-inflammatory activities in vitro and in vivo. Compared with curcumin and parent NSAID (salicylic acid and salsalate), topical application of A11 and B13 onto mouse ear edema, prior to TPA treatment markedly suppressed the expression of IL-1?, IL-6 and TNF-?, respectively. Mechanistically, A11 and B13 blocked the phosphorylation of I?B? and suppressed the activation of p65 and I?B?. It was found that A11 and B13 may be potent anti-inflammatory agents for the treatment of inflammatory diseases. PMID:26048786

  16. QSAR and docking studies on capsazepine derivatives for immunomodulatory and anti-inflammatory activity.

    PubMed

    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-? (TNF-?) 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-?. 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

  17. 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-? (TNF-?) 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-?. 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

  18. Microextraction by packed sorbent and high performance liquid chromatography determination of seven non-steroidal anti-inflammatory drugs in human plasma and urine.

    PubMed

    Locatelli, Marcello; Ferrone, Vincenzo; Cifelli, Roberta; Barbacane, Renato Carmine; Carlucci, Giuseppe

    2014-11-01

    This paper reports a new MEPS-HPLC-PDA method for the simultaneous analysis of seven non-steroidal anti-inflammatory drugs (Furprofen, Indoprofen, Ketoprofen, Fenbufen, Flurbiprofen, Indomethacin, and Ibuprofen) in human plasma and urine. NSAIDs were resolved on a Gemini C18 column (4.6 mm × 250 mm; 5 ?m particle size) using a gradient elution mode with a run time of 25 min, comprising re-equilibration, without further purification. The method was validated over the concentration range from 0.1 to 10 ?g/mL for all the analytes both in human plasma and urine, using Benzyl 4-hydroxybenzoate as the internal standards. This method was successfully tested to NSAIDs analyses in real matrices, in order to check the method potentiality and the correct response. The results from assay validations show that the method is selective, sensitive and robust. The limit of quantification of the method was 0.1 ?g/mL for all analytes, and weighted-matrix-matched standard curves showed a good linearity up to 10 ?g/mL. In order to check the correct response for over-range samples, parallelism tests were also assessed. In the entire analytical range the intra and inter-day precision (RSD%) values were ? 7.31% and ? 13.5%, respectively. For all the analytes the intra and inter-day trueness (Bias%) values ranged from -11.3% to 10.2%. To our knowledge, this is the first MEPS-HPLC-PDA based method that uses MEPS procedure for simultaneous determination of these seven NSAIDs in plasma and urine samples. PMID:25278162

  19. Anti-inflammatory effects of tocopherol metabolites

    Microsoft Academic Search

    Paula Grammas; Ladan Hamdheydari; Elaine J Benaksas; Shenyun Mou; Quentin N Pye; William J Wechter; Robert A Floyd; Charles Stewart; Kenneth Hensley

    2004-01-01

    Our objective was to assess the anti-inflammatory effects of ?-tocopherol, ?-tocopherol, and their metabolites 2,5,7,8-tetramethyl-2-(?-carboxyethyl)-6-hydroxychroman (?-CEHC) and 2,7,8-trimethyl-2-(?-carboxyethyl)-6-hydroxychroman (?-CEHC) in defined cell culture systems. Rat aortic endothelial cells and mouse microglial cultures were treated with tumor necrosis factor TNF? or bacterial lipopolysaccharide (LPS) and nitrite and prostaglandin E2 (PGE2) were measured. ?-CEHC suppressed TNF?-stimulated nitrite production in both cell types,

  20. Anti-inflammatory phloroglucinol derivatives from Hypericum empetrifolium

    PubMed Central

    Crockett, Sara L.; Wenzig, Eva-Maria; Kunert, Olaf; Bauer, Rudolf

    2010-01-01

    Phytochemical investigation of Hypericum empetrifolium Willd. (Clusiaceae), a species native to Greece and Turkey has led to the bioassay-guided identification of two acylphloroglucinol derivatives with potent in vitro anti-inflammatory activity. Using NMR spectroscopy and mass spectrometry, the acylphloroglucinol derivatives were characterized as 3-geranyl-1-(2?-methylpropanoyl)phloroglucinol (1) and 3-geranyl-1-(2?-methylbutanoyl)phloroglucinol (2). Hypotheses are proposed regarding the biosynthetic origin of these and similar acylphloroglucinols from related Hypericum species. Compounds 1 and 2 were evaluated for in vitro inhibitory activity against COX-1, COX-2 and 5-LOX catalyzed LTB4 formation. Compound 1 displayed good activity (IC50 values: 6.0, 29.9, and 2.2 ?M, respectively) in all three assays. Compound 2 showed good activity (IC50 value: 5.8 ?M) against LTB4 formation and moderate activity (IC50 value: 26.2 ?M) against COX-1. PMID:21151761

  1. Novel N-phenylcarbamothioylbenzamides with anti-inflammatory activity and prostaglandin E2 inhibitory properties

    PubMed Central

    Limban, Carmen; Missir, Alexandru Vasile; Fahelelbom, Khairi Mustafa Salem; Al-Tabakha, Moawia Mohammad; Caproiu, Miron Teodor; Sadek, Bassem

    2013-01-01

    A number of 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl) benzamides (1a–h) were synthesized via reaction of 2-((4-ethylphenoxy)methyl)benzoyl isothiocyanate (2) as a key intermediate with several substituted primary aromatic amines. The new compounds were characterized by proton nuclear magnetic resonance (1H-NMR), carbon-13 nuclear magnetic resonance (13C-NMR), infrared spectrometry (IR), mass spectrometry (MS), and elemental analysis. The anti-inflammatory activity of 1a–h was investigated by acute carrageenan-induced paw edema in mice using the reference drug indomethacin. The results obtained indicated that, of the derivatives developed, 1a and 1d–h exhibited significantly higher anti-inflammatory activity (26.81%–61.45%) when compared with the reference drug indomethacin (22.43%) (P = 0.0490 for 1a, 0.0015 for 1d, 0.0330 for 1f, and P < 0.001 for 1e and 1h). Moreover, the ulcer incidence of 20% for 1e and 1h was clearly lower when compared with the indomethacin group (in which the ulcer incidence was 80%). Of particular note, the ulcer index of 0.2 for 1e was significantly less than that in the indomethacin group (0.6, P = 0.014). Additionally, prostaglandin E2 (PGE2) inhibitory properties were found to be high with 1e (68.32 pg/mL), significantly different from those of the placebo group (530.13 pg/mL, P < 0.001), and equipotent to the effect observed in the indomethacin-pretreated group (96.13 pg/mL, P > 0.05). Moreover, the PGE2 level of 54.15 pg/mL with 1h was also significantly different from that of the placebo group (P < 0.001) and of the indomethacin group (P < 0.05). The significant inhibition of PGE2 observed with 1e (68.32 pg/mL) and 1h (54.15 pg/mL) agree with their observed ulcer incidences. Our overall findings for N-phenylcarbamothioylbenzamides 1a–h clearly suggest that the compounds exhibit an anti-inflammatory effect, potently inhibit PGE2 synthesis, and markedly demonstrate low ulcer incidence. PMID:24039398

  2. Evaluation of the antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities of ethanolic extract of Ammi majus seeds in albino rats and mice.

    PubMed

    Koriem, Khaled M M; Asaad, Gihan F; Megahed, Hoda A; Zahran, Hanan; Arbid, Mahmoud S

    2012-06-01

    Pharmacological and biochemical studies on the Ammi majus seeds L. (family Umbelliferae) grown in Egypt are limited. Furocoumarins are the major constituents in the plant seeds. In the present study, the evaluation of the antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities on albino rats and mice was done. After 2 months of administration, both the doses (50 and 100 mg/kg body weight [bwt], respectively) of the alcoholic extract of the A. majus seed result in a significant decrease in the concentrations of cholesterol, triglycerides, and low-density lipoprotein and increase in the concentration of high-density lipoprotein. The extract was found to inhibit the rat paw edema at both the doses, which means that it exerts a significant anti-inflammatory activity compared with control-untreated groups at the intervals of 30 and 60 minutes posttreatment. The antipyretic effect of the extract was quite obvious; it showed that 100 mg/kg bwt was more potent in lowering body temperature starting after 1 hour of treatment than the lower dose (50 mg/kg bwt). It is worth to mention that the A. majus extract with its coumarin contents as well as the tested biological activities of the plant was investigated for the first time in the current study. In conclusion, ethanolic extract of the A. majus seeds had antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities that are dose dependant. PMID:22550046

  3. Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet.

    PubMed

    Jin, Chunhua; O'Boyle, Sean; Kleven, Daniel T; Pollock, Jennifer S; Pollock, David M; White, John J

    2014-08-01

    Metabolic syndrome (MetS) and chronic kidney disease are global health issues. Metabolic syndrome induces hypertension and commonly results in renal damage. The optimal therapy for hypertension in MetS is unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects. In the present study we investigated the effects of azilsartan (AZL), chlorthalidone (CLTD) and their combination on blood pressure and renal injury in a rodent model with features of MetS. Dahl salt-sensitive rats were fed high-fat (36% fat), high-salt (4% NaCl) diet. Groups were then treated with vehicle, AZL (3 mg/kg per day), CLTD (5 mg/kg per day) or AZL + CLTD. Mean arterial pressure was recorded continuously by telemetry. After 26 days, rats were killed humanely and their kidneys were harvested for histology. Both AZL and CLTD attenuated the rise in blood pressure compared with vehicle and the combination further reduced blood pressure compared with CLTD alone. All treatments reduced proteinuria and albuminuria. Nephrinuria was prevented only in groups treated with AZL. Nephrinuria was 57% lower and proteinuria was 47% lower with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells in the kidney. In conclusion, in our model, AZL and CLTD lower blood pressure and exhibit renal protective effects. Treatment with AZL offers additional protection, as evidenced by lower nephrinuria and plasma monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice for hypertensive therapy in MetS. PMID:24798707

  4. In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa

    Microsoft Academic Search

    Jae Youl Cho; Kyong Up Baik; Jee H Jung; Myung Hwan Park

    2000-01-01

    We investigated in vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone from Saussurea lappa, on tumor necrosis factor (TNF)-? and nitric oxide (NO) release, and lymphocyte proliferation. Cynaropicrin strongly inhibited TNF-? release from lipopolysaccharide-stimulated murine macrophage, RAW264.7 cells, and differentiated human macrophage, U937 cells, proved to produce notable amount of TNF-?. It also potently attenuated the accumulation of NO released

  5. H2S-releasing drugs: anti-inflammatory, cytoprotective and chemopreventative potential.

    PubMed

    Gemici, Burcu; Elsheikh, Wagdi; Feitosa, Karla B; Costa, Soraia K P; Muscara, Marcelo N; Wallace, John L

    2015-04-30

    Hydrogen sulfide exerts a number of cytoprotective and anti-inflammatory effects in many organ systems. In an effort to exploit these potent and beneficial effects, a number of hydrogen sulfide-releasing derivatives of existing drugs have been developed and extensively tested in pre-clinical models. In particular, efforts have been made by several groups to develop hydrogen sulfide-releasing derivatives of a number of nonsteroidal anti-inflammatory drugs. The main goal of this approach is to reduce the gastrointestinal ulceration and bleeding caused by this class of drugs, particularly when used chronically such as in the treatment of arthritis. However, these drugs may also have utility for prevention of various types of cancer. This paper provides an overview of some of the mechanisms underlying the anti-inflammatory and cytoprotective actions of hydrogen sulfide. It also gives some examples of hydrogen sulfide-releasing anti-inflammatory drugs, and their actions in terms of reducing inflammation and attenuating the development of cancer in experimental models. PMID:25461269

  6. Anti-inflammatory and anti-hyperalgesic activities of Acanthopanax trifoliatus (L) Merr leaves

    PubMed Central

    Hamid, Roslida Abdul; Kee, Teoh Hui; Othman, Fezah

    2013-01-01

    Context: Acanthopanax trifoliatus is a ginseng-like plant, which has been widely used to treat various diseases including inflammatory-related diseases. Aims: The present study has been designed to investigate the anti-inflammatory and anti-hyperalgesic effects of various fractions of Acanthopanax trifoliatus leaves ethanolic extract in rats. Materials and Methods: Anti-inflammatory activity was studied by using carrageenan-induced edema on rat paw whilst anti-hyperalgesic was assessed by using carrageenan-evoked thermal hyperalgesia on plantar test. Statistical Analysis Used: Data were analyzed using Student t-test to compare with control. Multiple comparisons for difference between control and extract-treated groups were evaluated by Tukey HSD (Honestly Significant Difference) test. P values less than 0.05 (P < 0.05) is considered significant. Results: Among three different fractions i.e., hexane, dichloromethane, and methanol tested, methanolic fraction displayed the most potent fraction amongst those three. It gave significant anti-inflammatory effect at highest dose, 500 mg/kg, with 77.24% of inhibition. Whilst for anti-hyperalgesic activity, methanolic fraction showed the highest efficacy at 375 mg/kg. Administration of methanolic fraction of Acanthopanax trifoliatus inhibited paw edema in a dose- dependent manner. The inhibition for both activities might be due to possible composition of polar compounds, which are flavonoids and phenolics content. Conclusions: Methanol fraction of Acanthopanax trifoliatus leaves has potential effect as anti-inflammatory and anti-hyperalgesia in acute inflammation model. PMID:23798889

  7. 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

  8. Structure-based design of phthalimide derivatives as potential cyclooxygenase-2 (COX-2) inhibitors: anti-inflammatory and analgesic activities.

    PubMed

    Alanazi, Amer M; El-Azab, Adel S; Al-Suwaidan, Ibrahim A; ElTahir, Kamal Eldin H; Asiri, Yousif A; Abdel-Aziz, Naglaa I; Abdel-Aziz, Alaa A-M

    2015-03-01

    A group of 30 cyclic imides (1-10a-c) was designed for evaluation as a selective COX-2 inhibitor and investigated in vivo for anti-inflammatory and analgesic activities. Compounds 6a, 6b, 7a and 7b exhibit optimal COX-2 inhibitory potency (IC50 = 0.18, 0.24, 0.28 and 0.36 ?M; respectively) and selectivity index (SI) range of 363-668. In vitro COX-1/COX-2 inhibition structure-activity studies identified compound 6a as a highly potent (IC50 = 0.18 ?M), and an extremely selective [COX-2 (SI) = 668] comparable to celecoxib [COX-2 (SI) > 384], COX-2 inhibitor that showed superior anti-inflammatory activity (ED50 = 54.0 mg/kg) relative to diclofenac (ED50 = 114 mg/kg). Molecular Docking study of the synthesized compound 6a into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. Docking study showed that the methoxy moeities of 6a inserted deep inside the 2°-pocket of the COX-2 active site, where the O-atoms of such groups underwent an H-bonding interaction with His(90) (3.02 ?), Arg(513) (1.94, 2.83 ?), and Gln(192) (3.25 ?). PMID:25549551

  9. 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

  10. Lyprinol—is it a Useful Anti-inflammatory Agent?

    Microsoft Academic Search

    Sheila A. Doggrell

    The New Zealand green lipped mussel preparation Lyprinol is available without a prescription from a supermarket, pharmacy or Web. The Food and Drug Administration have recently warned Lyprinol USA about their extravagant anti-inflammatory claims for Lyprinol appearing on the web. These claims are put to thorough review. Lyprinol does have anti-inflammatory mechanisms, and has anti-inflammatory effects in some animal models

  11. 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

  12. Anti-inflammatory potential of silk sericin.

    PubMed

    Aramwit, Pornanong; Towiwat, Pasarapa; Srichana, Teerapol

    2013-04-01

    Silk sericin was found to suppress the production of pro-inflammatory cytokines, which are related to the inflammatory reaction. The objectives of this study were to investigate the anti-inflammatory effect of sericin in vivo using the carrageenan-induced rat edema model and changes in the histology of tissues. The effects of sericin on the expression of COX-2 and iNOS were also evaluated. Sericin solutions at 0.004-0.080 mg/mL were applied topically to the top of the hind paw and carrageenan (1.0 mg) was injected subcutaneously to the plantar surface of the right hind paw. Our results indicated that sericin significantly reduced the inflammation in rats' paw compared with the negative control (water and acetone) and its effect at 0.080 mg/mL was only slightly lower than that of 1.0% w/v indomethacin. Similar numbers of polymorphonuclear and macrophage cells were found in rats' tissue treated with indomethacin and sericin solution, while the numbers were significantly higher in their absence. The gene expression results by RT-PCR showed that the COX-2 and iNOS genes were down-regulated in samples treated with sericin in a dose dependent manner. These data indicated that the anti-inflammatory properties of sericin may be partly attributable to the suppression of the COX-2 enzyme and nitric oxide production. PMID:23738464

  13. Anti-inflammatory effects of resolvin-D1 on human corneal epithelial cells: in vitro study

    PubMed Central

    2014-01-01

    Background This study evaluated the anti-inflammatory effects of Resolvin-D1 (RV-D1) and its mechanism of action in human corneal epithelial (HCE) cells. Methods HCE cells were incubated with different concentrations of RV-D1 for different time periods. Oleic acid (OA) and Dexamethasone (DM) served as negative and positive controls, respectively. Cells were stimulated with polyriboinosinic:polyribocytidylic acids (poly I:C). The protein contents and mRNA expression levels of Tumor necrosis factor-? (TNF-?), Interleukin (IL)-6, IL-1? and IL-8 were evaluated with multiplex fluorescent bead immunoassay (FBI) and real time-PCR, respectively. In addition, the expression of inhibitory factor-?B? (I-?B?) was evaluated with real time-PCR. Results The protein level of pro-inflammatory cytokines TNF-?, IL-6, IL-1? and IL-8 significantly increased after stimulation with Poly I:C. RV-D1 treatment at concentration of 1 ?M decreased the protein level of TNF-? to 20.76?±?9.3% (P??0.05) and IL-8 to 51.15?±?13.01% (P?highly significant dose response curve was demonstrated for RV-D1 treated HCE cells for TNF-? and IL-1?. DM treatment decreased the protein content for all of the pro-inflammatory cytokines, similar results were demonstrated at the mRNA level. The anti-inflammatory effects of RV-D1 were similar to those of DM for TNF-?, IL-6 and IL-8. Conclusions RV-D1 may serve as a potent anti-inflammatory agent in ocular surface inflammation, as evaluated in cultured HCE cells. The anti-inflammatory effects of RV-D1 were comparable to those of DM, and were mediated through nuclear factor kappa B (NF-?B) signal transduction. PMID:24580770

  14. Heme oxygenase-1 and anti-inflammatory M2 macrophages.

    PubMed

    Naito, Yuji; Takagi, Tomohisa; Higashimura, Yasuki

    2014-12-15

    Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting enzymatic step of heme degradation and produces carbon monoxide, free iron, and biliverdin. HO-1, a stress-inducible protein, is induced by various oxidative and inflammatory signals. Consequently, HO-1 expression has been regarded as an adaptive cellular response against inflammatory response and oxidative injury. Although several transcriptional factors and signaling cascades are involved in HO-1 regulation, the two main pathways of Nrf2/Bach1 system and IL-10/HO-1 axis exist in monocyte/macrophage. Macrophages are broadly divisible into two groups: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. More recently, several novel macrophage subsets have been identified including Mhem, Mox, and M4 macrophages. Of these, M2 macrophages, Mhem, and Mox are HO-1 highly expressing macrophages. HO-1 has been recognized as having major immunomodulatory and anti-inflammatory properties, which have been demonstrated in HO-1 deficient mice and human cases of genetic HO-1 deficiency. However, the mechanism underlying the immunomodulatory actions of HO-1 remains poorly defined. This review specifically addresses macrophage polarization. The present current evidence indicates that HO-1 induction mediated by multiple pathways can drive the phenotypic shift to M2 macrophages and suggests that HO-1 induction in macrophages is a potential therapeutic approach to immunomodulation in widely diverse human diseases. PMID:25241054

  15. Anti-Inflammatory Effects of Macrophilin-lnteracting Drugs in Animal Models of Irritant and Allergic Contact Dermatitis

    Microsoft Academic Search

    J. G. Meingassner; A. Stütz

    1992-01-01

    The macrolide antibiotics, FK 506 and rapamycin, have been reported to be potent immunosuppressive drugs. Both FK506 and rapamycin bind to the immunophilin macrophilin-12. Rapamycin, however, acts on T cells by a different mode of action which does not affect the transcription of lymphokines. The anti-inflammatory effects of FK 506 and rapamycin have been tested in mouse models of irritant

  16. Enhanced anti-inflammatory effect and reduced immunogenicity of bovine liver superoxide dismutase by conjugation with homologous albumin

    Microsoft Academic Search

    K. Wong; L. G. Cleland; M. J. Poznansky

    1980-01-01

    Bovine liver superoxide dismutase (SOD) can be crosslinked to albumin to form soluble conjugates with up to 70% retention of original enzyme activity. These conjugates have markedly prolonged plasma half-times of enzymatic activity (15 h) compared to native SOD (6 min). The conjugates have potent anti-inflammatory effects in vivo and reduced immunogenicity and antigenicity compared to native SOD. These conjugates

  17. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress

    Microsoft Academic Search

    Roberto Motterlini; Roberta Foresti; Rekha Bassi; Colin J Green

    2000-01-01

    Curcumin, a widely used spice and coloring agent in food, has been shown to possess potent antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. The mechanism(s) of such pleiotropic action by this yellow pigment is unknown; whether induction of distinct antioxidant genes contributes to the beneficial activities mediated by curcumin remains to be investigated. In the present

  18. FDA Strengthens Warning of Heart Attack and Stroke Risk for Non-Steroidal Anti-Inflammatory Drugs

    MedlinePLUS

    ... Health and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your Health A to ... and Stroke Risk for Non-Steroidal Anti-Inflammatory Drugs Search the Consumer Updates Section Get this high- ...

  19. Evaluation of anti-inflammatory and anti oxidant activity of a poly herbal formulation - Chyavana drink

    PubMed Central

    Poornima, K.; Thangal, Haseeb Koya; Karpagavalli, S.

    2008-01-01

    The study was designed to evaluate the anti-inflammatory and antioxidant activity of a poly herbal formulation-Chyavana drink. The inflammation was induced in albino rats by carrageenan. The formulation was effective when compared with a known anti-inflammatory drug. The antioxidant activity was studied by invitro methods. The DPPH radical scavenging activity was found to be showing higher percentage of inhibition and reducing power at high concentrations. The phenolic content of Chyavana drink was observed to be high showing a good antioxidant effect. PMID:22557286

  20. Anti-inflammatory effect of caffeic acid methyl ester and its mode of action through the inhibition of prostaglandin E 2, nitric oxide and tumor necrosis factor-? production

    Microsoft Academic Search

    Kyung-Min Shin; In-Tae Kim; Young-Mi Park; Joohun Ha; Jong-Won Choi; Hee-Juhn Park; Yong Sup Lee; Kyung-Tae Lee

    2004-01-01

    The anti-inflammatory effects of caffeic acid (CA), caffeic acid methyl ester (CM) and di-O-acetylcaffeic acid (DAC) were investigated in rats using the carrageenin-induced edema model and the antinociceptive effects of these compounds were also assessed in mice by means of the acetic acid-induced abdominal constriction test and hot plate test. CM (10mg\\/kg, p.o.) showed the most potent anti-inflammatory and antinociceptive

  1. Repositioning drugs for inflammatory disease - fishing for new anti-inflammatory agents.

    PubMed

    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

    2014-09-01

    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

  2. A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-?B inhibition.

    PubMed

    Kobayashi, Yoshiki; Wada, Hiroo; Rossios, Christos; Takagi, Dai; Higaki, Manabu; Mikura, Shin'ichiro; Goto, Hajime; Barnes, Peter J; Ito, Kazuhiro

    2013-04-01

    Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease, such as chronic obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro and in vivo. However the anti-inflammatory efficacies of current macrolides are relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior anti-inflammatory effects to macrolides in current clinical use. The effects of solithromycin (SOL) on lipopolysaccharide-induced TNF? (tumor necrosis factor ?) and/or CXCL8 (C-X-C motif chemokine ligand 8; interleukin-8) release, phorbol 12-myristate 13-acetate-induced MMP9 (matrix metalloproteinase 9) activity and NF-?B (nuclear factor-?B) activity under conditions of oxidative stress have been evaluated and compared with the effects of erythromycin, clarithromycin, azithromycin, and telithromycin in macrophage-like PMA-differentiated U937 cells and peripheral blood mononuclear cells (PBMC) obtained from COPD patients. We also examined effect of SOL on cigarette smoke-induced airway inflammation in mice. SOL exerted superior inhibitory effects on TNF?/CXCL8 production and MMP9 activity in monocytic U937 cells. In addition, SOL suppressed TNF? release and MMP9 activity in PBMC from COPD patients at 10 µM, which is 10 times more potent than the other macrolides tested. Activated NF-?B by oxidative stress was completely reversed by SOL. SOL also inhibited cigarette smoke-induced neutrophilia and pro-MMP9 production in vivo, although erythromycin did not inhibit them. Thus, SOL showed better anti-inflammatory profiles compared with macrolides currently used in the clinic and may be a promising anti-inflammatory and antimicrobial macrolide for the treatment of COPD in future. PMID:23359665

  3. Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

    PubMed Central

    Steel, Helen C.; Theron, Annette J.; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

    2012-01-01

    Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance. PMID:22778497

  4. Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil.

    PubMed

    Intahphuak, S; Khonsung, P; Panthong, A

    2010-02-01

    This study investigated some pharmacological properties of virgin coconut oil (VCO), the natural pure oil from coconut [Cocos nucifera Linn (Palmae)] milk, which was prepared without using chemical or high-heat treatment. The anti-inflammatory, analgesic, and antipyretic effects of VCO were assessed. In acute inflammatory models, VCO showed moderate anti-inflammatory effects on ethyl phenylpropiolate-induced ear edema in rats, and carrageenin- and arachidonic acid-induced paw edema. VCO exhibited an inhibitory effect on chronic inflammation by reducing the transudative weight, granuloma formation, and serum alkaline phosphatase activity. VCO also showed a moderate analgesic effect on the acetic acid-induced writhing response as well as an antipyretic effect in yeast-induced hyperthermia. The results obtained suggest anti-inflammatory, analgesic, and antipyretic properties of VCO. PMID:20645831

  5. Anti-inflammatory effects of yerba maté extract ( Ilex paraguariensis) ameliorate insulin resistance in mice with high fat diet-induced obesity

    Microsoft Academic Search

    Demétrius P. Arçari; Waldemar Bartchewsky; Tanila W. dos Santos; Karim A. Oliveira; Carlorine C. DeOliveira; Érica M. Gotardo; José Pedrazzoli; Alessandra Gambero; Lucio F. C. Ferraz; Patricia de O. Carvalho; Marcelo L. Ribeiro

    2011-01-01

    The aim of the present study was to evaluate the effects of yerba maté extract upon markers of insulin resistance and inflammatory markers in mice with high fat diet-induced obesity. The mice were introduced to either standard or high fat diets. After 12 weeks on a high fat diet, mice were randomly assigned to one of the two treatment conditions,

  6. 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

  7. Anti-inflammatory Effect of Palmitoylethanolamide on Human Adipocytes

    Microsoft Academic Search

    Laurence Hoareau; Marion Buyse; Franck Festy; Palaniyandi Ravanan; Marie-Paule Gonthier; Isabel Matias; Stefania Petrosino; Frank Tallet; Christian Lefebvre d'Hellencourt; Maya Cesari; Vincenzo Di Marzo; Régis Roche

    2009-01-01

    Obesity leads to the appearance of an inflammatory process, which can be initiated even with a moderate weight gain. Palmitoylethanolamide (PEA) is an endogenous lipid, secreted by human adipocytes, that possesses numerous anti-inflammatory properties. The main purpose of this study was to investigate the anti-inflammatory effect of PEA on human adipocytes, as well as in a murine model. The production

  8. Anti-inflammatory and antinociceptive activity assessment of plants used as remedy in Turkish folk medicine.

    PubMed

    Erdemoglu, Nurgun; Küpeli, Esra; Ye?ilada, Erdem

    2003-11-01

    Ethanolic and aqueous extracts from seven plant species used in Turkish traditional medicine were evaluated for in vivo anti-inflammatory and antinociceptive activities; Helleborus orientalis Lam. roots and herbs, Juglans regia L. leaves, Laurocerasus officinalis Roemer leaves, Nerium oleander L. dried and fresh flowers and leaves, Rhododendron ponticum L. leaves, Rubus hirtus Walds. et Kit aerial parts and Rubus sanctus Schreber aerial parts and roots. All the plant extracts, except the aqueous extract of Rubus hirtus, were shown to possess significant antinociceptive activity in varying degrees against p-benzoquinone-induced abdominal contractions in mice. However, only the ethanolic extracts of Helleborus orientalis roots, Juglans regia leaves, Laurocerasus officinalis leaves, Nerium oleander dried and fresh flowers, and Rhododendron ponticum leaves exhibited potent anti-inflammatory activity against carrageenan-induced hind paw edema model in mice without inducing any gastric damage. Results of the present study confirmed the folkloric claim that all the selected materials to possess potent antinociceptive and anti-inflammatory activity. PMID:14522443

  9. 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

  10. In vitro anti-inflammatory effects of naturally-occurring compounds from two Lauraceae plants.

    PubMed

    Coy-Barrera, Ericsson D; Cuca-Suarez, Luis E

    2011-12-01

    The in vitro anti-inflammatory effects of seven known lignans and one dihydrochalcone isolated from the leaves of two Lauraceae species (Pleurothyrium cinereum and Ocotea macrophylla), were evaluated through the inhibition of COX-1, COX-2, 5-LOX and the aggregation of rabbit platelets induced by PAF, AA and ADP. (+)-de-4"-O-methylmagnolin 4 was found to be a potent COX-2/5-LOX dual inhibitor and PAF-antagonist (COX-2 IC(50) 2.27 µM; 5-LOX IC(50) 5.05 µM; PAF IC(50) 2.51 µM). However, all compounds exhibited an activity at different levels, indicating good anti-inflammatory properties to be considered in further structural optimization studies. PMID:22011769

  11. Dying and necrotic neutrophils are anti-inflammatory secondary to the release of ?-defensins

    PubMed Central

    Miles, Katherine; Clarke, David J.; Lu, Wuyuan; Sibinska, Zaneta; Beaumont, Paula E.; Davidson, Donald J.; Barr, Tom A.; Campopiano, Dominic J.; Gray, Mohini

    2010-01-01

    Neutrophils are recruited to sites of injury but their timely removal is thought to be vital to prevent exacerbating inflammation. In addition, the recognition of apoptotic cells by cells of the innate immune system provides potent anti-inflammatory and anti-immunogenic signals. In this paper we describe how human neutrophils dying by apoptosis or necrosis release anti-inflammatory peptides, the alpha defensins. This family of small cationic peptides, effectively inhibits the secretion of multiple pro-inflammatory cytokines and nitric oxide from macrophages, the main innate immune cell found at sites of chronic inflammation. In addition, the systemic administration of necrotic neutrophil supernatants and alpha defensins protects mice from a murine model of peritonitis. Hence their effects may be far reaching and serve to kill microbes whilst regulating a potentially tissue destructive inflammatory response. PMID:19596979

  12. Assessment of Anti-inflammatory Activity of Taxus Baccata Linn. Bark Extract.

    PubMed

    Dutta, Satyajit; Mariappan, G; Sarkar, Dipankar; Sarkar, Piyali

    2010-01-01

    Taxus baccata (L) known as Sthauneyaka in Sanskrit(1) has wide range of biological activities including analgesic, anti-malarial, anti-rheumatic, sedative, anti-spasmodic, aphrodisiac and anti-asthmatic. In the present study, the dried and powdered bark of Taxus baccata (L) was extracted with 95% ethanol and ether at room temperature and screened for their anti--inflammatory activity by Carrageenan-induced paw edema method in rat. 95% ethanol extract exhibits potent anti-inflammatory activity at 200mg/kg four hours after administration in comparison with ether extract, as well reference standard, Aspirin. The observed pharmacological activities provide a scientific basis for the folklore use of the plant in treating acute inflammation. PMID:22557354

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

    PubMed

    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

    2015-03-17

    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

  14. 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

  15. Reduction of glucose intolerance with high fat feeding is associated with anti-inflammatory effects of thioredoxin 1 overexpression in mice

    PubMed Central

    Salmon, Adam B.; Flores, Lisa C.; Li, Yan; Van Remmen, Holly; Richardson, Arlan; Ikeno, Yuji

    2012-01-01

    Aging is associated with reduced ability to maintain normal glucose homeostasis. It has been suggested that an age-associated increase in chronic pro-inflammatory state could drive this reduction in glucoregulatory function. Thioredoxins (Trx) are oxido-reductase enzymes that play an important role in the regulation of oxidative stress and inflammation. In this study, we tested whether overexpression of Trx1 in mice [Tg(TRX1)+/0] could protect from glucose metabolism dysfunction caused by high fat diet feeding. Body weight and fat mass gains with high fat feeding were similar in Tg(TRX1)+/0 and wild-type mice; however, high fat diet induced glucose intolerance was reduced in Tg(TRX1)+/0 mice relative to wild-type mice. In addition, expression of the pro-inflammatory cytokine TNF-? was reduced in adipose tissue of Tg(TRX1)+/0 mice compared to wild-type mice. These findings suggest that activation of thioredoxins may be a potential therapeutic target for maintenance of glucose metabolism with obesity or aging. PMID:22953037

  16. Esculentic acid, a novel and selective COX-2 inhibitor with anti-inflammatory effect in vivo and in vitro.

    PubMed

    Niu, Xiaofeng; Mu, Qingli; Li, Weifeng; Yao, Huan; Li, Huani; Huang, Huimin

    2014-10-01

    Esculentic acid (EA), a pentacyclic triterpenoids compound extracted from the Chinese herb Phytolacca esculenta, has long been used in traditional Chinese medicine for the treatment of rheumatoid arthritis, edema, hepatitis and bronchitis disease. The present study aimed to investigate the anti-inflammatory effect of EA in vivo and in vitro and the effect of EA on cyclooxygenase (COX) protein expression. To gain insight into the anti-inflammatory effect of EA both in vivo and in vitro and its effect on COX-2 expression, we used animal inflammatory models and lipopolysaccharide (LPS)-induced mouse peritoneal macrophages to examine the anti-inflammatory action of EA. Our findings demonstrated that EA possessed potent anti-inflammatory activity both in vivo and in vitro, while the anti-inflammation action in vitro may be attributed to the inhibition of the level of TNF-? and IL-6 pro-inflammatory cytokines and PGE2 inflammatory mediator in macrophages. Meanwhile, the production of PGE2 was possibly associated with COX-2 protein expression which was similar to that of NSAIDS. The study extends our understanding of the anti-inflammatory effect of EA both in vivo and in vitro and provides clarification of the molecular mechanisms underlying the effect of EA on PGE2 production, extending a novel aspect to the pharmacological activity of EA. PMID:24991788

  17. High-performance liquid chromatography analysis of anti-inflammatory pharmaceuticals with ultraviolet and electrospray-mass spectrometry detection in suspected counterfeit homeopathic medicinal products.

    PubMed

    Panusa, Alessia; Multari, Giuseppina; Incarnato, Giampaolo; Gagliardi, Luigi

    2007-03-12

    A simple high-performance liquid chromatography (HPLC) method with both ultraviolet (UV) and electrospray ionisation mass spectrometry (ESI-MS) detection has been developed for the determination of seven pharmaceuticals in counterfeit homeopathic preparations. Naproxen, Ketoprofen, Ibuprofen, Diclofenac, Piroxicam, Nimesulide and Paracetamol were separated by reversed phase chromatography with acetonitrile-water (0.1% acetic acid) mobile phase, and detected by UV at 245 nm and by ESI-MS in negative ionisation mode with the exception of Paracetamol which was detected in positive ionisation mode. Benzoic acid was used as internal standard (IS). This method was successfully applied to the analysis of homeopathic preparations like mother tinctures, solutions, tablets, granules, creams, and suppositories. Linearity was studied with UV detection in the 50-400 microg mL(-1) range and with ESI-MS in the 0.1-50 microg mL(-1) range. Good correlation coefficients were found in both UV and ESI-MS. Detection limits ranged from 0.18 to 41.5 ng in UV and from 0.035 to 1.00 ng in ESI-MS. PMID:17127029

  18. 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...

  19. 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 ?M 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

  20. 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

  1. Antioxidant, Antinociceptive and Anti-inflammatory Activities of Ethanolic Extract of Leaves of Alocasia indica (Schott.).

    PubMed

    Mulla, Wa; Kuchekar, Sb; Thorat, Vs; Chopade, Ar; Kuchekar, Bs

    2010-04-01

    Extracts obtained from the leaves of various Alocasia species have been used in India as folk remedy for the treatment of various inflammatory ailments including rheumatism and bruise. The ethanolic extract of leaves of Alocasia indica Schott. was evaluated by using different in vitro antioxidant models of screening like scavenging of 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical, nitric oxide radical, superoxide anion radical, and hydroxyl radical. The antinociceptive activity was tested by acetic acid-induced writhing response, hot plate method, and tail flick method in albino rats. The anti-inflammatory potential of gels of ethanolic extract has been determined by using carrageenan-induced paw edema assay, formalin-induced paw edema assay, arachidonic acid-induced ear edema assay, and xylene-induced ear edema assay. The extract showed remarkable antioxidant activity in all models, comparable to the standard reference drug ascorbic acid. The ethanolic extract of Alocasia indica and its gels produced dose-dependent antinociceptive and anti-inflammatory activity, respectively. This finding suggests that ethanolic extract of A. indica possess potent antinociceptive and anti-inflammatory activity possibly due to its free radical scavenging properties. PMID:21264115

  2. Doxycycline exhibits anti-inflammatory activity in CF bronchial epithelial cells.

    PubMed

    Bensman, Timothy J; Nguyen, Albert N; Rao, Adupa P; Beringer, Paul M

    2012-10-01

    A hallmark of cystic fibrosis is the massive recruitment of neutrophils into the lung compartment in response to chronic Pseudomonas aeruginosa infection. The overexuberant neutrophilic response results in release of proteases (e.g. neutrophil elastase and matrix metalloproteinase-9) leading to matrix breakdown, airway remodeling, and progressive loss of lung function. Doxycycline is used clinically for the management of periodontitis due to its potent direct inhibition of matrix metalloproteinases; however, little is known regarding its potential anti-inflammatory properties and clinical utility in the context of cystic fibrosis airway disease. CF (IB3-1) and corrected (S9) bronchial epithelial cell lines were used to determine the cytotoxicity and anti-inflammatory effects of doxycycline in-vitro. Exposure to doxycycline, at low concentrations, resulted in minimal cell death and dose dependent reductions in release of CXCL-8 and MMP-9 protein. To confirm these findings, mechanistic analysis revealed ERK 1/2, p38, and JNK, but not NF-?B p65 dependent cell signaling inhibition with doxycycline treatment. These findings indicate that doxycycline exhibits anti-inflammatory activity in CF lung epithelial cells at concentrations below the cytotoxic potential. These data are encouraging and indicate in-vivo studies are warranted. PMID:22771903

  3. 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.

  4. Valosin containing protein (VCP) interacts with macrolide antibiotics without mediating their anti-inflammatory activities.

    PubMed

    Nuji?, Krunoslav; Smith, Marjorie; Lee, Michael; Belamari?, Daniela; Tomaškovi?, Linda; Alihodži?, Sulejman; Malnar, Ivica; Polan?ec, Denis; Schneider, Klaus; Erakovi? Haber, Vesna

    2012-02-29

    In addition to antibacterial activity, some macrolide antibiotics, such as azithromycin and clarithromycin, also exhibit anti-inflammatory properties in vitro and in vivo, although the targets and mechanism(s) of action remain unknown. The aim of the present study was to identify protein targets of azithromycin and clarithromycin which could potentially explain their anti-inflammatory effects. Using chemical proteomics approach, based on compound-immobilized affinity chromatography, valosin containing protein (VCP) was identified as a potential target of the macrolides. Validation studies confirmed the interaction of macrolides and VCP and gave some structural characteristics of this interaction. Cell based assays however, including the use of gene silencing and the study of VCP specific cellular functions in J774.A1 (murine macrophage) and IB3-1 (human cystic fibrotic epithelial) cell lines, failed to confirm an association between the binding of the macrolides to VCP and anti-inflammatory effects. These findings suggest the absence of an abundant high affinity protein target and the potential involvement of other biological molecules in the anti-inflammatory activity of macrolides. PMID:22209877

  5. Evaluation of the antioxidant, anti-inflammatory, and anticancer activities of Euphorbia hirta ethanolic extract.

    PubMed

    Sharma, Neelesh; Samarakoon, Kalpa W; Gyawali, Rajendra; Park, Yang-Ho; Lee, Sung-Jin; Oh, Sung Jong; Lee, Tae-Hoon; Jeong, Dong Kee

    2014-01-01

    This study evaluated the chemical composition, antioxidant, anti-inflammatory and anticancer activities of a Euphorbia hirta L. extract. The antioxidant activities of whole E. hirta ethanol extract were determined by electron spin resonance spectrophotometric analysis of 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl, and alkyl radical levels and by using an online high-performance liquid chromatography (HPLC)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay. The E. hirta ethanol extract (0.5 mg/mL) exhibited DPPH-scavenging activity of 61.19% ± 0.22%, while the positive control (0.5 mg/mL ascorbic acid) had 100% ± 0.22% activity. The concentration of the extract required to trap 50% of DPPH (IC50) was 0.205 mg/mL. Online HPLC analysis of the extract also showed strong antioxidant activity. The anti-inflammatory activity of the E. hirta extract was assessed in lipopolysaccharide-induced RAW 264.7 macrophages. The anti-inflammatory activity was highest in the presence of 200 µg/mL E. hirta extract, and nitric oxide production was decreased significantly (p < 0.05). The extract also showed selective anticancer activity at a concentration of 100 µg/mL (p < 0.05). These results indicated that E. hirta may warrant further investigation for the development of antioxidant, anti-inflammatory, and anticancer herbal medications. PMID:25225720

  6. Anti-inflammatory and analgesic activities of Melanthera scandens

    PubMed Central

    Okokon, Jude E; Udoh, Anwanga E; Frank, Samuel G; Amazu, Louis U

    2012-01-01

    Objective To evaluate the anti-inflammatory and analgesic activities of leaf extract of Melanthera scandens (M. scandens). Methods The crude leaf extract (39–111 mg/kg) of M. scandens was investigated for anti-inflammatory and analgesic activities using various experimental models. The anti-inflammatory activity was investigated using carragenin, egg-albumin induced oedema models, while acetic acid, formalin-induced paw licking and thermal-induced pain models were used to evaluate the antinociceptive property. Results The extract caused a significant (P<0.05 – 0.001) dose-dependent reduction of inflammation and pains induced by different agents used. Conclusions The leaf extract possesses anti-inflammatory and analgesic effects which may be mediated through the phytochemical constituents of the plant. PMID:23569885

  7. Anti-inflammatory therapies for cardiovascular disease.

    PubMed

    Ridker, Paul M; Lüscher, Thomas F

    2014-07-14

    Atherothrombosis is no longer considered solely a disorder of lipoprotein accumulation in the arterial wall. Rather, the initiation and progression of atherosclerotic lesions is currently understood to have major inflammatory influences that encompass components of both the innate and acquired immune systems. Promising clinical data for 'upstream' biomarkers of inflammation such as interleukin-6 (IL-6) as well as 'downstream' biomarkers such as C-reactive protein, observations regarding cholesterol crystals as an activator of the IL-1? generating inflammasome, and recent Mendelian randomization data for the IL-6 receptor support the hypothesis that inflammatory mediators of atherosclerosis may converge on the central IL-1, tumour necrosis factor (TNF-?), IL-6 signalling pathway. On this basis, emerging anti-inflammatory approaches to vascular protection can be categorized into two broad groups, those that target the central IL-6 inflammatory signalling pathway and those that do not. Large-scale Phase III trials are now underway with agents that lead to marked reductions in IL-6 and C-reactive protein (such as canakinumab and methotrexate) as well as with agents that impact on diverse non-IL-6-dependent pathways (such as varespladib and darapladib). Both approaches have the potential to benefit patients and reduce vascular events. However, care should be taken when interpreting these trials as outcomes for agents that target IL-6 signalling are unlikely to be informative for therapies that target alternative pathways, and vice versa. As the inflammatory system is redundant, compensatory, and crucial for survival, evaluation of risks as well as benefits must drive the development of agents in this class. PMID:24864079

  8. 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-1?, TNF-?, 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-1?, TNF-?, 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-1?, TNF-?, PGE2 and MPO in inflamed paws. PMID:24351869

  9. Anti-inflammatory Strategies to Prevent Diabetic Cardiovascular Disease.

    PubMed

    Jialal, I; Devaraj, S

    2015-08-01

    Diabetes is a proinflammatory state and inflammation is crucial in the genesis of vascular complications. While there are many anti-inflammatory strategies, most of which have been shown to reduce inflammation in diabetes, there is sparse data on reduction in cardiovascular events (CVEs). To date, the only anti-inflammatory strategies that have been shown to reduce CVE in diabetes include statins, angiotensin receptor blockers, metformin, and pioglitazone. We also discuss the role of novel emerging therapies. PMID:25732108

  10. Anti-inflammatory effect of microalgal extracts from Tetraselmis suecica

    Microsoft Academic Search

    Wol Soon Jo; Yoo Jin Choi; Hyoun Ji Kim; Byung Hyouk Nam; Sook Hee Hong; Gye An Lee; Sang Wha Lee; Su Yeong Seo; Min Ho Jeong

    2010-01-01

    The aim of the present study was to examine the anti-inflammatory activities of extracts from Tetraselmis suecica with respect to nitric oxide (NO) production, tumor necrosis factor (TNF)-? and interlukin (IL)-6 release in lipopolysaccharide\\u000a (LPS)-stimulated RAW 264.7 cells. We prepared methanolic extracts and water extract using protease. Of all the prepared extracts,\\u000a 80% methanol extract exhibited the strongest anti-inflammatory effect.

  11. Anti-inflammatory glucocorticoid drugs: reflections after 60 years

    Microsoft Academic Search

    Michael W. Whitehouse

    2011-01-01

    This review considers the problem of the serious concomitant side effects of powerful anti-inflammatory drugs modelled upon\\u000a the principal human glucocorticoid hormone, cortisol. The very nature of the original bio-assays to validate their cortisol-like\\u000a hormonal and anti-inflammatory activities ensured that pleiotropic toxins were selected for clinical studies. Other complicating\\u000a factors have been (1) considerable reliance on bio-assays conducted in laboratory

  12. 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 ?-glucan (14.20%) was prominently higher than ?-glucan (1.45%). Its FTIR confirmed the presence of ?-linkages between sugars, and intramolecular amide bonds between sugars and amino acids. Its 1H-NMR spectrum showed that antrodan was a complex union of ?- and ?-glucans, which had (1?4)-linked ?-Glcp and (1?3)-linked ?-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 ?g/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 ?g/mL. PMID:24451244

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

    Microsoft Academic Search

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

    2002-01-01

    Adenosine (ADO) is an inhibitory neuromodulator that can increase nociceptive thresholds in response to noxious stimulation. Inhibition of the ADO-metabolizing enzyme, adenosine kinase (AK) increases extracellular ADO concentrations at sites of tissue trauma and AK inhibitors may have therapeutic potential as analgesic and anti-inflammatory agents. N7-((1?R,2?S,3?R,4?S)-2?,3?-dihydroxy-4?-amino-cyclopentyl)-4-amino-5-bromo-pyrrolo[2,3-a]pyrimidine (A-286501) is a novel and potent (IC50=0.47nM) carbocyclic nucleoside AK inhibitor that has no

  14. Furan fatty acid as an anti-inflammatory component from the green-lipped mussel Perna canaliculus

    PubMed Central

    Wakimoto, Toshiyuki; Kondo, Hikaru; Nii, Hirohiko; Kimura, Kaori; Egami, Yoko; Oka, Yusuke; Yoshida, Masae; Kida, Eri; Ye, Yiping; Akahoshi, Saeko; Asakawa, Tomohiro; Matsumura, Koichi; Ishida, Hitoshi; Nukaya, Haruo; Tsuji, Kuniro; Kan, Toshiyuki; Abe, Ikuro

    2011-01-01

    A lipid extract of Perna canaliculus (New Zealand green-lipped mussel) has reportedly displayed anti-inflammatory effects in animal models and in human controlled studies. However, the anti-inflammatory lipid components have not been investigated in detail due to the instability of the lipid extract, which has made the identification of the distinct active components a formidable task. Considering the instability of the active component, we carefully fractionated a lipid extract of Perna canaliculus (Lyprinol) and detected furan fatty acids (F-acids). These naturally but rarely detected fatty acids show potent radical-scavenging ability and are essential constituents of plants and algae. Based on these data, it has been proposed that F-acids could be potential antioxidants, which may contribute to the protective properties of fish and fish oil diets against chronic inflammatory diseases. However, to date, in vivo data to support the hypothesis have not been obtained, presumably due to the limited availability of F-acids. To confirm the in vivo anti-inflammatory effect of F-acids in comparison with that of eicosapentaenoic acid (EPA), we developed a semisynthetic preparation and examined its anti-inflammatory activity in a rat model of adjuvant-induced arthritis. Indeed, the F-acid ethyl ester exhibited more potent anti-inflammatory activity than that of the EPA ethyl ester. We report on the in vivo activity of F-acids, confirming that the lipid extract of the green-lipped mussel includes an unstable fatty acid that is more effective than EPA. PMID:21972415

  15. Prediction of Anti-inflammatory Plants and Discovery of Their Biomarkers by Machine Learning Algorithms and Metabolomic Studies.

    PubMed

    Chagas-Paula, Daniela Aparecida; Oliveira, Tiago Branquinho; Zhang, Tong; Edrada-Ebel, RuAngelie; Da Costa, Fernando Batista

    2015-04-01

    Nonsteroidal anti-inflammatory drugs are the most used anti-inflammatory medicines in the world. Side effects still occur, however, and some inflammatory pathologies lack efficient treatment. Cyclooxygenase and lipoxygenase pathways are of utmost importance in inflammatory processes; therefore, novel inhibitors are currently needed for both of them. Dual inhibitors of cyclooxygenase-1 and 5-lipoxygenase are anti-inflammatory drugs with high efficacy and low side effects. In this work, 57 leaf extracts (EtOH-H2O 7?:?3, v/v) from Asteraceae species with in vitro dual inhibition of cyclooxygenase-1 and 5-lipoxygenase were analyzed by high-performance liquid chromatography-high-resolution-ORBITRAP-mass spectrometry analysis and subjected to in silico studies using machine learning algorithms. The data from all samples were processed by employing differential expression analysis software coupled to the Dictionary of Natural Products for dereplication studies. The 6052 chromatographic peaks (ESI positive and negative modes) of the extracts were selected by a genetic algorithm according to their respective anti-inflammatory properties; after this procedure, 1241 of them remained. A study using a decision tree classifier was carried out, and 11 compounds were determined to be biomarkers due to their anti-inflammatory potential. Finally, a model to predict new biologically active extracts from Asteraceae species using liquid chromatography-mass spectrometry information with no prior knowledge of their biological data was built using a multilayer perceptron (artificial neural networks) with the back-propagation algorithm using the biomarker data. As a result, a new and robust artificial neural network model for predicting the anti-inflammatory activity of natural compounds was obtained, resulting in a high percentage of correct predictions (81?%), high precision (100?%) for dual inhibition, and low error values (mean absolute error?=?0.3), as also shown in the validation test. Thus, the biomarkers of the Asteraceae extracts were statistically correlated with their anti-inflammatory activities and can therefore be useful to predict new anti-inflammatory extracts and their anti-inflammatory compounds using only liquid chromatography-mass spectrometry data. PMID:25615275

  16. Evaluation of anti-inflammatory and antioxidant activities of mixed-ligand Cu(II) complexes of dien and its Schiff dibases with heterocyclic aldehydes and 2-amino-2-thiazoline

    Microsoft Academic Search

    E. Pontiki; D. Hadjipavlou-Litina; A. T. Chaviara; C. A. Bolos

    2006-01-01

    A new series of complexes of the type [Cu(dien)(2a-2tzn)Y2] and [Cu(dienXX)(2a-2tzn)Y2] has been tested for anti-inflammatory and antioxidant activity. The tested compounds inhibit significantly the carrageenin induced paw edema (36.4–55.8%) and present important scavenging activities. Although their interaction with the free stable radical DPPH is not high they proxide anions. Compound 7 is the most potent (55.8%) in the in

  17. Cyclooxygenase2-selective Nonsteroidal Anti-Inflammatory Drugs Inhibit Hepatocyte Growth Factor\\/Scatter Factor-induced Angiogenesis

    Microsoft Academic Search

    Shiladitya Sengupta; Lynda A. Sellers; Tereza Cindrova; Jeremy Skepper; Ermanno Gherardi; Ram Sasisekharan; Tai-Ping D. Fan

    2003-01-01

    Epidemiological studies have indicated a reduced risk of malignancies with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), although the exact mechanisms are debated. NSAIDs inhibit angiogenesis, which is a key step for tumor growth. Hepatocyte growth factor\\/scatter factor (HGF\\/SF), a potent and independent angiogenic factor, has been impli- cated in tumorigenesis, but limited knowledge exists on the potential targets for

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

    Microsoft Academic Search

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

    2006-01-01

    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 2?-hydroxy

  19. The Effect of Polyphenols Isolated from Cynanchi wilfordii Radix with Anti-inflammatory, Antioxidant, and Anti-bacterial Activity.

    PubMed

    Jeong, Sunyoung; Lee, Sunwoo; Choi, Woo Jin; Sohn, Uy Dong; Kim, Wonyong

    2015-03-01

    Recently, Cynanchi wilfordii Radix has gained wide use in Asian countries as a functional food effective for relieving fatigue, osteoporosis, and constipation, particularly in menopausal disorders. However, its anti-inflammatory and anti-microbial activities have not been explored in detail to date. The anti-inflammatory, antioxidant, and anti-bacterial properties of the Cynanchi wilfordii Radix extracts obtained with water, methanol, ethanol, and acetone were compared. All 4 polyphenol-containing extracts exhibited anti-inflammatory and antioxidant effects. The ethanol extract was found to elicit the most potent reduction of nitric oxide (NO), prostaglandin E2 (PGE2), and cytokine (IL-1?, IL-6, IL-10, and TNF-?) levels, as well as inhibit the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a concentration-dependent manner. The evaluation of antioxidant activity also revealed the ethanol extract to have the highest free radical scavenging activity, measured as 85.3±0.4%, which is equivalent to 99.9% of the activity of ? -tocopherol. In the assessment of anti-bacterial activity, only ethanol extract was found to inhibit the growth of the Bacillus species Bacillus cereus and Bacillus anthracis. These results show that polyphenols of Cynanchi wilfordii Radix have anti-inflammatory, antioxidant, and anti-bacterial properties that can be exploited and further improved for use as a supplementary functional food, in cosmetics, and for pharmaceutical purposes. PMID:25729277

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

    PubMed Central

    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-?B p65 could be derived. PMID:23554828

  1. 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

  2. Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model.

    PubMed

    Luangsay, Souphalone; Wittamer, Valérie; Bondue, Benjamin; De Henau, Olivier; Rouger, Laurie; Brait, Maryse; Franssen, Jean-Denis; de Nadai, Patricia; Huaux, François; Parmentier, Marc

    2009-11-15

    Chemerin is the ligand of the ChemR23 receptor and a chemoattractant factor for human immature dendritic cells (DCs), macrophages, and NK cells. In this study, we characterized the mouse chemerin/ChemR23 system in terms of pharmacology, structure-function, distribution, and in vivo biological properties. Mouse chemerin is synthesized as an inactive precursor (prochemerin) requiring, as in human, the precise processing of its C terminus for generating an agonist of ChemR23. Mouse ChemR23 is highly expressed in immature plasmacytoid DCs and at lower levels in myeloid DCs, macrophages, and NK cells. Mouse prochemerin is expressed in most epithelial cells acting as barriers for pathogens but not in leukocytes. Chemerin promotes calcium mobilization and chemotaxis on DCs and macrophages and these functional responses were abrogated in ChemR23 knockout mice. In a mouse model of acute lung inflammation induced by LPS, chemerin displayed potent anti-inflammatory properties, reducing neutrophil infiltration and inflammatory cytokine release in a ChemR23-dependent manner. ChemR23 knockout mice were unresponsive to chemerin and displayed an increased neutrophil infiltrate following LPS challenge. Altogether, the mouse chemerin/ChemR23 system is structurally and functionally conserved between human and mouse, and mouse can therefore be considered as a good model for studying the anti-inflammatory role of this system in the regulation of immune responses and inflammatory diseases. PMID:19841182

  3. 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 ?M), 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, 3?-acetoxy-8,24-dienetirucallic acid (6) and 3?-acetoxy-7,24-dienetirucallic acid (10) inhibited mPGES-1 activity in a cell-free assay with IC50 = 0.4 ?M, 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 ?M). 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

  4. Effects of C-glycosylation on anti-diabetic, anti-Alzheimer's disease and anti-inflammatory potential of apigenin.

    PubMed

    Choi, Jae Sue; Islam, Md Nurul; Ali, Md Yousof; Kim, Eon Ji; Kim, Young Myeong; Jung, Hyun Ah

    2014-02-01

    Apigenin has gained particular interests in recent years as a beneficial and health promoting agent because of its low intrinsic toxicity. Vitexin and isovitexin, naturally occurring C-glycosylated derivatives of apigenin, have been known to possess potent anti-diabetic, anti-Alzheimer's disease (anti-AD), and anti-inflammatory activities. The present study was designed to investigate the anti-diabetic, anti-AD, and anti-inflammatory potential of apigenin and its two C-glycosylated derivatives, vitexin and isovitexin by in vitro assays including rat lens aldose reductase (RLAR), human recombinant aldose reductase (HRAR), advanced glycation endproducts (AGEs), protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), ?-site amyloid precursor (APP) cleaving enzyme 1 (BACE1), and nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, isovitexin was found as the most potent inhibitor against RLAR, HRAR, AGE, AChE, and BChE while vitexin showed the most potent PTP1B inhibitory activity. Despite the relatively weak anti-diabetic and anti-AD potentials, apigenin showed powerful antiinflammatory activity by inhibiting NO production and iNOS and COX-2 expression while vitexin and isovitexin were inactive. Therefore, it could be speculated that C-glycosylation of apigenin at different positions might be closely linked to relative intensity of anti-diabetic, anti-AD, and anti-inflammatory potentials. PMID:24291393

  5. Design and optimization of oleanolic/ursolic acid-loaded nanoplatforms for ocular anti-inflammatory applications.

    PubMed

    Alvarado, Helen L; Abrego, Guadalupe; Garduño-Ramirez, María L; Clares, Beatriz; Calpena, Ana C; García, María L

    2015-04-01

    Oleanolic acid (OA) and ursolic acid (UA) are ubiquitous pentacyclic triterpenes compounds in plants with great interest as anti-inflammatory therapeutics. The aim of this study was the design and optimization of polymeric nanoparticles (NPs) loaded with natural and synthetic mixtures (NM, SM) of these drugs for ophthalmic administration. A 2(3) + star central rotatable composite design was employed to perform the experiments. Results showed optimal and stable formulations with suitable physicochemical properties (mean diameter<225 nm), homogeneous distribution (polydispersity index?0.1), negatively charged surface (?-27 mV) and high entrapment efficiency (?77%). Release and corneal permeation studies showed that NM release was faster than SM. Amounts of drug retained in the corneal tissue were also higher for NM. In vitro and in vivo tests showed no signs of irritation or toxicity and successful in vivo anti-inflammatory efficacy for both formulations, being NM-OA/UA NPs the most effective. From the clinical editor: Oleanolic acid (OA) and ursolic acid (UA) are compounds found in plants with anti-inflammatory properties. The authors in this paper designed nanoparticles (NPs) using poly(dl-lactide-coglycolide) acid (PLGA) loaded with these compounds for ophthalmic administration. Both in vitro and in vivo experiments showed no toxicity and significant anti-inflammatory efficacy. This may provide new drugs for ocular anti-inflammatory treatment. PMID:25659643

  6. Biological evaluation of synthetic chalcone and flavone derivatives as anti-inflammatory agents

    PubMed Central

    Mateeva, Nelly; Gangapuram, Madhavi; Mazzio, Elizabeth; Eyunni, Suresh; Soliman, Karam F. A.

    2015-01-01

    Flavonoids and chalcones are natural plant derived compounds with inherent therapeutic value for a range of human pathologies. In this study, a series of 24 substituted chalcones and flavones were synthesized and subsequently screened for anti-inflammatory effects on lipopolysaccharide (1 µg/ml)-activated BV-2 microglial cells by assessing initial production/release of nitric oxide (NO). The data obtained eliminate the majority of compounds as weak or non-effective, whereas 2?-hydroxy-3,4,5,3?,4?-pentamethoxychalcone (1) and 2?-hydroxy-3,4,5-trimethoxychalcone (2) were potent, having an IC50 of 1.10 and 2.26 µM, respectively; with greater potency than L-N6-(1-iminoethyl)lysine selective iNOS inhibitor (IC50 = 3.1 µM) but less than steroidal dexamethasone (IC50 < 200 nM). The most potent compound (chalcone 1) attenuated NO parallel to reducing iNOS protein expression, events also corresponding to reduction of IL-1?, IL-10 and IL-6 pro-inflammatory cytokines. These findings suggest that the presence of electron donating groups OH and OCH3 on both A and B rings of synthetic compounds correlate to stronger anti-inflammatory potency. PMID:25866456

  7. Anti-inflammatory activity of Sapindus trifoliatus Linn.

    PubMed

    Arul, B; Kothai, R; Jacob, Philip; Sangameswaran, B; Sureshkumar, K

    2004-01-01

    Anti-inflammatory activity of the ethanolic extract of the seeds of Sapindus trifoliatus Linn. was studied in wister rats using the carrageenan induced left hind paw edema, carrageenan induced pleurisy and cotton pellet induced granuloma model. The ethanolic extract (150 mg/kg, p.o.) produced the inhibition of carrageenan induced rat paw edema. It also showed an inhibitory effect on leukocyte migration and a reduction on the pleural exudates as well as reduction on the granuloma weight in the cotton pellet granuloma method. The results indicated that the ethanolic extract produced significant (P < 0.001) anti-inflammatory activity when compared with the standard and untreated control. PMID:15927924

  8. Enhancement of antioxidant and anti-inflammatory activities of bioflavonoid rutin by complexation with transition metals

    Microsoft Academic Search

    Igor B Afanas’eva; Elena A Ostrakhovitch; Elena V Mikhal’chik; Galina A Ibragimova; Ludmila G Korkina

    2001-01-01

    The antioxidant and anti-inflammatory activities of two transition metal complexes of bioflavonoid rutin, Fe(rut)Cl3 and Cu(rut)Cl2, were studied. It was found that Cu(rut)Cl2 was a highly efficient in vitro and ex vivo free radical scavenger that sharply decreased (by 2–30 times compared to the parent rutin): oxygen radical production by xanthine oxidase, rat liver microsomes, and rat peritoneal macrophages; the

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

    Microsoft Academic Search

    Bouchra Gharib; Stéphane Hanna; Ould M. S. Abdallahi; Hubert Lepidi; Bernard Gardette; Max De Reggia

    2001-01-01

    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

  10. Anti-inflammatory effects of essential oil in Echinacea purpurea L.

    PubMed

    Yu, Deqiang; Yuan, Yi; Jiang, Ling; Tai, Yuling; Yang, Xiumei; Hu, Fang; Xie, Zhongwen

    2013-03-01

    Echinacea purpurea L. is a medicinal plant originally from North America. It has become a commonly used herbal medicine worldwide because it contains various biologically active compounds. This study was designed to investigate the anti-inflammatory effects of essential oils from E. purpurea in both mice and rats. The extract was obtained from flower of E. purpurea by steam distillation. The anti-inflammatory potential was evaluated in vivo by using different animal models such as xylene-induced mouse ear edema, egg-white-induced rat paw edema, and cotton-induced granuloma tissue proliferating inflammation in mice. The serial dosages were used in vivo: the low dosage, the medium dosage and the high dosage. The low, medium and high dosages of extracts produced inhibitions of 39.24%, 47.22% and 44.79% respectively in the ear edema induced by xylene when compare with the control group. Only the high dosage group showed statistically significant inhibition (48.51%) of paw edema formation induced three hours by egg white compared with the control group (P<0.01). Moreover, the granulation formation was also significantly reduced the most by 28.52% in the high dose groups compared with the control group (P <0.05). The pro-inflammatory cytokines such as IL-2, IL-6 and TNF-? in the blood were reduced in the treated groups. The essential oils from extracts of E. purpurea have anti-inflammatory effects. PMID:23455214

  11. Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.

    PubMed

    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-1? 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-1?-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

  12. Analgesic and anti-inflammatory studies of cyclopeptide alkaloid fraction of leaves of Ziziyphus nummularia

    PubMed Central

    Goyal, Manoj; Ghosh, Manik; Nagori, B.P.; Sasmal, D.

    2013-01-01

    Ziziyphus nummularia (family: Rhamnaceae) is a thorny small bush, grows in abundance in the grazing lands of the arid areas of Rajasthan, India. It is an important ethnomedicinal plant of the Thar Desert; local inhabitants use every part of the plant as medicine. Kernels are prescribed in pregnancy as soporific, antiemetic and for relieving abdominal pain. The insect gall is powered and given orally with water to cure bone fracture. Crushed root is applied on the paining shoulder of the bullock. The decoction of leaves is used for the treatment of cough and cold; leaves are also regarded as diaphoretic and prescribed in typhoid. Paste of leaves is used for healing of cuts, boils and cutaneous disease. It is widely used in pain and inflammatory conditions. Z. nummularia contains a unique group of alkaloids known as cyclopeptide alkaloids, in continuation of our work carried out on the leaves of Z. nummularia, present study was initiated to explore antiinflammatory and analgesic potential of cyclopeptide alkaloids isolated from the leaves of Z. nummularia (IFZN). Anti-inflammatory activity was tested against rat paw oedema, mouse peritonitis and cotton pellet granuloma. For screening of analgesic activity, acetic acid induced writhing, tail flick and hot plate test were performed. IFZN 30 mg/kg shows the anti-oedematogenic effect against paw oedema induced by carrageenan, dextran, serotonin and histamine; IFZN 20 and 30 mg/kg were found to have highly significant anti-nociceptive effects. Result of pharmacological studies indicated that IFZN is a potent and efficacious analgesic agent. The analgesic activity of IFZN is mediated by the peripheral as well as central pathways. PMID:24235873

  13. Anti-inflammatory and antioxidant properties of Helichrysum italicum.

    PubMed

    Sala, Araceli; Recio, MaríadelCarmen; Giner, Rosa Marfa; Máñez, Salvador; Tournier, Horacio; Schinella, Guillermo; Ríos, José-Luis

    2002-03-01

    The anti-inflammatory and antioxidant activities of the aerial part of Helichrysum italicum extracts have been established in various in-vivo and in-vitro experimental models. The results obtained on the acute oedemas induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) and ethyl phenylpropiolate in the mouse ear, by serotonin and phospholipase A2 (PLA2) in the mouse paw, on chronic inflammation induced by repeated application of TPA in the mouse ear and on the delayed-type hypersensitivity induced by sheep red blood cells suggest that said anti-inflammatory activity is due to the effects of compounds expressed via a corticoid-like mechanism. In addition, the antioxidant activity of the extracts seems to be implicated in this anti-inflammatory activity, as the former inhibits enzymatic and non-enzymatic lipid peroxidation and has free-radical scavenger properties. We conclude that the anti-inflammatory activity of Helichrysum italicum can be explained by multiple effects, including inflammatory enzyme inhibition, free-radical scavenging activity and corticoid-like effects. PMID:11902802

  14. Plant phenylpropanoids as emerging anti-inflammatory agents.

    PubMed

    Korkina, L; Kostyuk, V; De Luca, C; Pastore, S

    2011-09-01

    Plant-derived phenylpropanoids (PPPs) compose the largest group of secondary metabolites produced by higher plants, mainly, for the protection against biotic or abiotic stresses such as infections, wounding, UV irradiation, exposure to ozone, pollutants, and herbivores. PPPs are parent molecules for biosynthesis of numerous structurally and functionally diverse plant polyphenols (simple phenolic acids and esters, glycosylated derivatives of primary PPPs, flavonoids, isoflavonoids, stilbenes, coumarins, curcuminoids, lignans, etc.), which play multiple essential roles in plant physiology. During the last few decades, extensive research has been dedicated to natural and biotechnologically produced PPPs for medicinal use as antioxidants, UV screens, anticancer, antiviral, anti-inflammatory, wound healing, and antibacterial agents. In the present review, the metabolic pathways of phenylpropanoid biosynthesis in plants and their re-construction in biotechnologically engineered systems are described. Chemical physical peculiarities of PPPs defining their antioxidant, metal chelating, and UV-protecting effects as a molecular basis for their anti-inflammatory properties are discussed as well. We focused also on the discovery of PPPs-based anti-inflammatory agents since distinct PPPs were found to modulate molecular pathways underlying inflammatory responses in human cells triggered by different pro-inflammatory stimuli in vitro and to inhibit inflammation in various tissues in vivo. The problem of low bioavailability, fast metabolism, and potential toxicity/sensitization as limiting factors for the development of PPPs-based anti-inflammatory drugs is also highlighted. PMID:21762105

  15. 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 ?g/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 ?g/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

  16. Anti-inflammatory effects of aspirin and sodium salicylate

    Microsoft Academic Search

    Rainer Amann; Bernhard A. Peskar

    2002-01-01

    Aspirin (acetylsalicylic acid) is one of the most widely used drugs worldwide. It acetylates cyclooxygenases thereby irreversibly blocking the conversion of arachidonic acid to prostanoids. Biotransformation of aspirin yields salicylate, a compound that possesses similar anti-inflammatory potency as aspirin but lacks aspirin's inhibitory effect on the activity of isolated cyclooxygenase. This article is aimed at providing an overview about the

  17. Anti-inflammatory effect of Houttuynia cordata injection

    Microsoft Academic Search

    H. M. Lu; Y. Z. Liang; L. Z. Yi; X. J. Wu

    2006-01-01

    Houttuynia cordata (Saururaceae) injection (HCI) is a traditional Chinese medicine used in China. It was chosen as one of eight types of traditional Chinese medicine that play a unique role in severe acute respiratory syndrome (SARS) owing to the effect of curbing inflammation. In order to validate this plausible anti-inflammatory property, the chemical composition of HCI has been analysed by

  18. Anti-inflammatory mechanism of inflamed-tissue factor

    Microsoft Academic Search

    I. L. Bonta; J. Noordhoek

    1973-01-01

    The early postulation that irritation of tissue could release a substance which acted as anti-inflammatory agent at a remote site of the body, led further to show that administration of inflammatory exudate results in suppression of experimental inflammations (Rindani [22], Robinson and Robson [23], Billingham, Robinson and Robson [2], Bonta and De Vos [6]). Little is known however as to

  19. 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)

  20. Type I Interferons as Anti-Inflammatory Mediators

    NSDL National Science Digital Library

    Etty N. Benveniste (University of Alabama at Birmingham; Department of Cell Biology REV)

    2007-12-11

    The type I interferons (IFNs), IFN-? and IFN-?, are cytokines that have antiviral, antiproliferative, and immunomodulatory activities. Data are now emerging that suggest that type I IFNs are also important mediators of anti-inflammatory responses. These findings, largely driven by studies to explain the beneficial effects of IFN-? in the treatment of multiple sclerosis, an autoimmune disease of the central nervous system, offer a number of mechanisms for the anti-inflammatory properties of type I IFNs. Type I IFNs, through their ability to induce the immunosuppressive cytokine interleukin-10 (IL-10), mediate the inhibition of proinflammatory gene products. In addition, type I IFNs induce other immunosuppressive mediators such as suppressor of cytokine signaling–1 (SOCS-1) and tristetrapolin (TTP), which act by divergent mechanisms to restore homeostasis to the immune system. Furthermore, type I IFNs mediate anti-inflammatory and protective effects in a variety of autoimmune disease models such as experimental colitis, experimental allergic encephalomyelitis, experimental arthritis, and neonatal inflammation. Here, we discuss the molecular basis for the anti-inflammatory properties of type I IFNs and their therapeutic potential in autoimmune and inflammatory diseases.

  1. Anti-inflammatory Activity of Some Essential Oils

    Microsoft Academic Search

    Salud Pérez G; Miguel Zavala S; Lucina Arias G; Miguel Ramos L

    2011-01-01

    There are many diseases that are associated with inflammation, such as infections by bacteria, virus and protozoa, autoimmune diseases such as arthritis and diabetes, Alzheimer's disease, and cancer. There are many medications available to prevent or minimize the progression of the inflammation; they include non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, but they have some secondary effects. Traditional medicine has been

  2. 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

  3. M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial Nitric Oxide Signaling.

    PubMed

    Lee, Woo Je; Tateya, Sanshiro; Cheng, Andrew M; Rizzo-DeLeon, Norma; Wang, Nicholas F; Handa, Priya; Wilson, Carole L; Clowes, Alexander W; Sweet, Ian R; Bomsztyk, Karol; Schwartz, Michael W; Kim, Francis

    2015-08-01

    Endothelial nitric oxide (NO) signaling plays a physiological role in limiting obesity-associated insulin resistance and inflammation. This study was undertaken to investigate whether this NO effect involves polarization of macrophages toward an anti-inflammatory M2 phenotype. Mice with transgenic endothelial NO synthase overexpression were protected against high-fat diet (HFD)-induced hepatic inflammation and insulin resistance, and this effect was associated with reduced proinflammatory M1 and increased anti-inflammatory M2 activation of Kupffer cells. In cell culture studies, exposure of macrophages to endothelial NO similarly reduced inflammatory (M1) and increased anti-inflammatory (M2) gene expression. Similar effects were induced by macrophage overexpression of vasodilator-stimulated phosphoprotein (VASP), a key downstream mediator of intracellular NO signaling. Conversely, VASP deficiency induced proinflammatory M1 macrophage activation, and the transplantation of bone marrow from VASP-deficient donor mice into normal recipients caused hepatic inflammation and insulin resistance resembling that induced in normal mice by consumption of an HFD. These data suggest that proinflammatory macrophage M1 activation and macrophage-mediated inflammation are tonically inhibited by NO ? VASP signal transduction, and that reduced NO ? VASP signaling is involved in the effect of HFD feeding to induce M1 activation of Kupffer cells and associated hepatic inflammation. Our data implicate endothelial NO ? VASP signaling as a physiological determinant of macrophage polarization and show that signaling via this pathway is required to prevent hepatic inflammation and insulin resistance. PMID:25845662

  4. 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

  5. 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

  6. Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: design, synthesis and evaluation as potential anti-inflammatory agents.

    PubMed

    Hassan, Ghaneya Sayed; Abou-Seri, Sahar Mahmoud; Kamel, Gehan; Ali, Mamdouh Moawad

    2014-04-01

    Novel series of celecoxib analogs endowed with benzofuran moiety 3a-e and 9a-d were synthesized and evaluated for COX-1/COX-2 inhibitory activity in vitro. The most potent and selective COX-2 inhibitors - compounds 3c, 3d, 3e, 9c and 9d - were assessed for their anti-inflammatory activity and ulcerogenic liability in vivo. The 3-(pyridin-3-yl)pyrazole derivatives 3c and 3e exhibited the highest anti-inflammatory activity, that is equipotent to celecoxib. Furthermore, the tested compounds proved to have better gastric safety profile compared to celecoxib. In particular, compound 3e demonstrated about 40% reduction in ulcerogenic potential relative to the reference drug. Finally, molecular docking simulation of the new compounds in COX-2 active site and drug likeness studies showed good agreement with the obtained pharmaco-biological results. PMID:24607877

  7. Bioassay-guided isolation of iridoid glucosides with antinociceptive and anti-inflammatory activities from Veronica anagallis-aquatica L.

    PubMed

    Küpeli, Esra; Harput, U Sebnem; Varel, Mehtap; Yesilada, Erdem; Saracoglu, Iclal

    2005-11-14

    Extracts obtained from the herbs of various Veronica species are used as folk remedy worldwide for the treatment of various inflammatory ailments including rheumatism. In vivo anti-inflammatory and antinociceptive activities of Veronica anagallis-aquatica L. aerial parts were investigated. Methanolic extract of the plant was shown to possess significant inhibitory activity against carrageenan-induced hind paw edema model and of p-benzoquinone-induced writhings in mice. Through bioassay-guided fractionation and isolation procedures eight compounds, aquaticoside A (1), aquaticoside B (2), aquaticoside C (3), veronicoside (4), catalposide (5), verproside (6), verminoside (7) and martynoside (8) were isolated and their structures were elucidated by spectral techniques. Catapol derivative iridoid glucosides, verproside (6) and catalposide (5), were found to possess potent antinociceptive and anti-inflammatory activities, per os without inducing any apparent acute toxicity as well as gastric damage. Results of the present study supported the utilization of the plant in Turkish folk medicine. PMID:16019176

  8. 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

  9. Synthesis of 2-mercapto-3-substituted-5,6-dimethylthieno[2,3-d] pyrimidin-4(3H)-ones as new analgesic, anti-inflammatory agents.

    PubMed

    Alagarsamy, V; Vijayakumar, S; Raja Solomon, V

    2007-06-01

    A new series of 2-mercapto-3-substituted-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-ones were synthesised by reacting 3-amino-2-mercapto-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one with different aldehydes and ketones. The starting material 3-amino-2-mercapto-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one was synthesised from 2-amino-3-carbethoxy-4,5-dimethyl thiophene by a novel innovative route. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. While the test compounds exhibited significant activity, among these compound AS1 showed more potent analgesic and anti-inflammatory activities and the compound AS3 showed equipotent analgesic and anti-inflammatory activities when compared to the reference standard diclofenac sodium. PMID:17391907

  10. Oral azithromycin combined with topical anti-inflammatory agents in the treatment of blepharokeratoconjunctivitis in children

    PubMed Central

    Choi, Daniel S.; Djalilian, Ali

    2013-01-01

    We report 3 children referred for recurrent blepharokeratoconjunctivitis, despite topical antibiotic and anti-inflammatory treatments. Oral azithromycin combined with anti-inflammatory treatment was effective in controlling the disease. PMID:23360914

  11. Arzanol, a prenylated heterodimeric phloroglucinyl pyrone, inhibits eicosanoid biosynthesis and exhibits anti-inflammatory efficacy in vivo.

    PubMed

    Bauer, Julia; Koeberle, Andreas; Dehm, Friederike; Pollastro, Federica; Appendino, Giovanni; Northoff, Hinnak; Rossi, Antonietta; Sautebin, Lidia; Werz, Oliver

    2011-01-15

    Based on its capacity to inhibit in vitro HIV-1 replication in T cells and the release of pro-inflammatory cytokines in monocytes, the prenylated heterodimeric phloroglucinyl ?-pyrone arzanol was identified as the major anti-inflammatory and anti-viral constituent from Helichrysum italicum. We have now investigated the activity of arzanol on the biosynthesis of pro-inflammatory eicosanoids, evaluating its anti-inflammatory efficacy in vitro and in vivo. Arzanol inhibited 5-lipoxygenase (EC 7.13.11.34) activity and related leukotriene formation in neutrophils, as well as the activity of cyclooxygenase (COX)-1 (EC 1.14.99.1) and the formation of COX-2-derived prostaglandin (PG)E(2)in vitro (IC(50)=2.3-9?M). Detailed studies revealed that arzanol primarily inhibits microsomal PGE(2) synthase (mPGES)-1 (EC 5.3.99.3, IC(50)=0.4?M) rather than COX-2. In fact, arzanol could block COX-2/mPGES-1-mediated PGE(2) biosynthesis in lipopolysaccharide-stimulated human monocytes and human whole blood, but not the concomitant COX-2-derived biosynthesis of thromboxane B(2) or of 6-keto PGF(1?), and the expression of COX-2 or mPGES-1 protein was not affected. Arzanol potently suppressed the inflammatory response of the carrageenan-induced pleurisy in rats (3.6mg/kg, i.p.), with significantly reduced levels of PGE(2) in the pleural exudates. Taken together, our data show that arzanol potently inhibits the biosynthesis of pro-inflammatory lipid mediators like PGE(2)in vitro and in vivo, providing a mechanistic rationale for the anti-inflammatory activity of H. italicum, and a rationale for further pre-clinical evaluation of this novel anti-inflammatory lead. PMID:20933508

  12. Nonsteroidal Anti-Inflammatory Drugs, Gastroprotection, and Benefit–Risk

    PubMed Central

    Moore, Robert Andrew; Derry, Sheena; Simon, Lee S; Emery, Paul

    2014-01-01

    Background Gastroprotective agents (GPA) substantially reduce morbidity and mortality with long-term nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin. Objective To evaluate efficacy of NSAIDs, protection against NSAID-induced gastrointestinal harm, and balance of benefit and risk. Methods Free text searches of PubMed (December 2012) supplemented with “related citation” and “cited by” facilities on PubMed and Google Scholar for patient requirements, NSAID effectiveness, pain relief benefits, gastroprotective strategies, adherence to gastroprotection prescribing, and serious harm with NSAIDs and GPA. Results Patients want 50% reduction in pain intensity and improved fatigue, distress, and quality of life. Meta-analyses of NSAID trials in musculoskeletal conditions had bimodal responses with good pain relief or little. Number needed to treat (NNTs) for good pain relief were 3 to 9. Proton pump inhibitors (PPI) and high-dose histamine-2 receptor antagonists (H2RA) provided similar gastroprotection, with no conclusive evidence of greater PPI efficacy compared with high-dose H2RA. Prescriber adherence to guidance on use of GPA with NSAIDS was 49% in studies published since 2005; patient adherence was less than 100%. PPI use at higher doses over longer periods is associated with increased risk of serious adverse events, including fracture; no such evidence was found for H2RA. Patients with chronic conditions are more willing to accept risk of harm for successful treatment than their physicians. Conclusion Guidance on NSAIDs use should ensure that patients have a good level of pain relief and that gastroprotection is guaranteed for the NSAID delivering good pain relief. Fixed-dose combinations of NSAID plus GPA offer one solution. PMID:23941628

  13. 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 ?. 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

  14. 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 ?-light-chain-enhancer of activated B cells ?B (NF-?B) 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-?B pathway. This review clarifies the anti-inflammatory role of vinpocetine in atherosclerosis and ischemic stroke. PMID:25549058

  15. Antioxidant, Anti-inflammatory, and Chemoprotective Properties of Acacia catechu Heartwood Extracts.

    PubMed

    Stohs, Sidney J; Bagchi, Debasis

    2015-06-01

    Aqueous extracts of Acacia catechu heartwood are rich source of catechin and epicatechin (gallic acid derivatives), with smaller amounts of flavonoids. Extracts have also been prepared with ethyl acetate, ethanol, and methanol, and the properties of these extracts have been studied and are reviewed. Potent antioxidant activity has been well established in both in vitro and in vivo studies. This antioxidant activity is believed to be responsible for the anti-inflammatory, tissue protectant, antineoplastic, and analgesic activities that have been demonstrated and clearly established in animal and cell culture systems. Furthermore, antihyperglycemic, antidiarrheal, antinociceptive, and antipyretic activities have been demonstrated in animal studies. No adverse effects have been observed in animal or human studies or in cell culture systems. In spite of the fact that Acacia products have been used for many years and the general safety of catechins and epicatechins is well documented, few human studies have ever been conducted on the efficacy or safety of A.?catechu heartwood extracts. Several studies have shown that a two-ingredient combination product containing A.?catechu extract exhibited no adverse effects when administered daily for up to 12?weeks while exhibiting significant anti-inflammatory activity in subjects with osteoarthritis of the knee. There is a need for additional human clinical studies with regard to efficacy and safety. © 2015 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd. PMID:25802170

  16. 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 ?g/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 (3?-O-?-D-glucopyranosyloxy-5?-stigmasta-7,9(11),24(28)Z-triene-6?,16?,26,29-tetrol) and 3 (3?-O-?-D-glucopyranosyloxy-5?-stigmasta-7,9(11),24(28)Z-triene-6?,16?,29-triol), only two and five fold less potent than the steroidal drug hydrocortisone (ID50=0.10, 0.21 and 0.04 ?mol/cm(2), respectively). Compound 1 (50 ?M) also completely inhibited the transcription factor NF-?B in vitro. PMID:24074552

  17. Enhancing the anti-inflammatory activity of chalcones by tuning the Michael acceptor site.

    PubMed

    Rücker, Hannelore; Al-Rifai, Nafisah; Rascle, Anne; Gottfried, Eva; Brodziak-Jarosz, Lidia; Gerhäuser, Clarissa; Dick, Tobias P; Amslinger, Sabine

    2015-03-14

    Inflammatory signaling pathways orchestrate the cellular response to infection and injury. These pathways are known to be modulated by compounds that alkylate cysteinyl thiols. One class of phytochemicals with strong thiol alkylating activity is the chalcones. In this study we tested fourteen chalcone derivatives, ?-X-substituted 2',3,4,4'-tetramethoxychalcones (?-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH), for their ability to modulate inflammatory responses, as monitored by their influence on heme oxygenase-1 (HO-1) activity, inducible nitric oxide synthase (iNOS) activity, and cytokine expression levels. We confirmed that the transcriptional activity of Nrf2 was activated by ?-X-TMCs while for NF-?B it was inhibited. For most ?-X-TMCs, anti-inflammatory activity was positively correlated with thiol alkylating activity, i.e. stronger electrophiles (X = CF3, Br and Cl) being more potent. Notably, this correlation did not hold true for the strongest electrophiles (X = CN and NO2) which were found to be ineffective as anti-inflammatory compounds. These results emphasize the idea that chemical fine-tuning of electrophilicity is needed to achieve and optimize desired therapeutic effects. PMID:25622264

  18. Toll-like receptor-mediated anti-inflammatory action of glaucine and oxoglaucine

    E-print Network

    Boyer, Edmond

    Toll-like receptor-mediated anti-inflammatory action of glaucine and oxoglaucine Mimi Remichkova investigated for their suggested anti-inflammatory influence concerning nitric oxide and cytokine production and increase of anti-inflammatory IL- 10 are indicative for their use in different acute and chronic

  19. Synthesis and anti-inflammatory effects of novel pimarane diterpenoid analogs

    E-print Network

    Suh, Young-Ger

    Synthesis and anti-inflammatory effects of novel pimarane diterpenoid analogs Young-Ger Suh Available online Abstract--Syntheses and excellent anti-inflammatory effects of a series of novel acanthoic acid analogs are reported. In particular, the mechanistic basis for their anti-inflammatory effects

  20. The Anti-inflammatory Effects of Selenium Are Mediated through 15-Deoxy-12,14

    E-print Network

    Omiecinski, Curtis

    The Anti-inflammatory Effects of Selenium Are Mediated through 15-Deoxy- 12,14 -prostaglandin J2 underlying the anti-inflammatory property of selenium, we examined the activity of a key kinase of the NF- B in the sele- nium-deficient macrophages. In addition, anti-inflammatory activities of selenium were also

  1. Role of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in Modulating Vascular

    E-print Network

    Paris-Sud XI, Université de

    14 Role of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in Modulating Vascular Smooth Muscle by a direct action of non-steroidal anti- inflammatory drugs (NSAIDs) to activate the K+ ion channels. The primary cellular action of non-steroidal anti-inflammatory drugs (NSAIDs) is thought to be through

  2. 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...

  3. 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

  4. Anti inflammatory activity of Myrica nagi Linn. Bark

    PubMed Central

    Patel, Tejaa; Dudhpejiya, Ashvin; Sheath, Navin

    2011-01-01

    The present study evaluated the anti inflammatory activity of ethyl acetate and aqueous extracts of bark of M. nagi using carrageenan and histamine induced rat paw edema. Adult Wistar albino rats were subjected to carrageenan and histamine induced rat paw edema tests. In carrageenan induced rat paw edema the effects of ethyl acetate and aqueous extract at 100 and 200 mg/kg showed % inhibition of edema 27% and 22% respectively than the standard drug aspirin (28%). These ethyl acetate and aqueous extract extracts also showed % inhibition of edema 25% and 18% respectively than the standard drug (27%) when rats challenged with histamine induced rat paw edema. Future research should focus on the identification and the anti inflammatory activity of the constituents from this plant. PMID:22557437

  5. 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

  6. Biochemical pharmacology of nonsteroidal anti-inflammatory drugs.

    PubMed

    Wu, K K

    1998-03-01

    Aspirin and conventional nonsteroidal anti-inflammatory drugs are nonselective inhibitors of cyclooxygenase-1 (COX-1) and COX-2 enzymes. Two classes of selective COX-2 inhibitors: (1) sulfonamides, such as L-745,337, and (2) tricyclic methyl sulfone derivatives, such as SC58125, have been developed. X-ray crystal structures of COX-1 and COX-2 have provided valuable information regarding the structural basis for their COX-2 selectivity. These compounds have less gastrointestinal complications in animal experiments. Their clinical efficacy and side-effects are being evaluated. Salicylate has very weak activity against either COX isoform and yet possesses anti-inflammatory actions. Recent studies indicate that it suppresses the expression of genes involved in inflammation. These activities may provide a plausible explanation for the pharmacological dilemma and, furthermore, may represent novel mechanisms for controlling inflammation. PMID:9515564

  7. Non-steroid anti-inflammatory drugs, prostaglandins, and cancer

    PubMed Central

    2013-01-01

    Fatty acids are involved in multiple pathways and play a pivotal role in health. Eicosanoids, derived from arachidonic acid, have received extensive attention in the field of cancer research. Following release from the phospholipid membrane, arachidonic acid can be metabolized into different classes of eicosanoids through cyclooxygenases, lipoxygenases, or p450 epoxygenase pathways. Non-steroid anti-inflammatory drugs (NSAIDs) are widely consumed as analgesics to relieve minor aches and pains, as antipyretics to reduce fever, and as anti-inflammatory medications. Most NSAIDs are nonselective inhibitors of cyclooxygenases, the rate limiting enzymes in the formation of prostaglandins. Long term use of some NSAIDs has been linked with reduced incidence and mortality in many cancers. In this review, we appraise the biological activities of prostanoids and their cognate receptors in the context of cancer biology. The existing literature supports that these lipid mediators are involved to a great extent in the occurrence and progression of cancer. PMID:23388178

  8. Anti-inflammatory activity of Coldenia procumbens Linn.

    PubMed

    Arul, B; Kothai, R; Sureshkumar, K; Christina, A J M

    2005-07-01

    Anti-inflammatory activity of the ethanolic extract of the aerial parts of Coldenia procumbens Linn. was studied in Wister rats using the carrageenan induced left hind paw edema, carrageenan induced pleurisy and cotton pellet induced granuloma model. The ethanolic extract (150 mg/kg, p.o.) produced the inhibition of carrageenan induced rat paw edema. It also showed an inhibitory effect on leukocyte migration and a reduction on the pleural exudates as well as reduction on the granuloma weight in the cotton pellet granuloma method. The results indicated that the ethanolic extract produced significant (P<0.001) anti-inflammatory activity when compared with the standard and untreated control. PMID:16380339

  9. [Anti-inflammatory effect of hydroxy-9-ellipticine].

    PubMed

    Cros, J; Thibault, A; Dat-Xuong, N

    1975-10-13

    The anti-inflammatory activity of 9-hydroxy-ellipticine is studied through various experimental models. It is particularly interesting in the guinea-pig cutaneous erythema, in the carragenin-induced oedema and in the adjuvant-induced polyarthritis in the rat. It appears in immune or non-immune induced inflammatory responses. Its important thymolytic activity can be related to its immunosuppressive effect. PMID:813888

  10. Anti-inflammatory activity of mangostins from Garcinia mangostana

    Microsoft Academic Search

    Lih-Geeng Chen; Ling-Ling Yang; Ching-Chiung Wang

    2008-01-01

    The fruit hull of Garcinia mangostana Linn (Guttiferae) is used as an anti-inflammatory drug in Southeast Asia. Two xanthones, ?- and ?-mangostins, were isolated from the fruit hull of G. mangostana, and both significantly inhibited nitric oxide (NO) and PGE2 production from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The IC50 values for the inhibition of NO production by ?- and ?-mangostins

  11. Endogenous anti-inflammatory substances, inter-?-inhibitor and bikunin

    Microsoft Academic Search

    Hiroshi Kobayashi

    2006-01-01

    There have been new developments in the elucidation of the biological functions of the inter-a-inhibitor (IaI) family. The anti-proteolytic activity of the IaI family originates from bikunin (also known as urinary trypsin inhibitor). Growing evidence indicates that bikunin is not just an anti-proteolytic agent, but can also be considered an anti-inflammatory agent that suppresses lipopolysaccha- ride (LPS)-induced cytokine synthesis. Bikunin

  12. Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia

    Microsoft Academic Search

    Jacek Musial; Anetta Undas; Piotr Gajewski; Milosz Jankowski; Wojciech Sydor; Andrzej Szczeklik

    2001-01-01

    Aims: Beneficial effects of statins in preventing cardiovascular events may depend, at least in part, on their anti-inflammatory action. The aim of the study was to assess the influence of simvastatin and aspirin on serum levels of C-reactive protein (CRP), tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) in hypercholesterolemic subjects. Methods and results: In 33 asymptomatic men with total cholesterol

  13. Pharmacological interactions of anti-inflammatory-analgesics in odontology

    Microsoft Academic Search

    Gerardo Gómez-Moreno; Javier Guardia; Antonio Cutando; José Luis Calvo Guirado

    2009-01-01

    In this second article we describe the more interesting pharmacological interactions in dental practice based on the prescription of analgesic narcotics, paracetamol and non-selective non-steroid anti-inflammatory drugs (NSAI) (which inhibit cyclooxigenase 1 -COX 1- and cyclooxigenase 2 -COX 2-) and selective NSAIs (COX 2 inhibitors). The importance of preventing the appearance of these pharmacological interactions is because these are medicaments

  14. Recent considerations in nonsteroidal anti-inflammatory drug gastropathy

    Microsoft Academic Search

    Gurkirpal Singh

    1998-01-01

    Conservative calculations estimate that approximately 107,000 patients are hospitalized annually for nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) complications and at least 16,500 NSAID-related deaths occur each year among arthritis patients alone. The figures for all NSAID users would be overwhelming, yet the scope of this problem is generally under-appreciated. The Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) Post-Marketing Surveillance

  15. Anti-inflammatory activity of emu oils in rats.

    PubMed

    Snowden, J M; Whitehouse, M W

    1997-01-01

    The anti-inflammatory activities of five different preparations of emu (Dromais Novae-Hollandiae) oil, applied topically, have been examined using an experimental polyarthritis- in rats. Four of the preparations were found to be active against adjuvant-induced arthritis in rats. The efficacies of the emu oils acting transdermally are compared with that of orally administered ibuprofen (40 mg/kg). PMID:17694361

  16. Anti-inflammatory activity of emu oils in rats

    Microsoft Academic Search

    J. M. Snowden; M. W. Whitehouse

    1997-01-01

    The anti-inflammatory activities of five different preparations of emu (Dromais Novae-Hollandiae) oil, applied topically, have been examined using an experimental polyarthritis- in rats. Four of the preparations were found\\u000a to be active against adjuvant-induced arthritis in rats. The efficacies of the emu oils acting transdermally are compared\\u000a with that of orally administered ibuprofen (40 mg\\/kg).

  17. AntiInflammatory and analgesic Activity of Anacardium Occidentale Leaf Extracts

    PubMed Central

    Pawar, S.P.; Sathwane, P.N.; Metkar, B.R.; Pal, S.C; Kasture, V.S.; Kasture, S.B.

    2000-01-01

    The extracts of the dried leaves of Anacardium occidentale  were screened for anti-inflammatory activity using carrageenan induced rat paw edema model. The petroleum ether and chloroform extract and acetone soluble fraction of methanolic extract showed 57.14%, 47.61% and 61.90% inhibition of paw edema respectively. Acetone soluble extract showed better activity than petroleum either and chloroform extracts. PMID:22556940

  18. Melittin-glutathione S-transferase fusion protein exhibits anti-inflammatory properties and minimal toxicity.

    PubMed

    Rayahin, Jamie E; Buhrman, Jason S; Gemeinhart, Richard A

    2014-12-18

    Although potent, proteins often require chemical modification for therapeutic use. Immunogenicity, difficult synthesis, and scale-up of these modifications are all engineering obstacles that stand in the way of expanding the use of these therapeutics. Melittin, a peptide derived from bee venom, has been shown to modulate inflammation. Although potentially therapeutic, the native peptide causes cell lysis and toxicity significantly hindering therapeutic application. Based upon the knowledge of the pore formation mechanism, we examined the toxicity and therapeutic effect of a melittin fusion protein with glutathione-S-transferase. The fusion of melittin and glutathione S-transferase results in diminished toxicity of the peptide and retained anti-inflammatory properties at doses that exceed toxic concentration of native melittin. Our results suggest that fusion proteins, particularly those of glutathione-S-transferase, may be facile modifications to control protein activity. PMID:25240321

  19. Flavonoid glycosides from Microtea debilis and their cytotoxic and anti-inflammatory effects.

    PubMed

    Bai, Naisheng; He, Kan; Roller, Marc; Lai, Ching-Shu; Shao, Xi; Pan, Min-Hsiung; Bily, Antoine; Ho, Chi-Tang

    2011-03-01

    Two new 5-O-glucosylflavones, 5-O-?-D-glucopyranosyl cirsimaritin (1) and 5, 4'-O-?-D-diglucopyranosyl cirsimaritin (2), four known flavonoids, cirsimarin (3), cirsimaritin (4), salvigenin (5), 4', 5-dihydroxy-7-methoxyflavone (6), and a norisoprenoid, vomifoliol (7), have been isolated from the aerial parts of Microtea debilis. All isolates were tested for cytotoxicity in human cancer cell lines (Hep G2, COLO 205, and HL-60) and anti-inflammatory activities in LPS-treated RAW264.7 macrophages. Compound 6 was found to be a potent inhibitor to nitrite production in macrophages. Compounds 2, 4, 6, and 7 showed moderate anti-proliferative activity against COLO-205 cells with IC(50) values of 7.1, 13.1, 6.1, and 6.8 ?M, respectively. PMID:20804824

  20. Anti-inflammatory effects of Allium schoenoprasum L. leaves.

    PubMed

    Parvu, A E; Parvu, M; Vlase, L; Miclea, P; Mot, A C; Silaghi-Dumitrescu, R

    2014-04-01

    Allium schoenoprasum has antimicrobial and antifungal properties and is used to relieve pain from sunburn and sore throat. The aim of the present study was to evaluate the anti-inflammatory effects of the extracts from A. schoenoprasum leaves. A 1:1 (w:v) extract was prepared by a modified Squibb repercolation method. The total phenolic content of 68.5±2 g gallic acid aquivalent (GAE)/g plant was determined using the Folin-Ciocalteu method. The in vitro antioxidant activity was determined using the 1,1-diphenyl-2-picrylhydrazyl bleaching method (6.72±0.44 g/mg DPPH) and the trolox equivalent antioxidant capacity (132.8±23 g trolox eq./g plant) assay. Analysis of the extracts using the hemoglobin ascorbate peroxidase activity inhibition assay or the electron spin resonance did not yield signals above the detection limit. The anti-inflammatory effects of three extract concentrations (25%, 50%, 100%) were evaluated in vivo on a model turpentine oil-induced inflammation in rats. These three extracts were also evaluated in vitro for the ability to inhibit phagocytosis, the accumulation of total nitrites and nitrates in the serum, the total oxidative status, the total antioxidant response and the oxidative stress index. Pure extracts (100% concentration) had the best inhibitory activity on phagocytosis and oxidative stress. In conclusion, these results support the hypothesis that extracts from A. schoenoprasum leaves exert anti-inflammatory activities by inhibiting phagocytosis through the reduction of nitro-oxidative stress. PMID:24781739

  1. Anti-inflammatory activity of traditional Chinese medicinal herbs

    PubMed Central

    Pan, Min-Hsiung; Chiou, Yi-Shiou; Tsai, Mei-Ling; Ho, Chi-Tang

    2011-01-01

    Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for various human diseases. Thus, suppressing chronic inflammation has the potential to delay, prevent, and control various chronic diseases, including cerebrovascular, cardiovascular, joint, skin, pulmonary, blood, lymph, liver, pancreatic, and intestinal diseases. Various natural products from traditional Chinese medicine (TCM) have been shown to safely suppress proinflammatory pathways and control inflammation-associated disease. In vivo and/or in vitro studies have demonstrated that anti-inflammatory effects of TCM occur by inhibition of the expression of master transcription factors (for example, nuclear factor-?B (NF-?B)), pro-inflammatory cytokines (for example, tumor necrosis factor-? (TNF-?), chemokines (for example, chemokine (C-C motif) ligand (CCL)-24), intercellular adhesion molecule expression and pro-inflammatory mediators (for example, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)). However, a handful of review articles have focused on the anti-inflammatory activities of TCM and explore their possible mechanisms of action. In this review, we summarize recent research attempting to identify the anti-inflammatory constituents of TCM and their molecular targets that may create new opportunities for innovation in modern pharmacology. PMID:24716101

  2. 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

  3. Synthesis, anti-inflammatory activity and modeling studies of cycloartane-type terpenes derivatives isolated from Parthenium argentatum.

    PubMed

    Romero, Juan Carlos; Martínez-Vázquez, Adriana; Herrera, Maribel Pineda; Martinez-Mayorga, Karina; Parra-Delgado, Hortensia; Pérez-Flores, Francisco J; Martínez-Vázquez, Mariano

    2014-12-15

    The 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema model in mice determined the anti-inflammatory activities in vivo of argentatins A, B and D, the main cycloartenol-type triterpenes present in Parthenium argentatum. Our results showed that argentatin B (ED50=1.5×10(-4)mmol/ear) and argentatin A (ED50=2.8×10(-4)mmol/ear) were more potent anti-inflammatory agents than indomethacin (ED50=4.5×10(-4)mmol/ear), the reference drug. Based on these findings, we decided to evaluate 13 derivatives of argentatins A and B. All the derivatives showed anti-inflammatory activity in the TPA-induced edema model in mice. The most active compound was 25-nor-cycloart-3, 16-dione-17-en-24-oic acid, obtained from argentatin A (ED50=1.4×10(-4)mmol/ear). Argentatin B was assayed as inhibitor of COX-2 activity one of the key enzymes involved in the TPA assay. The results showed that argentatin B at 15?M doses inhibited 77% COX-2 activity. Docking studies suggest that argentatin B interacts with Arg 120, a key residue for COX-2 activity. PMID:25456078

  4. 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?potent anti-inflammatory effects in the formalin-induced paw inflammation model and significantly reduced the paw oedema in all applied doses (p?anti-inflammatory effect suggest both central and peripheral mechanisms of action for the essential oil obtained from N. crispa. PMID:21981349

  5. Chlorophyll revisited: anti-inflammatory activities of chlorophyll a and inhibition of expression of TNF-? gene by the same.

    PubMed

    Subramoniam, Appian; Asha, Velikkakathu V; Nair, Sadasivan Ajikumaran; Sasidharan, Sreejith P; Sureshkumar, Parameswaran K; Rajendran, Krishnan Nair; Karunagaran, Devarajan; Ramalingam, Krishnan

    2012-06-01

    In view of the folklore use of green leaves to treat inflammation, the anti-inflammatory property of chlorophylls and their degradation products were studied. Chlorophyll a and pheophytin a (magnesium-free chlorophyll a) from fresh leaves showed potent anti-inflammatory activity against carrageenan-induced paw edema in mice and formalin-induced paw edema in rats. Chlorophyll a inhibited bacterial lipopolysaccharide-induced TNF-? (a pro-inflammatory cytokine) gene expression in HEK293 cells, but it did not influence the expression of inducible nitric acid synthase and cyclooxygenase-2 genes. Chlorophyll b only marginally inhibited both inflammation and TNF-? gene expression. But both chlorophyll a and chlorophyll b showed the same level of marginal inhibition on 12-O-tetradecanoyl-phorbol-13-acetate-induced NF-?B activation. Chlorophylls and pheophytins showed in vitro anti-oxidant activity. The study shows that chlorophyll a and its degradation products are valuable and abundantly available anti-inflammatory agents and promising for the development of phytomedicine or conventional medicine to treat inflammation and related diseases. PMID:22038065

  6. Differences in Anti-Inflammatory Actions of Intravenous Immunoglobulin between Mice and Men: More than Meets the Eye.

    PubMed

    Tjon, Angela S W; van Gent, Rogier; Geijtenbeek, Teunis B; Kwekkeboom, Jaap

    2015-01-01

    Intravenous immunoglobulin (IVIg) is a therapeutic preparation of polyspecific human IgGs purified from plasma pooled from thousands of individuals. When administered at a high dose, IVIg inhibits inflammation and has proven efficacy in the treatment of various autoimmune and systemic inflammatory diseases. Importantly, IVIg therapy can ameliorate both auto-antibody-mediated and T-cell mediated immune pathologies. In the last few decades, extensive research in murine disease models has resulted in the elucidation of two novel anti-inflammatory mechanisms-of-action of IVIg: induction of Fc?RIIB expression by sialylated Fc, and stimulation of regulatory T cells. Whereas controversial findings in mice studies have recently inspired intense scientific debate regarding the validity of the sialylated Fc-Fc?RIIB model, the most fundamental question is whether these anti-inflammatory mechanisms of IVIg are operational in humans treated with IVIg. In this review, we examine the evidence for the involvement of these anti-inflammatory mechanisms in the therapeutic effects of IVIg in humans. We demonstrate that although several elements of both immune-modulatory pathways of IVIg are activated in humans, incorrect extrapolations from mice to men have been made on the molecular and cellular components involved in these cascades that warrant for critical re-evaluation of these anti-inflammatory mechanisms of IVIg in humans. PMID:25972869

  7. 2-substituted indazolinones: orally active and selective 5-lipoxygenase inhibitors with anti-inflammatory activity.

    PubMed Central

    Foster, S. J.; Bruneau, P.; Walker, E. R.; McMillan, R. M.

    1990-01-01

    1. This paper describes the pharmacological profile of ICI207968, a novel, orally-active and selective inhibitor of 5-lipoxygenase. 2. Inhibition of leukotriene B4 (LTB4) synthesis by 2-substituted indazolinones was not directly related to redox potential but was critically dependent on the nature of the N2 substituent. 2-(3-Pyridylmethyl)-indazolinone (ICI207968) combined selectivity and oral potency. 3. In several in vitro systems ICI207968 exhibited similar lipoxygenase inhibitory potency (IC50 values from 1.5 microM to 6.0 microM) and was approximately 300 times less potent against cyclo-oxygenase, as measured by inhibition of prostaglandin E2 (PGE2) synthesis. 4. ICI207968 also produced selective lipoxygenase inhibition following oral administration in the rat. ED50 values of 2.5, 10 and 25 mg kg-1 p.o. for inhibition of LTB4 release from A23187-stimulated blood were obtained 1, 3 and 5 h after dosing. The compound did not inhibit PGE2 synthesis at oral doses up to 300 mg kg-1. 5. Co-administration of ICI207968 with arachidonic acid, into rabbit dermis, potently inhibited both plasma extravasation and polymorphonuclear leucocyte (PMNL) infiltration induced by this inflammatory fatty acid. The anti-inflammatory potency of a number of intradermally administered indazolinones, with similar redox potentials, was related to their inhibitory potency against leukotriene generation in blood. Oral administration of ICI207968 (100 mg kg-1) in the rabbit inhibited ex vivo leukotriene generation in blood and arachidonic acid-induced skin inflammation. 6. These data demonstrate that ICI207968 is an orally active and selective inhibitor of 5-lipoxygenase which has anti-inflammatory properties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2110012

  8. 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 ?g/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. PMID:20920210

  9. 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 ?-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. 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

  11. 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 (?-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 ?-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 ?-3 PUFA-EE revealed well resolved (1)H resonances from highly mobile ?-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ?-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale. Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ?-3 PUFA-EE within the membrane domain. Water diffusion weighted spectra, indicated that the goticules of ?-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 ?-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 ?-3 PUFA-EE may become useful anti-inflammatory agents for image guided drug delivery. PMID:25767616

  12. 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; Ko?mider, 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 IC?? around 5 ?g/ml and 25 ?g/ml. The inhibition of hyaluronidase is related with the presence of OeB, a strong inhibitor of this enzyme (IC??) 1.1 ?M). Additionally, the extracts inhibited myeloperoxidase (MPO) release from stimulated neutrophils. OeB inhibited MPO release similarly to the anti-inflammatory drug indomethacin with IC?? 7.7 ?M and 15.4 ?M, respectively. Tested extracts significantly reduced the production of reactive oxygen species (ROS) from f-MLP and PMA induced neutrophils with IC?? 5 ?g/ml and 25 ?g/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

  13. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage.

    PubMed

    Sasso, Oscar; Migliore, Marco; Habrant, Damien; Armirotti, Andrea; Albani, Clara; Summa, Maria; Moreno-Sanz, Guillermo; Scarpelli, Rita; Piomelli, Daniele

    2015-06-01

    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

  14. Modulation of Intestinal Inflammation by Yeasts and Cell Wall Extracts: Strain Dependence and Unexpected Anti-Inflammatory Role of Glucan Fractions

    PubMed Central

    Jawhara, Samir; Habib, Khalid; Maggiotto, François; Pignede, Georges; Vandekerckove, Pascal; Maes, Emmanuel; Dubuquoy, Laurent; Fontaine, Thierry; Guerardel, Yann; Poulain, Daniel

    2012-01-01

    Yeasts and their glycan components can have a beneficial or adverse effect on intestinal inflammation. Previous research has shown that the presence of Saccharomyces cerevisiae var. boulardii (Sb) reduces intestinal inflammation and colonization by Candida albicans. The aim of this study was to identify dietary yeasts, which have comparable effects to the anti-C. albicans and anti-inflammatory properties of Sb and to assess the capabilities of yeast cell wall components to modulate intestinal inflammation. Mice received a single oral challenge of C. albicans and were then given 1.5% dextran-sulphate-sodium (DSS) for 2 weeks followed by a 3-day restitution period. S. cerevisiae strains (Sb, Sc1 to Sc4), as well as mannoprotein (MP) and ?-glucan crude fractions prepared from Sc2 and highly purified ?-glucans prepared from C. albicans were used in this curative model, starting 3 days after C. albicans challenge. Mice were assessed for the clinical, histological and inflammatory responses related to DSS administration. Strain Sc1-1 gave the same level of protection against C. albicans as Sb when assessed by mortality, clinical scores, colonization levels, reduction of TNF? and increase in IL-10 transcription. When Sc1-1 was compared with the other S. cerevisiae strains, the preparation process had a strong influence on biological activity. Interestingly, some S. cerevisiae strains dramatically increased mortality and clinical scores. Strain Sc4 and MP fraction favoured C. albicans colonization and inflammation, whereas ?-glucan fraction was protective against both. Surprisingly, purified ?-glucans from C. albicans had the same protective effect. Thus, some yeasts appear to be strong modulators of intestinal inflammation. These effects are dependent on the strain, species, preparation process and cell wall fraction. It was striking that ?-glucan fractions or pure ?-glucans from C. albicans displayed the most potent anti-inflammatory effect in the DSS model. PMID:22848391

  15. Anti-inflammatory and immune-modulatory therapies for preventing atherosclerotic cardiovascular disease.

    PubMed

    Yamashita, Tomoya; Sasaki, Naoto; Kasahara, Kazuyuki; Hirata, Ken-Ichi

    2015-07-01

    Atherosclerosis is believed to be a chronic inflammation of the arterial wall and various immune cells of innate and adaptive immunity involves in the pathogenesis of atherosclerosis. Based on this notion, several anti-inflammatory strategies for prevention of atherosclerosis have been examined mainly using animal models. Vaccination or mucosal immunization with athero-antigens comes under candidate therapeutic methods for antigen-specific prevention of atherosclerosis. Immune suppression mediated by regulatory T cells (Tregs) could be another method to regulate pathogenic chronic inflammation in atherogenesis. Inducible Tregs are reported to differentiate peripherally in the intestine and we have been interested in the oral tolerance, in which not only Tregs but also tolerogenic dendritic cells play crucial roles. We demonstrated that modulation of the intestinal immunity including oral tolerance could be a novel therapy against atherosclerosis. Further, downregulation of effector T cell response and/or Treg predominant condition was shown to induce atherosclerosis regression and inhibit the progression of aneurysm. In clinical situations, none of the approaches to specifically and directly treat inflammation to prevent cardiovascular events or reduce atherosclerosis in human individuals were successful, although high-sensitive C-reactive protein is shown to have a strong relationship with recurrent events of cardiovascular diseases in several randomized clinical trials. Now two randomized placebo-controlled clinical trials evaluating anti-inflammatory agents are being conducted in the USA and Canada to clarify whether targeting the inflammation itself will reduce cardiovascular events and risks. In this review, we present the current understanding of anti-inflammatory and immune-modulation therapies against atherosclerosis and discuss the future perspectives. PMID:25744783

  16. 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-?-d-(3'-angeloxy-6'-deoxy)-glucopyranoside and 1(5)-guaiene-11-O-?-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 7.2?M, respectively, comparable to that of the positive control, indomethacin (IC50=18.2 ?M), with no cytotoxic effects (IC50 ? 198 ?M). 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

  17. 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 (?-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

  18. Anti-inflammatory and chemopreventive effects of triterpene cinnamates and acetates from shea fat.

    PubMed

    Akihisa, Toshihiro; Kojima, Nobuo; Kikuchi, Takashi; Yasukawa, Ken; Tokuda, Harukuni; T Masters, Eliot; Manosroi, Aranya; Manosroi, Jiradej

    2010-01-01

    Four triterpene acetates, alpha-amyrin acetate (1a), beta-amyrin acetate (2a), lupeol acetate (3a), and butyrospermol acetate (4a), and four triterpene cinnamates, alpha-amyrin cinnamate (1c), beta-amyrin cinnamate (2c), lupeol cinnamate (3c), and butyrospermol cinnamate (4c), were isolated from the kernel fat (n-hexane extract) of the shea tree (Vitellaria paradoxa; Sapotaceae). Upon evaluation of these eight triterpene esters for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds tested exhibited marked anti-inflammatory activity, with ID50 values in the range of 0.15-0.75 micromol/ear, and among which compound 3c showed the highest activity with ID(50) of 0.15 micromol/ear. Compound 3c (10 mg/kg) further exhibited anti-inflammatory activity on rat hind paw edema induced by carrageenan, with the percentage of inflammation at 1, 3, and 5 h of 35.4, 41.5, and 45.5%, respectively. The eight triterpene esters were then evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) in Raji cells as a primary screening test for inhibitors of tumor promoters. All the compounds showed moderate inhibitory effects. Furthermore, compound 3c exhibited inhibitory effect on skin tumor promotion in an in vivo two-stage carcinogenesis test using 7,12-dimethylbenz [a] anthracene (DMBA) as an initiator and TPA as a promoter. The biological activities of triterpene acetate and cinnamate esters, together with the exceptionally high levels of these triterpenes in shea fat, indicate that shea nuts and shea fat (shea butter) constitute a significant source of anti-inflammatory and anti-tumor promoting compounds. PMID:20484832

  19. Probiotics, Nuclear Receptor Signaling, and Anti-Inflammatory Pathways

    PubMed Central

    Yoon, Sonia S.; Sun, Jun

    2011-01-01

    There is increased investigation of the human microbiome as it relates to health and disease. Dysbiosis is implicated in various clinical conditions including inflammatory bowel disease (IBD). Probiotics have been explored as a potential treatment for IBD and other diseases. The mechanism of action for probiotics has yet to be fully elucidated. This paper discusses novel mechanisms of action for probiotics involving anti-inflammatory signaling pathways. We highlight recent progress in probiotics and nuclear receptor signaling, such as peroxisome-proliferator-activated receptor gamma (PPAR?) and vitamin D receptor (VDR). We also discuss future areas of investigation. PMID:21808643

  20. Anti-inflammatory anthraquinones from the crinoid Himerometra magnipinna.

    PubMed

    Lin, Yen-You; Tsai, Su-June; Chiang, Michael Y; Wen, Zhi-Hong; Su, Jui-Hsin

    2015-02-01

    Chemical investigation of a crinoid Himerometra magnipinna has afforded three anthraquinones (1-3), including one new metabolite, (+)-rhodoptilometrin (1). The structures of these compounds were elucidated on the basis of their spectroscopic data and the absolute configuration of 1 was further confirmed by single-crystal X-ray diffraction analysis. In the in vitro anti-inflammatory effects test, compound 2 was found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein of the LPS-stimulated RAW264.7 macrophage cells. PMID:25920272

  1. Anti-inflammatory agents of the carbamoylmethyl ester class: synthesis, characterization, and pharmacological evaluation

    PubMed Central

    Sadek, Bassem; Hamruoni, Amar Mansuor; Adem, Abdu

    2013-01-01

    In this study, target compounds 5–12 were synthesized via acid amine coupling of ibuprofen and naproxen with methyl ester derivatives of amino acids, namely, l-proline, sarcosine, l-tyrosine, and l-glutamic acid. When tested for anti-inflammatory activity using the acute carrageenan-induced hind paw method in rats, compounds 5–12 showed significantly greater anti-inflammatory activity, in the range of 40.64%–87.82%, compared with a placebo control group (P < 0.001). Among the newly synthesized compounds 5–12, naproxen derivatives 9–12 with anti-inflammatory activity ranging between 66.99% and 87.82% showed significantly higher (P < 0.05) potency than ibuprofen derivatives 5–8 with inhibition in the range of 22.03%–52.91% and control groups of ibuprofen (76.34%) or naproxen (75.59%, P < 0.05). Moreover, derivatives 9–12 derived from naproxen, in particular compounds 9 and 10 which achieved 83.91% and 87.82% inhibition of inflammation, respectively, showed significantly (P < 0.05) higher potency than naproxen derivatives 11 and 12. Notably, among naproxen derivatives 9–12, the gastric ulcerogenicity for 9 (ulcer index 11.73) and 10 (ulcer index 12.30) was found to be significantly lower (P < 0.05) than that of the active ibuprofen and naproxen control groups with ulcer indices of 22.87 and 24.13, respectively. On the other hand, naproxen derivatives 9–11 showed significant inhibition (P < 0.05) of prostaglandin E2 synthesis when compared with the active control group receiving indomethacin, suggesting a correlation between the observed low ulcerogenicity and effect on prostaglandin E2 synthesis for compounds 9 and 10. However, significant inhibition of prostaglandin E2 observed for naproxen derivative 11 (107.51) did not correlate with its observed ulcer index (16.84). Our overall findings for carbamoylmethyl ester derivatives named 5–12 clearly suggest that the compounds showing potent antiinflammatory effect. PMID:23576876

  2. Heme Oxygenase-1 Couples Activation of Mitochondrial Biogenesis to Anti-inflammatory Cytokine Expression*

    PubMed Central

    Piantadosi, Claude A.; Withers, Crystal M.; Bartz, Raquel R.; MacGarvey, Nancy Chou; Fu, Ping; Sweeney, Timothy E.; Welty-Wolf, Karen E.; Suliman, Hagir B.

    2011-01-01

    The induction of heme oxygenase-1 (HO-1; Hmox1) by inflammation, for instance in sepsis, is associated both with an anti-inflammatory response and with mitochondrial biogenesis. Here, we tested the idea that HO-1, acting through the Nfe2l2 (Nrf2) transcription factor, links anti-inflammatory cytokine expression to activation of mitochondrial biogenesis. HO-1 induction after LPS stimulated anti-inflammatory IL-10 and IL-1 receptor antagonist (IL-1Ra) expression in mouse liver, human HepG2 cells, and mouse J774.1 macrophages but blunted tumor necrosis factor-? expression. This was accompanied by nuclear Nfe2l2 accumulation and led us to identify abundant Nfe2l2 and other mitochondrial biogenesis transcription factor binding sites in the promoter regions of IL10 and IL1Ra compared with pro-inflammatory genes regulated by NF-??. Mechanistically, HO-1, through its CO product, enabled these transcription factors to bind the core IL10 and IL1Ra promoters, which for IL10 included Nfe2l2, nuclear respiratory factor (NRF)-2 (Gabpa), and MEF2, and for IL1Ra, included NRF-1 and MEF2. In cells, Hmox1 or Nfe2l2 RNA silencing prevented IL-10 and IL-1Ra up-regulation, and HO-1 induction failed post-LPS in Nfe2l2-silenced cells and post-sepsis in Nfe2l2?/? mice. Nfe2l2?/? mice compared with WT mice, showed more liver damage, higher mortality, and ineffective CO rescue in sepsis. Nfe2l2?/? mice in sepsis also generated higher hepatic TNF-? mRNA levels, lower NRF-1 and PGC-1? mRNA levels, and no enhancement of anti-inflammatory Il10, Socs3, or bcl-xL gene expression. These findings disclose a highly structured transcriptional network that couples mitochondrial biogenesis to counter-inflammation with major implications for immune suppression in sepsis. PMID:21454555

  3. In Vivo anti-nociceptive and anti-inflammatory effect of the two triterpenes, ursolic acid and 23-hydroxyursolic acid, from cussonia bancoensis

    Microsoft Academic Search

    L. A. Tapondjou; David Lontsi; Sondengam Beibam Luc; Choi Jongwon; Lee Kyung-Tae; Jung Hyun-Ju; Park Hee-Juhn

    2003-01-01

    Triterpenoids, ursolic acid (1) and 23-hydroxyursolic acid (2) were obtained from the hydrolysis of BuOH fraction ofCussonia bancoensis extract to test antinociceptive and anti-inflammatory effect ofC. bancoensis (Araliaceae). Compound1 and2 exhibited anti-nociceptive effects, which were determined by acetic acid-induced writhing test and hot plate test. The effect\\u000a of2 was much more potent in acetic acid-induced writhing test than in hot

  4. Assessment of the anti-inflammatory activity and free radical scavenger activity of tiliroside.

    PubMed

    Sala, Araceli; Recio, M Carmen; Schinella, Guillermo R; Máñez, Salvador; Giner, Rosa M; Cerdá-Nicolás, Miguel; Rosí, José Luis

    2003-02-01

    Three flavonoids, gnaphaliin, pinocembrin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their antioxidant and/or scavenger properties and in vivo in different models of inflammation. In vitro tests included lipid peroxidation in rat liver microsomes, superoxide radical generation in the xanthine/xanthine oxidase system and the reduction of the stable radical 1,1-diphenyl-2-pycryl-hydrazyl (DPPH). Acute inflammation was induced by application of 12-O-tetradecanoylphorbol 13-acetate (TPA) to the mouse ear or by subcutaneous injection of phospholipase A(2) or serotonin in the mouse paw. Eczema provoked on the mouse ear by repeated administration of TPA was selected as a model of chronic inflammation. The flavonoids were assayed against sheep red blood cell-induced mouse paw oedema as a model of delayed-type hypersensitivity reaction. The most active compound, both in vitro and in vivo, was tiliroside. It significantly inhibited enzymatic and non-enzymatic lipid peroxidation (IC(50)=12.6 and 28 microM, respectively). It had scavenger properties (IC(50)=21.3 microM) and very potent antioxidant activity in the DPPH test (IC(50)=6 microM). In vivo, tiliroside significantly inhibited the mouse paw oedema induced by phospholipase A(2)(ED(50)=35.6 mg/kg) and the mouse ear inflammation induced by TPA (ED(50)=357 microg/ear). Pinocembrin was the only flavonoid that exhibited anti-inflammatory activity in the sheep red blood cell-induced delayed-type hypersensitivity reaction. However, only tiliroside significantly reduced the oedema and leukocyte infiltration induced by TPA. As in the case of other flavonoids, the anti-inflammatory activity of tiliroside could be based on its antioxidant properties, although other mechanisms are probably involved. PMID:12568916

  5. Imbricaric acid and perlatolic acid: multi-targeting anti-inflammatory depsides from Cetrelia monachorum.

    PubMed

    Oettl, Sarah K; Gerstmeier, Jana; Khan, Shafaat Y; Wiechmann, Katja; Bauer, Julia; Atanasov, Atanas G; Malainer, Clemens; Awad, Ezzat M; Uhrin, Pavel; Heiss, Elke H; Waltenberger, Birgit; Remias, Daniel; Breuss, Johannes M; Boustie, Joel; Dirsch, Verena M; Stuppner, Hermann; Werz, Oliver; Rollinger, Judith M

    2013-01-01

    In vitro screening of 17 Alpine lichen species for their inhibitory activity against 5-lipoxygenase, microsomal prostaglandin E2 synthase-1 and nuclear factor kappa B revealed Cetrelia monachorum (Zahlbr.) W.L. Culb. & C.F. Culb. As conceivable source for novel anti-inflammatory compounds. Phytochemical investigation of the ethanolic crude extract resulted in the isolation and identification of 11 constituents, belonging to depsides and derivatives of orsellinic acid, olivetolic acid and olivetol. The two depsides imbricaric acid (4) and perlatolic acid (5) approved dual inhibitory activities on microsomal prostaglandin E2 synthase-1 (IC50 = 1.9 and 0.4 µM, resp.) and on 5-lipoxygenase tested in a cell-based assay (IC50 = 5.3 and 1.8 µM, resp.) and on purified enzyme (IC50 = 3.5 and 0.4 µM, resp.). Additionally, these two main constituents quantified in the extract with 15.22% (4) and 9.10% (5) showed significant inhibition of tumor necrosis factor alpha-induced nuclear factor kappa B activation in luciferase reporter cells with IC50 values of 2.0 and 7.0 µM, respectively. In a murine in vivo model of inflammation, 5 impaired the inflammatory, thioglycollate-induced recruitment of leukocytes to the peritoneum. The potent inhibitory effects on the three identified targets attest 4 and 5 a pronounced multi-target anti-inflammatory profile which warrants further investigation on their pharmacokinetics and in vivo efficacy. PMID:24130812

  6. Anti-inflammatory effects of freeze-dried black raspberry powder in ulcerative colitis.

    PubMed

    Montrose, David C; Horelik, Nicole A; Madigan, James P; Stoner, Gary D; Wang, Li-Shu; Bruno, Richard S; Park, Hea Jin; Giardina, Charles; Rosenberg, Daniel W

    2011-03-01

    Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa that can dramatically increase the risk of colon cancers. In the present study, we evaluated the effects of a dietary intervention of freeze-dried black raspberries (BRB), a natural food product with antioxidant and anti-inflammatory bioactivities, on disease severity in an experimental mouse model of UC using 3% dextran sodium sulfate (DSS). C57BL/6J mice were fed either a control diet or a diet containing BRB (5 or 10%) for 7-14 days and then the extent of colonic injury was assessed. Dietary BRB markedly reduced DSS-induced acute injury to the colonic epithelium. This protection included better maintenance of body mass and reductions in colonic shortening and ulceration. BRB treatment, however, did not affect the levels of either plasma nitric oxide or colon malondialdehyde, biomarkers of oxidative stress that are otherwise increased by DSS-induced colonic injury. BRB treatment for up to 7 days suppressed tissue levels of several key pro-inflammatory cytokines, including tumor necrosis factor ? and interleukin 1?. Further examination of the inflammatory response by western blot analysis revealed that 7 day BRB treatment reduced the levels of phospho-I?B? within the colonic tissue. Colonic cyclooxygenase 2 levels were also dramatically suppressed by BRB treatment, with a concomitant decrease in the plasma prostaglandin E? (276 versus 34 ng/ml). These findings demonstrate a potent anti-inflammatory effect of BRB during DSS-induced colonic injury, supporting its possible therapeutic or preventive role in the pathogenesis of UC and related neoplastic events. PMID:21098643

  7. A Polysaccharide Virulence Factor from Aspergillus fumigatus Elicits Anti-inflammatory Effects through Induction of Interleukin-1 Receptor Antagonist

    PubMed Central

    Gresnigt, Mark S.; Bozza, Silvia; Becker, Katharina L.; Joosten, Leo A. B.; Abdollahi-Roodsaz, Shahla; van der Berg, Wim B.; Dinarello, Charles A.; Netea, Mihai G.; Fontaine, Thierry; De Luca, Antonella; Moretti, Silvia; Romani, Luigina; Latge, Jean-Paul; van de Veerdonk, Frank L.

    2014-01-01

    The galactosaminogalactan (GAG) is a cell wall component of Aspergillus fumigatus that has potent anti-inflammatory effects in mice. However, the mechanisms responsible for the anti-inflammatory property of GAG remain to be elucidated. In the present study we used in vitro PBMC stimulation assays to demonstrate, that GAG inhibits proinflammatory T-helper (Th)1 and Th17 cytokine production in human PBMCs by inducing Interleukin-1 receptor antagonist (IL-1Ra), a potent anti-inflammatory cytokine that blocks IL-1 signalling. GAG cannot suppress human T-helper cytokine production in the presence of neutralizing antibodies against IL-1Ra. In a mouse model of invasive aspergillosis, GAG induces IL-1Ra in vivo, and the increased susceptibility to invasive aspergillosis in the presence of GAG in wild type mice is not observed in mice deficient for IL-1Ra. Additionally, we demonstrate that the capacity of GAG to induce IL-1Ra could also be used for treatment of inflammatory diseases, as GAG was able to reduce severity of an experimental model of allergic aspergillosis, and in a murine DSS-induced colitis model. In the setting of invasive aspergillosis, GAG has a significant immunomodulatory function by inducing IL-1Ra and notably IL-1Ra knockout mice are completely protected to invasive pulmonary aspergillosis. This opens new treatment strategies that target IL-1Ra in the setting of acute invasive fungal infection. However, the observation that GAG can also protect mice from allergy and colitis makes GAG or a derivative structure of GAG a potential treatment compound for IL-1 driven inflammatory diseases. PMID:24603878

  8. 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-1? (IL-1?), tumor necrosis factor ? (TNF-?), 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-?B-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-? (P < 0.01), IL-1? (P < 0.01), and IL-6 (P < 0.01), enhanced SIRT1 expression, and depressed Ac-NF-?B-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-?B-p65 expression. PMID:26146507

  9. Anti-inflammatory activity of ‘TAF’ an active fraction from the plant Barleria prionitis Linn

    Microsoft Academic Search

    B. Singh; S. Bani; D. K. Gupta; B. K. Chandan; A. Kaul

    2003-01-01

    ‘TAF’ fraction from the methanol–water extract of Barleria prionitis Linn. was evaluated for anti-inflammatory and anti-arthritic activities against different acute and chronic animal test models. It exhibited significant anti-inflammatory activity against different inflammagens like carrageenan, histamine and dextran. The anti-inflammatory activity in adrenalectomised rats was maintained showing that the effect of fraction ‘TAF’ is not activated by the pituitary–adrenal axis.

  10. 1,5-Diphenylpent-3-en-1-ynes and methyl naphthalene carboxylates from Lawsonia inermis and their anti-inflammatory activity.

    PubMed

    Liou, Jing-Ru; El-Shazly, Mohamed; Du, Ying-Chi; Tseng, Chao-Neng; Hwang, Tsong-Long; Chuang, Yueh-Lin; Hsu, Yu-Ming; Hsieh, Pei-Wen; Wu, Chin-Chun; Chen, Shu-Li; Hou, Ming-Feng; Chang, Fang-Rong; Wu, Yang-Chang

    2013-04-01

    Lawsonia inermis (Lythraceae) known as henna is one of the most popular and ancient plants used in cosmetics and hair dying. It is cultivated for its leaves but other parts such as seeds, flowers, stem bark and roots are also used in traditional medicine for millennia. Henna tattoo paste also proved to be beneficial for wound healing and in several skin diseases suggesting potent anti-inflammatory activity. To evaluate henna anti-inflammatory activity, 31 compounds, including three 1,5-diphenylpent-3-en-1-yne derivatives, lawsochylin A-C and three methyl naphthalene carboxylates, lawsonaphthoate A-C, were isolated from the stems and leaves of henna utilizing a bioassay-guided fractionation. The structures of the compounds were elucidated by spectroscopic data. Two compounds, lawsochylin A and lawsonaphthoate A showed potent anti-inflammatory activity by inhibition of superoxide anion generation (IC(50)=1.80 and 1.90 ?g/ml) and elastase release (IC(50)=1.58 and 3.17 ?g/ml) of human neutrophils in response to fMLP or cytochalasin B. Moreover, the known compounds, luteolin, apigenin, 4S-4-hydroxy-?-tetralone, and 2-butoxysuccinic acid, also showed potent inhibition of superoxide anion generation (IC(50)=0.75-1.78 ?g/ml) and elastase release (IC(50)=1.62-3.61 ?g/ml). PMID:23351982

  11. 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

  12. Antioxidant activity of anti-inflammatory plant extracts.

    PubMed

    Schinella, G R; Tournier, H A; Prieto, J M; Mordujovich de Buschiazzo, P; Ríos, J L

    2002-01-18

    The antioxidant properties of twenty medical herbs used in the traditional Mediterranean and Chinese medicine were studied. Extracts from Forsythia suspensa, Helichrysum italicum, Scrophularia auriculata, Inula viscosa, Coptis chinensis, Poria cocos and Scutellaria baicalensis had previously shown anti-inflammatory activity in different experimental models. Using free radical-generating systems H. italicum. I. viscosa and F. suspensa protected against enzymatic and non-enzymatic lipid peroxidation in model membranes and also showed scavenging property on the superoxide radical. All extracts were assayed at a concentration of 100 microg/ml. Most of the extracts were weak scavengers of the hydroxyl radical and C. chinensis and P. cocos exhibited the highest scavenging activity. Although S. baicalensis inhibited the lipid peroxidation in rat liver microsomes and red blood cells, the extract showed inhibitory actions on aminopyrine N-demethylase and xanthine oxidase activities as well as an pro-oxidant effect observed in the Fe3+-EDTA-H2O2 system. The results of the present work suggest that the anti-inflammatory activities of the same extracts could be explained, at least in part, by their antioxidant properties. PMID:11860151

  13. 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

  14. ?-Mangostin: anti-inflammatory activity and metabolism by human cells.

    PubMed

    Gutierrez-Orozco, Fabiola; Chitchumroonchokchai, Chureeporn; Lesinski, Gregory B; Suksamrarn, Sunit; Failla, Mark L

    2013-04-24

    Information about the anti-inflammatory activity and metabolism of ?-mangostin (?-MG), the most abundant xanthone in mangosteen fruit, in human cells is limited. On the basis of available literature, we hypothesized that ?-MG will inhibit the secretion of pro-inflammatory mediators by control and activated macrophage-like THP-1, hepatic HepG2, enterocyte-like Caco-2, and colon HT-29 human cell lines, as well as primary human monocyte-derived macrophages (MDM), and that such activity would be influenced by the extent of metabolism of the xanthone. ?-MG attenuated TNF-? and IL-8 secretion by the various cell lines but increased TNF-? output by both quiescent and LPS-treated MDM. The relative amounts of free and phase II metabolites of ?-MG and other xanthones present in media 24 h after addition of ?-MG was shown to vary by cell type and inflammatory insult. Increased transport of xanthones and their metabolites across Caco-2 cell monolayers suggests enhanced absorption during an inflammatory episode. The anti-inflammatory activities of xanthones and their metabolites in different tissues merit consideration. PMID:23578285

  15. Anti-inflammatory drugs, antioxidants, and prostate cancer prevention

    PubMed Central

    Bardia, Aditya; Platz, Elizabeth A; Yegnasubramanian, Srinivasan; De Marzo, Angelo M; Nelson, William G

    2015-01-01

    Prostate cancer may be the most common preventable cancer among men in the United States (US) and the rest of the developed world. Emerging insights into the molecular pathogenesis of prostate cancer suggest that damage to the prostate epithelium, potentially inflicted by a variety of exposures, triggers procarcinogenic inflammatory processes to promote disease development. In this milieu, the damaged epithelium may generate proliferative inflammatory atrophy (PIA) lesions, which may progress to prostatic intraepithelial neoplasia (PIN) or to prostate cancer. To attenuate prostatic carcinogenesis driven by chronic or recurrent prostate inflammation, rational chemoprevention has thus far featured anti-inflammatory drugs and antioxidants. Results from clinical trials of these approaches have been mixed, emphasizing the need for mechanistic studies of the contribution of inflammation to prostatic carcinogenesis, more extensive analyses of the pharmacology, including distribution of drugs into target tissue, and, rational development of biomarkers to identify patients that are most likely to respond to anti-inflammatory drugs and antioxidants (targeted chemoprevention), alone, or in combination (combination chemoprevention). PMID:19574101

  16. Anti-inflammatory activity of hamamelis distillate applied topically to the skin. Influence of vehicle and dose.

    PubMed

    Korting, H C; Schäfer-Korting, M; Hart, H; Laux, P; Schmid, M

    1993-01-01

    The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle. UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P < or = 0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry. The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity. PMID:8513841

  17. Incorporation of eicosatrienoic acid exerts mild anti-inflammatory properties in murine RAW264.7 cells.

    PubMed

    Chen, Szu-Jung; Chuang, Lu-Te; Chen, Sung-Nien

    2015-04-01

    Eicosatrienoic acid (?11,14,17-20:3; ETrA) is a rare naturally occurring n-3 polyunsaturated fatty acid (PUFA). Using murine RAW264.7 cells, the objectives were to determine how ETrA modulated phospholipid fatty acid compositions and the production of pro-inflammatory mediators. Incubation cells with ETrA dose-dependently increased the proportions of phospholipid ETrA and its metabolites to 33 % of the fatty acid total. Incorporation of ETrA also reduced the proportions of total n-6 PUFA and monounsaturated fatty acids (MUFA) by 30 and 60 %, respectively. ETrA suppressed LPS-stimulated nuclear factor-kappa B (NF-?B)-mediated nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression. However, no such suppressive effect on the production of prostaglandin E2 (PGE2), cytokines, or expression of cyclooxygenase-2 (COX-2) was observed. As compared with ETrA, eicosapentaenoic acid (EPA) exerted a more potent anti-inflammatory effect. In conclusion, although ETrA suppresses significant NO synthesis and iNOS expression, this n-3 PUFA was a less potent anti-inflammatory agent than EPA. PMID:24993153

  18. Anti-inflammatory response following uptake of apoptotic bodies by meningothelial cells

    PubMed Central

    2014-01-01

    Background Meningothelial cells (MECs) are the cellular components of the meninges. As such, they provide important barrier function for the central nervous system (CNS) building the interface between neuronal tissue and the cerebrospinal fluid (CSF), and are also part of the immune response of the CNS. Methods Human, immortalized MECs were analyzed by flow cytometry and confocal microscopy to study the uptake of apoptotic cells. Furthermore, cytokine and chemokine production by MECs was analyzed by cytokine array and ELISA. Results We found that MECs are highly active phagocytes able of ingesting and digesting large amounts of apoptotic cells. Furthermore, the uptake of apoptotic cells by MECs was immune suppressive via inhibiting the secretion of pro-inflammatory and chemoattractant cytokines and chemokines IL-6, IL-8, IL-16, MIF, and CXCL1, while increasing the secretion of anti-inflammatory IL-1 receptor antagonist by MECs. Conclusion MECs respond with the secretion of anti-inflammatory cytokines and chemokines following the uptake of apoptotic cells potentially connecting these cells to processes important for the shut-down of immune responses in the brain. PMID:24565420

  19. Substrate-anchored and degradation-sensitive anti-inflammatory coatings for implant materials.

    PubMed

    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

  20. 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-?, interleukin-6 and -1?. PMID:25172694

  1. Ultrasound Prevents Renal Ischemia-Reperfusion Injury by Stimulating the Splenic Cholinergic Anti-Inflammatory Pathway

    PubMed Central

    Gigliotti, Joseph C.; Huang, Liping; Ye, Hong; Bajwa, Amandeep; Chattrabhuti, Kryt; Lee, Sangju; Klibanov, Alexander L.; Kalantari, Kambiz; Rosin, Diane L.

    2013-01-01

    AKI affects both quality of life and health care costs and is an independent risk factor for mortality. At present, there are few effective treatment options for AKI. Here, we describe a nonpharmacologic, noninvasive, ultrasound-based method to prevent renal ischemia-reperfusion injury in mice, which is a model for human AKI. We exposed anesthetized mice to an ultrasound protocol 24 hours before renal ischemia. After 24 hours of reperfusion, ultrasound-treated mice exhibited preserved kidney morphology and function compared with sham-treated mice. Ultrasound exposure before renal ischemia reduced the accumulation of CD11b+Ly6Ghigh neutrophils and CD11b+F4/80high myeloid cells in kidney tissue. Furthermore, splenectomy and adoptive transfer studies revealed that the spleen and CD4+ T cells mediated the protective effects of ultrasound. Last, blockade or genetic deficiency of the ?7 nicotinic acetylcholine receptor abrogated the protective effect of ultrasound, suggesting the involvement of the cholinergic anti-inflammatory pathway. Taken together, these results suggest that an ultrasound-based treatment could have therapeutic potential for the prevention of AKI, possibly by stimulating a splenic anti-inflammatory pathway. PMID:23907510

  2. [How to manage the interruption of a treatment with anti-inflammatory corticosteroids?].

    PubMed

    Kuhn, Jean-Marc; Prévost, Gaëtan

    2014-04-01

    A prolonged treatment with anti-inflammatory corticosteroids induces an inhibition of ACTH secretion from pituitary corticotroph cells. An abrupt interruption of such a treatment potentially leads to the risk of an acute adrenal failure, in particular in stressing situations. The inertia in reactivation of the secretion of the stimulating hypothalamic factors (CRH and AVP) and consecutively of ACTH can be responsible for an inability to adapt the secretion of glucocorticoids in response to stress. A short-time treatment (<3 weeks) with anti-inflammatory corticoids does not expose to this risk. On the contrary, a more prolonged treatment, especially with high daily doses, needs to perform an evaluation of the level of corticotroph secretion. This evaluation should be done before to consider that either stopping the treatment is out of risk or if the initiation of a substitutive treatment with hydrocortisone is required. The measurement of morning plasma cortisol level already provides a significant information. As to whether that is needed, a dynamic evaluation can be performed. Among the available tests, the Synacthen(®)test, easy to perform and using at best 1?g of ?1-24 ACTH, appears the most finely informative to answer this question and to choose the most adapted follow-up. PMID:24613064

  3. Nonsteroidal anti-inflammatory drugs upregulate function of wild-type and mutant CFTR.

    PubMed

    Li, J; Xiang, Y-Y; Ye, L; Tsui, L-C; Macdonald, J F; Hu, J; Lu, W-Y

    2008-08-01

    Small-scale clinical trials show that treatment of cystic fibrosis (CF) patients with ibuprofen, a nonsteroidal anti-inflammatory drug, improves the symptoms of CF and slows down the decline of lung function. Paradoxically, ibuprofen inhibits ligand-stimulated CF transmembrance conductance regulator (CFTR) activity. The aim of the present study was to investigate the effects of ibuprofen on CFTR function under different conditions. Patch-clamp recordings were performed in two lines of human airway epithelial cells: IB3-8-3-7 cells, which express wild-type CFTR; and IB3-1 cells, which express the variant CFTR with deletion of phenylalanine 580 (DeltaF580CFTR). Addition of ibuprofen to the extracellular solution caused a rapid inhibition of CFTR activity in IB3-8-3-7 cells in the presence of a high intracellular concentration of cAMP, whereas ibuprofen enhanced the CFTR conductance at low levels of cAMP. Introducing ibuprofen into the interior of cells occluded the enhancing effect of ibuprofen. Notably, the variant CFTR-mediated conductance was detected in IB3-1 cells treated with myoinositol and was enhanced by ibuprofen at endogenous levels of cAMP. In summary, nonsteroidal anti-inflammatory drugs increase the function of both wild-type cystic fibrosis transmembrane conductance regulator and the phenylalanine 580 deletion in cultured human airway epithelial cells at endogenous levels of cAMP. PMID:18385167

  4. Anti-inflammatory and antifibrotic effects of methyl palmitate

    SciTech Connect

    El-Demerdash, Ebtehal, E-mail: ebtehal_dm@yahoo.com

    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.

  5. Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived from Wasabi (Wasabia japonica).

    PubMed

    Uto, Takuhiro; Hou, De-Xing; Morinaga, Osamu; Shoyama, Yukihiro

    2012-01-01

    6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously reported that 6-MSITC strongly suppresses cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokines, which are important factors that mediate inflammatory processes. Moreover, molecular analysis demonstrated that 6-MSITC blocks the expressions of these factors by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. Structure-activity relationships of 6-MSITC and its analogues containing an isothiocyanate group revealed that methylsulfinyl group and the length of alkyl chain of 6-MSITC might be related to high inhibitory potency. In this paper, we review the anti-inflammatory properties of 6-MSITC and discuss potential molecular mechanisms focusing on inflammatory responses by macrophages. PMID:22927840

  6. Molecular Mechanisms Underlying Anti-Inflammatory Actions of 6-(Methylsulfinyl)hexyl Isothiocyanate Derived from Wasabi (Wasabia japonica)

    PubMed Central

    Uto, Takuhiro; Hou, De-Xing; Morinaga, Osamu; Shoyama, Yukihiro

    2012-01-01

    6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously reported that 6-MSITC strongly suppresses cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokines, which are important factors that mediate inflammatory processes. Moreover, molecular analysis demonstrated that 6-MSITC blocks the expressions of these factors by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. Structure-activity relationships of 6-MSITC and its analogues containing an isothiocyanate group revealed that methylsulfinyl group and the length of alkyl chain of 6-MSITC might be related to high inhibitory potency. In this paper, we review the anti-inflammatory properties of 6-MSITC and discuss potential molecular mechanisms focusing on inflammatory responses by macrophages. PMID:22927840

  7. Harnessing the anti-inflammatory potential of palmitoylethanolamide.

    PubMed

    Alhouayek, Mireille; Muccioli, Giulio G

    2014-10-01

    Palmitoylethanolamide (PEA) is a peroxisome proliferator-activated receptor alpha (PPAR-?) ligand that exerts anti-inflammatory, analgesic and neuroprotective actions. PEA is synthetized from phospholipids through the sequential actions of N-acyltransferase and N-acylphosphatidylethanolamine-preferring phospholipase D (NAPE-PLD), and its actions are terminated by its hydrolysis by two enzymes, fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolysing acid amidase (NAAA). Here, we review the impact of PEA administration in inflammatory and neurodegenerative settings and the differential role of FAAH and NAAA in controlling PEA levels. Recent studies with NAAA inhibitors put forth this enzyme as capable of increasing PEA levels in vivo in inflammatory processes, and identified it as an interesting target for drug discovery research. Thus, PEA hydrolysis inhibitors could constitute potential therapeutic alternatives in chronic inflammatory and neurodegenerative diseases. PMID:24952959

  8. The role of anti-inflammatory treatment in psychiatric disorders.

    PubMed

    Müller, Norbert

    2013-09-01

    Anti-inflammatory treatment could be expected to show positive effects in the subgroup of psychiatric patients who show signs of inflammation, i.e. an increase in proinflammatory cytokines and PGE2. Cyclooxygenase-2 (COX-2) not only reduces the levels of proinflammatory cytokines, but also affects glutamatergic neurotransmission and tryptophan/kynurenine metabolism. In the meantime, several studies have been performed with the COX-2 inhibitor celecoxib in schizophrenia; the studies found a therapeutic effect, mainly in the early stages of the disorder. We were able to demonstrate a statistically significant therapeutic effect of celecoxib on depressive symptoms in a study in patients with major depression (MD). Another study in fifty patients with MD also showed a statistically significant better outcome with celecoxib. This paper will discuss immune-based therapeutic approaches in both schizophrenia and depression. PMID:24048400

  9. 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-1? and TNF? 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

  10. Anti-inflammatory action of glucagon in rats.

    PubMed Central

    Garcia Leme, J; Morato, M; Souza, M Z

    1975-01-01

    1 Subcutaneous administration of glucagon (1 and 0.5 mg/kg) 30 min before the injection of carrageenin or dextran into the rat's paw reduced oedema and the local exudation of Evans blue previously given intravenously. 2 The effect persisted after removal of the adrenal medulla but not after adrenalectomy. 3 When glucagon (1 mg/kg, s.c.) was given daily after a local reaction to Freund's adjuvant injected into the paw had developed, a decrease in the reaction was observed up to 12 days. Blood sugar levels remained within the normal range. 4 Glucagon may exert an anti-inflammatory effect through the release of adrenal corticosteroids and thus help modulate inflammatory reactions. PMID:1182350

  11. Non-Steroidal Anti-Inflammatory Drug-Induced Enteropathy

    PubMed Central

    Lim, Yun Jeong

    2012-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed drugs in the world. NSAID-induced lower gastrointestinal (GI) complications are increasing while upper GI complications are decreasing. Lower GI events accounted for 40% of all serious GI events in patients on NSAIDs. Capsule endoscopy and device assisted enteroscopy are available for detection of small intestinal lesions. Capsule endoscopy studies have demonstrated that NSAIDs use in healthy volunteers raised the incidence (55% to 75%) of intestinal damage. It appears that selective cyclooxygenase-2 inhibitors (coxibs) improved upper and lower GI safety based on results of clinical trials. Selective coxibs are still capable of triggering GI adverse events and cardiovascular toxicity issues were the main focus of concerns. Unfortunately, definite strategies are not available to prevent or heal NSAID-induced intestinal injuries. Thus, there is still a strong clinical need for effective drugs with improved safety profiles than the existing NSAIDs. PMID:22866254

  12. Mechanism of action of nonsteroidal anti-inflammatory agents.

    PubMed

    Goodwin, J S

    1984-07-13

    Recent data from several laboratories, which suggest that generally accepted concepts relating to the mechanism of action of nonsteroidal, anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis may be incorrect, are reviewed. Over the past decade, most researchers have espoused the idea that NSAIDs act by inhibiting cyclooxygenase, thereby removing prostaglandins, which are thought to be responsible for pain and inflammation. Recent studies demonstrating that prostaglandins have important immunomodulating properties and that NSAIDs actually provide partial correction of several immunoregulatory dysfunctions in patients with rheumatoid arthritis are described. In addition, some NSAIDs inhibit migration along with other monocyte and polymorphonuclear leukocyte functions. Data suggest that these actions are not related to inhibition of cyclooxygenase. PMID:6431808

  13. Anti-inflammatory effects of hydroxycinnamic acid derivatives

    SciTech Connect

    Nagasaka, Reiko [Department of Food Science and Technology, Tokyo University of Marine Science and Technology, 5-7 Konan 4, Minato, Tokyo 108-8477 (Japan); Chotimarkorn, Chatchawan [Department of Food Science and Technology, Tokyo University of Marine Science and Technology, 5-7 Konan 4, Minato, Tokyo 108-8477 (Japan); Shafiqul, Islam Md. [Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657 (Japan); Hori, Masatoshi [Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657 (Japan); Ozaki, Hiroshi [Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657 (Japan); Ushio, Hideki [Department of Food Science and Technology, Tokyo University of Marine Science and Technology, 5-7 Konan 4, Minato, Tokyo 108-8477 (Japan)]. 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. Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

    PubMed

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

    2014-06-01

    Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-? in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p.?o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-? induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i.?p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation. Finally, multiple mechanisms, including the inhibition of the production of inflammatory mediators and activation of endogenous opioid pathways, may mediate azadirachtin activities in experimental models of inflammation and pain. PMID:24871207

  15. Anti-inflammatory treatment induced regenerative oligodendrogenesis in parkinsonian mice

    PubMed Central

    2012-01-01

    Introduction The adult mammalian brain retains niches for neural stem cells (NSCs), which can generate glial and neuronal components of the brain tissue. However, it is barely established how chronic neuroinflammation, as it occurs in neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, affects adult neurogenesis and, therefore, modulates the brain's potential for self-regeneration. Methods Neural stem cell culture techniques, intraventricular tumor necrosis factor (TNF)-? infusion and the 6-hydroxydopamine mouse model were used to investigate the influence of neuroinflammation on adult neurogenesis in the Parkinson's disease background. Microscopic methods and behavioral tests were used to analyze samples. Results Here, we demonstrate that differences in the chronicity of TNF-? application to cultured NSCs result in opposed effects on their proliferation. However, chronic TNF-? treatment, mimicking Parkinson's disease associated neuroinflammation, shows detrimental effects on neural progenitor cell activity. Inversely, pharmacological inhibition of neuroinflammation in a 6-hydroxydopamine mouse model led to increased neural progenitor cell proliferation in the subventricular zone and neuroblast migration into the lesioned striatum. Four months after surgery, we measured improved Parkinson's disease-associated behavior, which was correlated with long-term anti-inflammatory treatment. But surprisingly, instead of newly generated striatal neurons, oligodendrogenesis in the striatum of treated mice was enhanced. Conclusions We conclude that anti-inflammatory treatment, in a 6-hydroxydopamine mouse model for Parkinson's disease, leads to activation of adult neural stem cells. These adult neural stem cells generate striatal oligodendrocytes. The higher numbers of newborn oligodendrocytes possibly contribute to axonal stability and function in this mouse model of Parkinson's disease and thereby attenuate dysfunctions of basalganglian motor-control. PMID:22892385

  16. Antimicrobial and Anti-Inflammatory Activities of Endophytic Fungi Talaromyces wortmannii Extracts against Acne-Inducing Bacteria

    PubMed Central

    Schwendinger, Katja; Kreiseder, Birgit; Wiederstein, Martina; Pretsch, Dagmar; Genov, Miroslav; Hollaus, Ralph; Zinssmeister, Daniela; Debbab, Abdesamad; Hundsberger, Harald; Eger, Andreas; Proksch, Peter; Wiesner, Christoph

    2014-01-01

    Acne vulgaris is the most common skin disease, causing significant psychosocial problems such as anxiety and depression similar to a chronic illness for those afflicted. Currently, obtainable agents for acne treatment have limited use. Thus, development of novel agents to treat this disease is a high medical need. The anaerobic bacterium Propionibacterium acnes has been implicated in the inflammatory phase of acne vulgaris by activating pro-inflammatory mediators such as the interleukin-8 (IL-8) via the NF-?B and MAPK pathways. Talaromyces wortmannii is an endophytic fungus, which is known to produce high bioactive natural compounds. We hypothesize that compound C but also the crude extract from T. wortmannii may possess both antibacterial activity especially against P. acnes and also anti-inflammatory properties by inhibiting TNF-?-induced ICAM-1 expression and P. acnes-induced IL-8 release. Treatment of keratinocytes (HaCaT) with P. acnes significantly increased NF-?B and activator protein-1 (AP-1) activation, as well as IL-8 release. Compound C inhibited P. acnes-mediated activation of NF-?B and AP-1 by inhibiting I?B degradation and the phosphorylation of ERK and JNK MAP kinases, and IL-8 release in a dose-dependent manner. Based on these results, compound C has effective antimicrobial activity against P. acnes and anti-inflammatory activity, and we suggest that this substance or the crude extract are alternative treatments for antibiotic/anti-inflammatory therapy for acne vulgaris. PMID:24887557

  17. Neurobiology of Aging, in press Steroid and nonsteroidal anti-inflammatory drugs, cognitive decline, and dementia

    E-print Network

    Paris-Sud XI, Université de

    decline, and dementia Marie-Laure Ancelin, PhD.a,b,§,* , Isabelle Carrière, PhD.a,b,§ , Catherine Helmer persons. Cognitive performance, clinical diagnosis of dementia, and anti-inflammatory use were evaluated of incident dementia over 7 years. Nonsteroidal anti- inflammatory drug use was not significantly associated

  18. Comparison of piroxicam pharmacokinetics and anti-inflammatory effect in rats after intra-articular and intramuscular administration.

    PubMed

    Park, Chan Woong; Ma, Kyung Wan; Jang, Sun Woo; Son, Miwon; Kang, Myung Joo

    2014-05-01

    This study evaluated the pharmacokinetic profile and therapeutic efficacy of piroxicam (PX), a long acting non-steroidal anti-inflammatory drug for the treatment of arthritis, following intra-articular (IA) injection in comparison to the pharmacokinetic profile and therapeutic efficacy of PX after intramuscular (IM) injection. In the pharmacokinetic study in rats, systemic exposure and pharmacokinetic parameters of PX after a single IA dose were compared with systemic exposure and pharmacokinetic parameters of PX after administration of the same dose IM (0.6 mg/kg). The anti-inflammatory and analgesic effects of IA PX were evaluated simultaneously in a monoiodoacetate-induced osteoarthritis rat model. The plasma PX concentration rapidly rose following IA injection, and it was comparable to the plasma PX concentration following IM injection, suggesting the rapid efflux of the drug molecule from the joint cavity. However, in the efficacy study, the IA PX administration significantly reduced the knee swelling by reducing the level of prostaglandin E2 in the joint, compared to that following administration of IA vehicle and after administration of the IM PX dose. In addition, we found that the anti-inflammatory and anti-nociceptive efficacies of IA PX were synergistically increased upon co-treatment with hyaluronic acid (HA), a potent agent for the treatment of osteoarthritis, at the weight ratio of 1:1 or 1:2, and these effects were more pronounced than those following administration of HA or PX alone. In conclusion, this study demonstrated the efficacy of the IA use of PX alone and/or in combination with HA in osteoarthritis. PMID:25009708

  19. 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 ?g/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

  20. Evidence for anti-inflammatory and antioxidative properties of dried plum polyphenols in macrophage RAW 264.7 cells.

    PubMed

    Hooshmand, Shirin; Kumar, Ajay; Zhang, Ji Yao; Johnson, Sarah A; Chai, Sheau C; Arjmandi, Bahram H

    2015-05-13

    This study presents the anti-inflammatory and antioxidative properties of dried plum (Prunus domestica L.) polyphenols in macrophage RAW 264.7 cells. We hypothesized that dried plum polyphenols have strong anti-inflammatory and antioxidant properties against lipopolysaccharide (LPS)-induced production of the pro-inflammatory markers, nitric oxide (NO) and cyclooxygenase-2 (COX-2), and the lipid peroxidation product, malondialdehyde, in activated macrophage RAW 264.7 cells. To test this hypothesis, macrophage RAW 264.7 cells were stimulated with either 1 ?g ml(-1) (for measurement of NO production) or 1 ng ml(-1) (for measurement of COX-2 expression) of LPS to induce inflammation and were treated with different doses of dried plum polyphenols (0.0, 0.1, 1, 10, 100 and 1000 ?g ml(-1)). Dried plum polyphenols at a dose of 1000 ?g ml(-1) was able to significantly (P < 0.05) reduce NO production by 43%. Additionally, LPS-induced expression of COX-2 was significantly (P < 0.05) reduced by 100 and 1000 ?g ml(-1) dried plum polyphenols. To investigate the antioxidant activity of dried plum polyphenols, macrophage RAW 264.7 cells were stimulated with 100 ?g ml(-1) of FeSO4 + 1 mM ml(-1) of H2O2 to induce lipid peroxidation. Dried plum polyphenols at a dose of 1000 ?g ml(-1) showed a 32% reduction in malondialdehyde production. These findings indicate that dried plum polyphenols are potent anti-inflammatory and antioxidative agents in vitro. PMID:25921826

  1. 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 [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)] [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Okajima, Fumikazu, E-mail: fokajima@showa.gunma-u.ac.jp [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)] [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)

    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.

  2. 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

  3. [Influence of prodigiozan, methyluracil and levamisole on the anti-inflammatory effect of nonsteroid antiphlogistics].

    PubMed

    Bogdanova, A Sh

    1984-06-01

    The efficacy of the combined use of immunostimulants and anti-inflammatory agents, such as acetylsalicylic acid, voltaren, indomethacin and naproxen was studied in carragenin-induced experimental inflammation. Noninbred albino mice of both sexes were used in the experiments. It was shown that prodigiosan as a therapeutic agent had a pronounced anti-inflammatory action. It potentiated the effect of voltaren used in a dose lower than the ED50 and did not change the anti-inflammatory activity of naproxen, indomethacin and acetylsalicylic acid used in the doses equal to the ED50. The potentiating effect of prodigiosan on voltaren was statistically significant Methyluracil used as a prophylactic agent had an anti-inflammatory effect. Levamisole used as a prophylactic agent or a therapeutic agent did not decrease the edema level. The anti-inflammatory effect of naproxen, indomethacin, acetylsalicylic acid and voltaren did not change, when the drugs were administered to the animals treated with methyluracil and levamisole. PMID:6476809

  4. Anti-inflammatory and analgesic activity of Indian Hypericum perforatum L.

    PubMed

    Kumar, V; Singh, P N; Bhattacharya, S K

    2001-04-01

    A standardised 50% aqueous ethanolic extract of the Indian variety of Hypericum perforatum (IHp) was examined for its putative anti-inflammatory and analgesic activity at the doses of 100 and 200 mg/kg, po. The experimental paradigms used were carrageenan induced pedal edema and cotton pellet induced granuloma for anti-inflammatory activity, whereas the tail flick, hot plate and acetic acid induced writhing methods were used to asses analgesic activity. Indomethacin (20 mg/kg, ip) was used as the standard anti-inflammatory drug. Pentazocine (10 mg/kg, ip) and aspirin (25 mg/kg, ip), both clinically used analgesics, were used as standard analgesics for comparison. IHp extract showed significant anti-inflammatory and analgesic activity at both dose levels, in all the paradigms used. Additionally, IHp potentiated the anti-inflammatory activity of indomethacin and analgesic activities of pentazocine and aspirin. PMID:11491578

  5. Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review)

    PubMed Central

    ARMUTCU, FERAH; AKYOL, SUMEYYA; USTUNSOY, SEYFETTIN; TURAN, FATIME FILIZ

    2015-01-01

    Caffeic acid phenethyl ester (CAPE), a naturally occurring compound isolated from propolis extract, has been reported to have a number of biological and pharmacological properties, exerting antioxidant, anti-inflammatory, anticarcinogenic, antibacterial and immunomodulatory effects. Recent in vivo and in vitro study findings have provided novel insights into the molecular mechanisms involved in the anti-inflammatory and immunomodulatory activities of this natural compound. CAPE has been reported to have anti-inflammatory properties involving the inhibition of certain enzyme activities, such as xanthine oxidase, cyclooxygenase and nuclear factor-?B (NF-?B) activation. Since inflammation and immune mechanisms play a crucial role in the onset of several inflammatory diseases, the inhibition of NF-?B represents a rationale for the development of novel and safe anti-inflammatory agents. The primary goal of the present review is to highlight the anti-inflammatory and immunomodulatory activities of CAPE, and critically evaluate its potential therapeutic effects. PMID:26136862

  6. A comparative anti-inflammatory activity of raw and processed Kupeelu (Strychnos nux-vomica Linn.) seeds on albino rats.

    PubMed

    Mitra, Swarnendu; Kumar, Vijay; Ashok, Bk; Acharya, R N; Ravishankar, B

    2011-10-01

    Seeds of Kupeelu (Strychnos nux-vomica Linn.), a known poisonous drug, is used extensively in various Ayurvedic formulations with great therapeutic significance. Ayurveda recommends the administration of Kupeelu only after passing through specific purificatory procedures in different media like cow's urine (Go mutra), cow's milk (Go dugdha), cow's ghee (Go ghrita), Kanji (thin gruel) etc. Strychnos nux vomica seeds are extensively advocated for nervous debility, paralysis, and weakness of limbs, sexual weakness, dyspepsia, and dysentery and in rheumatism where it can be assumed that besides other properties, Kupeelu may have some sort of anti-inflammatory activity too. In the present study, the powder of raw and processed Kupeelu seeds (processed / purified with Kanji i.e sour gruel) as test drugs were assessed for anti-inflammatory activity by employing Carrageenan and Formaldehyde induced hind paw oedema in Wistar strain albino rats at a dose of 22.5 mg/kg body weight orally. This study reveals that both raw and purified Kupeelu showed presence of highly significant anti-inflammatory activity against formaldehyde induced hind paw oedema, but did not have similar activity against Carrageenan induced hind paw oedema. PMID:23284209

  7. Effect of anti-inflammatory and antioxidant drugs on the long-term repair of severely injured mouse skeletal muscle.

    PubMed

    Vignaud, A; Cebrian, J; Martelly, I; Caruelle, J-P; Ferry, A

    2005-07-01

    Non-steroidal anti-inflammatory drugs are frequently prescribed after skeletal muscle injury. It is not known whether this type of medication can interfere with muscle repair, although inflammatory response is thought to play an important role in this process. Tibialis anterior muscles of mice were injured by myotoxic agent (snake venom) or crushed. Then, animals were treated daily for 10-14 days with different types of non-steroidal anti-inflammatory and antioxidant drugs. The long-term repair was studied 10-42 days after injury by analysing the recovery of in situ muscle force production, size of regenerating muscle cells and expression of myosin heavy chain. Our results show that diclofenac, diferuloylmethane (curcumin), dimethylthiourea or pyrrolidine dithiocarbamate treatment did not significantly affect muscle recovery after myotoxic injury (P > 0.05). Similarly, diferuloylmethane, dimethyl sulphoxide or indomethacin administration did not markedly change muscle repair after crush injury. However, we noted that high doses (> 2 mg kg(-1)) of diferuloylmethane or indomethacin increased lethality and reduced muscle repair after crush injury. In conclusion, non-steroidal anti-inflammatory and antioxidant drugs did not exhibit long-term detrimental effects on muscle recovery after injury, except at lethal doses. PMID:15728135

  8. N-butanol Extract from Melilotus Suaveolens Ledeb Affects Pro- and Anti-Inflammatory Cytokines and Mediators.

    PubMed

    Zhao, Lei; Tao, Jun-Yan; Zhang, Shu-Ling; Jin, Feng; Pang, Ran; Dong, Ji-Hua

    2010-03-01

    Melilotus suaveolens Ledeb is a traditional medicinal plant for treating inflammation-related disease. This explores the inner anti-inflammatory mechanism of n-butanol extract from M. suaveolens Ledeb. Inflammatory cellular model was established by lipopolysaccharide intervention on RAW264.7 cell line. Levels of secreted cytokines TNF-?, IL-1?, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-?, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, activation of NF-?B and ingredients in the extract were assayed by ELISA, real time quantitative PCR, western blot, immunocytochemical test and HPLC fingerprint test, respectively. As a result, the extract could not only markedly reduce the production of pro-inflammatory mediators to different extents by blocking NF-?B activation but also promote the release of anti-inflammatory mediator HO-1 significantly. Each 1 g extract contained 0.023531 mg coumarin and another two high polar ingredients, probably saponins. It can be concluded that the extract has similar effects on antagonizing pro-inflammatory mediators and cytokines like Dexamethasone, and has effects on promoting the production of anti-inflammatory mediators. PMID:18955281

  9. 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

  10. Liquid chromatography/tandem mass spectrometry study of anti-inflammatory activity of plantain (Plantago L.) species.

    PubMed

    Beara, Ivana N; Orci?, Dejan Z; Lesjak, Marija M; Mimica-Duki?, Neda M; Pekovi?, Biljana A; Popovi?, Mira R

    2010-09-01

    To evaluate anti-inflammatory activity of selected Plantago species (P. lanceolata L. and P. major L.) an optimized in vitro test for determination of cyclooxygenase-1 (COX-1) and 12-lipoxygenase (12-LOX) inhibition potency was undertaken. By using intact cell system (platelets) as a source of COX-1 and 12-LOX enzymes and highly sensitive and specific LC-MS/MS technique for detection of main arachidonic acid metabolites formed by COX-1 and 12-LOX, this test provides efficient method for evaluation of anti-inflammatory potential of plant extracts and isolated compounds. Our results validated the well-known COX-1 inhibitory activity of P. lanceolata and P. major methanol extracts (concentration required for 50% inhibition (IC(50)) was 2.00 and 0.65 mg/ml, respectively). Furthermore, 12-LOX inhibitory activity of examined extracts was reported for the first time (IC(50)=0.75 and 1.73 mg/ml for P. lanceolata and P. major, respectively). Although renowned inhibitors, such as acetylsalicylic acid and quercetin showed higher activity, this study verifies P. lanceolata and P. major as considerable anti-inflammatory agents. PMID:20219312

  11. Anti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cells.

    PubMed

    Jin, Da-Qing; Lim, Chol Seung; Hwang, Jae Kwan; Ha, Ilho; Han, Jung-Soo

    2005-06-17

    Epidemiological studies suggest that the treatments of anti-inflammatory agents and anti-oxidants slow the progress of neurological diseases. Lignans are anti-oxidants and phytoestrogens found in a variety of plants. In this study, we investigated the neuroprotective effect of macelignan on glutamate-induced neurotoxicity and reactive oxygen species (ROS) in murine hippocampal HT22 cell line. Macelignan significantly attenuated the ROS production and neurotoxicity induced by glutamate in HT22 cell. Also, the properties of macelignan as an anti-inflammatory agent were investigated in microglials activation by lipopolysaccharide (LPS). It potently suppressed the expression of cyclooxygenase-2 and inducible nitric oxide synthase, that consequently resulted in the reduction of nitric oxide in LPS-treated microglial cells. It also significantly suppressed the production of pro-inflammatory cytokine tumor necrosis factor-alpha and interleukin-6. These results suggest that macelignan possesses therapeutic potentials against neurodegenerative diseases with oxidative stress and neuroinflammation. PMID:15883012

  12. Synthesis and pharmacological investigation of novel 3-(3-methylphenyl)-2-substituted amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents.

    PubMed

    Alagarsamy, Veerachamy; Dhanabal, Kumarasamy; Parthiban, Periyasamy; Anjana, Gobi; Deepa, Govinhan; Murugesan, Balakrishnan; Rajkumar, Subramanian; Beevi, Abdulrahim Janath

    2007-05-01

    A variety of novel 3-(3-methylphenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(3-methylphenyl)-3H-quinazolin-4-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(3-methylphenyl)-3H-quinazolin-4-one was synthesized from 3-methyl aniline. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. Compound 2-(1-ethylpropylidene-hydrazino)-3-(3-methylphenyl)-3H-quinazolin-4-one (AS2) was the most active analgesic agent. Compound 2-(1-methylbutylidene-hydrazino)-3-(3-methylphenyl)-3H-quinazolin-4-one (AS3) was the most active anti-inflammatory agent and was moderately more potent than the reference standard diclofenac sodium. The test compounds showed only mild ulcerogenic potential compared with aspirin. PMID:17524232

  13. Synthesis of novel 3-butyl-2-substituted amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents.

    PubMed

    Alagarsamy, V; Meena, S; Ramaseshu, K V; Solomon, V Raja; Kumar, T Durai Ananda; Thirumurugan, K

    2007-09-01

    A variety of novel 3-butyl-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 3-butyl-2-hydrazino-3H-quinazolin-4-one with various aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. The compound 3-butyl-2-(1-methylbutylidene-hydrazino)-3H-quinazolin-4-one (AS3) emerged as the most active analgesic agent. Compound 3-butyl-2-(1-ethylpropylidene-hydrazino)-3H-quinazolin-4-one (AS2) emerged as the most active anti-inflammatory agent and is moderately more potent when compared to the reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to aspirin. PMID:17718720

  14. 3-(3-ethylphenyl)-2-substituted hydrazino-3H-quinazolin-4-one derivatives: new class of analgesic and anti-inflammatory agents.

    PubMed

    Alagarsamy, V; Raja Solomon, V; Sheorey, R V; Jayakumar, R

    2009-04-01

    A new series of 3-(3-ethylphenyl)-2-substituted hydrazino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(3-ethylphenyl)-3H-quinazolin-4-one with a variety of aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index behavior. The compound 2-(N'-3-pentylidene-hydrazino)-3-(3-ethylphenyl)-3H-quinazolin-4-one (AS2) emerged as the most active compound in exhibiting analgesic activity and the compound 2-(N'-2-pentylidene-hydrazino)-3-(3-ethylphenyl)-3H-quinazolin-4-one (AS3) emerged as the most active compound in exhibiting anti-inflammatory activity; and these compounds are moderately potent when compared with the reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared with aspirin. PMID:19291107

  15. 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

  16. 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

  17. Antioxidant and Anti-inflammatory Activities of Broccoli Florets in LPS-stimulated RAW 264.7 Cells

    PubMed Central

    Hwang, Joon-Ho; Lim, Sang-Bin

    2014-01-01

    Broccoli (Brassica oleracea var. italia) florets were extracted with 80% methanol and the extract was sequentially fractionated with n-hexane, ethyl acetate, n-butanol, and distilled water. The extract and the fractions were evaluated for total phenolic content, sulforaphane content, antioxidant activity, and anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The total phenolic content and sulforaphane content of the ethyl acetate fraction (EF) were 35.5 mg gallic acid equivalents/g and 620.2 ?g/g, respectively. These values were higher than those of the 80% methanol extract and organic solvent fractions. The oxygen radical absorbance capacity of the EF [1,588.7 ?M Trolox equivalents (TE)/mg] was 11-fold higher than that of the distilled water fraction (143.7 ?M TE/mg). The EF inhibited nitric oxide release from LPS-stimulated RAW 264.7 cells in a dose-dependent manner and inhibited I?B-? degradation and nuclear factor-?B activation in LPS-stimulated RAW 264.7 cells. In conclusion, the EF of broccoli florets exerted potent antioxidant and anti-inflammatory effects. PMID:25054107

  18. Nitric oxide release is not required to decrease the ulcerogenic profile of nonsteroidal anti-inflammatory drugs.

    PubMed

    Jain, Sarthak; Tran, Susan; El Gendy, Mohamed A M; Kashfi, Khosrow; Jurasz, Paul; Velázquez-Martínez, Carlos A

    2012-01-26

    The objective of this work was to evaluate the biological properties of a new series of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) possessing a tyrosol linker between the NSAID and the NO-releasing moiety (PROLI/NO); however, initial screening of ester intermediates without the PROLI/NO group showed the required (desirable) efficacy/safety ratio, which questioned the need for NO in the design. In this regard, NSAID ester intermediates were potent and selective COX-2 inhibitors in vitro, showed equipotent anti-inflammatory activity compared to the corresponding parent NSAID, but showed a markedly reduced gastric toxicity when administered orally. These results provide complementary evidence to challenge the currently accepted notion that hybrid NO-NSAIDs exert their cytoprotective effects by releasing NO. Results obtained in this work constitute a good body of evidence to initiate a debate about the future replacement of NSAID prodrugs for unprotected NSAIDs (possessing a free carboxylic acid group) currently in clinical use. PMID:22148253

  19. Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells.

    PubMed

    Weichhart, Thomas; Haidinger, Michael; Katholnig, Karl; Kopecky, Chantal; Poglitsch, Marko; Lassnig, Caroline; Rosner, Margit; Zlabinger, Gerhard J; Hengstschläger, Markus; Müller, Mathias; Hörl, Walter H; Säemann, Marcus D

    2011-04-21

    A central role for the mammalian target of rapamycin (mTOR) in innate immunity has been recently defined by its ability to limit proinflammatory mediators. Although glucocorticoids (GCs) exert potent anti-inflammatory effects in innate immune cells, it is currently unknown whether the mTOR pathway interferes with GC signaling. Here we show that inhibition of mTOR with rapamycin or Torin1 prevented the anti-inflammatory potency of GC both in human monocytes and myeloid dendritic cells. GCs could not suppress nuclear factor-?B and JNK activation, the expression of proinflammatory cytokines, and the promotion of Th1 responses when mTOR was inhibited. Interestingly, long-term activation of monocytes with lipopolysaccharide enhanced the expression of TSC2, the principle negative regulator of mTOR, whereas dexamethasone blocked TSC2 expression and reestablished mTOR activation. Renal transplant patients receiving rapamycin but not those receiving calcineurin inhibitors displayed a state of innate immune cell hyper-responsiveness despite the concurrent use of GC. Finally, mTOR inhibition was able to override the healing phenotype of dexamethasone in a murine lipopolysaccharide shock model. Collectively, these data identify a novel link between the glucocorticoid receptor and mTOR in innate immune cells, which is of considerable clinical importance in a variety of disorders, including allogeneic transplantation, autoimmune diseases, and cancer. PMID:21368289

  20. Sulphurous thermal water increases the release of the anti-inflammatory cytokine IL-10 and modulates antioxidant enzyme activity.

    PubMed

    Prandelli, C; Parola, C; Buizza, L; Delbarba, A; Marziano, M; Salvi, V; Zacchi, V; Memo, M; Sozzani, S; Calza, S; Uberti, D; Bosisio, D

    2013-01-01

    The beneficial effects of hot springs have been known for centuries and treatments with sulphurous thermal waters are recommended in a number of chronic pathologies as well as acute recurrent infections. However, the positive effects of the therapy are often evaluated in terms of subjective sense of wellbeing and symptomatic clinical improvements. Here, the effects of an S-based compound (NaSH) and of a specific sulphurous thermal water characterized by additional ions such as sodium chloride, bromine and iodine (STW) were investigated in terms of cytokine release and anti-oxidant enzyme activity in primary human monocytes and in saliva from 50 airway disease patients subjected to thermal treatments. In vitro, NaSH efficiently blocked the induction of pro-inflammatory cytokines and counterbalanced the formation of ROS. Despite STW not recapitulating these results, possibly due to the low concentration of S-based compounds reached at the minimum non-toxic dilution, we found that it enhanced the release of IL-10, a potent anti-inflammatory cytokine. Notably, higher levels of IL-10 were also observed in patients' saliva following STW treatment and this increase correlated positively with salivary catalase activity (r2 = 0.19, *p less than 0.01). To our knowledge, these results represent the first evidence suggesting that S-based compounds and STW may prove useful in facing chronic inflammatory and age-related illness due to combined anti-inflammatory and anti-oxidant properties. PMID:24067460

  1. Controlled release of dexamethasone from subcutaneously-implanted biosensors in pigs: localized anti-inflammatory benefit without systemic effects.

    PubMed

    Ward, W Kenneth; Hansen, Jillian C; Massoud, Ryan G; Engle, Julia M; Takeno, Marc M; Hauch, Kip D

    2010-07-01

    Chronically implanted biosensors typically lose sensitivity 1-2 months after implantation, due in large part to the development of a collagen-rich capsule that prevents analytes of interest from reaching the biosensor. Corticosteroids are likely candidates for reducing collagen deposition but these compounds have many serious side effects when given over a prolonged period. One method of assessing whether or not locally released corticosteroids have a systemic effect is to measure cortisol concentrations in venous serum. We hypothesized that a very low release rate of the potent corticosteroid, dexamethasone, would lead to a localized anti-inflammatory effect without systemic effects. We found that reduction in subcutaneous granulocytes (primarily eosinophils), and to a lesser extent, reduction of macrophages served as a good local indicator of the steroid effect. When released over a 28-day period, a total dexamethasone dose of < or =0.1 mg/kg led to a consistent reduction in the number of granulocytes and macrophages found in the local vicinity of the implant without a reduction of these cells at distant tissue locations. The lack of suppression of serum cortisol with these doses confirmed that low-release rates of dexamethasone can lead to consistent local anti-inflammatory effects without distant, systemic effects. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010. PMID:20186727

  2. 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 2.57?M, respectively, beside a cyclostatic activity TGI (MG-MID) 9.54, 8.51, 24.0, 19.9 and 8.71?M, 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

  3. Anti-inflammatory effect of catechin on cultured human dental pulp cells affected by bacteria-derived factors.

    PubMed

    Nakanishi, Tadashi; Mukai, Kayo; Yumoto, Hiromichi; Hirao, Kouji; Hosokawa, Yoshitaka; Matsuo, Takashi

    2010-04-01

    Catechins (bioactive polyphenols in green tea) are known to exhibit potent anti-inflammatory properties. However, the anti-inflammatory effects of catechins on inflamed dental pulp tissue are not known. In this study, we investigated the effect of epigallocatechin-3-gallate (EGCG) and epicatechin gallate (ECG), the major components of green tea catechins, on the expression of pro-inflammatory cytokines and adhesion molecules in human dental pulp cells stimulated with bacteria-derived factors such as lipopolysaccharide (LPS) and peptidoglycan (PG). The expression of interleukin (IL)-6 and of IL-8 was examined using the reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays. The expression of intercellular adhesion molecule-1 (ICAM-1) and of vascular cell adhesion molecule-1 (VCAM-1) on dental pulp cells was analyzed using flow cytometry. The presence of EGCG and ECG significantly reduced, in a concentration-dependent manner, the expression of IL-6 and IL-8 in dental pulp cells exposed to LPS or PG. Increased expression of ICAM-1 and VCAM-1 on the dental pulp cells in response to bacterial components was also decreased by treatment with EGCG and ECG. These findings suggest that green tea catechins may prevent the exacerbation of pulpitis. PMID:20487003

  4. Cytotoxic and anti-inflammatory constituents from the seeds of Descurainia sophia.

    PubMed

    Lee, You Jin; Kim, No Soo; Kim, Haejin; Yi, Jin-Mu; Oh, Se-Mi; Bang, Ok-Sun; Lee, Jun

    2013-05-01

    A new sinapoyl glycoside, 1,3-di-O-sinapoyl-?-D-glucopyranose (1) along with 13 known compounds, including, sinapoyl glycosides (2 and 3), cardenolide glycoside (4), flavonoids (5-10), lignan (11), phenolic acids (12 and 13), and phytosterol (14), were isolated from the seeds of Descurainia sophia by chromatographic separation methods. The structures of 1-14 were determined by the interpretation of spectroscopic data as well as by comparison of that data with previously reported values. Compounds 2, 3, 5, 6, and 11 were identified in and isolated from this plant for the first time in this study. All isolates were evaluated for in vitro cytotoxic activities against seven human cancer cell lines and for in vitro anti-inflammatory potential using LPS-stimulated RAW264.7 murine macrophages. Compound 4 showed potent cytotoxicity (IC50 values ranging from 0.034 to 0.596 ?M) against all human cancer cell lines tested and was identified as the main active cytotoxic constituent of this plant. Compound 8 (ED50 = 5.45 ?M) and 11 (ED50 = 10.02 ?M) exerted dose-dependent inhibitory effects on NO production in LPS-stimulated RAW264.7 cells. PMID:23435946

  5. Re-evaluation of anti-inflammatory activity of mastic using activated macrophages.

    PubMed

    Zhou, Li; Satoh, Kazue; Takahashi, Keiso; Watanabe, Shuji; Nakamura, Wataru; Maki, Jun; Hatano, Hajime; Takekawa, Fumihiro; Shimada, Chiyako; Sakagami, Hiroshi

    2009-01-01

    Mastic is a resinous exudate obtained from the stem and the main leaves of Pistacia lentiscus. Mastic has shown several beneficial pharmaceutical properties such as antibacterial and apoptosis-modulating activities. The aim of this study was to investigate whether mastic affects the function of activated macrophages. Both solid and liquid types of mastic inhibited the production of pro-inflammatory substances such as nitric oxide (NO) and prostaglandin (PG)E(2) by lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells. This was accompanied by the decline of viable cell number. Western blot and RT-PCR analyses showed that mastic inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 at both protein and mRNA levels. ESR spectroscopy revealed that mastic scavenged NO and superoxide radicals very poorly, in contrast to its potent hydroxyl radical scavenging activity. These data demonstrate that mastic inhibits the production of both NO and PGE(2) by activated macrophages mostly via its cytotoxic action. The narrow range of effective concentration of mastic due to its cytotoxicity may limit its potential application as an anti-inflammatory agent. PMID:19567394

  6. Anti-inflammatory and potential cancer chemopreventive constituents of the fruits of Morinda citrifolia (Noni).

    PubMed

    Akihisa, Toshihiro; Matsumoto, Kazumi; Tokuda, Harukuni; Yasukawa, Ken; Seino, Ken-ichi; Nakamoto, Katsuo; Kuninaga, Hideki; Suzuki, Takashi; Kimura, Yumiko

    2007-05-01

    A new anthraquinone, 1,5,15-tri-O-methylmorindol (1), and two new saccharide fatty acid esters, 2-O-(beta-D-glucopyranosyl)-1-O-hexanoyl-beta-D-gluropyranose (4) and 2-O-(beta-D-glucopyranosyl)-1-O-octanoyl-beta-D-gluropyranose (5), have been isolated from a methanol extract of the fruits of Morinda citrifolia (noni) along with 10 known compounds, namely, two anthraquinones (2, 3), six saccharide fatty acid esters (6-11), an iridoid glycoside (12), and a flavanol glycoside (13). Upon evaluation of six compounds (5-7, 9, 10, and 13) for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, four saccharide fatty acid esters, 5-7 and 9, exhibited potent anti-inflammatory activity, with ID50 values of 0.46-0.79 mg per ear. In addition, when compounds 1-13 were evaluated against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA, all of the compounds exhibited moderate inhibitory effects (IC50 values of 386-578 mol ratio/32 pmol TPA). PMID:17480098

  7. Anti-inflammatory properties of a novel peptide interleukin 1 receptor antagonist

    PubMed Central

    2014-01-01

    Background Interleukin 1 (IL-1) is implicated in neuroinflammation, an essential component of neurodegeneration. We evaluated the potential anti-inflammatory effect of a novel peptide antagonist of IL-1 signaling, Ilantide. Methods We investigated the binding of Ilantide to IL-1 receptor type I (IL-1RI) using surface plasmon resonance, the inhibition of Il-1?-induced activation of nuclear factor ?B (NF-?B) in HEK-Blue cells that contained an IL-1?-sensitive reporter, the secretion of TNF-? in macrophages, protection against IL-1-induced apoptosis in neonatal pancreatic islets, and the penetration of Ilantide through the blood–brain barrier using competitive enzyme-linked immunosorbent assay (ELISA). We studied the effects of the peptide on social behavior and memory in rat models of lipopolysaccharide (LPS)- and amyloid-induced neuroinflammation, respectively, and its effect in a rat model of experimental autoimmune enchephalomyelitis. Results Ilantide bound IL-1RI, inhibited the IL-1?-induced activation of NF-?B, and inhibited the secretion of TNF-? in vitro. Ilantide protected pancreatic islets from apoptosis in vitro and reduced inflammation in an animal model of arthritis. The peptide penetrated the blood–brain barrier. It reduced the deficits in social activity and memory in LPS- and amyloid-treated animals and delayed the development of experimental autoimmune enchephalomyelitis. Conclusions These findings indicate that Ilantide is a novel and potent IL-1RI antagonist that is able to reduce inflammatory damage in the central nervous system and pancreatic islets. PMID:24490798

  8. Anti-inflammatory effect of miglustat in bronchial epithelial cells.

    PubMed

    Dechecchi, Maria Cristina; Nicolis, Elena; Norez, Caroline; Bezzerri, Valentino; Borgatti, Monica; Mancini, Irene; Rizzotti, Paolo; Ribeiro, Carla M P; Gambari, Roberto; Becq, Frederic; Cabrini, Giulio

    2008-11-01

    The role of CFTR deficiency in promoting inflammation remains unclear. Perez et al. [A. Perez, A.C. Issler, C.U. Cotton, T.J. Kelley, A.S. Verkman and P.B. Davis, CFTR inhibition mimics the cystic fibrosis inflammatory profile. Am J Physiol Lung Cell Mol Physiol 2007; 292:L383-L395.] recently demonstrated that the inhibition of function of w/t CFTR produces an inflammatory profile that resembles that observed in CF patients, whereas we found that correction of F508del-CFTR function with MPB-07 down-modulates the inflammatory response to P. aeruginosa in CF bronchial cells [M.C. Dechecchi, E. Nicolis, V. Bezzerri, A. Vella, M. Colombatti, B.M. Assael, et al., MPB-07 reduces the inflammatory response to Pseudomonas aeruginosa in cystic fibrosis bronchial cells. Am J Respir Cell Mol Biol 2007; 36, 615-624.]. Since both evidence support a link between CFTR function and inflammation, we extended our investigation to other F508del-CFTR correctors, such as miglustat (Norez, 2006), an approved drug for Gaucher disease, in comparison with the galactose analogue NB-DGJ. We report here that miglustat but not NB-DGJ restores F508del-CFTR function in CF bronchial epithelial IB3-1 and CuFi-1 cells. Miglustat and NB-DGJ reduce the inflammatory response to P. aeruginosa in both CF and non-CF bronchial cells, indicating that the anti-inflammatory effect is independent of the correction of F508del-CFTR function. Miglustat also inhibits the inflammatory response induced by the supernatant of mucopurulent material obtained from the lower airway tract of cystic fibrosis patients with chronic bacterial colonization (Ribeiro, 2005). Both compounds do not interfere with the adherence of P. aeruginosa to the cells and reduce the expression of IL-8 not only after challenge with P. aeruginosa but also after exposure to TNF alpha or IL-1 beta, suggesting an effect on transduction proteins downstream and in common with different receptors for pathogens. Finally, miglustat has no major effects on overall binding activity of transcription factors NF-kappaBNF-kB and AP-1. Since miglustat is an approved drug, it could be investigated as a novel anti-inflammatory molecule to ameliorate lung inflammation in CF patients. PMID:18815075

  9. Phytochemical analysis and anti-inflammatory potential of Hyphaene thebaica L. fruit.

    PubMed

    Farag, Mohamed A; Paré, Paul W

    2013-10-01

    Metabolite profiling and biological activity are reported from organic and aqueous extracts of the fruit from the desert palm Hyphaene thebaica. Phenolics and oxylipids profiles were determined using UPLC-PDA-TOF (ultra performance-photodiode array-time of flight) high-resolution mass spectrometry in order to obtain the molecular formula and exact mass Under optimized conditions, 17 compounds were simultaneously identified and quantified including 2 cinnamic acid derivatives, 5 flavonoids, 6 fatty acids, 2 sphingolipids, a lignan, and a stilbene. Sugars composition in the fruit was characterized and quantified by (1) H-NMR (nuclear magnetic resonance) with sucrose detected as the major component in fruit at a level of 219 mg/g. Fruit organic extracts anti-inflammatory potential was assessed in vitro by cyclooxygenase-1 enzyme inhibition. PMID:24025087

  10. Ammonium glycyrrhizinate-loaded niosomes as a potential nanotherapeutic system for anti-inflammatory activity in murine models

    PubMed Central

    Marianecci, Carlotta; Rinaldi, Federica; Di Marzio, Luisa; Mastriota, Marica; Pieretti, Stefano; Celia, Christian; Paolino, Donatella; Iannone, Michelangelo; Fresta, Massimo; Carafa, Maria

    2014-01-01

    Background Liquorice extracts demonstrate therapeutic efficacy in treating dermatitis, eczema, and psoriasis when compared with corticosteroids. In this work, nonionic surfactant vesicles (niosomes, NSVs) containing polysorbate 20 (Tween 20), cholesterol, and cholesteryl hemisuccinate at different molar concentrations were used to prepare monoammonium glycyrrhizinate (AG)-loaded NSVs. The anti-inflammatory properties of AG-loaded NSVs were investigated in murine models. Methods The physicochemical properties of the NSVs were characterized using dynamic light scattering. The fluidity of the lipid bilayer was evaluated by measuring the fluorescence intensity of diphenylhexatriene. The drug entrapment efficiency of AG was assessed using high-performance liquid chromatography. The physicochemical stability of the NSVs was evaluated as a function of time using dynamic light scattering combined with Turbiscan Lab® Expert analysis. Serum stability was determined by incubating the NSVs with 10% v/v fetal bovine serum. The cytotoxic effects of the NSVs were investigated in human dermal fibroblasts using the Trypan blue dye exclusion assay (for cell mortality) and an MTT assay (for cell viability). Release profiles for the AG-loaded NSVs were studied in vitro using cellulose membranes. NSVs showing the most desirable physicochemical properties were selected to test for in vivo anti-inflammatory activity in murine models. The anti-inflammatory activity of the NSVs was investigated by measuring edema and nociception in mice stimulated with chemical agents. Results NSVs showed favorable physicochemical properties for in vitro and in vivo administration. In addition, they demonstrated long-term stability based on Turbiscan Lab Expert analysis. The membrane fluidity of the NSVs was not affected by self-assembling of the surfactants into colloidal structures. Fluorescence anisotropy was found to be independent of the molar ratios of cholesteryl hemisuccinate and/or cholesterol during preparation of the NSVs. The anti-inflammatory AG drug showed no effect on the stability of the NSVs. In vivo experiments demonstrated that AG-loaded NSVs decreased edema and nociceptive responses when compared with AG alone and empty NSVs. In vitro and in vivo results demonstrated that pH sensitive and neutral NSVs show no statistical significant difference. Conclusion NSVs were nontoxic and showed features favorable for potential administration in vivo. In addition, neutral NSVs showed signs of increased anti-inflammatory and antinociceptive responses when compared with AG. PMID:24493924

  11. [Host inflammatory and anti-inflammatory response during sepsis].

    PubMed

    Adib-Conquy, M; Cavaillon, J-M

    2012-10-01

    Sepsis still remains the major complication for patients admitted in intensive care units (ICU), and is responsible for numerous deaths. ICU patients admitted after sepsis, hemorrhagic shock, severe trauma, severe burns or major surgery show a systemic inflammatory response syndrome (SIRS). This syndrome is characterized by an exacerbation of inflammation, with increased levels of pro- (IL-1?, TNF?, IL-6, IL-8) as well as anti-inflammatory (IL-10, IL-1Ra, TGF?) cytokines into their bloodstream. During sepsis, the bacteria release microbial motifs such as peptidoglycan, lipopolysaccharide (LPS) and DNA that initiate the inflammatory response, and are involved in the onset of multiple organ failure. The same microbial motifs can also be found in patients with a SIRS of non-infectious origin, following the translocation of bacteria from their digestive tract. This translocation is certainly contributing to the difficulty of discriminating between septic and SIRS patients using biological markers. Furthermore, the host response is accompanied by an alteration of the ex vivo response of circulating leukocytes, particularly monocytes. This hyporesponsiveness to LPS is associated with a decreased activation of the transcription factor NF-?B (required for the expression of pro-inflammatory cytokines) and an increased expression of negative regulators of the NF-?B pathway. However, the leukocyte hyporesponsiveness is not a global phenomenon, it depends on the type of patient, on the receptor-activator pair, on the timing, and on the cytokine. PMID:22542429

  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. Membranous nephropathy and nonsteroidal anti-inflammatory agents.

    PubMed

    Nawaz, Fareha A; Larsen, Christopher P; Troxell, Megan L

    2013-11-01

    Membranous nephropathy presents clinically as nephrotic syndrome, with subepithelial immune complex deposits seen on biopsy. Historically, in about three-quarters of membranous cases, no obvious etiologic agent or condition can be identified. More recently, serum antibodies to the phospholipase A2 receptor have been discovered in many patients with primary/idiopathic membranous nephropathy. About one-quarter of patients have membranous nephropathy as a manifestation of another systemic disorder, such as autoimmune conditions, infection, malignancy, toxin exposure, or drugs (classically gold or penicillamine). In this report, we present a case of recurrent nephrotic syndrome with biopsy-proven membranous nephropathy closely associated with use of the nonsteroidal anti-inflammatory drugs (NSAIDs) naproxen and piroxicam. Characterization of the immunoglobulin G (IgG) subclass profile of the deposits showed abundant IgG1, weak IgG4, and positive staining for phospholipase A2 receptor. This case serves to highlight membranous nephropathy as an under-recognized renal complication of NSAID use. Other kidney effects of NSAIDs, such as hemodynamic compromise, interstitial nephritis, and minimal change disease, are more broadly recognized. PMID:23773370

  14. 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)-?, interleukin (IL)-1?, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-activated microglia cells. In addition, GLB inhibited activation of nuclear factor-?B (NF-?B), 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

  15. Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.

    PubMed

    Hodkinson, Duncan J; Khawaja, Nadine; O?Daly, 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

  16. Nucleic acid-binding polymers as anti-inflammatory agents

    PubMed Central

    Lee, Jaewoo; Sohn, Jang Wook; Zhang, Ying; Leong, Kam W.; Pisetsky, David; Sullenger, Bruce A.

    2011-01-01

    Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundancy of the TLR family encouraged us to seek materials that can neutralize the proinflammatory effects of any nucleic acid regardless of its sequence, structure or chemistry. Herein we demonstrate that certain nucleic acid-binding polymers can inhibit activation of all nucleic acid-sensing TLRs irrespective of whether they recognize ssRNA, dsRNA or hypomethylated DNA. Furthermore, systemic administration of such polymers can prevent fatal liver injury engendered by proinflammatory nucleic acids in an acute toxic shock model in mice. Therefore these polymers represent a novel class of anti-inflammatory agent that can act as molecular scavengers to neutralize the proinflammatory effects of various nucleic acids. PMID:21844380

  17. Anti-inflammatory activity of the steroid alkaloid glycoside, tomatine

    PubMed Central

    Filderman, R. B.; Kovacs, B. A.

    1969-01-01

    1. Tomatine, isolated from extracts of crown gall-infected tomato plants or obtained commercially, was tested for anti-inflammatory activity using three different methods. 2. Tomatine administered to intact rats intramuscularly in a dose range of 1-10 mg/kg or orally in doses of 15-30 mg/kg exerted a significant dose dependent inhibition of carrageenan induced paw oedema. The inhibitory effect of tomatine when given in a dose of 10 mg/kg intramuscularly to intact rats lasted more than 24 hr. 3. In adrenalectomized rats significant dose-related inhibition of paw oedema was obtained with tomatine and the inhibition at each dose level (0·5-10 mg/kg) was found to be greater than that found in intact animals. 4. Tomatine administered subcutaneously to intact rats daily for 7 days in doses of 5 or 10 mg/kg exerted a significant, dose dependent inhibition of granulation tissue formation induced by the subcutaneous implantation of carrageenan impregnated cotton pellets. 5. Tomatine administered to intact mice in a dose of 10 mg/kg subcutaneously 1 hr before the intraperitoneal injection of acidified saline and intravenous pontamine sky blue significantly decreased the leakage of the protein bound dye into the peritoneal cavity. 6. Tomatidine, the aglycone of tomatine, was not effective at dose levels of 10-20 mg/kg in any of the three tests. PMID:5348476

  18. Anti-inflammatory properties of the plant Verbascum mallophorum.

    PubMed

    Speranza, L; Franceschelli, S; Pesce, M; Menghini, L; Patruno, A; Vinciguerra, I; De Lutiis, M A; Felaco, M; Felaco, P; Grilli, A

    2009-01-01

    Verbascum mallophorum is part of a large family of Scrophulariaceae consisting of more than 360 species. Verbascum mallophorums contains diverse polysaccharides, iroid glycosides, flavonoids, saponins, volatile oils and phenylentanoids. Verbascum has been used in popular medicine for treating wounds, chilblains, respiratory ailments, acne and arthritic disturbances. Inducible nitric oxide synthase (iNOS) represents one of the three isoforms that produce nitric oxide using L-arginine as a substrate in response to an increase in superoxide anion activated by NF-kappaB. It is implicated in different pathophysiological events and its expression increases greatly during an inflammatory process due to oxidative stress. In our study we reproduced an inflammatory state by treating THP-1 cells (human myelomonocytic leukaemia) with pro-inflammatory stimuli, such as LPS and IFN-gamma, obtaining an up-regulation both in the expression and in the activity of iNOS. The aim of our work is to investigate the possible antiinflammatory action of verbascoside extract from Verbascum mallophorum using a concentration of 100 muM. Our results show a significant decrease in the expression and activity of iNOS and extracellular O2- when cells were treated with verbascoside. Based on these results we hypothesize that verbascoside extract from Verbascum mallophorum has anti-inflammatory properties since it reduces the production of superoxide radicals and consequently reduces the activity of iNOS. PMID:19828096

  19. 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

  20. Anti-inflammatory and mast cell protective effect of ficus religiosa.

    PubMed

    Viswanathan, S; Thirugnanasambantham, P; Reddy, M K; Narasimhan, S; Subramaniam, G A

    1990-10-01

    The aqueous extract of bark of Ficus religiosa was prepared and investigated for its anti-inflammatory effect and for its protective effect on mast cells against degranulation. A significant anti-inflammatory effect was observed in both acute and chronic models of inflammation. The extract also protected mast cells from degranulation induced by various degranulatiors. The observed anti-inflammatory and mast cell protective effect may be responsible for the beneficial effect of Ficus religiosa in kumkum dermatitis and other inflammatory conditions. PMID:22556521

  1. ANTI-INFLAMMATORY AND MAST CELL PROTECTIVE EFFECT OF FICUS RELIGIOSA

    PubMed Central

    Viswanathan, S.; Thirugnanasambantham, P.; Reddy, M. Kannappa; Narasimhan, S.; Subramaniam, G. Anantha

    1990-01-01

    The aqueous extract of bark of Ficus religiosa was prepared and investigated for its anti-inflammatory effect and for its protective effect on mast cells against degranulation. A significant anti-inflammatory effect was observed in both acute and chronic models of inflammation. The extract also protected mast cells from degranulation induced by various degranulatiors. The observed anti-inflammatory and mast cell protective effect may be responsible for the beneficial effect of Ficus religiosa in kumkum dermatitis and other inflammatory conditions. PMID:22556521

  2. The role of non-steroidal anti-inflammatory drugs in acute liver injury

    Microsoft Academic Search

    L. A. García Rodríguez; S. Pérez Gutthann; A. M. Walker; L. Lueck

    1992-01-01

    OBJECTIVE--To investigate the association between use of non-steroidal anti-inflammatory drugs and serious, acute non-infectious liver injury. DESIGN--Retrospective cohort study, cross over design. SETTING--Health records from provincial database in Saskatchewan, Canada, 1982-6. SUBJECTS--228,392 adults who contributed 645,456 person years. All were either using or had used non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES--Number and type of prescriptions for non-steroidal anti-inflammatory drugs. Admission

  3. Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway

    PubMed Central

    Tian, Yikui; Piras, Bryan A.; Kron, Irving L.; French, Brent A.; Yang, Zequan

    2015-01-01

    Background. Activation of the adenosine A2B receptor (A2BR) can reduce myocardial ischemia/reperfusion (IR) injury. However, the mechanism underlying the A2BR-mediated cardioprotection is less clear. The present study was designed to investigate the potential mechanisms of cardioprotection mediated by A2BR. Methods and Results. C57BL/6 mice underwent 40-minute ischemia and 60-minute reperfusion. ATL-801, a potent selective A2BR antagonist, could not block ischemic preconditioning induced protection. BAY 60-6583, a highly selective A2BR agonist, significantly reduced myocardial infarct size, and its protective effect could be blocked by either ATL-801 or wortmannin. BAY 60-6583 increased phosphorylated Akt (p-Akt) levels in the heart at 10?min of reperfusion, and this phosphorylation could also be blocked by ATL-801 or wortmannin. Furthermore, BAY 60-6583 significantly increased M2 macrophages and decreased M1 macrophage and neutrophils infiltration in reperfused hearts, which also could be blocked by wortmannin. Meanwhile, confocal imaging studies showed that the majority of Akt phosphorylation in the heart was colocalized to CD206+ cells in both control and BAY 60-6583 pretreated hearts. Conclusion. Our results indicated that pretreatment with BAY 60-6583 protects the heart against myocardial IR injury by its anti-inflammatory effects, probably by modulating macrophages phenotype switching via a PI3K/Akt pathway.

  4. Extracorporeal shock wave therapy in inflammatory diseases: molecular mechanism that triggers anti-inflammatory action.

    PubMed

    Mariotto, Sofia; de Prati, Alessandra Carcereri; Cavalieri, Elisabetta; Amelio, Ernesto; Marlinghaus, Ernst; Suzuki, Hisanori

    2009-01-01

    Shock waves (SW), defined as a sequence of single sonic pulses characterised by high peak pressure (100 MPa), a fast rise in pressure (< 10 ns) and a short lifecycle (10 micros), are conveyed by an appropriate generator to a specific target area at an energy density ranging from 0.03 to 0.11 mJ/mm(2). Extracorporeal SW (ESW) therapy was first used on patients in 1980 to break up kidney stones. During the last ten years, this technique has been successfully employed in orthopaedic diseases such as pseudoarthosis, tendinitis, calcarea of the shoulder, epicondylitis, plantar fasciitis and several inflammatory tendon diseases. In particular, treatment of the tendon and muscle tissues was found to induce a long-time tissue regeneration effect in addition to having a more immediate anthalgic and anti-inflammatory outcome. In keeping with this, an increase in neoangiogenesis in the tendons of dogs was observed after 4-8 weeks of ESW treatment. Furthermore, clinical observations indicate an immediate increase in blood flow around the treated area. Nevertheless, the biochemical mechanisms underlying these effects have yet to be fully elucidated. In the present review, we briefly detail the physical properties of ESW and clinical cases treated with this therapy. We then go on to describe the possible molecular mechanism that triggers the anti-inflammatory action of ESW, focusing on the possibility that ESW may modulate endogenous nitric oxide (NO) production either under normal or inflammatory conditions. Data on the rapid enhancement of endothelial NO synthase (eNOS) activity in ESW-treated cells suggest that increased NO levels and the subsequent suppression of NF-kappaB activation may account, at least in part, for the clinically beneficial action on tissue inflammation. PMID:19601786

  5. The Anti-Inflammatory Effects of Flavanol-Rich Lychee Fruit Extract in Rat Hepatocytes

    PubMed Central

    Yamanishi, Ryota; Yoshigai, Emi; Okuyama, Tetsuya; Mori, Masatoshi; Murase, Hiromitsu; Machida, Toru; Okumura, Tadayoshi; Nishizawa, Mikio

    2014-01-01

    Flavanol (flavan-3-ol)-rich lychee fruit extract (FRLFE) is a mixture of oligomerized polyphenols primarily derived from lychee fruit and is rich in flavanol monomers, dimers, and trimers. Supplementation with this functional food has been shown to suppress inflammation and tissue damage caused by high-intensity exercise training. However, it is unclear whether FRLFE has in vitro anti-inflammatory effects, such as suppressing the production of the proinflammatory cytokine tumor necrosis factor ? (TNF-?) and the proinflammatory mediator nitric oxide (NO), which is synthesized by inducible nitric oxide synthase (iNOS). Here, we analyzed the effects of FRLFE and its constituents on the expression of inflammatory genes in interleukin 1? (IL-1?)-treated rat hepatocytes. FRLFE decreased the mRNA and protein expression of the iNOS gene, leading to the suppression of IL-1?-induced NO production. FRLFE also decreased the levels of the iNOS antisense transcript, which stabilizes iNOS mRNA. By contrast, unprocessed lychee fruit extract, which is rich in flavanol polymers, and flavanol monomers had little effect on NO production. When a construct harboring the iNOS promoter fused to the firefly luciferase gene was used, FRLFE decreased the luciferase activity in the presence of IL-1?, suggesting that FRLFE suppresses the promoter activity of the iNOS gene at the transcriptional level. Electrophoretic mobility shift assays indicated that FRLFE reduced the nuclear transport of a key regulator, nuclear factor ?B (NF-?B). Furthermore, FRLFE inhibited the phosphorylation of NF-?B inhibitor ? (I?B-?). FRLFE also reduced the mRNA levels of NF-?B target genes encoding cytokines and chemokines, such as TNF-?. Therefore, FRLFE inhibited NF-?B activation and nuclear translocation to suppress the expression of these inflammatory genes. Our results suggest that flavanols may be responsible for the anti-inflammatory and hepatoprotective effects of FRLFE and may be used to treat inflammatory diseases. PMID:24705335

  6. Peptoid-Substituted Hybrid Antimicrobial Peptide Derived from Papiliocin and Magainin 2 with Enhanced Bacterial Selectivity and Anti-inflammatory Activity.

    PubMed

    Shin, Areum; Lee, Eunjung; Jeon, Dasom; Park, Young-Guen; Bang, Jeong Kyu; Park, Yong-Sun; Shin, Song Yub; Kim, Yangmee

    2015-06-30

    Antimicrobial peptides (AMPs) are important components of the host innate immune system. Papiliocin is a 37-residue AMP purified from larvae of the swallowtail butterfly Papilio xuthus. Magainin 2 is a 23-residue AMP purified from the skin of the African clawed frog Xenopus laevis. We designed an 18-residue hybrid peptide (PapMA) incorporating N-terminal residues 1-8 of papiliocin and N-terminal residues 4-12 of magainin 2, joined by a proline (Pro) hinge. PapMA showed high antimicrobial activity but was cytotoxic to mammalian cells. To decrease PapMA cytotoxicity, we designed a lysine (Lys) peptoid analogue, PapMA-k, which retained high antimicrobial activity but displayed cytotoxicity lower than that of PapMA. Fluorescent dye leakage experiments and confocal microscopy showed that PapMA targeted bacterial cell membranes whereas PapMA-k penetrated bacterial cell membranes. Nuclear magnetic resonance experiments revealed that PapMA contained an N-terminal ?-helix from Lys(3) to Lys(7) and a C-terminal ?-helix from Lys(10) to Lys(17), with a Pro(9) hinge between them. PapMA-k also had two ?-helical structures in the same region connected with a flexible hinge residue at Nlys(9), which existed in a dynamic equilibrium of cis and trans conformers. Using lipopolysaccharide-stimulated RAW264.7 macrophages, the anti-inflammatory activity of PapMA and PapMA-k was confirmed by inhibition of nitric oxide and inflammatory cytokine production. In addition, treatment with PapMA and PapMA-k decreased the level of ultraviolet irradiation-induced expression of genes encoding matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), and tumor necrosis factor-? (TNF-?) in human keratinocyte HaCaT cells. Thus, PapMA and PapMA-k are potent peptide antibiotics with antimicrobial and anti-inflammatory activity, with PapMA-k displaying enhanced bacterial selectivity. PMID:26053120

  7. A novel pyrimidine derivatives with aryl urea, thiourea and sulfonamide moieties: synthesis, anti-inflammatory and antimicrobial evaluation.

    PubMed

    Keche, Ashish P; Hatnapure, Girish D; Tale, Rajesh H; Rodge, Atish H; Birajdar, Satish S; Kamble, Vandana M

    2012-05-15

    A series of novel 4-(3-(trifluoromethyl)phenylamino-6-(4-(3-arylureiodo/arylthioureido/arylsulfonamido)-pyrimidine derivatives of biological interest were prepared by the sequential Suzuki cross coupling, acid amination, reduction followed by reaction of resulting amine with different arylisocyantes or arylisothiocyantes or arylsulfonyl chlorides. All the synthesized compounds (1-25) were screened for their pro-inflammatory cytokines (TNF-? and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological data revealed that among all the compounds screened, compounds 5, 6, 11, 12, 16 and 20 were found to have moderate to potent anti-inflammatory activity (up to 48-78% TNF-? and 56-96% IL-6 inhibitory activity) with reference to standard dexamethasone at 10 ?M. The compounds 10, 12, 13, 18, 20, 22, 24 and 25 found to have promising antimicrobial activity against all the selected pathogenic bacteria and fungi. PMID:22520258

  8. Evaluation of In Vitro Anti-Inflammatory Activities and Protective Effect of Fermented Preparations of Rhizoma Atractylodis Macrocephalae on Intestinal Barrier Function against Lipopolysaccharide Insult

    PubMed Central

    Bose, Shambhunath; Kim, Hojun

    2013-01-01

    Lipopolysaccharide (LPS), a potent inducer of systemic inflammatory responses, is known to cause impairment of intestinal barrier function. Here, we evaluated the in vitro protective effect of an unfermented formulation of Rhizoma Atractylodis Macrocephalae (RAM), a traditional Chinese herbal medicine widely used in the treatment of many digestive and gastrointestinal disorders, and two fermented preparations of RAM, designated as FRAM-1 (prepared in Luria-Bertani broth) and FRAM-2 (prepared in glucose), on intestinal epithelial cells (IECs) against LPS insult. In general, fermented formulations, especially FRAM-2, but not unfermented RAM, exerted an appreciable protective effect on IECs against LPS-induced perturbation of membrane resistance and permeability. Both fermented formulations exhibited appreciable anti-inflammatory activities in terms of their ability to inhibit LPS-induced gene expression and induced production of a number of key inflammatory mediators and cytokines in RAW 264.7 macrophage cells. However, in most cases, FRAM-2 exhibited stronger anti-inflammatory effects than FRAM-1. Our findings also suggest that suppression of nuclear factor-?? (NF-??) activity might be one of the possible mechanisms by which the fermented RAM exerts its anti-inflammatory effects. Collectively, our results highlight the benefits of using fermented products of RAM to protect against LPS-induced inflammatory insult and impairment in intestinal barrier function. PMID:23573125

  9. Analgesic and Anti-Inflammatory Properties of Extracts from the Bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae) in Mice and Rats

    PubMed Central

    Mbiantcha, M.; Kamanyi, A.; Teponno, R. B.; Tapondjou, A. L.; Watcho, P.; Nguelefack, T. B.

    2011-01-01

    The aqueous and methanol extracts from the dry bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae)—evaluated orally at the doses of 300 and 600?mg/kg against pain induced by acetic acid, formalin, pressure and against inflammation induced by carrageenan, histamine, serotonin and formalin in mice and rats, showed a dose dependant inhibition of pain and inflammation with a maximum effect of 56.38%, 73.06% and 42.79% produced by the aqueous extract, respectively on pain induced by acetic acid, formalin and pressure while the methanol extract at the same dose respectively inhibited these models of pain by 62.70%, 84.54% and 47.70%. The oral administration of aqueous and methanol extracts caused significant anti-inflammatory activity on paw oedema induced by histamine, serotonin and formalin. The present results show that the bulbils of Dioscorea bulbifera var sativa possess potent analgesic and anti-inflammatory activities. These activities may results from the inhibition of inflammatory mediators such as histamine, serotonin and prostaglandins. Thus, the analgesic activity of the bulbils of Dioscorea bulbifera may be at least partially linked to its anti-inflammatory activity. PMID:20953397

  10. Synthesis and biological evaluation of a novel class of curcumin analogs as anti-inflammatory agents for prevention and treatment of sepsis in mouse model

    PubMed Central

    Zhao, Chengguang; Zhang, Yali; Zou, Peng; Wang, Jian; He, Wenfei; Shi, Dengjian; Li, Huameng; Liang, Guang; Yang, Shulin

    2015-01-01

    A novel class of asymmetric mono-carbonyl analogs of curcumin (AMACs) were synthesized and screened for anti-inflammatory activity. These analogs are chemically stable as characterized by UV absorption spectra. In vitro, compounds 3f, 3m, 4b, and 4d markedly inhibited lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines tumor necrosis factor-? and interleukin-6 in a dose-dependent manner, with IC50 values in low micromolar range. In vivo, compound 3f demonstrated potent preventive and therapeutic effects on LPS-induced sepsis in mouse model. Compound 3f downregulated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 MAPK and suppressed I?B? degradation, which suggests that the possible anti-inflammatory mechanism of compound 3f may be through downregulating nuclear factor kappa binding (NF-?B) and ERK pathways. Also, we solved the crystal structure of compound 3e to confirm the asymmetrical structure. The quantitative structure–activity relationship analysis reveals that the electron-withdrawing substituents on aromatic ring of lead structures could improve activity. These active AMACs represent a new class of anti-inflammatory agents with improved stability, bioavailability, and potency compared to curcumin. Our results suggest that 3f may be further developed as a potential agent for prevention and treatment of sepsis or other inflammation-related diseases. PMID:25834403

  11. Evaluation of the new anti-inflammatory compound ethyl salicylate 2-O-?-D-glucoside and its possible mechanism of action.

    PubMed

    Xin, Wenyu; Huang, Chao; Zhang, Xue; Zhang, Guidong; Ma, Xiaowei; Sun, Lan; Wang, Chao; Zhang, Dongming; Zhang, Tiantai; Du, Guanhua

    2013-02-01

    Ethyl salicylate 2-O-?-d-glucoside (ESG) is a derivative of natural salicylate isolated from Gaultheria yunnanensis (Franch.) Rehder, it has been used for the treatments of rheumatoid arthritis, swelling and pain. The aim of this study was to evaluate the anti-inflammatory effects of ESG and explore the anti-inflammatory mechanisms. We found that ESG had potent anti-inflammatory effects on the lipopolysaccharide (LPS)-activated murine macrophages RAW264.7. ESG exerted a dose-dependent inhibition of the LPS-stimulated release of the pro-inflammatory cytokines TNF-? and IL-1?. Moreover, it significantly inhibited LPS-stimulated the production of NO and PGE2 by repressing the expression of iNOS and COX protein respectively. Western blot analysis showed that ESG prominently inhibited LPS-induced activation of NF-?B in RAW264.7 cells by blocking phosphorylation of inhibitor I?B? and p65. Consistent with these results, we found that ESG prevented the nuclear translocation of NF-?B induced by LPS. Our study suggests that ESG may be effective in the treatment of inflammatory diseases by inhibiting the pro-inflammatory cytokine production and regulating the NF-?B signal pathway. PMID:23219581

  12. Discovery of dual inhibitors of the immune cell PI3Ks p110? and p110?: a prototype for new anti-inflammatory drugs

    PubMed Central

    Williams, Olusegun; Houseman, Benjamin T.; Kunkel, Eric J.; Aizenstein, Brian; Hoffman, Randy; Knight, Zachary A.; Shokat, Kevan M.

    2010-01-01

    SUMMARY PI3K? and PI3K? regulate immune cell signaling, while the related PI3K? and PI3K? regulate cell survival and metabolism. Selective inhibitors of PI3K?/? represent a potential class of anti-inflammatory agents lacking the anti-proliferative effects associated with PI3K?/? inhibition. Here we report the discovery of PI3K?/? inhibitors that display up to 1,000-fold selectivity over PI3K?/? and evaluate these compounds in a high-content inflammation assay using mixtures of primary human cells. We find selective inhibition of only PI3K? is weakly anti-inflammatory, but PI3K?/? inhibitors show superior inflammatory marker suppression through suppression of LPS-induced TNF? production and T-cell activation. Moreover, PI3K?/? inhibition yields an anti-inflammatory signature distinct from pan-PI3K inhibition and known anti-inflammatory drugs, yet bears striking similarities to glucocorticoid receptor agonists. These results highlight the potential of selectively designing drugs that target kinases with shared biological function. PMID:20189103

  13. A study of the novel anti-inflammatory agent florifenine topical anti-inflammatory activity and influence on arachidonic acid metabolism and neutrophil functions

    Microsoft Academic Search

    Gloria Bustos; Maria Luisa Ferrándiz; Maria Jesús Sanz; Miguel Payá; Maria José Alcaraz

    1995-01-01

    We have evaluated the effects of the novel anti-inflammatory agent florifenine, 2-(1-Pyrrolidinyl)ethyl N-[7-(trifluoromethyl)-4-quinolyl]anthranilate, on topical inflammation in mice, free radical-mediated reactions, arachidonic acid metabolism and some neutrophil functions. Topical administration of florifenine produced dose-related anti-inflammatory activity in 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear oedema and with a lower potency, in the response induced by arachidonic acid (AA). Florifenine also inhibited neutrophil migration

  14. Nickel(II) Complex of Polyhydroxybenzaldehyde N4-Thiosemicarbazone Exhibits Anti-Inflammatory Activity by Inhibiting NF-?B Transactivation

    PubMed Central

    Loh, Sheng Wei; Looi, Chung Yeng; Hassandarvish, Pouya; Phan, Alicia Yi Ling; Wong, Won Fen; Wang, Hao; Paterson, Ian C.; Ea, Chee Kwee; Mustafa, Mohd Rais; Maah, Mohd Jamil

    2014-01-01

    Background The biological properties of thiosemicarbazone have been widely reported. The incorporation of some transition metals such as Fe, Ni and Cu to thiosemicarbazone complexes is known to enhance its biological effects. In this study, we incorporated nickel(II) ions into thiosemicarbazone with N4-substitution groups H3L (H; H3L1, CH3; H3L2, C6H5; H3L3 and C2H5; H3L4) and examined its potential anti-inflammatory activity. Methodology/Principal Findings Four ligands (1–4) and their respective nickel-containing complexes (5–8) were synthesized and characterized. The compounds synthesized were tested for their effects on NF-?B nuclear translocation, pro-inflammatory cytokines secretion and NF-?B transactivation activity. The active compound was further evaluated on its ability to suppress carrageenan-induced acute inflammation in vivo. A potential binding target of the active compound was also predicted by molecular docking analysis. Conclusions/Significance Among all synthesized compounds tested, we found that complex [Ni(H2L1)(PPh3)]Cl (5) (complex 5), potently inhibited I?B? degradation and NF-?B p65 nuclear translocation in LPS-stimulated RAW264.7 cells as well as TNF?-stimulated HeLa S3 cells. In addition, complex 5 significantly down-regulated LPS- or TNF?-induced transcription of NF-?B target genes, including genes that encode the pro-inflammatory cytokines TNF?, IFN? and IL6. Luciferase reporter assays confirmed that complex 5 inhibited the transactivation activity of NF-?B. Furthermore, the anti-inflammatory effect of complex 5 was also supported by its suppressive effect on carrageenan-induced paw edema formation in wild type C57BL/6 mice. Interestingly, molecular docking study showed that complex 5 potentially interact with the active site of IKK?. Taken together, we suggest complex 5 as a novel NF-?B inhibitor with potent anti-inflammatory effects. PMID:24977407

  15. Kaurenic acid: An in vivo experimental study of its anti-inflammatory and antipyretic effects

    PubMed Central

    Sosa-Sequera, Miriam C.; Suárez, Omar; Daló, Nelson L.

    2010-01-01

    Objective: This study was designed to investigate the anti-inflammatory and antipyretic effects of kaurenic acid (KA), a tetracyclic diterpenoid carboxylic acid, using in vivo experimental animal models. Material and Methods: The anti-inflammatory activity of KA was evaluated in rats, using egg albumin-induced paw edema (acute test) and Freund’s complete adjuvant-induced paw edema (subacute test), whereas the antipyretic effect was studied in rabbits by peptone-induced pyresis. Acute and subacute toxicity of KA were analyzed in NMRI mice. Results: KA showed anti-inflammatory and antipyretic properties, and the effect caused was significantly dose-related (P < 0.001) in both cases. The mean lethal doses of KA were 439.2 and 344.6 mg/kg for acute and subacute toxicity, respectively. Conclusion: On the basis of these findings, it may be inferred that KA has an anti-inflammatory and antipyretic potential. PMID:21206621

  16. Anti-inflammatory activity of 2-acyl-5(3)-hydroxytetrahydro-1H-pyrazole derivatives.

    PubMed

    Zelenin, K N; Bezhan, I P; Pastushenkov, L V; Gromova, E G; Lesiovskaja, E E; Chakchir, B A; Melnikova, L F

    1999-10-01

    The anti-inflammatory effects of five pyrazolidine derivatives on white mice and laboratory rats were studied using models of thermal aseptic inflammation and inflammation induced by injection of carragenin and histamine, as well as models of "cotton-ball granuloma" and epinephrine (adrenaline)-induced pulmonary edema. These effects were compared with those of the most commonly used non-steroid anti-inflammatory drugs, such as phenylbutazone (CAS 50-33-9) and diclofenac (CAS 15307-79-6). It was found that the pyrazolidine compounds studied induced a pronounced anti-inflammatory effect by inhibiting both the proliferative and exudative phases of inflammation. At the same time, as compared to natural non-steroid anti-inflammatory drugs, these compounds had a lower toxicity and induced neither gastric ulcers nor suppression of hemopoiesis. PMID:10554662

  17. Evaluation of anti-inflammatory potential of Pavetta indica Linn. leaf extract (family: Rubiaceae) in rats.

    PubMed

    Mandal, Subhash C; Mohana Lakshmi, S; Ashok Kumar, C K; Sur, Tapas K; Boominathan, R

    2003-08-01

    The anti-inflammatory potential of methanol extract of Pavetta indica Linn. leaves (Family: Rubiaceae) was evaluated against several models of inflammation such as carragenin, histamine and dextran induced pedal inflammation in rats. The extract showed 48.41%, 41.10% and 24.22% inhibition respectively; when compared to that of control animals. The effect was comparable with that of the standard drug indomethacin, a standard non-steroidal anti-inflammatory drug. Simultaneous subplantar administration of the extract and carrageenin in a mixture helps in differentiating true anti-inflammatory action from an apparent anti-inflammatory effect due to counter-irritant activity. The methanol extract also effectively and significantly reduced cotton pellet induced granuloma. The percentage of inhibition was 62.78 at the dose 500 mg/kg, thereby suggesting its activity in the proliferative phase of the inflammatory process. PMID:12916086

  18. Anti-inflammatory Protein TSG-6 Promotes Early Gingival Wound Healing: An In Vivo Study 

    E-print Network

    Beltran, Stacy Renay

    2014-04-14

    the inflammatory cascade; reducing levels of proinflammatory cytokines and cellular infiltrate. Gingival injection of TSG-6 may offer significant promise as an anti-inflammatory agent for patients requiring gingival surgery....

  19. Anti-inflammatory Properties of Cowpea Phenotypes with different Phenolic Profiles 

    E-print Network

    Ojwang, Leonnard

    2012-07-16

    activity, anti-inflammatory properties on non-malignant colonic (CCD18co) cells challenged with a lipopolysaccharide (LPS), and the effect of boiling on their individual and total flavonoid content. Only the black and green phenotypes had detectable...

  20. Experimental evaluation of analgesic and anti-inflammatory potential of Oyster mushroom Pleurotus florida

    PubMed Central

    Ganeshpurkar, Aditya; Rai, Gopal

    2013-01-01

    Background: Edible mushrooms have been used as flavorful foods and as health nutritional supplements for several centuries. A number of bioactive molecules have been identified in numerous mushroom species Objective: To evaluate the analgesic and anti-inflammatory potential of Oyster Mushroom Pleurotus florida using various experimental models in Wistar rats. Materials and Methods: Acute toxicity studies were performed whereby dose of 250 mg/ kg and 500 mg/kg was selected for present study, Analgesic activity was determined using hot plate method, tail flick method, acetic acid induced writhing and formalin induced pain in rats, while carrageenan was used to induce inflammation and anti-inflammatory studies were performed. Results: HEE showed significant (P < 0.01) analgesic and anti-inflammatory response against all experimental models. Conclusion: These studies conclude that Pleurotus florida possesses analgesic and anti- inflammatory potential which might be due to presence of myochemicals like flavonoids, phenolics and polysaccharides. PMID:23543896

  1. Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities.

    PubMed

    Wang, Yuanyuan; Yang, Xiaorong; Zheng, Xinqiang; Li, Jing; Ye, Chuangxing; Song, Xiaohong

    2010-09-01

    The anti-inflammatory and analgesic effects of theacrine (1, 3, 7, 9-tetramethyluric acid), a purine alkaloid which is abundantly present in Camellia kucha, were investigated. Xylene-induced ear edema, acetic acid-induced vascular permeability and lambda-carrageenan-induced paw edema were used to investigate anti-inflammatory activity, and acetic acid-induced writhing and hot-plate tests were used to determine analgesic effect. Oral administration of theacrine (8-32 mg/kg) induced dose-related anti-inflammatory and analgesic effects. On the other hand, oral caffeine administration (8-32 mg/kg) did not show an inhibitory effect on the inhibition of inflammatory response or cause analgesia. Additionally, the result of the acute toxicity test showed that the LD(50) of theacrine was 810.6 mg/kg (769.5-858.0mg/kg). The data obtained suggest theacrine possessed analgesic and anti-inflammatory activities. PMID:20227468

  2. Analgesic and anti-inflammatory effects of Cassia siamea Lam. stem bark extracts

    Microsoft Academic Search

    G. F. Nsonde Ntandou; J. T. Banzouzi; B. Mbatchi; R. D. G. Elion-Itou; A. W. Etou-Ossibi; S. Ramos; F. Benoit-Vical; A. A. Abena; J. M. Ouamba

    2010-01-01

    Aim of the studyThe present study was carried out to investigate analgesic and anti-inflammatory activities of Cassia siamea Lam stem bark extracts. We have also determined the cytotoxicity of each extract.

  3. Determination of Teloschistes flavicans (sw) norm anti-inflammatory activity

    PubMed Central

    Pereira, Eugênia C.; da Silva, Nicácio H.; Santos, Renata Almeida; Sudário, Ana Patrícia Paiva; Rodrigues e Silva, Antonio Alfredo; de Sousa Maia, Maria Bernadete

    2010-01-01

    Background: Lichens produce a variety of substances that possesses pharmacological actions. However, rare products are submitted to rigorous scientific tests or have the risk potential or side effects evaluated. The lack of medical and sanitary control, absence of accurate botanical identification or purity certification, founded in diverse natural products, may represent great danger to population health. This work aimed to evaluate toxic effects and anti-inflammatory action in vivo of Teloschistes flavicans (Sw.) Norm. (TFN) unrefined extracts, as well as determinate its main constituents. Methods: The carrageenan induced paw edema and cotton pellet implant induced granuloma methods were utilized, besides a classic acute toxicity test. TFN acetone extract inhibited carrageenan paw edema on 60, 120, and 180 min (inhibition percentiles of 45.03%, 60.59% and 41.72%). Results: TFN ethereal (inhibition percentiles of 23.95% and 29.01%) and chloroform (inhibition percentiles of 28.8% and 22.04%) extracts inhibited edema on 120 and 180 min. None of the extract inhibited the granuloma development. None of the extract caused death or other acute toxicity signs. Vicanicine (60.26% in ethereal extract and 51.17% in acetone extract), parietine (9.60% in ethereal extract and 15.38% on second), falacinol (0.78% in ether and 14.95% in acetone) and very low concentration of falacinal (0.15% in ethereal extract and 3.32% in acetone extract) were detected in the medicine. Conclusions: The tested extracts have antiedematogenic activity, but are not effective on subchronic inflammation. The extracts do not present toxic effects in administered doses. PMID:21808568

  4. The neuroimmune basis of anti-inflammatory acupuncture.

    PubMed

    Kavoussi, Ben; Ross, B Evan

    2007-09-01

    This review article presents the evidence that the antiinflammatory actions of acupuncture are mediated via the reflexive central inhibition of the innate immune system. Both laboratory and clinical evidence have recently shown the existence of a negative feedback loop between the autonomic nervous system and the innate immunity. There is also experimental evidence that the electrical stimulation of the vagus nerve inhibits macrophage activation and the production of TNF, IL-1beta , IL-6, IL-18, and other proinflammatory cytokines. It is therefore conceivable that along with hypnosis, meditation, prayer, guided imagery, biofeedback, and the placebo effect, the systemic anti-inflammatory actions of traditional and electro-acupuncture are directly or indirectly mediated by the efferent vagus nerve activation and inflammatory macrophage deactivation. In view of this common physiological mediation, assessing the clinical efficacy of a specific acupuncture regimen using conventional double-blind placebo-controlled trials inherently lacks objectivity due to (1) the uncertainty of ancient rules for needle placement, (2) the diffuse noxious inhibitory control triggered by control-needling at irrelevant points, (3) the possibility of a dose-response relationship between stimulation and effects, and (4) the possibility of inadequate blinding using an inert sham procedure. A more objective assessment of its efficacy could perhaps consist of measuring its effects on the surrogate markers of autonomic tone and inflammation. The use of acupuncture as an adjunct therapy to conventional medical treatment for a number of chronic inflammatory and autoimmune diseases seems plausible and should be validated by confirming its cholinergicity. PMID:17761638

  5. Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response

    PubMed Central

    2010-01-01

    Background Ciguatoxins (CTXs) are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO) and molecular pathway enrichment of the gene expression data. Results A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p < 0.0001) with microarray results. Conclusions Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against neuroinflammation. Pathologic activity of the complement/coagulation cascade has been shown in patients suffering from a chronic form of ciguatera poisoning and is of particular interest in this model. Anti-inflammatory processes were at work not only in the brain but were also seen in whole blood and liver of these animals, creating a systemic anti-inflammatory environment to protect against the initial cellular damage caused by the toxin. PMID:20796285

  6. Glomerular tip lesion associated with nonsteroidal anti-inflammatory drug-induced nephrotic syndrome.

    PubMed

    Sekhon, Inderpreet; Munjal, Sandeep; Croker, Byron; Johnson, Richard J; Ejaz, A Ahsan

    2005-10-01

    Glomerular tip lesion and its relation to different glomerular diseases is a subject of controversy. The therapeutic and prognostic clinical implications of glomerular tip lesions are ambiguous. We present a case of glomerular tip lesion associated with nonsteroidal anti-inflammatory drug-induced nephrotic syndrome that further complicates this issue. To our knowledge, this is the first case report of glomerular tip lesion associated with nonsteroidal anti-inflammatory drug-induced nephrotic syndrome. PMID:16183408

  7. Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats

    Microsoft Academic Search

    Naveen K Jain; Shrinivas K Kulkarni

    1999-01-01

    Oral administration of the feverfew (Tanacetum parthenium) extract led to significant antinociceptive and anti-inflammatory effects against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. These responses were dose-dependent (10, 20, 40 mg\\/kg, p.o.). Parthenolide (1, 2 mg\\/kg i.p.), the active constituent of the extract also produced antinociceptive and anti-inflammatory effects. Naloxone (1 mg\\/kg i.p.), an opiate

  8. Anti-inflammatory and antiulcerogenic effects of the aqueous extract of Lobaria pulmonaria (L.) Hoffm.

    PubMed

    Süleyman, H; Odabasoglu, F; Aslan, A; Cakir, A; Karagoz, Y; Gocer, F; Halici, M; Bayir, Y

    2003-01-01

    An aqeuous extract of Lobaria pulmonaria (L.) Hoffm., from which a tea is prepared and consumed as treatment for various diseases in northeastern Turkey, was tested for its anti-inflammatory and antiulcerogenic effects in rats. The carrageenan-induced paw edema, cotton pellet granuloma and indomethacin-induced gastric damage models were used to determine these effects. The extract exhibited moderate anti-inflammatory and strong antiulcerogenic activities. PMID:13678242

  9. Cellular and molecular mechanisms of anti-inflammatory effect of Aflapin: a novel Boswellia serrata extract

    Microsoft Academic Search

    Krishanu Sengupta; Jayaprakash N. Kolla; Alluri V. Krishnaraju; Nandini Yalamanchili; Chirravuri V. Rao; Trimurtulu Golakoti; Smriti Raychaudhuri; Siba P. Raychaudhuri

    2011-01-01

    There is significant number of evidences suggesting the anti-inflammatory properties of gum resin extracts of Boswellia serrata containing 3-O-acetyl-11-keto-?-boswellic acid (AKBA) and their promising potential as therapeutic interventions against inflammatory diseases\\u000a such as osteoarthritis (OA). Unfortunately, the poor bioavailability of AKBA following oral administration might limit the\\u000a anti-inflammatory efficacy of standardized Boswellia extract(s). To address this issue, we describe a

  10. Anti-inflammatory effects of enteral diet components on Crohn's disease-affected tissues in vitro

    Microsoft Academic Search

    D Meister; J Bode; A Shand; S Ghosh

    2002-01-01

    Background. The mechanism of action of elemental diet in Crohn's disease treatment, is unknown. Alteration of bacterial flora, low antigenicity, low fat content and improvement of nutritional status are postulated to play a role in the anti-inflammatory effect of elemental diet.Aim. To determine whether elemental diet or its modifications has a direct anti-inflammatory effect on colonic tissue biopsies in vitro.Patients

  11. Studies on the anti-inflammatory effect of fluoxetine in the rat

    Microsoft Academic Search

    Omar M. E Abdel-Salam; Ayman R Baiuomy; Mahmoud S Arbid

    2004-01-01

    The anti-inflammatory activity of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), was studied on the carrageenan-induced paw inflammation in the rat. Fluoxetine (10–60mgkg?1) given intraperitoneally (i.p.) 30min before carrageenan, displayed marked anti-inflammatory activity, inhibiting paw oedema by 38.6–77.7% at 2h post-carrageenan. Fluoxetine administered at time of carrageenan injection or 30min after carrageenan challenge, markedly inhibited the paw oedema response. Rats

  12. Anti-Inflammatory Effects of Synthetic Retinoids May Be Related to Their Immunomodulatory Action

    Microsoft Academic Search

    Ursula M. Ney; Ian J. Ball; Roger P. Hill; Donald Westmacott; David P. Bloxham

    1987-01-01

    The effects of retinoids have been studied in a model of delayed-type hypersensitivity using the T-cell-dependent antigen, methylated bovine serum albumin to elicit inflammation in the hind paws of mice. A number of synthetic retinoids, including etretinate and arotinoids, showed a marked anti-inflammatory action in this model. Using differential dosing schedules, the anti-inflammatory effect of retinoids was clearly distinguished from

  13. Anti-Inflammatory Effect of Hamamelis Lotion in a UVB Erythema Test

    Microsoft Academic Search

    B. J. Hughes-Formella; K. Bohnsack; F. Rippke; G. Benner; M. Rudolph; I. Tausch; J. Gassmueller

    1998-01-01

    Background: Although Hamamelis virginiana has long been used in the traditional treatment of skin diseases, there are few controlled clinical studies defining the extent of its anti-inflammatory action. Objective:The anti-inflammatory efficacy of pH5 Eucerin aftersun lotion with 10% hamamelis distillate, the vehicle and a prior aftersun formulation were tested in 30 healthy volunteers using a modified UVB erythema test as

  14. Enhanced anti-inflammatory effects of a nitric oxide–releasing derivative of mesalamine in rats

    Microsoft Academic Search

    John L. Wallace; Nathalie Vergnolle; Marcelo N. Muscará; Samuel Asfaha; Kevin Chapman; Webb McKnight; Piero Del Soldato; Antonio Morelli; Stefano Fiorucci

    1999-01-01

    Background & Aims: Nitric oxide (NO)-releasing derivatives of cyclooxygenase inhibitors exhibit enhanced anti-inflammatory activity and greatly reduced gastrointestinal toxicity. We evaluated whether a similar derivatization of mesalamine (5-aminosalicylic acid) would improve its anti-inflammatory activity. Methods: Effects of an NO-releasing derivative of mesalamine (NCX-456; NO-mesalamine) were compared with those of mesalamine itself and 2 other NO donors in a rat model

  15. Anti-inflammatory effect of Acacia visco extracts in animal models

    Microsoft Academic Search

    Ana María Pedernera; Teresita Guardia; Carola Elisa Guardia Calderón; Alejandra Ester Rotelli; Nadir Ernesto de la Rocha; José Roberto Saad; María Alejandra Lopez Verrilli; Susana Garcia Aseff; Lilian Eugenia Pelzer

    2010-01-01

    The aqueous and organic extracts of Acacia visco Lor. Ap Griseb (Fabaceae) were tested for anti-inflammatory activity in experimental models in rat. Besides, the free-radical\\u000a scavenging capacity of extracts from A. visco was determined. The extracts revealed anti-inflammatory effect against carrageenan-induced oedema, phospholipase A2-induced oedema, cotton pellet-induced granuloma and they did not show acute toxic effect. Among the class of

  16. In vivo anti-inflammatory effect and toxicological screening of Maytenus heterophylla and Maytenus senegalensis extracts

    Microsoft Academic Search

    G. da Silva; M. Taniça; J. Rocha; R. Serrano; E. T. Gomes; B. Sepodes; O. Silva

    2011-01-01

    Maytenus heterophylla (Eckl & Zeyh.) Robson and Maytenus senegalensis (Lam). Exell are two African medicinal plants used to treat painful and inflammatory diseases. We evaluated the in vivo (per os) anti-inflammatory activity of M. heterophylla leaf, stem and root extracts and of M. senegalensis leaf and stem extracts. Additionally, we assessed their in vivo acute and sub-acute toxicities. Anti-inflammatory activities

  17. Studies on the anti-inflammatory effects of clerodendron trichotomum thunberg leaves

    Microsoft Academic Search

    Jung-Ho Choi; Wan-Kyun Whang; Hong-Jin Kim

    2004-01-01

    Clerodendron trichotomum Thunberg Leaves (CTL) have been used for centuries in Chinese folk medicine for their anti-inflammatory\\u000a properties. We have studied the anti-inflammatory effects of CTL extracts in rats, mice and in Raw 264.7 cells. 1 mg\\/kg solutions\\u000a of the 30% and 60% methanol extracts of CTL were used and a 1 mg\\/kg of indomethacin was used as a positive

  18. Anti-inflammatory effect of Pinus sibirica oil extract in animal models

    Microsoft Academic Search

    Alexander N. Shikov; Olga N. Pozharitskaya; Valery G. Makarov; Marina N. Makarova

    2008-01-01

    The anti-inflammatory effect of the oil extract of seeds of Pinus sibirica Du Tour was evaluated and compared with phenylbutazone. Oral administration of this extract at a dose of 300 mg\\/kg showed\\u000a anti-inflammatory activity in the carrageenin-induced edema test in rats. In addition, P. sibirica oil extract showed analgesic properties in the hot-plate test and antipyretic properties in adjuvant-induced local hyperthermia,

  19. Antinociceptive and anti-inflammatory effects of Croton malambo bark aqueous extract

    Microsoft Academic Search

    Al??rica I Suárez; Reinaldo S Compagnone; Maria M Salazar-Bookaman; Stephen Tillett; Franco Delle Monache; Camilo Di Giulio; Gustavo Bruges

    2003-01-01

    Croton malambo (K.) bark aqueous extract, popularly known in Venezuela as “palomatias” or “torco” was tested for acute toxicity and for its anti-inflammatory and antinociceptive effects using tail flick and writhing syndrome tests models, respectively. Croton malambo aqueous extract (6.15mg\\/kg i.p.) administered intraperitoneally had a significant antinociceptive and anti-inflammatory effects compared to acetylsalicylic acid (200mg\\/kg p.o.) and sodium diclofenac (5.64mg\\/kg

  20. Lipoxins: Potential anti-inflammatory, proresolution, and antifibrotic mediators in renal disease

    Microsoft Academic Search

    Niamh E. Kieran; PAOLA MADERNA; CATHERINE GODSON

    2004-01-01

    Lipoxins: Potential anti-inflammatory, proresolution, and antifibrotic mediators in renal disease. Lipoxins are lipoxygenase-derived lipid mediators with both anti-inflammatory and proresolution properties that have been demonstrated in vivo and in vitro. The bioactivity profile of lipoxins in vitro suggests that they have therapeutic potential in acute renal failure and glomerulonephritis; predictions that have been borne out to date in experimental models

  1. Boswellic acids and glucosamine show synergistic effect in preclinical anti-inflammatory study in rats

    Microsoft Academic Search

    Surjeet Singh; Anamika Khajuria; Subhash Chandra Taneja; Ravi Kant Khajuria; Jaswant Singh; Ghulam Nabi Qazi

    2007-01-01

    The present study revealed the synergistic effect of boswellic acid mixture (BA) and glucosamine for anti-inflammatory and anti-arthritic activities in rats. Two studies were conducted, that is, acute anti-inflammatory by carrageenan edema and chronic anti-arthritic by Mycobacterium-induced developing arthritis. Five groups of animals were included in each of the study: the vehicle control, positive control (ibuprofen 100mg\\/kg), boswellic acids (250mg\\/kg),

  2. Antimicrobial, Antiparasitic, Anti-Inflammatory, and Cytotoxic Activities of Lopezia racemosa

    PubMed Central

    Cruz Paredes, Carla; Bolívar Balbás, Paulina; Juárez, Zaida Nelly; Sánchez Arreola, Eugenio; Hernández, Luis Ricardo

    2013-01-01

    The present study investigates the potential benefits of the Mexican medicinal plant Lopezia racemosa (Onagraceae). Extracts and fractions from aerial parts of this plant were assessed to determine their antibacterial, antifungal, antiparasitic, anti-inflammatory and cytotoxic activities in vitro. Aerial parts of the plant were extracted with various solvents and fractionated accordingly. Extracts and fractions were tested against a panel of nine bacterial and four fungal species. The antiparasitic activity was tested against Leishmania donovani, whereas the anti-inflammatory activity of the compounds was determined by measuring the secretion of interleukin-6 from human-derived macrophages. The same macrophage cell line was used to investigate the cytotoxicity of the compounds. Various extracts and fractions showed antibacterial, antifungal, antiparasitic, and anti-inflammatory activities. The hexanic fraction HF 11-14b was the most interesting fraction with antimicrobial, and anti-inflammatory activities. The benefit of L. racemosa as a traditional medicinal plant was confirmed as shown by its antibacterial, antifungal and anti-inflammatory activities. To the best of our knowledge, this is the first study reporting the biological activities of L. racemosa, including antiparasitic and anti-inflammatory activities. PMID:23843731

  3. Topical Anti-inflammatory Activity of New Hybrid Molecules of Terpenes and Synthetic Drugs.

    PubMed

    Theoduloz, Cristina; Delporte, Carla; Valenzuela-Barra, Gabriela; Silva, Ximena; Cádiz, Solange; Bustamante, Fernanda; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2015-01-01

    The aim of the study was to assess changes in the activity of anti-inflammatory terpenes from Chilean medicinal plants after the formation of derivatives incorporating synthetic anti-inflammatory agents. Ten new hybrid molecules were synthesized combining terpenes (ferruginol (1), imbricatolic acid (2) and oleanolic acid (3)) with ibuprofen (4) or naproxen (5). The topical anti-inflammatory activity of the compounds was assessed in mice by the arachidonic acid (AA) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) induced ear edema assays. Basal cytotoxicity was determined towards human lung fibroblasts, gastric epithelial cells and hepatocytes. At 1.4 µmol/mouse, a strong anti-inflammatory effect in the TPA assay was observed for oleanoyl ibuprofenate 12 (79.9%) and oleanoyl ibuprofenate methyl ester 15 (80.0%). In the AA assay, the best activity was observed for 12 at 3.2 µmol/mouse, with 56.8% reduction of inflammation, in the same range as nimesulide (48.9%). All the terpenyl-synthetic anti-inflammatory hybrids showed better effects in the TPA assay, with best activity for 6, 12 and 15. The cytotoxicity of the compounds 8 and 10 with a free COOH, was higher than that of 2. The derivatives from 3 were less toxic than the triterpene. Several of the new compounds presented better anti-inflammatory effect and lower cytotoxicity than the parent terpenes. PMID:26096431

  4. Synthesis and anti-inflammatory activity of alkyl/arylidene-2-aminobenzothiazoles and 1-benzothiazol-2-yl-3-chloro-4-substituted-azetidin-2-ones.

    PubMed

    Khedekar, Pramod B; Bahekar, Rajesh H; Chopade, Rajendra S; Umathe, Sudhir N; Rao, Akkinpalli Raghu Ram; Bhusari, Kishore P

    2003-01-01

    Ten new derivatives of 1-benzothiazol-2-yl-3-chloro-4-substituted-azetidin-2-ones (3a-j) were synthesized using various Schiff bases (alkyl/arylidene-2-aminobenzothiazoles; 2a-j), which in turn were prepared starting from 2-aminobenzothiazole (1). All the synthesised compounds were characterised by elemental analyses and spectral (IR, 1H-NMR, 13C-NMR and EI-MS) data. The title compounds 2a-j and 3a-j were screened in vivo using carrageenan-induced rat paw edema model. All the test compounds showed anti-inflammatory activity when tested in vivo. In general, compounds 3a-j were found to be more potent compared to compounds 2a-j. Among the compounds tested, compound 2g in the alkyl/arylidene-2-aminobenzothiazoles series and compound 3 g in the 1-benzothiazol-2-yl-3-chloro-4-substituted-azetidin-2-ones series were found to be the most potent. All the test compounds were also evaluated to check the gastric ulcer incidence. In gastric ulceration studies, all the test compounds were generally found to be safe at the 100 mg/kg dose level. Furthermore the most potent compounds 2 g and 3 g from each series were screened in vitro for inhibition of both COX-2 and COX-1 catalysed prostaglandin biosynthesis (radiochemical assay). Like most of the commercially available non-steroidal anti-inflammatory drugs (NSAIDs), in the in vitro study, compounds 2 g and 3 g showed anti-inflammatory activity by blocking the metabolism of arachidonic acid to prostaglandin via the cyclooxygenase pathways. In general, in the vitro assay, test compounds 2 g and 3 g were found to be more active after 15 min pre-incubation with the enzyme. Compound 3 g was found to be more COX-2 selective, while compound 2 g was found to be equally COX-2 and COX-1 selective. PMID:14558438

  5. Anti-inflammatory effects of the gorgonian Pseudopterogorgia elisabethae collected at the Islands of Providencia and San Andrés (SW Caribbean)

    PubMed Central

    Correa, Hebelin; Valenzuela, Alba Lucia; Ospina, Luis Fernando; Duque, Carmenza

    2009-01-01

    Background We are reporting for the first time the in vivo anti-inflammatory activity of extracts and fractions, and in vitro anti-inflammatory activity of pure compounds, all isolated from Pseudopterogorgia elisabethae collected at the Providencia (chemotype 1) and San Andrés (chemotype 2) Islands (SW Caribbean). Methods Extracts from P. elisabethae were fractionated on silica gel to yield fractions: F-1 (pseudopterosins PsQ, PsS and PsU) and F-2 (amphilectosins A and B, PsG, PsK, PsP and PsT and seco-pseudopterosins seco-PsJ and seco-PsK) from chemotype 1, and F-3 (elisabethatrienol, 10-acetoxy-9-hydroxy- and 9-acetoxy-10-hydroxy-amphilecta-8,10,12,14-tetraenes (interconverting mixture) and amphilecta-8(13),11,14-triene-9,10-dione) from chemotype 2. By using preparative RP-HPLC and spectroscopic means, we obtained the pure PsG, PsK, PsP, PsQ, PsS, PsT, PsU, seco-PsK and the interconverting mixture of non-glycosylated diterpenes (IMNGD). The anti-inflammatory properties of extracts and fractions were evaluated using in vivo model "12-O-tetradecanoyl-phorbol-acetate (TPA)-induced mouse ear oedema". The activities of pure compounds and of the IMNGD were evaluated using in vitro assays myeloperoxidase (MPO) release (by human polymorphonuclear neutrophils (PMNs)), nitric oxide release (by J-774 cells) and scavenger activity on NO. Results In the in vivo anti-inflammatory assay, extracts and F-3 showed low inhibition levels of inflammation compared to indomethacin, F-1 and F-2. Additionally, we evaluated the MPO release to the inflammation site, and found a marked inhibition of MPO levels by all extracts and fractions, even superior to the inhibition shown by indomethacin. Furthermore, in the MPO in vitro assay, IMNGD, PsQ, PsS, PsT and PsU, exhibited higher inhibition levels compared to dexamethasone and indomethacin. In the NO release in vitro, IMNGD, PsP and PsT were the most potent treatments. Finally, because the PsG, PsP and seco-PsK did not exhibit any NO scavenger activity, they should inhibit the inducible Nitric Oxide Synthase (iNOS) or other routes that influence this enzyme. Alternatively, PsQ, PsS, and PsU did show scavenger activity. Conclusion All results presented contribute to demonstrate that the compounds isolated in this work from P. elisabethae are promising molecules with an interesting anti-inflammatory activity profile. Additionally, the results obtained could provide preliminary insights towards their structure-activity relationship. PMID:19284567

  6. The effect of concomitantly administered antacids on the bioavailability of lornoxicam, a novel highly potent NSAID.

    PubMed

    Dittrich, P; Radhofer-Welte, S; Magometschnigg, D; Kukovetz, W R; Mayerhofer, S; Ferber, H P

    1990-01-01

    Antacids are used in the treatment of upper gastrointestinal side-effects during therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). Since pharmacokinetic interactions between antacids and NSAIDs have been reported, it was investigated whether aluminium and magnesium hydroxide (Maalox as oral suspension) or aluminium hydroxide and calcium carbonate (Solugastril as oral gel) influenced the bioavailability of Lornoxicam (rINN), a new potent NSAID from the chemical group of the oxicams. Eighteen male volunteers were given 4 mg of Lornoxicam as a film-coated tablet either alone or together with 10 ml of Maalox or 10 g of Solugastril in an open, randomized, three-way cross-over study. The levels of Lornoxicam in plasma were determined by HPLC following solid-phase extraction. It was found that none of the antacids changed significantly any of the following pharmacokinetic parameters: elimination half-life (t1/2 beta), concentration at peak time (Cmax), time to reach the peak (tmax) and area under the curve to infinity (AUCo-infinity). The results indicate that the concomitant administration of antacids did not influence the pharmacokinetic profile of Lornoxicam. Furthermore they confirm the short elimination half-life of Lornoxicam in man, which is markedly shorter than that of other oxicam-type compounds. PMID:2401187

  7. Amorfrutins Are Natural PPAR? Agonists with Potent Anti-inflammatory Properties.

    PubMed

    Fuhr, Luise; Rousseau, Morten; Plauth, Annabell; Schroeder, Frank C; Sauer, Sascha

    2015-05-22

    Amorfrutins are isoprenoid-substituted benzoic acid derivatives, which were found in Amorpha fruticosa L. (bastard indigo) and in Glycyrrhiza foetida Desf. (licorice). Recently, amorfrutins were shown to be selective activators of the nuclear receptor PPAR?. Here, we investigated the effects and PPAR?-based mechanisms of reducing inflammation in colon cells by treatment with amorfrutins. In TNF-?-stimulated colon cells amorfrutin A (1) reduced significantly the expression and secretion of several inflammation mediators, in part due to interaction with PPAR?. These results support the hypothesis that amorfrutins may have the potential to treat inflammation disorders such as chronic inflammatory bowel diseases. PMID:25938459

  8. Role of vascular inflammation in coronary artery disease: potential of anti-inflammatory drugs in the prevention of atherothrombosis. Inflammation and anti-inflammatory drugs in coronary artery disease.

    PubMed

    Moreira, Daniel Medeiros; da Silva, Roberto Leo; Vieira, Jefferson Luís; Fattah, Tammuz; Lueneberg, Maria Emilia; Gottschall, Carlos Antonio Mascia

    2015-02-01

    Coronary artery disease (CAD) and acute myocardial infarction (AMI) are inflammatory pathologies, involving interleukins (ILs), such as IL-1?, IL-6 and tumor necrosis factor (TNF)-?, and acute phase proteins production, such as for C reactive protein (CRP). The process begins with retention of low-density lipoprotein (LDL) and its oxidation inside the intima, with the formation of the "foam cells." Toll-like receptors and inflamassomes participate in atherosclerosis formation, as well as in the activation of the complement system. In addition to innate immunity, adaptive immunity is also associated with atherosclerosis through antigen-presenting cells, T and B lymphocytes. AMI also increases the expression of some ILs and promotes macrophage and lymphocyte accumulation. Reperfusion increases the expression of anti-inflammatory ILs (such as IL-10) and generates oxygen free radicals. Although CAD and AMI are inflammatory disorders, the only drugs with anti-inflammatory effect so far widely used in ischemic heart disease are aspirin and statins. Some immunomodulatory or immunosuppressive promising therapies, such as cyclosporine and colchicine, may have benefits in CAD. Methotrexate also has potential cardioprotective anti-inflammatory effects, through increased adenosine levels. The TETHYS trial (The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS trial) will evaluate low-dose methotrexate in ST elevation AMI. The CIRT (Cardiovascular Inflammation Reduction Trial), in turn, will evaluate low-dose methotrexate in patients with a high prevalence of subclinical vascular inflammation. The CANTOS (The Canakinumab Antiinflammatory Thrombosis Outcomes Study) will evaluate canakinumab in patients with CAD and persistently elevated CRP. The blockage of other potential targets, such as the IL-6 receptor, CC2 chemokine receptor and CD20, could bring benefits in CAD. PMID:25369900

  9. Anti-inflammatory effects of atorvastatin: Modulation by the T-786C polymorphism in the endothelial nitric oxide synthase gene

    Microsoft Academic Search

    Débora C. Souza-Costa; Valéria C. Sandrim; Lívia F. Lopes; Raquel F. Gerlach; Eduardo M. Rego; Jose E. Tanus-Santos

    2007-01-01

    Statins produce cholesterol-independent, anti-inflammatory effects, which result at least in part from increased endothelial nitric oxide production. These effects may be modulated by polymorphisms in the endothelial nitric oxide synthase (eNOS) gene. Here, we examined whether the T-786C polymorphism of eNOS gene affects the concentrations of markers of atherosclerosis and inflammation (sCD40L, sVCAM-1, sICAM-1, sP-selectin, MCP-1, high sensitivity (hs)-CRP, MMP-2,

  10. Effects of commonly used non steroidal anti-inflammatory drugs on gastric mucosa. A clinical, endoscopic and histopathological study.

    PubMed

    Misra, R; Pandey, H; Chandra, M; Chandra, M; Agarwal, P K; Pandeya, S N

    1990-09-01

    Non steroidal anti-inflammatory drugs (NSAIDS) are known to produce gastro-intestinal lesions. In the present work we found that aspirin, indomethacin and oxyphenbutazone caused gastric mucosal damage in 90.9%, 100% and 100% respectively, while ibuprofen and paracetamol caused damage in 33.3% and 37.5% of cases respectively. Thus the latter two drugs were much safer NSAIDs. Furthermore we demonstrated that endoscopic monitoring of patients on NSAIDs is a sensitive method for early detection of gastric mucosal damage. This monitoring may be particularly valuable in high risk subjects on NSAIDs. PMID:2266080

  11. Indomethacin/ibuprofen-like anti-inflammatory agents selectively potentiate the gamma-aminobutyric acid-antagonistic effects of several norfloxacin-like quinolone antibacterial agents on [35S]t-butylbicyclophosphorothionate binding.

    PubMed

    Squires, R F; Saederup, E

    1993-05-01

    Four piperazinoquinolone antibacterial drugs (norfloxacin, ciprofloxacin, enoxacin, and pipemidic acid), known to be gamma-aminobutyric acid (GABA) antagonists, fully reversed the inhibitory effect of GABA on [35S]t-butylbicyclophosphorothionate ([35S] TBPS) binding to rat brain membranes in vitro. Twelve indomethacin/ibuprofen-like arylalkanoic acid (AAA) anti-inflammatory drugs alone had no effect on [35S]TBPS binding, or on its inhibition by GABA, but potentiated the GABA-antagonistic effects of the four quinolones. Felbinac (4-biphenylacetic acid) was most potent in this respect (EC50 = 110 nM, together with 5 microM norfloxacin), followed by flurbiprofen > anirolac > metiazinic acid > tolmetin = ketoprofen = fenbufen = indomethacin > fenoprofen > ibuprofen = (+)-naproxen = sulindac. Other anti-inflammatory analgesic drugs, including aspirin, diclofenac, diflunisal, meclofenamic acid, mefenamic acid, nambumetone, phenacetin, piroxicam, and phenylbutazone, failed to potentiate the GABA-antagonistic effect of norfloxacin. Felbinac (1 microM) increased the GABA-antagonistic potencies of norfloxacin and enoxacin about 26-fold, while increasing those of ciprofloxacin and pipemidic acid 7-fold and 2.3-fold, respectively. Using subsaturating concentrations of the four quinolones, concentration-response curves for felbinac yielded EC50 values ranging from 110 nM with 5 microM norfloxacin to 1.3 microM with 100 microM pipemidic acid. Three other piperazinoquinolone antibacterial agents (amifloxacin, difloxacin, and fleroxacin) and four nonpiperazinoquinolone anti-bacterial agents (oxolinic acid, cinoxacin, nalidixic acid, and piromidic acid) were much weaker GABA antagonists and were not significantly potentiated by felbinac. All other known GABAA receptor blockers tested, including R 5135, pitrazepin, bicuculline, SR 95531, strychnine, D-tubocurarine, thebaine, securinine, theophylline, and caffeine, were not potentiated by felbinac. Our results suggest that norfloxacin and related piperazinoquinolones, acting at GABAA receptors, may induce a high affinity binding site for indomethacin/ibuprofen-like anti-inflammatory agents (the AAA site) that, when occupied, reciprocally increases the affinities of the quinolones for GABAA receptors. The AAA binding site may be a new site in the GABAA receptor complex. PMID:8388990

  12. Activation of TRPA1 channels by fenamate nonsteroidal anti-inflammatory drugs.

    PubMed

    Hu, Hongzhen; Tian, Jinbin; Zhu, Yingmin; Wang, Chunbo; Xiao, Rui; Herz, Jeffrey M; Wood, Jackie D; Zhu, Michael X

    2010-03-01

    Transient receptor potential A1 (TRPA1) forms nonselective cation channels implicated in acute inflammatory pain and nociception. The mechanism of ligand activation of TRPA1 may involve either covalent modification of cysteine residues or conventional reversible ligand-receptor interactions. For certain electrophilic prostaglandins, covalent modification has been considered as the main mechanism involved in their stimulatory effect on TRPA1. Because some nonsteroidal anti-inflammatory drugs (NSAIDs) are structural analogs of prostaglandins, we examined several nonelectrophilic NSAIDs on TRPA1 activation using electrophysiological techniques and intracellular Ca(2+) measurements and found that a selected group of NSAIDs can act as TRPA1 agonists. Extracellularly applied flufenamic, niflumic, and mefenamic acid, as well as flurbiprofen, ketoprofen, diclofenac, and indomethacin, rapidly activated rat TRPA1 expressed in Xenopus oocytes and human TRPA1 endogenously expressed in WI-38 fibroblasts. Similarly, the NSAID ligands activated human TRPA1 inducibly expressed in HEK293 cells, but the responses were absent in uninduced and parental HEK293 cells. The response to fenamate agonists was blocked by TRPA1 antagonists, AP-18, HC-030031, and ruthenium red. At subsaturating concentrations, the fenamate NSAIDs also potentiate the activation of TRPA1 by allyl isothiocyanate, cinnamaldehyde, and cold, demonstrating positive synergistic interactions with other well-characterized TRPA1 activators. Importantly, among several thermosensitive TRP channels, the stimulatory effect is specific to TRPA1 because flufenamic acid inhibited TRPV1, TRPV3, and TRPM8. We conclude that fenamate NSAIDs are a novel class of potent and reversible direct agonists of TRPA1. This selective group of TRPA1-stimulating NSAIDs should provide a structural basis for developing novel ligands that noncovalently interact with TRPA1 channels. PMID:19888597

  13. Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats

    PubMed Central

    Rubio-Ruiz, María Esther; Pérez-Torres, Israel; Diaz-Diaz, Eulises; Pavón, Natalia; Guarner-Lans, Verónica

    2014-01-01

    Aim: Metabolic syndrome (MS) and aging are low-grade systemic inflammatory conditions, and inflammation is a key component of endothelial dysfunction. The aim of this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) upon the vascular reactivity in aging MS rats. Methods: MS was induced in young male rats by adding 30% sucrose in drinking water over 6, 12, and 18 months. When the treatment was finished, the blood samples were collected, and aortas were dissected out. The expression of COX isoenzymes and PLA2 in the aortas was analyzed using Western blot analysis. The contractile responses of aortic rings to norepinephrine (1 ?mol/L) were measured in the presence or absence of different NSAIDs (10 ?mol/L for each). Results: Serum levels of pro-inflammatory cytokines (IL-6, TNF-?, and IL-1?) in control rats were remained stable during the aging process, whereas serum IL-6 in MS rats were significantly increased at 12 and 18 months. The levels of COX isoenzyme and PLA2 in aortas from control rats increased with the aging, whereas those in aortas from MS rats were irregularly increased with the highest levels at 6 months. Pretreatment with acetylsalicylic acid (a COX-1 preferential inhibitor), indomethacin (a non-selective COX inhibitor) or meloxicam (a COX-2 preferential inhibitor) decreased NE-induced contractions of aortic rings from MS rats at all the ages, with meloxicam being the most potent. Acetylsalicylic acid also significantly reduced the maximum responses of ACh-induced vasorelaxation of aortic rings from MS rats, but indomethacin and meloxicam had no effect. Conclusion: NSAIDs can directly affect vascular responses in aging MS rats. Understanding the effects of NSAIDs on blood vessels may improve the treatment of cardiovascular diseases and MS in the elders. PMID:25263337

  14. Toll-like receptors as a target of food-derived anti-inflammatory compounds.

    PubMed

    Shibata, Takahiro; Nakashima, Fumie; Honda, Kazuya; Lu, Yu-Jhang; Kondo, Tatsuhiko; Ushida, Yusuke; Aizawa, Koichi; Suganuma, Hiroyuki; Oe, Sho; Tanaka, Hiroshi; Takahashi, Takashi; Uchida, Koji

    2014-11-21

    Toll-like receptors (TLRs) play a key role in linking pathogen recognition with the induction of innate immunity. They have been implicated in the pathogenesis of chronic inflammatory diseases, representing potential targets for prevention/treatment. Vegetable-rich diets are associated with the reduced risk of several inflammatory disorders. In the present study, based on an extensive screening of vegetable extracts for TLR-inhibiting activity in HEK293 cells co-expressing TLR with the NF-?B reporter gene, we found cabbage and onion extracts to be the richest sources of a TLR signaling inhibitor. To identify the active substances, we performed activity-guiding separation of the principal inhibitors and identified 3-methylsulfinylpropyl isothiocyanate (iberin) from the cabbage and quercetin and quercetin 4'-O-?-glucoside from the onion, among which iberin showed the most potent inhibitory effect. It was revealed that iberin specifically acted on the dimerization step of TLRs in the TLR signaling pathway. To gain insight into the inhibitory mechanism of TLR dimerization, we developed a novel probe combining an isothiocyanate-reactive group and an alkyne functionality for click chemistry and detected the probe bound to the TLRs in living cells, suggesting that iberin disrupts dimerization of the TLRs via covalent binding. Furthermore, we designed a variety of iberin analogues and found that the inhibition potency was influenced by the oxidation state of the sulfur. Modeling studies of the iberin analogues showed that the oxidation state of sulfur might influence the global shape of the isothiocyanates. These findings establish the TLR dimerization step as a target of food-derived anti-inflammatory compounds. PMID:25294874

  15. Endoplasmic reticulum stress mediates the anti-inflammatory effect of ethyl pyruvate in endothelial cells.

    PubMed

    Wang, Ge; Liu, Kan; Li, Yue; Yi, Wei; Yang, Yang; Zhao, Dajun; Fan, Chongxi; Yang, Honggang; Geng, Ting; Xing, Jianzhou; Zhang, Yu; Tan, Songtao; Yi, Dinghua

    2014-01-01

    Ethyl pyruvate (EP) is a simple aliphatic ester of the metabolic intermediate pyruvate that has been demonstrated to be a potent anti-inflammatory agent in a variety of in vivo and in vitro model systems. However, the protective effects and mechanisms underlying the actions of EP against endothelial cell (EC) inflammatory injury are not fully understood. Previous studies have confirmed that endoplasmic reticulum stress (ERS) plays an important role in regulating the pathological process of EC inflammation. In this study, our aim was to explore the effects of EP on tumor necrosis factor-? (TNF-?)-induced inflammatory injury in human umbilical vein endothelial cells (HUVECs) and to explore the role of ERS in this process. TNF-? treatment not only significantly increased the adhesion of monocytes to HUVECs and inflammatory cytokine (sICAM1, sE-selectin, MCP-1 and IL-8) production in cell culture supernatants but it also increased ICAM and MMP9 protein expression in HUVECs. TNF-? also effectively increased the ERS-related molecules in HUVECs (GRP78, ATF4, caspase12 and p-PERK). EP treatment effectively reversed the effects of the TNF-?-induced adhesion of monocytes on HUVECs, inflammatory cytokines and ERS-related molecules. Furthermore, thapsigargin (THA, an ERS inducer) attenuated the protective effects of EP against TNF-?-induced inflammatory injury and ERS. The PERK siRNA treatment not only inhibited ERS-related molecules but also mimicked the protective effects of EP to decrease TNF-?-induced inflammatory injury. In summary, we have demonstrated for the first time that EP can effectively reduce vascular endothelial inflammation and that this effect at least in part depends on the attenuation of ERS. PMID:25470819

  16. Synthesis of N-arylidene-2-(2-Phenoxyphenyl) Acetohydrazides as Anti-Inflammatory Agents

    PubMed Central

    Shekarchi, Maral; Navidpour, Latifeh; Rajabi Khorami, Afshin; shekarchi, Mahtab; Partoazar, Alireza; Shafaroodi, Hamed; Rahmanipour, Narges; Shafiee, Abbas; Shekarchi, Maryam

    2011-01-01

    Diclofenac sodium has been used for its anti-inflammatory actions for about 28 years, but since all the non-steroidal anti-inflammatory drugs (NSAIDs) suffer from the lethal gastro intestinal (GI) toxicities, diclofenac sodium is not an exception. The free –COOH group is thought to be responsible for the GI toxicity associated with all traditional NSAIDs. In the present research, the main motto was to develop new chemical entities as potential anti-inflammatory agents with no GI toxicities. A new type of 2-(2-phenoxyphenyl) acetohydrazide possessing N-arylidene substituents, was synthesized for evaluation as anti-inflammatory agents. The starting material 2-(2-Phenoxyphenyl) acetohydrazide was synthesized from 2-phenoxybenzoic acid in several steps according to the previous published method. Various substituted arylidene-2-phenoxynicotinic acid hydrazide derivatives were synthesized by the reaction of hydrazide 17 with selected aldehydes and screened for their potential anti-inflammatory activity. The structure of synthesized compounds was confirmed by different nuclear magnetic resonance technique, Fourier transform infrared spectroscopy (FTIR) and Mass-spectrometry data format. Qualitative structure-activity relationship data, acquired using the carrageenan-induced rat paw edema assay, showed that this group of arylidene-2-phenoxybenzoic acid hydrazides exhibit anti-inflammatory activity with significant reduction of rat paw edema (17-58% reduction in inflammation at different time intervals) in comparison with control group and a moderate to good activity range in comparison with diclofenac as the reference drug. Compounds 9a, 9d and 9e exhibited the most prominent and consistent anti-inflammatory activity. The compound, N-(4-Chlorobenzylidene)-2-(2-phenoxyphenyl) acetohydrazide (9d), exhibited the most in-vivo activity (32-58% reduction in inflammation) compared to the reference drug diclofenac (35-74% reduction in inflammation) in a carrageenan induced rat paw-edema assay. PMID:24250367

  17. Anti-Inflammatory Action of an Antimicrobial Model Peptide That Suppresses the TRIF-Dependent Signaling Pathway via Inhibition of Toll-Like Receptor 4 Endocytosis in Lipopolysaccharide-Stimulated Macrophages

    PubMed Central

    Shim, Do-Wan; Heo, Kang-Hyuck; Kim, Young-Kyu; Sim, Eun-Jeong; Kang, Tae-Bong; Choi, Jae-Wan; Sim, Dae-Won; Cheong, Sun-Hee; Lee, Seung-Hong; Bang, Jeong-Kyu; Won, Hyung-Sik; Lee, Kwang-Ho

    2015-01-01

    Antimicrobial peptides (AMPs), also called host defense peptides, particularly those with amphipathic helical structures, are emerging as target molecules for therapeutic development due to their immunomodulatory properties. Although the antimicrobial activity of AMPs is known to be exerted primarily by permeation of the bacterial membrane, the mechanism underlying its anti-inflammatory activity remains to be elucidated. We report potent anti-inflammatory activity of WALK11.3, an antimicrobial model peptide with an amphipathic helical conformation, in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. This peptide inhibited the expression of inflammatory mediators, including nitric oxide, COX-2, IL-1?, IL-6, INF-?, and TNF-?. Although WALK11.3 did not exert a major effect on all downstream signaling in the MyD88-dependent pathway, toll-like receptor 4 (TLR4)- mediated pro-inflammatory signals were markedly attenuated in the TRIF-dependent pathway due to inhibition of the phosphorylation of STAT1 by attenuation of IRF3 phosphorylation. WALK11.3 specifically inhibited the endocytosis of TLR4, which is essential for triggering TRIF-mediated signaling in macrophage cells. Hence, we suggest that specific interference with TLR4 endocytosis could be one of the major modes of the anti-inflammatory action of AMPs. Our designed WALK11 peptides, which possess both antimicrobial and anti-inflammatory activities, may be promising molecules for the development of therapies for infectious inflammation. PMID:26017270

  18. Anti-inflammatory effects of Stephania tetrandra S. Moore on interleukin-6 production and experimental inflammatory disease models

    PubMed Central

    Kang, H-S.; Kim, Y-H.; Lee, C-S.; Lee, J-J.; Pyun, K-H.

    1996-01-01

    Deregulation of interleukin-6 (IL-6) expression caused the synthesis and release of many inflammatory mediators. It is involved in chronic inflammation, autoimmune diseases, and malignancy. Stephania tetrandra S. Moore is a Chinese medicinal herb which has been used traditionary as a remedy for neuralgia and arthritis in China. To investigate the anti-inflammatory effects of S. tetrandra S. Moore in vitro and in vivo, its effects on the production of IL-6 and inflammatory mediators were analysed. When human monocytes/macrophages stimulated with silica were treated with 0.1–10 ?g/ml S. tetranda S. Moore, the production of IL-6 was inhibited up to 50%. At these concentrations, it had no cytotoxicity effect on these cells. It also suppressed the production of IL-6 by alveolar macrophages stimulated with silica. In addition, it inhibited the release of superoxide anion and hydrogen peroxide from human monocytes/macrophages. To assess the anti-fibrosis effects of S. tetrandra S. Moore, its effects on in vivo experimental inflammatory models were evaluated. In the experimental silicosis model, IL-6 activities in the sera and in the culture supernatants of pulmonary fibroblasts were also inhibited by it. In vitro and in vivo treatment of S. tetrandra S. Moore reduced collagen production by rat lung fibroblasts and lung tissue. Also, S. tetrandra S. Moore reduced the levels of serum GOT and GPT in the rat cirrhosis model induced by CCL4, and it was effective in reducing hepatic fibrosis and nodular formation. Taken together, these data indicate that it has a potent anti-inflammatory and antifibrosis effect by reducing IL-6 production. PMID:18475741

  19. In vitro anti-inflammatory and antioxidant potential of Si-Miao-San, its modifications and pure compounds.

    PubMed

    Lower-Nedza, Agnieszka D; Kuess, Carmen; Zhao, Haiyu; Bian, Baolin; Brantner, Adelheid H

    2013-08-01

    The ancient Chinese prescription Si-Miao-San (SMS), which is widely used for the treatment of various diseases, e.g. rheumatic disorders, has been modified (m1SMS, m2SMS). The purpose of this study was to investigate the anti-inflammatory, antioxidant, and anti-tyrosinase effects of Si-Miao-San, of its two modifications, the component herbs, and its main pure ingredients. In vitro tyrosinase, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and lipid peroxidation (LPO) assays were carried out in order to determine the inhibitory potential of the samples. The traditionally applied decoctions as well as their fractions (n-hexane, DCM, n-BuOH) were tested for their activities in concentrations of 100 microg/mL and 400 microg/mL, and the pure compounds in a range 6.25 microg/mL to 100 microg/mL. In conclusion, the decoction of m2SMS exhibited strong antioxidant activity in the DPPH assay, while the decoction of the classical SMS formulation showed low activity. The present results have shown the modifications to be more efficient scavengers of free radicals, such as superoxide and peroxide radicals. In addition, the decoctions of the two modifications have been shown to be more potent tyrosinase inhibitors. These formulas may thus be used as antiinflammatory and anti-aging prescriptions, as they may help to prevent cell damage. This study clearly establishes the two modifications of Si-Miao-San as valuable sources of natural antioxidants and anti-inflammatory agents, and also as candidates in the search for modem pharmaceuticals. PMID:24079188

  20. In vivo evaluation of analgesic, anti-inflammatory, and neuropharmacological activities of the chemical constituent from Nepeta clarkei.

    PubMed

    Hussain, Javid; Rehman, Najeeb Ur; Al-Harrasi, Ahmed; Khan, Abdul Latif; Rizvi, Tania Shamim; Mohammad, Faryal Vali; Mehjabeen; Ali, Liaqat

    2015-06-01

    The plant species of genus Nepeta are used to treat various human diseases and for ornamental purposes as well. Nepethalate B (1) was isolated as a result of phytochemical investigations of Nepeta clarkei and was subjected in the present study for investigation of analgesic, anti-inflammatory, and central nervous system (CNS) depressant activities. The percentage inhibition in phase I of the acetic acid induced writhing test of compound 1 (dose of 0.1, 0.2 and 0.4 mg/kg of body weight) was 53.3, 58.0 and 86.7 % respectively. These results were found significantly higher (P < 0.01) as compared to the negative control. Moreover, the percentage inhibitions of three phases for 0.1, 0.2 and 0.4 mg/kg were higher than the values obtained for Aspirin (positive control). In formalin test, the percentage pain inhibition between 0 and 5 min (early phase) was 68.0, 25.5, and 75.5 % for 0.1, 0.2 and 0.4 mg/kg intra-peritoneal doses of compound 1 respectively. In case of late phase (20-30 min) it was 63.0, 66.7 and 48.1 %, respectively. In comparison to aspirin, overall percentage inhibition of compound 1 was significantly higher in early and late phases. Interestingly, at all doses compound 1 showed more potent anti-inflammatory effects in terms of intensity and duration as compared to aspirin. The gross behavioral study of nepethalate B (1) was also carried out and the results revealed that it exhibited CNS depression in the mice and showed a prominent decrease in locomotor activity. PMID:25245563

  1. Anti-inflammatory and antioxidant activities of the nonlipid (aqueous) components of sesame oil: potential use in atherosclerosis.

    PubMed

    Selvarajan, Krithika; Narasimhulu, Chandrakala Aluganti; Bapputty, Reena; Parthasarathy, Sampath

    2015-04-01

    Dietary intervention to prevent inflammation and atherosclerosis has been a major focus in recent years. We previously reported that sesame oil (SO) was effective in inhibiting atherosclerosis in low-density lipoprotein-receptor negative mice. We also noted that the levels of many proinflammatory markers were lower in the SO-treated animals. In this study we tested whether the non-lipid, aqueous components associated with SO would have anti-inflammatory and antioxidant effects. Polymerase chain reaction array data indicated that sesame oil aqueous extract (SOAE) was effective in reducing lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells. Expression of inflammatory cytokines such as interleukin (IL)-1?, IL-6, and tumor necrosis factor ? (TNF-?) was also analyzed independently in cells pretreated with SOAE followed by inflammatory assault. Effect of SOAE on TNF-?-induced MCP-1 and VCAM1 expression was also tested in human umbilical vein endothelial cells. We observed that SOAE significantly reduced inflammatory markers in both macrophages and endothelial cells in a concentration-dependent manner. SOAE was also effective in inhibiting LPS-induced TNF-? and IL-6 levels in vivo at different concentrations. We also noted that in the presence of SOAE, transcription and translocation of NF-kappaB was suppressed. SOAE was also effective in inhibiting oxidation of lipoproteins in vitro. These results suggest the presence of potent anti-inflammatory and antioxidant compounds in SOAE. Furthermore, SOAE differentially regulated expression of scavenger receptors and increased ATP-binding cassette A1 (ABCA1) mRNA expression by activating liver X receptors (LXRs), suggesting additional effects on lipid metabolism. Thus, SOAE appears multipotent and may serve as a valuable nonpharmacological agent in atherosclerosis and other inflammatory diseases. PMID:25692333

  2. Chloroformic and Methanolic Extracts of Olea europaea L. Leaves Present Anti-Inflammatory and Analgesic Activities

    PubMed Central

    Chebbi Mahjoub, R; Khemiss, M.; Dhidah, M.; Dellaï, A.; Bouraoui, A.; Khemiss, F.

    2011-01-01

    Olea europaea L. is used in traditional medicine in the Mediterranean areas. Its natural products are used in the treatment of different disorders, like fighting fever and some infectious diseases such as malaria, the treatment of arrhythmia, and relief of intestinal spasms. The aim of the current study is to investigate the possible anti-inflammatory and anatinociceptive effects of methanol and chloroformic extracts prepared from leaves of Olea europaea L. The anti-inflammatory and antinociceptive effects of the different extracts of Olea europaea leaves were assessed after intraperitoneal administration into rats and mice, using the carrageenan-induced paw edema model in rats to test the anti-inflammatory effect and the acetic acid-induced writhing in mice to test the analgesic effect. The chloroformic and methanolic leaves extracts, studied at the doses of 50, 100, and 200?mg/kg (Body Weight: BW), exhibited significant dose-dependent anti-inflammatory and analgesic activities. Based on the results obtained, it can be concluded that Olea europaea leaves extracts have anti-inflammatory and antinociceptive effects. PMID:22084717

  3. A Systematic Review for Anti-Inflammatory Property of Clusiaceae Family: A Preclinical Approach

    PubMed Central

    de Melo, Mônica Santos; Quintans, Jullyana de Souza Siqueira; Araújo, Adriano Antunes de Souza; Duarte, Marcelo Cavalcante; Bonjardim, Leonardo Rigoldi; Moraes, Valéria Regina de Souza; de Araújo-Júnior, João Xavier

    2014-01-01

    Background. Clusiaceae family (sensu lato) is extensively used in ethnomedicine for treating a number of disease conditions which include cancer, inflammation, and infection. The aim of this review is to report the pharmacological potential of plants of Clusiaceae family with the anti-inflammatory activity in animal experiments. Methods. A systematic review about experiments investigating anti-inflammatory activity of Clusiaceae family was carried out by searching bibliographic databases such as Medline, Scopus and Embase. In this update, the search terms were “anti-inflammatory agents,” “Clusiaceae,” and “animals, laboratory.” Results. A total of 255 publications with plants this family were identified. From the initial 255 studies, a total of 21 studies were selected for the final analysis. Studies with genera Allanblackia, Clusia, Garcinia or Rheedia, and Hypericum showed significant anti-inflammatory activity. The findings include a decrease of total leukocytes, a number of neutrophils, total protein concentration, granuloma formation, and paw or ear edema formation. Other interesting findings included decreased of the MPO activity, and inflammatory mediators such as NF-?B and iNOS expression, PGE2 and Il-1? levels and a decrease in chronic inflammation. Conclusion. The data reported suggests the anti-inflammatory effect potential of Clusiaceae family in animal experiments. PMID:24976853

  4. Anti-inflammatory sesquiterpene lactones from Lychnophora trichocarpha Spreng. (Brazilian Arnica).

    PubMed

    Ferrari, Fernanda C; Ferreira, Leidiane C; Souza, Maíra R; Grabe-Guimarães, Andrea; Paula, Carmen A; Rezende, Simone A; Saúde-Guimarães, Dênia A

    2013-03-01

    The aerial parts of Lychnophora trichocarpha Spreng. (Asteraceae) are used macerated in water or ethanol to treat inflammation, pain, rheumatism, contusions, bruises and insect bites in Brazilian traditional medicine. In this study, anti-inflammatory activity of ethanol extract from aerial parts of L. trichocarpha and its ethyl acetate fraction was investigated. Sesquiterpene lactones, lychnopholide (Lyc) and eremantholide C (EreC), isolated of ethyl acetate fraction, were also assayed for in vitro and in vivo anti-inflammatory activity. Topical treatment with ointments containing ethanol extract, its ethyl acetate fraction and sesquiterpene lactones significantly reduced carrageenan-induced mice paw oedema. In vitro assays demonstrated that Lyc inhibited interferon -?/lipopolysaccharide -stimulated nitric oxide (NO) production in J774A.1 macrophages and increased production of IL-10 anti-inflammatory cytokine. The reduction of tumor necrosis factor-? (TNF-?) production by EreC was accompanied by an increased production of IL-10 in a concentration-dependent manner in J774A.1 macrophages. The anti-inflammatory effect of Lyc seems to involve the inhibition of production of NO and increased production of IL-10. The mechanism of the effect of EreC on the reduction of carrageenan-induced paw oedema may be attributed to inhibition of production of TNF-? and stimulation of IL-10 production. The results corroborate the use of ethanol extract from Lychnophora trichocarpha in folk medicine for anti-inflammatory action and indicate that the topical route is suitable for use. PMID:22619042

  5. Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells

    PubMed Central

    Coleman, Paul R.; Chang, Garry; Hutas, Gabor; Grimshaw, Matthew; Vadas, Mathew A.; Gamble, Jennifer R.

    2013-01-01

    Age is the greatest risk factor for cardiovascular disease. In addition, inflammation and age (senescence) have been linked at both the clinical and molecular levels. In general, senescent cells have been described as pro-inflammatory based on their senescence associated secretory phenotype (SASP). However, we have previously shown that senescence induced by overexpression of SENEX (or ARHGAP18), in endothelial cells results in an anti-inflammatory phenotype. We have investigated, at the individual cellular level, the senescent phenotype of endothelial cells following three of the chief signals associated with ageing; oxidative stress, disturbed flow and hypoxia. All three stimuli induce senescence and, based on neutrophil adhesion and expression of the adhesion molecules E-selectin and VCAM-1, a population of senescent cells is seen that is resistant to inflammatory stimuli and thus we define as anti-inflammatory. The proportion of anti-inflammatory cells increases with time but remains stable at approximately 50% by eight days after induction of senescence, suggesting that these are stable phenotypes of endothelial cell senescence. Similar to other senescent cell types, p38MAPK blockade inhibits the development of the pro-inflammatory phenotype but unique to EC, there is a corresponding increase in the number of anti-inflammatory senescent cells. Thus stress-induced senescent endothelial cells display a mosaic of inflammatory phenotypes. The anti-inflammatory population suggests that senescent endothelial cells may have an unique protective role, to inhibit uncontrolled proliferation and to limit the local inflammatory response. PMID:24334613

  6. Anti-inflammatory and arthritic effects of thiacremonone, a novel sulfurcompound isolated from garlic via inhibition of NF-?B

    Microsoft Academic Search

    Jung Ok Ban; Ju Hoon Oh; Tae Myoung Kim; Dae Joong Kim; Heon-Sang Jeong; Sang Bae Han; Jin Tae Hong

    2009-01-01

    INTRODUCTION: Sulfur compounds isolated from garlic exert anti-inflammatory properties. We recently isolated thiacremonone, a novel sulfur compound from garlic. Here, we investigated the anti-inflammatory and arthritis properties of thiacremonone through inhibition of NF-?B since NF-?B is known to be a target molecule of sulfur compounds and an implicated transcription factor regulating inflammatory response genes. METHODS: The anti-inflammatory and arthritis effects

  7. Anti-inflammatory functions of Houttuynia cordata Thunb. and its compounds: A perspective on its potential role in rheumatoid arthritis

    PubMed Central

    LI, JUN; ZHAO, FUTAO

    2015-01-01

    The aim of this review was to take a look at the anti-inflammatory functions of Houttuynia cordata Thunb. (HCT) that have been illustrated in the literature and to explore new fields in which HCT could be used in the future. The use of HCT has been described in broad inflammatory domains, where it has exhibited a variety of activities, including antiviral, antibacterial, antiparasitic and immunostimulant activity, with high efficiency, mild features and definite therapeutic effects. The numerous anti-inflammatory functions of HCT have demonstrated that HCT has wide application prospects. New uses of HCT and the full extent of its utilization await further investigation. The basic pathological change of rheumatoid arthritis (RA) is synovial proliferation which leads to joint destruction in the long-term. There are types of drugs that have been used clinically for patients with RA, however, due to their side-effects or high prices their broad usage is limited. A safe and low-cost drug is urgently required to be developed for the clinical usage of patients with RA. Thus, HCT has the potential to be a good candidate in the treatment of rheumatoid arthritis. PMID:26170903

  8. Synthesis and sar study of diarylpentanoid analogues as new anti-inflammatory agents.

    PubMed

    Leong, Sze Wei; Faudzi, Siti Munirah Mohd; Abas, Faridah; Aluwi, Mohd Fadhlizil Fasihi Mohd; Rullah, Kamal; Wai, Lam Kok; Bahari, Mohd Nazri Abdul; Ahmad, Syahida; Tham, Chau Ling; Shaari, Khozirah; Lajis, Nordin H

    2014-01-01

    A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-?)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83, 84, 86, 88 and 97) exhibited greater or similar NO inhibitory activity in comparison with curcumin (14.7 ± 0.2 µM), notably compounds 88 and 97, which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 µM and 9.6 ± 0.5 µM, respectively. A structure-activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta- and para-positions of ring-B could be the marker for highly active diarylpentanoid derivatives. PMID:25302700

  9. Phytochemical analysis, antioxidant and anti-inflammatory activity of calyces from Physalis peruviana.

    PubMed

    Toro, Reina M; Aragón, Diana M; Ospina, Luis F; Ramos, Freddy A; Castellanos, Leonardo

    2014-11-01

    Physalis peruviana calyces are used extensively in folk medicine. The crude ethanolic extract and some fractions of calyces were evaluated in order to explore antioxidant and anti-inflammatory activities. The anti-inflammatory activity was evaluated by the TPA-induced ear edema model. The antioxidant in vitro activity was measured by means of the superoxide and nitric oxide scavenging activity of the extracts and fractions. The butanolic fraction was found to be promising due to its anti-inflammatory and antioxidant activities. Therefore, a bio-assay guided approach was employed to isolate and identify rutin (1) and nicotoflorin (2) from their NMR spectroscopic and MS data. The identification of rutin in calyces of P. peruviana supports the possible use of this waste material for phytotherapeutic, nutraceutical and cosmetic preparations. PMID:25532284

  10. Antinociceptive and anti-inflammatory activities of a pomegranate (Punica granatum L.) extract rich in ellagitannins.

    PubMed

    González-Trujano, María Eva; Pellicer, Francisco; Mena, Pedro; Moreno, Diego A; García-Viguera, Cristina

    2015-06-01

    Pomegranate (Punica granatum L.) has been used for centuries for the treatment of inflammatory diseases. However, there is a lack of comprehensive information focused on the properties of a certain pomegranate (poly)phenolic profile to cure pain and gastric injury induced by anti-inflammatory drugs. This study investigated the systemic effects of different doses of a HPLC-characterized pomegranate extract on the formalin-induced nociceptive behavior in mice. The effect of the extract against gastric injury caused by non-steroidal anti-inflammatory drugs and ethanol was also assessed. Pomegranate reduced nociception in both phases of the formalin test, suggesting central and peripheral activities to inhibit nociception. Indomethacin-induced gastric injury was not produced in the presence of pomegranate, which also protected against ethanol-induced gastric lesions. The present results reinforce the benefits of pomegranate (poly)phenolics in the treatment of pain as well as their anti-inflammatory properties. PMID:25822007

  11. Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L.

    PubMed Central

    Kim, Wan-Su; Choi, Woo Jin; Lee, Sunwoo; Kim, Woo Joong; Lee, Dong Chae; Sohn, Uy Dong; Shin, Hyoung-Shik

    2015-01-01

    The anti-inflammatory, antioxidant, and antimicrobial properties of artemisinin derived from water, methanol, ethanol, or acetone extracts of Artemisia annua L. were evaluated. All 4 artemisinin-containing extracts had anti-inflammatory effects. Of these, the acetone extract had the greatest inhibitory effect on lipopolysaccharide-induced nitric oxide (NO), prostaglandin E2 (PGE2), and proinflammatory cytokine (IL-1? , IL-6, and IL-10) production. Antioxidant activity evaluations revealed that the ethanol extract had the highest free radical scavenging activity, (91.0±3.2%), similar to ?-tocopherol (99.9%). The extracts had antimicrobial activity against the periodontopathic microorganisms Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum subsp. animalis, Fusobacterium nucleatum subsp. polymorphum, and Prevotella intermedia. This study shows that Artemisia annua L. extracts contain anti-inflammatory, antioxidant, and antimicrobial substances and should be considered for use in pharmaceutical products for the treatment of dental diseases. PMID:25605993

  12. Analgesic and Anti-inflammatory action of Opuntia elatior Mill fruits

    PubMed Central

    Chauhan, Sanjay P.; Sheth, Navin R.; Suhagia, Bhanubhai N.

    2015-01-01

    Background: Opuntia elatio Mill is a xerophytic plant with potentially active nutrients. It is traditionally appreciated for its pharmacological properties; however, the scientific information on this plant is insufficient. Objective: The present study evaluates the antinociceptive and anti-inflammatory action of prickly pear. Materials and Methods: Writhing and tail-immersion tests were carried out to evaluate analgesic action, while the carrageenan-induced paw edema and neutrophil adhesion tests were conducted in Albino wistar rats to assess anti-inflammatory action. Results: ED50 values of the fruit juice in writhing, tail immersion, and paw edema test were 0.919, 2.77, and 9.282 ml/kg, respectively. The fruits of Opuntia produced analgesic and anti-inflammatory action in a dose-dependent manner. Conclusion: The results establish the folklore use of prickly pear may be due to the presence of betacyanin and/or other phenolic compounds.

  13. ?-Amino acid and amino-alcohol conjugation of a nonsteroidal anti-inflammatory drug (NSAID) imparts hydrogelation displaying remarkable biostability, biocompatibility, and anti-inflammatory properties.

    PubMed

    Majumder, Joydeb; Das, Mahua Rani; Deb, Jolly; Jana, Siddhartha Sankar; Dastidar, Parthasarathi

    2013-08-13

    A well-known nonsteroidal anti-inflammatory drug (NSAID), namely, naproxen (Np), was conjugated with ?-alanine and various combinations of amino alcohols and l-alanine. Quite a few bioconjugates, thus synthesized, were capable of gelling pure water, NaCl solution (0.9 wt %), and phosphate-buffered saline (PBS) (pH 7.4). The hydrogels were characterized by rheology and electron microscopy. Hydrogelation was probed by FT-IR and temperature-variable (1)H NMR studies. Single-crystal X-ray diffraction (SXRD) of a nonhydrogelator and a hydrogelator in the series established a useful structure-property (gelation) correlation. MTT assay of the hydrogelators in the mouse macrophage RAW 264.7 cell line showed excellent biocompatibility. The prostaglandin E2 (PGE2) assay of the hydrogelators revealed their anti-inflammatory response, which was comparable to that of the parent NSAID naproxen sodium (Ns). PMID:23859562

  14. Nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and gastrointestinal injury: contrasting interactions in the stomach and small intestine.

    PubMed

    Marlicz, Wojciech; Loniewski, Igor; Grimes, David S; Quigley, Eamonn M

    2014-12-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) are among the most frequently prescribed groups of drugs worldwide. The use of NSAIDs is associated with a high number of significant adverse effects. Recently, the safety of PPIs has also been challenged. Capsule endoscopy studies reveal that even low-dose NSAIDs are responsible for gut mucosal injury and numerous clinical adverse effects, for example, bleeding and anemia, that might be difficult to diagnose. The frequent use of PPIs can exacerbate NSAID-induced small intestinal injury by altering intestinal microbiota. Thus, the use of PPI is considered to be an independent risk factor associated with NSAID-associated enteropathy. In this review, we discuss this important clinical problem and review relevant aspects of epidemiology, pathophysiology, and management. We also present the hypothesis that even minor and subclinical injury to the intestinal mucosa can result in significant, though delayed, metabolic consequences, which may seriously affect the health of an individual. PubMed was searched using the following key words (each key word alone and in combination): gut microbiota, microbiome, non-steroidal anti inflammatory drugs, proton pump inhibitors, enteropathy, probiotic, antibiotic, mucosal injury, enteroscopy, and capsule endoscopy. Google engine search was also carried out to identify additional relevant articles. Both original and review articles published in English were reviewed. PMID:25440891

  15. Antinocieptive and anti-inflammatory effects of Toddalia asiatica (L) Lam. (Rutaceae) root extract in Swiss albino mice

    PubMed Central

    Kariuki, Hellen Nyambura; Kanui, Titus Ikusya; Yenesew, Abiy; Patel, Nilesh; Mbugua, Paul Mungai

    2013-01-01

    Introduction Toddalia asiatica is a commonly used medicinal plant in East Africa for the management of pain and inflammatory conditions. The present study investigated the antinociceptive and the anti-inflammatory effects of T. asiatica in Swiss albino mice. Methods The antinociceptive and the anti-inflammatory effects of T. asiatica were investigated using formalin-induced pain test and the carrageenin-induced oedema paw. The extract solvent (vehicle), aspirin and indomethacin were employed as negative and positive controls respectively. Eight mice were used in each experiment. Results In the early phase of the formalin test, the 100mg/kg dose showed no significant antinociceptive activity while the 200mg/kg showed significant (p < 0.01) antinociceptive activity. The 100 mg/kg dose showed highly significant antinociceptive activity (p < 0.001) in the late phase of the formalin test while the 200mg/kg dose showed no significant antinociceptive activity. A reduction in carragenin induced acute inflammation paw oedema was significant (p < 0.01) following administration of 100mg/kg dose but not with the 200mg/kg dose. Conclusion The present study therefore lends support to the anecdotal evidence for use of T. asiatica in the management of painful and inflammatory conditions. PMID:23734278

  16. The effects of COX-2 anti-inflammatory drugs on soft tissue healing: a review of the literature.

    PubMed

    Randelli, Pietro; Randelli, F; Cabitza, P; Vaienti, L

    2010-01-01

    COX-2 specific inhibitors (coxibs) have become a popular treatment for musculoskeletal disorders given that the incidence of gastrointestinal side effects is lower with these drugs than with traditional non-steroidal anti-inflammatory drugs. The aim of this review is to discuss the results of animal studies investigating the role of coxibs in the healing of soft tissues. MEDLINE was searched (years 2001-2009) for studies analyzing the effect of coxibs on the healing of soft tissues. There are relatively few data in the literature suggesting that coxibs can impair soft tissue healing and the data existing have the limitation of having been generated in animal studies. In fact, the method of administration and the doses used make it difficult to translate these results to the clinical setting. Short-term use of coxibs following lesions to ligaments or tendons remains a prudent choice. Traditional anti-inflammatory drugs are a safer treatment for patients with a high cardiovascular risk. These drugs should, however, be evaluated carefully with regards to gastrointestinal events and their still poorly defined effect on tissue healing. PMID:20487623

  17. Flavonoid-modified surfaces: multifunctional bioactive biomaterials with osteopromotive, anti-inflammatory, and anti-fibrotic potential.

    PubMed

    Córdoba, Alba; Satué, María; Gómez-Florit, Manuel; Hierro-Oliva, Margarita; Petzold, Christiane; Lyngstadaas, Staale P; González-Martín, María Luisa; Monjo, Marta; Ramis, Joana M

    2015-03-11

    Flavonoids are small polyphenolic molecules of natural origin with antioxidant, anti-inflammatory, and antibacterial properties. Here, a bioactive surface based on the covalent immobilization of flavonoids taxifolin and quercitrin on titanium substrates is presented, using (3-aminopropyl)triethoxysilane (APTES) as coupling agent. FTIR and XPS measurements confirm the grafting of the flavonoids to the surfaces. Using 2-aminoethyl diphenylborinate (DPBA, a flavonoid-specific dye), the modified surfaces are imaged by fluorescence microscopy. The bioactivity of the flavonoid-modified surfaces is evaluated in vitro with human umbilical cord derived mesenchymal stem cells (hUC-MSCs) and human gingival fibroblasts (HGFs) and compared to that of simple flavonoid coatings prepared by drop casting. Flavonoid-modified surfaces show anti-inflammatory and anti-fibrotic potential on HGF. In addition, Ti surfaces covalently functionalized with flavonoids promote the differentiation of hUC-MSCs to osteoblasts--enhancing the expression of osteogenic markers, increasing alkaline phosphatase activity and calcium deposition; while drop-casted surfaces do not. These findings could have a high impact in the development of advanced implantable medical devices like bone implants. Given the broad range of bioactivities of flavonoid compounds, these surfaces are ready to be explored for other biomedical applications, e.g., as stent surface or tumor-targeted functionalized nanoparticles for cardiovascular or cancer therapies. PMID:25335455

  18. Analgesic and anti-inflammatory activities of a fraction rich in gaultherin isolated from Gaultheria yunnanensis (FRANCH.) REHDER.

    PubMed

    Zhang, Bin; Li, Jian-Bei; Zhang, Dong-Ming; Ding, Yi; Du, Guan-Hua

    2007-03-01

    The analgesic and anti-inflammatory activities of a salicylate derivatives fraction (SDF) isolated from Gaultheria yunnanensis (FRANCH.) REHDER and the mechanisms of actions were investigated in the present study. The major constituent of SDF, which represented around 50% of this fraction, was a methyl salicylate diglycoside named gaultherin. SDF showed a significant inhibition on the hind paw edema in rats (200, 400 mg/kg body wt., p.o.) and ear swelling in mice (200, 400, 800 mg/kg body wt., p.o.) caused by carrageenin and croton oil, respectively. In addition, SDF (400, 800 mg/kg body wt., p.o.) inhibited only the second phase (inflammatory) in the formalin test, and showed no effect in the hot-plate test in mice. The antinociceptive activity of SDF was predominantly peripheral and independent of the opioid system. These findings demonstrate that SDF from Gaultheria yunnanensis (FRANCH.) REHDER possesses analgesic and anti-inflammatory activities, which may be mediated, at least partly, through the suppression of inflammatory mediators or their release suggested by the animal experiment. The observed effects of SDF are probably due to the presence of high content of salicylate derivatives (80%), including gaultherin, MSTG-A and MSTG-B. PMID:17329839

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

    PubMed Central

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

    2012-01-01

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

  20. Genetically Engineered Immunomodulatory Streptococcus thermophilus Strains Producing Antioxidant Enzymes Exhibit Enhanced Anti-Inflammatory Activities

    PubMed Central

    del Carmen, Silvina; de Moreno de LeBlanc, Alejandra; Martin, Rebeca; Chain, Florian; Langella, Philippe; Bermúdez-Humarán, Luis G.

    2014-01-01

    The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti-inflammatory activities. PMID:24242245

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

    PubMed

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

    2015-05-01

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

  2. Anti-inflammatory macrophages improve skeletal muscle recovery from ischemia-reperfusion.

    PubMed

    Hammers, David W; Rybalko, Viktoriya; Merscham-Banda, Melissa; Hsieh, Pei-Ling; Suggs, Laura J; Farrar, Roger P

    2015-04-15

    The presence of macrophages (MPs) is essential for skeletal muscle to properly regenerate following injury. The aim of this study was the evaluation of MP profiles and their importance in skeletal muscle recovering from tourniquet-induced ischemia-reperfusion (I/R). Using flow cytometry, we identified two distinct CD11b(+) MP populations that differ in expression of the surface markers Ly-6C and F4/80. These populations are prominent at 3 and 5 days of reperfusion and molecularly correspond to inflammatory and anti-inflammatory MP phenotypes. Sorted MP populations demonstrated high levels of IGF-I expression, and whole muscle post-I/R IGF-I expression strongly correlates with F4/80 expression. This suggests MPs largely influence postinjury IGF-I upregulation. We additionally demonstrate that direct intramuscular injection of FACS-isolated CD11b(+)Ly-6C(lo)F4/80(hi) MPs improves the functional and histological recovery of I/R-affected muscle. Taken together, these data further support the substantial influence of the innate immune system on muscle regeneration and suggest MP-focused therapeutic approaches may greatly facilitate skeletal muscle recovery from substantial injury. PMID:25678696

  3. Anti-inflammatory and free radial scavenging activities of the constituents isolated from Machilus zuihoensis.

    PubMed

    Mao, Yi-Wen; Tseng, Hsiang-Wen; Liang, Wen-Li; Chen, Ih-Sheng; Chen, Shui-Tein; Lee, Mei-Hsien

    2011-01-01

    A new biflavonol glycoside, quercetin-3-O-?-D-glucopyranoside-(3'?O-3''')-quercetin-3-O-?-D-galactopyranoside (9), together with eight known compounds was isolated for the first time from the leaves of Machilus zuihoensis Hayata (Lauraceae). The structure of compound 9 was elucidated by various types of spectroscopic data analysis. Analysis of the biological activity assay found that compound 9 showed significant superoxide anion scavenging activity (IC?? is 30.4 ?M) and markedly suppressed LPS-induced high mobility group box 1 (HMGB-1) protein secretion in RAW264.7 cells. In addition, the HMGB-1 protein secretion was also inhibited by quercitrin (3), ethyl caffeate (6), and ethyl 3-O-caffeoylquinate (7) treatment. In the LPS-stimulated inducible nitric oxide synthase (iNOS) activation analysis, two known compounds, quercetin (1) and ethyl caffeate (6), were found to markedly suppress nitric oxide (NO) production (IC?? value, 27.6 and 42.9 ?M, respectively) in RAW264.7 cells. Additionally, it was determined that ethyl caffeate (6) down-regulated mRNA expressions of iNOS, IL-1?, and IL-10 in the LPS-treatment of RAW264.7 cells via a suppressed NF-kB pathway. These results suggested for the first time that the new compound 9 and other constituents isolated from M. zuihoensis have potential anti-inflammatory and superoxide anion scavenging effects. These constituents may be useful for treating various inflammatory diseases. PMID:22075574

  4. Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review.

    PubMed

    White, C Roger; Garber, David W; Anantharamaiah, G M

    2014-10-01

    Reduced levels of HDL cholesterol (HDL-C) are a strong independent predictor of coronary artery disease (CAD) risk. The major anti-atherogenic function of HDL is to mediate reverse cholesterol transport. This response is highly dependent on apoA-I and apoE, protein components of HDL. Randomized clinical trials have assessed effects of several classes of drugs on plasma cholesterol levels in CAD patients. Agents including cholestyramine, fibrates, niacin, and statins significantly lower LDL cholesterol (LDL-C) and induce modest increases in HDL-C, but tolerance issues and undesirable side effects are common. Additionally, residual risk may be present in patients with persistently low HDL-C and other complications despite a reduction in LDL-C. These observations have fueled interest in the development of new pharmacotherapies that positively impact circulating lipoproteins. The goal of this review is to discuss the therapeutic potential of synthetic apolipoprotein mimetic peptides. These include apoA-I mimetic peptides that have undergone initial clinical assessment. We also discuss newer apoE mimetics that mediate the clearance of atherogenic lipids from the circulation and possess anti-inflammatory properties. One of these (AEM-28) has recently been given orphan drug status and is undergoing clinical trials. PMID:25157031

  5. Anti-inflammatory effects and chemical study of a flavonoid-enriched fraction from adlay bran.

    PubMed

    Chen, Hong-Jhang; Chung, Cheng-Pei; Chiang, Wenchang; Lin, Yun-Lian

    2011-06-15

    Anti-inflammation-guided fractionation and purification were used to evaluate the bioactivity and components of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) bran. Results showed that the fraction with high phenolic and flavonoid contents from the ethanol extracts of adlay bran suppressed LPS-stimulated IL-6 and TNF-? secretions in a concentration-dependent manner in RAW 264.7 cells and murine peritoneal macrophages. Fifteen compounds, including a novel aurone derivative, two chromones, one dihydrochalcone, one chalcone, four flavanones, five flavones and one isoflavone, were isolated from the active fraction. The structure of the new compound was elucidated by spectroscopic methods, including 1D and 2D NMR and MS. All of the isolates are reported for the first time from adlay except naringenin. LC/MS was also provided as an analytical platform. Our results suggest that flavonoids in adlay bran, partially at least, contribute to its anti-inflammatory effect. Thus, adlay bran may be beneficial to the health of consumers. PMID:25213953

  6. Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species

    PubMed Central

    Lee, Kim-Chung; Tam, Emily W. T.; Lo, Ka-Ching; Tsang, Alan K. L.; Lau, Candy C. Y.; To, Kelvin K. W.; Chan, Jasper F. W.; Lam, Ching-Wan; Yuen, Kwok-Yung; Lau, Susanna K. P.; Woo, Patrick C. Y.

    2015-01-01

    Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu–Glu–Leu–Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu–Glu–Leu–Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species. PMID:26090713

  7. Structural Studies of an Anti-Inflammatory Lectin from Canavalia boliviana Seeds in Complex with Dimannosides

    PubMed Central

    Moura, Tales Rocha; Delatorre, Plínio; Rocha, Bruno Anderson Matias; do Nascimento, Kyria Santiago; Figueiredo, Jozi Godoy; Bezerra, Ingrid Gonçalves; Teixeira, Cicero Silvano; Simões, Rafael Conceição; Nagano, Celso Shiniti; de Alencar, Nylane Maria Nunes; Gruber, Karl; Cavada, Benildo Sousa

    2014-01-01

    Plant lectins, especially those purified from species of the Leguminosae family, represent the best-studied group of carbohydrate-binding proteins. Lectins purified from seeds of the Diocleinae subtribe exhibit a high degree of sequence identity notwithstanding that they show very distinct biological activities. Two main factors have been related to this feature: variance in key residues influencing the carbohydrate-binding site geometry and differences in the pH-dependent oligomeric state profile. In this work, we have isolated a lectin from Canavalia boliviana (Cbol) and solved its x-ray crystal structure in the unbound form and in complex with the carbohydrates Man(?1-3)Man(?1-O)Me, Man(?1-4)Man(?1-O)Me and 5-bromo-4-chloro-3-indolyl-?-D-mannose. We evaluated its oligomerization profile at different pH values using Small Angle X-ray Scattering and compared it to that of Concanavalin A. Based on predicted pKa-shifts of amino acids in the subunit interfaces we devised a model for the dimer-tetramer equilibrium phenomena of these proteins. Additionally, we demonstrated Cbol anti-inflammatory properties and further characterized them using in vivo and in vitro models. PMID:24865454

  8. Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species.

    PubMed

    Lee, Kim-Chung; Tam, Emily W T; Lo, Ka-Ching; Tsang, Alan K L; Lau, Candy C Y; To, Kelvin K W; Chan, Jasper F W; Lam, Ching-Wan; Yuen, Kwok-Yung; Lau, Susanna K P; Woo, Patrick C Y

    2015-01-01

    Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu-Glu-Leu-Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu-Glu-Leu-Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species. PMID:26090713

  9. Anti-Inflammatory Effects of the Chinese Herbal Formula Sini Tang in Myocardial Infarction Rats

    PubMed Central

    Liu, Jiangang; Peter, Karoline; Shi, Dazhuo; Zhang, Lei; Dong, Guoju; Zhang, Dawu; Breiteneder, Heimo; Bauer, Rudolf; Ma, Yan

    2014-01-01

    The aim of this study was to evaluate the anti-inflammatory profiling of the Chinese herbal formula Sini Tang (SNT) in myocardial infarction (MI) rats. SNT, a decoction consisting of four herbs: Aconitum carmichaelii, Cinnamomum cassia, Zingiber officinale, and Glycyrrhiza uralensis, was characterized as a remedy to treat syndromes corresponding to heart failure and MI in China. Potential biomarkers, which reflect the extent of myocardial necrosis and correlate with cardiac outcomes following MI, such as atrial natriuretic peptide (ANP), high sensitivity C-reactive protein (hs-CRP), and proinflammatory cytokines such as tumor necrosis factor-?, interleukin-6, and interleukin-1? (TNF-?, IL-6, and IL-1?) were determined in plasma, serum, and in myocardial tissue of MI rats after treatment with SNT. Our data indicate that SNT decreased significantly the levels of hs-CRP, TNF-?, IL-6, and IL-1? in MI rats. SNT decreased the expression of ANP levels in plasma and increased the vascular active marker nitric oxide, which limits vascular inflammation. In addition, SNT could decrease the expression of endothelin-1 levels in rat plasma post-MI. Our data suggest that the Chinese herbal formula SNT has the potential to improve cardiac function after MI. SNT may be a candidate for treating MI and its associated inflammatory responses. PMID:24723959

  10. Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials

    PubMed Central

    Gold, Ben; Pingle, Maneesh; Brickner, Steven J.; Shah, Nilesh; Roberts, Julia; Rundell, Mark; Bracken, W. Clay; Warrier, Thulasi; Somersan, Selin; Venugopal, Aditya; Darby, Crystal; Jiang, Xiuju; Warren, J. David; Fernandez, Joseph; Ouerfelli, Ouathek; Nuermberger, Eric L.; Cunningham-Bussel, Amy; Rath, Poonam; Chidawanyika, Tamutenda; Deng, Haiteng; Realubit, Ronald; Glickman, J. Fraser; Nathan, Carl F.

    2012-01-01

    Existing drugs are slow to eradicate Mycobacterium tuberculosis (Mtb) in patients and have failed to control tuberculosis globally. One reason may be that host conditions impair Mtb’s replication, reducing its sensitivity to most antiinfectives. We devised a high-throughput screen for compounds that kill Mtb when its replication has been halted by reactive nitrogen intermediates (RNIs), acid, hypoxia, and a fatty acid carbon source. At concentrations routinely achieved in human blood, oxyphenbutazone (OPB), an inexpensive anti-inflammatory drug, was selectively mycobactericidal to nonreplicating (NR) Mtb. Its cidal activity depended on mild acid and was augmented by RNIs and fatty acid. Acid and RNIs fostered OPB’s 4-hydroxylation. The resultant 4-butyl-4-hydroxy-1-(4-hydroxyphenyl)-2-phenylpyrazolidine-3,5-dione (4-OH-OPB) killed both replicating and NR Mtb, including Mtb resistant to standard drugs. 4-OH-OPB depleted flavins and formed covalent adducts with N-acetyl-cysteine and mycothiol. 4-OH-OPB killed Mtb synergistically with oxidants and several antituberculosis drugs. Thus, conditions that block Mtb’s replication modify OPB and enhance its cidal action. Modified OPB kills both replicating and NR Mtb and sensitizes both to host-derived and medicinal antimycobacterial agents. PMID:23012453

  11. Hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs).

    PubMed

    de Weck, A L; Gamboa, P M; Esparza, R; Sanz, M L

    2006-01-01

    Hypersensitivity to aspirin and other non steroidal anti-inflammatory drugs (NSAIDs) manifesting in the airways (rhinosinusitis, polyps, asthma) or in the skin (urticaria, angioedema) is the second most frequent untoward allergic reaction to drugs. Various aspects of this syndrome, such as its clinical features, the cell types and mediators involved, the role of underlying chronic inflammatory processes, the patterns of cross-reactivity between NSAIDs, the major role of sulfidoleukotrienes (LTC4) and of some other mediators such as prostaglandin E2 (PGE2) and C5a are briefly reviewed. It has been assumed for a long time that there were no reliable in vitro tests for that condition and that diagnostic confirmation can only be ascertained by provocation challenge. This appears no longer to be true, since several recent studies using a leukotriene release test (CAST) or a basophil activation test (BAT) on blood basophils, or a combination of both tests, yields positive results (70-75%) in a sizeable number of clinically validated cases, with a high specificity (above 85%). The finding in that syndrome of hyperreactive basophils suggests that the NSAID hypersensitivity syndrome is due to the associated effect of several factors: 1) Localized inflammatory processes causing a non specific cellular hyperreactivity; 2) An abnormal pharmacogenetic reaction to NSAIDs resulting in a hyperproduction of LTC4 and other mediators by activated mast cells, basophils and eosinophils. PMID:17017929

  12. In vitro anti-inflammatory and anticancer activities of extracts of Acalypha alopecuroidea (Euphorbiaceae).

    PubMed

    Madlener, Sibylle; Svacinová, Jana; Kitner, Miloslav; Kopecky, Jirí; Eytner, Ruth; Lackner, Andreas; Vo, Than Phuong Nha; Frisch, Richard; Grusch, Michael; De Martin, Rainer; Dolezal, Karel; Strnad, Miroslav; Krupitza, Georg

    2009-10-01

    More than 60% of conventional drugs are derived from natural compounds, some of the most effective pharmaceuticals (e.g. aspirin, quinine and various antibiotics) originate from plants or microbes, and large numbers of potentially valuable natural substances remain to be discovered. Plants with considerable medicinal potential include members of the genus Acalypha. Notably, extracts of A. platyphilla, A. fruticosa, A. siamensis, A. guatemalensis and A. wilkesiana have been recently shown to have antioxidant, antimicrobial and cytotoxic effects. In the study presented here we investigated the anti-inflammatory, anti-proliferative and pro-apoptotic activities of A. alopecuroidea, which is endemic in parts of Central America and is traditionally used by the Mopan- and Itza-Maya in the form of decoctions to treat skin conditions, and as a tea to treat stomach and urinary complaints. We demonstrate here that extracts of A. alopecuroidea can inhibit TNFalpha-induced E-selectin production, providing a mechanistic validation of its traditional use against inflammatory diseases. Furthermore, a fraction of A. alopecuroidea root extracts purified by solid phase extraction and separated by HPLC displayed strong cell cycle inhibitory activity by down-regulating and inactivating two proto-oncogenes (cyclin D1 and Cdc25A), and simultaneously inducing cyclin A, thereby disturbing orchestrated cell cycle arrest, and thus (presumably) triggering caspase 3-dependent apoptosis. The results of this study indicate that there are high prospects for purifying an active principle from A. alopecuroidea for further in vivo and preclinical studies. PMID:19724926

  13. Altered membrane lipid dynamics and chemoprevention by non-steroidal anti inflammatory drugs during colon carcinogenesis.

    PubMed

    Singh Kanwar, S; Vaish, V; Nath Sanyal, S

    2011-01-01

    The present work focuses on the anti-neoplastic role of non steroidal anti-inflammatory drugs (NSAIDs) in modulating the biophysical parameters of the colonic membranes in 1,2-dimethylhydrazine dihydrochloride (DMH) induced carcinogenesis. The steady-state fluorescence polarization technique was applied to assess membrane fluidity, membrane polarity and lipid phase states. The decline in cholesterol content, biosynthesis and cholesterol: phospholipids ratio with DMH treatment indicates more fluidity associated with carcinogenesis. The DMH group had shown lower order parameter indicating more fluidity whereas NSAIDs resulted in increasing the membrane lipid order. The converging effects of these changes were more in membrane phase separations and membrane phase state. In DMH treatment membrane shows lesser phase separation or high polarity, and more liquid crystalline state while for NSAID groups membranes have higher phase separations or low polarity, and more of the gel phase. Further, NSAIDs induced anti-proliferative effects were evidently observed by apoptosis in the colonocytes by using acridine orange-ethidium bromide fluorescent staining and Terminal de-oxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The results suggest that NSAIDs induced alteration in the membrane biophysical parameters may be an important initiating event for the chemopreventive action. PMID:22072366

  14. Anti-Inflammatory Activity of Aqueous Extract of Beta Vulgaris L.

    PubMed Central

    Jain, Swati; Garg, Vipin Kumar; Sharma, Pramod Kumar

    2011-01-01

    The present study deals with the investigation of phytochemically evaluated aqueous extract of leaves of Beta vulgaris for its anti-inflammatory activity. The anti-inflammatory activity was evaluated by carrageenan induced rat paw oedema method for acute inflammation and cotton pellet granuloma method for chronic inflammation. The standard drug used was indomethacin (10 mg/kg) for both the models. In both methods, aqueous extract at a dose level of 1000 mg/kg has shown significant activity which is comparable to that of the standard PMID:24826006

  15. Development of anti-inflammatory drugs - the research and development process.

    PubMed

    Knowles, Richard Graham

    2014-01-01

    The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. PMID:23981595

  16. [Aspirin and other nonsteroidal anti-inflammatory drugs hypersensitivity--mechanisms, diagnostics and treatment].

    PubMed

    Kupczyk, Maciej; Kuna, Piotr

    2008-01-01

    Aspirin hypersensitivity syndrome includes several symptoms from the respiratory tract, skin and digestive system triggered by ingestion of aspirin or other nonsteroidal anti-inflammatory drugs. Asthmatic attacks precipitated by aspirin or other nonsteroidal anti-inflammatory drugs occur in about 10% of all asthmatic patients. In subjects with aspirin hypersensitivity disruption of synthesis of prostaglandin E2 (PGE2) and overproduction of cysteinyl leukotrienes (Cys-LT) seem to be crucial in the pathogenesis of bronchial symptoms. Double blind, placebo controlled challenges are regarded as a gold standard in the diagnosis of aspirin hypersensitivity. PMID:19003768

  17. Gastroprotective and anti-inflammatory properties of green lipped mussel (Perna canaliculus) preparation.

    PubMed

    Rainsford, K D; Whitehouse, M W

    1980-01-01

    Freeze-dried powdered preparations of whole (i.e. without shell) green-lipped mussel (Perna canaliculus) from New Zealand given orally to rats showed some modest anti-inflammatory activity (carrageenan paw oedema). This material strikingly reduced the gastric ulcerogenicity of several non-steroid anti-inflammatory drugs in rats and pigs. The gastroprotective activity in rats was primarily associated with particular lipid fractions, which exhibited differential protective activity against acetylsalicylic acid on the one hand and indometacin on the other. PMID:7194074

  18. Preventing non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: are older strategies more cost-effective in the general population?

    Microsoft Academic Search

    R. A. Elliott; L. Hooper; K. Payne; T. J. Brown; C. Roberts; D. Symmons

    2005-01-01

    Objectives. To assess the relative cost-effectiveness of five gastroprotective strategies for patients in the general population not judged to be at high gastrointestinal (GI) risk requiring regular traditional (t) non-steroidal anti-inflammatory drugs (NSAIDs) for over 3 weeks: tNSAID\\/H2 receptor antagonists (H2RAs); tNSAID\\/proton pump inhibitors (PPIs); tNSAID\\/ misoprostol; COX-2 preferential NSAIDs or COX-2-specific NSAIDs (COXIBs). Methods. A systematic review of outcomes

  19. Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A3 adenosine receptor expression

    Microsoft Academic Search

    Avivit Ochaion; Sara Bar-Yehuda; Shira Cohn; Luis Del Valle; Georginia Perez-Liz; Lea Madi; Faina Barer; Motti Farbstein; Sari Fishman-Furman; Tatiana Reitblat; Alexander Reitblat; Howard Amital; Yair Levi; Yair Molad; Reuven Mader; Moshe Tishler; Pnina Langevitz; Alexander Zabutti; Pnina Fishman

    2006-01-01

    Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A3 adenosine receptor (A3AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A3AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of

  20. Dietary fish oil n?3 fatty acids increase regulatory cytokine production and exert anti-inflammatory effects in two murine models of inflammation

    Microsoft Academic Search

    Saleta Sierra; Federico Lara-Villoslada; Mònica Comalada; Mónica Olivares; Jordi Xaus

    2006-01-01

    The higher incidence of inflammatory diseases in Western countries might be related, in part, to a high consumption of saturated\\u000a fatty acids and n?6 polyunsaturated fatty acids (PUFA) and an insufficient intake of n?3 fatty acids. The purpose of this\\u000a study was to examine the effects of dietary n?3 fatty acids on innate and specific immune response and their anti-inflammatory

  1. Anti-inflammatory Effects of Ethanol Extract from Kummerowia striata (Thunb.) Schindl on LPS-Stimulated RAW 264.7 Cell

    Microsoft Academic Search

    Jun-Yan Tao; Lei Zhao; Zhi-Jun Huang; Xiao-Yu Zhang; Shu-Ling Zhang; Qiong-Guang Zhang; Fei-Xiao; Bao-Hui Zhang; Qi-Lin Feng; Guo-Hua Zheng

    2008-01-01

    Kummerowia striata (Thunb.) Schindl has long been used as a fork herb in inflammation-related therapy. This study was undertaken to determine the anti-inflammatory\\u000a effect of the plant. High performance liquid chromatography (HPLC) was used for evaluating the extract. While dexamethasone\\u000a (DM) was used as a positive control, the effects of ethanol extract on the production of IL-1?, IL-6, NO, COX-2

  2. Anti-inflammatory/antioxidant use in long-term maintenance cancer therapy: a new therapeutic approach to disease progression and recurrence

    PubMed Central

    2014-01-01

    The chronic, progressive clinical characteristics of many adult solid tumor malignancies suggest that a more effective therapeutic approach to cancer management may require long-term intervention using nontoxic systemic agents that block critical components of abnormal tumor physiology. Two highly promising systemic targets common to the development, progression and recurrence of many common cancers are dysregulated inflammatory and oxidation/reduction (redox) pathways. Compelling clinical data support the use of anti-inflammatory and antioxidant agents as a therapeutic modality for long-term use in patients diagnosed with several common cancers, including colon cancer and breast cancer. The therapeutic paradigm presented in this paper is the product of a synthesis of what is currently understood about the biological effects of inflammation and oxidative stress that contribute to tumorigenesis, disease progression and recurrence as well as results obtained from research on the use of prophylactics with anti-inflammatory or antioxidant properties in cancer prevention and treatment. PMID:24587831

  3. Unbiased Screening of Marine Sponge Extracts for Anti-Inflammatory Agents Combined with Chemical Genomics Identifies Girolline as an Inhibitor of Protein Synthesis

    PubMed Central

    Fung, Shan-Yu; Sofiyev, Vladimir; Schneiderman, Julia; Hirschfeld, Aaron F.; Victor, Rachel E.; Woods, Kate; Piotrowski, Jeff S.; Deshpande, Raamesh; Li, Sheena C.; de Voogd, Nicole J.; Myers, Chad L.; Boone, Charlie; Andersen, Raymond J.; Turvey, Stuart E.

    2013-01-01

    Toll-like receptors (TLRs) play a critical role in innate immunity, but activation of TLR signaling pathways is also associated with many harmful inflammatory diseases. Identification of novel anti-inflammatory molecules targeting TLR signaling pathways is central to the development of new treatment approaches for acute and chronic inflammation. We performed high throughput screening from crude marine sponge extracts on TLR5 signaling and identified girolline. We demonstrated that girolline inhibits signaling through both MyD88-dependent and –independent TLRs (i.e. TLR2, 3, 4, 5 and 7), and reduces cytokine (IL-6 and IL-8) production in human peripheral blood mononuclear cells and macrophages. Using a chemical genomics approach, we identified Elongation factor 2 as the molecular target of girolline, which inhibits protein synthesis at the elongation step. Together these data identify the sponge natural product girolline as a potential anti-inflammatory agent acting through inhibition of protein synthesis. PMID:24117378

  4. Design, synthesis and biological evaluation of paralleled Aza resveratrol-chalcone compounds as potential anti-inflammatory agents for the treatment of acute lung injury.

    PubMed

    Chen, Wenbo; Ge, Xiangting; Xu, Fengli; Zhang, Yali; Liu, Zhiguo; Pan, Jialing; Song, Jiao; Dai, Yuanrong; Zhou, Jianmin; Feng, Jianpeng; Liang, Guang

    2015-08-01

    Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. It has been reported that both resveratrol and chalcone derivatives could ameliorate lung injury induced by inflammation. A series of paralleled Aza resveratrol-chalcone compounds (5a-5m, 6a-6i) were designed, synthesized and screened for anti-inflammatory activity. A majority showed potent inhibition on the IL-6 and TNF-? expression-stimulated by LPS in macrophages, of which compound 6b is the most potent analog by inhibition of LPS-induced IL-6 release in a dose-dependent manner. Moreover, 6b exhibited protection against LPS-induced acute lung injury in vivo. These results offer further insight into the use of Aza resveratrol-chalcone compounds for the treatment of inflammatory diseases, and the use of compound 6b as a lead compound for the development of anti-ALI agents. PMID:26048788

  5. Highly potent and specific inhibitors of human renin.

    PubMed

    Kokubu, T; Hiwada, K; Murakami, E; Imamura, Y; Matsueda, R; Yabe, Y; Koike, H; Iijima, Y

    1985-01-01

    Small peptide analogues representing the C-terminal portion of angiotensin I sequence were designed as inhibitors of human renin. Among synthesized compounds, benzyloxycarbonyl (-"Z")-(1-naphthyl)Ala-His-leucinal (ES-188), Z-(1-naphthyl)Ala-His-statine ethyl ester (ES-226), and Z-(1-naphthyl)Ala-His-statine 2-methylbutylamide (ES-254) markedly inhibited human and primate renins (inhibitory concentration, 50% [IC50], near 10(-7) M). These peptide analogues inhibited rabbit renin with one or two orders of magnitude less potency. They were very weak inhibitors of renins from pig, goat, dog, and rat. ES-188 had no discernible effect on cathepsin D, pepsin, or human angiotensin-converting enzyme at the concentration of 10(-4)M. ES-226 had little effect on the three enzymes at the concentration of 10(-5)M; however, ES-254 had a considerable inhibitory effect on cathepsin D (IC50 of 1.4 X 10(-5)M), pepsin (IC50 of 4.2 X 10(-5)M), and human angiotensin-converting enzyme (IC50 of 7.1 X 10(-6)M). Our results indicate that 1-naphthylalanine-containing tripeptide analogues are highly potent human renin inhibitors. PMID:2987128

  6. Rapid 'one-pot' synthesis of a novel benzimidazole-5-carboxylate and its hydrazone derivatives as potential anti-inflammatory and antimicrobial agents.

    PubMed

    Vasantha, Kumar; Basavarajaswamy, Guru; Vaishali Rai, M; Boja, Poojary; Pai, Vinitha R; Shruthi, N; Bhat, Mahima

    2015-04-01

    A novel series of N-arylidene-2-(2,4-dichloro phenyl)-1-propyl-1H-benzo[d] imidazole-5-carbohydrazides having different substitution on the arylidene part were synthesized in good yield. The core nucleus benzimidazole-5-carboxylate (5) was efficiently synthesized by 'one-pot' nitro reductive cyclization reaction between ethyl-3-nitro-4-(propylamino)benzoate and 2,4-dichlorobenzaldehyde using sodium dithionite in dimethylsulfoxide. This 'one-pot' reaction was proceeded very smoothly, in short reaction time with an excellent yield. All the compounds (7a-r) were screened for their in vivo anti-inflammatory and in vitro antimicrobial activity. Most of the compounds exhibited remarkable paw-edema inhibition in the initial one hour of administration indicating the higher potentiality of these molecules. In particular, compounds 7a, 7d, 7f and 7g displayed a high level of carrageenan-induced paw edema inhibition compared to that of indomethacin. Compound 7p exhibited very good antibacterial activity and antifungal activity with a MIC of 3.12 ?g/mL against most of the tested organisms. Furthermore, compounds 7d, 7f, 7h and 7p found to be good inhibitors of Aspergillus niger with MIC of 3.12 ?g/mL. Cytotoxicity of the potent compounds 7d, 7f and 7p was checked using MDA MB-231 breast cancer cell line and are found to be non toxic at the highest concentration used (i.e., 10 ?g/mL). PMID:25765910

  7. Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype

    PubMed Central

    2010-01-01

    Background Luteolin, a plant derived flavonoid, exerts a variety of pharmacological activities and anti-oxidant properties associated with its capacity to scavenge oxygen and nitrogen species. Luteolin also shows potent anti-inflammatory activities by inhibiting nuclear factor kappa B (NFkB) signaling in immune cells. To better understand the immuno-modulatory effects of this important flavonoid, we performed a genome-wide expression analysis in pro-inflammatory challenged microglia treated with luteolin and conducted a phenotypic and functional characterization. Methods Resting and LPS-activated BV-2 microglia were treated with luteolin in various concentrations and mRNA levels of pro-inflammatory markers were determined. DNA microarray experiments and bioinformatic data mining were performed to capture global transcriptomic changes following luteolin stimulation of microglia. Extensive qRT-PCR analyses were carried out for an independent confirmation of newly identified luteolin-regulated transcripts. The activation state of luteolin-treated microglia was assessed by morphological characterization. Microglia-mediated neurotoxicity was assessed by quantifying secreted nitric oxide levels and apoptosis of 661W photoreceptors cultured in microglia-conditioned medium. Results Luteolin dose-dependently suppressed pro-inflammatory marker expression in LPS-activated microglia and triggered global changes in the microglial transcriptome with more than 50 differentially expressed transcripts. Pro-inflammatory and pro-apoptotic gene expression was effectively blocked by luteolin. In contrast, mRNA levels of genes related to anti-oxidant metabolism, phagocytic uptake, ramification, and chemotaxis were significantly induced. Luteolin treatment had a major effect on microglial morphology leading to ramification of formerly amoeboid cells associated with the formation of long filopodia. When co-incubated with luteolin, LPS-activated microglia showed strongly reduced NO secretion and significantly decreased neurotoxicity on 661W photoreceptor cultures. Conclusions Our findings confirm the inhibitory effects of luteolin on pro-inflammatory cytokine expression in microglia. Moreover, our transcriptomic data suggest that this flavonoid is a potent modulator of microglial activation and affects several signaling pathways leading to a unique phenotype with anti-inflammatory, anti-oxidative, and neuroprotective characteristics. With the identification of several novel luteolin-regulated genes, our findings provide a molecular basis to understand the versatile effects of luteolin on microglial homeostasis. The data also suggest that luteolin could be a promising candidate to develop immuno-modulatory and neuroprotective therapies for the treatment of neurodegenerative disorders. PMID:20074346

  8. Anti-inflammatory norditerpenoids from the soft coral Sinularia maxima.

    PubMed

    Thao, Nguyen Phuong; Nam, Nguyen Hoai; Cuong, Nguyen Xuan; Quang, Tran Hong; Tung, Pham The; Dat, Le Duc; Chae, Doobyeong; Kim, Sohyun; Koh, Young-Sang; Kiem, Phan Van; Minh, Chau Van; Kim, Young Ho

    2013-01-01

    Chemical investigation of the soft coral Sinularia maxima resulted in the isolation of seven norditerpenoids, including two new compounds, 12-hydroxy-scabrolide A (2) and 13-epi-scabrolide C (6). The structures of the isolated compounds were elucidated based on extensive spectroscopic evidence including Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and both one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR, respectively), in comparison with reported data. Compound 6 potently inhibited IL-12 and IL-6 production in LPS-stimulated bone marrow derived dendritic (BMDCs) with IC(50) values of 5.30 ± 0.21 and 13.12 ± 0.64 ?M, respectively. Compound 1 exhibited moderate inhibitory activity against IL-12 and IL-6 production with IC(50) values of 23.52 ± 1.37 and 69.85 ± 4.11 ?M, respectively. PMID:23200246

  9. Use of anti-inflammatory drugs by patients admitted with small or large bowel perforations and haemorrhage

    Microsoft Academic Search

    M J Langman; L Morgan; A Worrall

    1985-01-01

    The intake of anti-inflammatory drugs by 268 patients with colonic or small bowel perforation or haemorrhage was compared with that by a group of patients, matched for age and sex, with uncomplicated lower bowel disease. Patients with perforation or haemorrhage were more than twice as likely to be takers of anti-inflammatory drugs, but no association was detected with the intake

  10. Anti-inflammatory effect of crude extract and isolated compounds from Baccharis illinita DC in acute skin inflammation

    Microsoft Academic Search

    Shirley Boller; Cristian Soldi; Maria C. A. Marques; Elide P. Santos; Daniela A. Cabrini; Moacir G. Pizzolatti; Aleksander R. Zampronio; Michel F. Otuki

    2010-01-01

    Ethnopharmacologycal relevanceThe tea from the leaves of Baccharis illinita DC (Asteraceae family) is commonly used by the population as anti-inflammatory (including topically), protective gastric and anti-infectious. However, no studies have been done with this species to confirm its topical anti-inflammatory action.

  11. The Anti-inflammatory Effects of Curcuma longa and Berberis aristata in Endotoxin-Induced Uveitis in Rabbits

    Microsoft Academic Search

    Suresh Kumar Gupta; Renu Agarwal; Sushma Srivastava; Puneet Agarwal; Shyam Sunder Agrawal; Rohit Saxena; Niranjan Galpalli

    PURPOSE. To investigate the anti-inflammatory effect of topical application of Curcuma longa (C. longa) and Berberis aristata (B. aristata) aqueous extracts on experimental uveitis in the rabbit. METHODS. Anterior uveitis was induced in rabbits by intravitreal injection of lipopolysaccharide from Escherichia coli after pre- treatment with C. longa and B. aristata aqueous extracts. Subsequently, the anti-inflammatory activity of C. longa

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

    Microsoft Academic Search

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

    Aim of the studyByrsonima intermedia is commonly used for its antiseptic, antimicrobial, and anti-inflammatory properties in the treatment of diarrhea and dysentery in Brazilian folk medicine. The purpose of this study was to examine the anti-inflammatory activity of the aqueous extract and fractions of Byrsonima intermedia leaves.

  13. COMBINED EFFECT OF ANTI-INFLAMMATORY AND ANTI-ANXIETY, ANALGESIC ACTIVITY OF HERBAL FORMULATION USING MEDICINAL ETHANLOIC EXTRACT LEAVES

    Microsoft Academic Search

    M. C. SHARMA; D. V. KOHLIb; Devi Ahilya Vishwavidyalaya; H. S. Gour

    The aim of present study was to assess the anti-inflammatory activity antianxiety activity, Analgesic activity of polyherbal formulation of leaves of Datura stramonium, Terminalia Arjuna. The mature green leaves of Datura stramonium, Terminalia Arjuna were collected and authenticated. Extractions of dried leaves and rhizome were carried out with ethanol in soxhlet apparatus. The polyherbal formulation showed the significant anti-inflammatory activity

  14. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease

    Microsoft Academic Search

    Nicolette C. Bishop; David J. Stensel; Martin R. Lindley; Sarabjit S. Mastana; Myra A. Nimmo; Michael Gleeson

    2011-01-01

    Regular exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, in part because exercise exerts anti-inflammatory effects. However, these effects are also likely to be responsible for the suppressed immunity that makes elite athletes more susceptible to infections. The anti-inflammatory effects of regular exercise may be mediated via both a reduction in visceral fat mass (with a subsequent decreased

  15. Expression and contributions of the Kir2.1 inward-rectifier K+ channel to proliferation, migration and chemotaxis of microglia in unstimulated and anti-inflammatory states

    PubMed Central

    Lam, Doris; Schlichter, Lyanne C.

    2015-01-01

    When microglia respond to CNS damage, they can range from pro-inflammatory (classical, M1) to anti-inflammatory, alternative (M2) and acquired deactivation states. It is important to determine how microglial functions are affected by these activation states, and to identify molecules that regulate their behavior. Microglial proliferation and migration are crucial during development and following damage in the adult, and both functions are Ca2+-dependent. In many cell types, the membrane potential and driving force for Ca2+ influx are regulated by inward-rectifier K+ channels, including Kir2.1, which is prevalent in microglia. However, it is not known whether Kir2.1 expression and contributions are altered in anti-inflammatory states. We tested the hypothesis that Kir2.1 contributes to Ca2+ entry, proliferation and migration of rat microglia. Kir2.1 (KCNJ2) transcript expression, current amplitude, and proliferation were comparable in unstimulated microglia and following alternative activation (IL-4 stimulated) and acquired deactivation (IL-10 stimulated). To examine functional roles of Kir2.1 in microglia, we first determined that ML133 was more effective than the commonly used blocker, Ba2+; i.e., ML133 was potent (IC50 = 3.5 ?M) and voltage independent. Both blockers slightly increased proliferation in unstimulated or IL-4 (but not IL-10)-stimulated microglia. Stimulation with IL-4 or IL-10 increased migration and ATP-induced chemotaxis, and blocking Kir2.1 greatly reduced both but ML133 was more effective. In all three activation states, blocking Kir2.1 with ML133 dramatically reduced Ca2+ influx through Ca2+-release-activated Ca2+ (CRAC) channels. Thus, Kir2.1 channel activity is necessary for microglial Ca2+ signaling and migration under resting and anti-inflammatory states but the channel weakly inhibits proliferation. PMID:26029054

  16. Ischaemic cardiovascular risk and prescription of non-steroidal anti-inflammatory drugs for musculoskeletal complaints

    PubMed Central

    Valkhoff, Vera E; Jong, Geert W't; Warlé-van Herwaarden, Margreet F; Bindels, Patrick Je; Sturkenboom, Miriam Cjm; Luijsterburg, Pim Aj; Bierma-Zeinstra, Sita Ma

    2014-01-01

    Abstract Objective. To determine the influence of ischaemic cardiovascular (CV) risk on prescription of non-steroidal anti-inflammatory drugs (NSAIDs) by general practitioners (GPs) in patients with musculoskeletal complaints. Design. Cohort study. Setting. A healthcare database containing the electronic GP medical records of over one million patients throughout the Netherlands. Patients. A total of 474 201 adults consulting their GP with a new musculoskeletal complaint between 2000 and 2010. Patients were considered at high CV risk if they had a history of myocardial infarction, angina pectoris, stroke, transient ischaemic attack, or peripheral arterial disease, and at low CV risk if they had no CV risk factors. Main outcome measures. Frequency of prescription of non-selective (ns)NSAIDs and selective cyclooxygenase-2 inhibitors (coxibs). Results. Overall, 24.4% of patients were prescribed an nsNSAID and 1.4% a coxib. Of the 41,483 patients with a high CV risk, 19.9% received an nsNSAID and 2.2% a coxib. These patients were more likely to be prescribed a coxib than patients with a low CV risk (OR 1.9, 95% CI 1.8–2.0). Prescription of nsNSAIDs decreased over time in all risk groups and was lower in patients with a high CV risk than in patients with a low CV risk (OR 0.8, 95% CI 0.7–0.8). Conclusion. Overall, patients with a high CV risk were less likely to be prescribed an NSAID for musculoskeletal complaints than patients with a low CV risk. Nevertheless, one in five high CV risk patients received an NSAID, indicating that there is still room for improvement. PMID:24931511

  17. In Vivo Potential Anti-Inflammatory Activity of Melissa officinalis L. Essential Oil.

    PubMed

    Bounihi, Amina; Hajjaj, Ghizlane; Alnamer, Rachad; Cherrah, Yahia; Zellou, Amina

    2013-01-01

    Melissa officinalis L. (Lamiaceae) had been reported in traditional Moroccan medicine to exhibit calming, antispasmodic, and strengthening heart effects. Therefore, this study is aimed at determining the anti-inflammatory activities of M. officinalis L. leaves. The effect of the essential oil of the leaves of this plant was investigated for anti-inflammatory properties by using carrageenan and experimental trauma-induced hind paw edema in rats. The essential oil extracted from leaves by hydrodistillation was characterized by means of gas chromatography-mass spectrometry (GC-MS). M. officinalis contained Nerol (30.44%), Citral (27.03%), Isopulegol (22.02%), Caryophyllene (2.29%), Caryophyllene oxide (1.24%), and Citronella (1.06%). Anti-inflammatory properties of oral administration of essential oil at the doses of 200, 400?mg/kg p.o., respectively, showed significant reduction and inhibition of edema with 61.76% and 70.58%, respectively, (P < 0.001) induced by carrageenan at 6?h when compared with control and standard drug (Indomethacin). On experimental trauma, M. officinalis L. essential oil showed pronounced reduction and inhibition of edema induced by carrageenan at 6?h at 200 and 400?mg/kg with 91.66% and 94.44%, respectively (P < 0.001). We can conclude that the essential oil of M. officinalis L. possesses potential anti-inflammatory activities, supporting the traditional application of this plant in treating various diseases associated with inflammation and pain. PMID:24381585

  18. Anti-Inflammatory and Anti-Superbacterial Properties of Sulforaphane from Shepherd's Purse

    PubMed Central

    Choi, Woo Jin; Kim, Seong Keun; Park, Hee Kuk; Sohn, Uy Dong

    2014-01-01

    Shepherd's purse, Capsella bursa-pastoris (L.) Medik., has been considered a health food for centuries in Asia and is known to contain the isothiocyanate compound sulforaphane. In this study, we evaluated the anti-inflammatory and antibacterial properties of a sulforaphane-containing solution (SCS) isolated from shepherd's purse. SCS had significant anti-inflammatory activity indicated by the decreased levels of nitric oxide (NO), cytokines (interleukin 1? [IL-1?], IL-6, and IL-10), and prostaglandin E2 (PGE2) in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. In addition, SCS decreased the inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) levels, which confirmed the anti-inflammatory activity of SCS. Further, SCS inhibited vancomycin-resistant enterococci (VRE) and Bacillus anthracis. The minimal inhibitory concentration was 250 µg/ml for VRE and 1,000 µg/ml for B. anthracis. Taken together, these data indicate that SCS has potential anti-inflammatory and anti-superbacterial properties, and thus it can be used as a functional food or pharmaceutical. PMID:24634594

  19. Anti-Inflammatory and Anti-Superbacterial Properties of Sulforaphane from Shepherd's Purse.

    PubMed

    Choi, Woo Jin; Kim, Seong Keun; Park, Hee Kuk; Sohn, Uy Dong; Kim, Wonyong

    2014-02-01

    Shepherd's purse, Capsella bursa-pastoris (L.) Medik., has been considered a health food for centuries in Asia and is known to contain the isothiocyanate compound sulforaphane. In this study, we evaluated the anti-inflammatory and antibacterial properties of a sulforaphane-containing solution (SCS) isolated from shepherd's purse. SCS had significant anti-inflammatory activity indicated by the decreased levels of nitric oxide (NO), cytokines (interleukin 1? [IL-1?], IL-6, and IL-10), and prostaglandin E2 (PGE2) in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. In addition, SCS decreased the inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) levels, which confirmed the anti-inflammatory activity of SCS. Further, SCS inhibited vancomycin-resistant enterococci (VRE) and Bacillus anthracis. The minimal inhibitory concentration was 250 µg/ml for VRE and 1,000 µg/ml for B. anthracis. Taken together, these data indicate that SCS has potential anti-inflammatory and anti-superbacterial properties, and thus it can be used as a functional food or pharmaceutical. PMID:24634594

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

    Microsoft Academic Search

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

    2010-01-01

    Ethnopharmacological relevanceSonchus oleraceus L. has been used to relieve headaches, general pain, hepatitis, infections, inflammation and rheumatism in Brazilian folk medicine. Nevertheless, scientific information regarding this species is scarce; there are no reports related to its possible anti-inflammatory effects.

  1. In vivo anti-inflammatory and antiarthritic activities of aqueous extracts from Thymelaea hirsuta

    PubMed Central

    Azza, Zora; Oudghiri, Mounia

    2015-01-01

    Background: The aerial parts of Thymelaea hirsuta (TH) are used as a decoction in the treatment of different pathologies in folk medicine in Morocco. Objective: The aqueous extracts were evaluated for its anti-inflammatory activity and in inhibition of adjuvant induction arthritis in male Wistar rats. Materials and Methods: The anti-inflammatory activity was carried out using carrageenan-induced rat paw edema model, and the antiarthritic activity was carried out using complete Freund's adjuvant-induced arthritis model. Results: The plant extract (500 mg/kg body weight) exhibited significant activity in acute inflammation produced 60% of inhibition after 4 h as compared with that of the standard anti-inflammatory drug, the diclofenac (100 mg/kg) which showed 40% of inhibition. In arthritis model, the extract produced 85% inhibition after 18 days when compared with the diclofenac (10 mg/kg; 72%). Conclusion: These results indicate that the aqueous extract of TH had an anti-inflammatory activity and inhibited the induction of adjuvant arthritis in male Wistar rats. PMID:25829798

  2. Anti-Inflammatory Activity of N-(3-Florophenyl) ethylcaffeamide in Mice

    PubMed Central

    Liao, Jung-Chun; Tsai, Jen-Chieh; Peng, Wen-Huang; Chiu, Yung-Jia; Sung, Ping-Jyun; Tsuzoki, Minoru; Kuo, Yueh-Hsiung

    2013-01-01

    In this study, we evaluated the anti-inflammatory activity of one synthetic product, N-(3-Florophenyl)ethylcaffeamide (abbrev. FECA), by using animal model of ?-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of FECA was determined by measuring the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor (TNF-?), interleukin-1? (IL-1?), 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 results showed that FECA reduced the paw edema at three, four and five hours after ?-carrageenan administration. The levels of COX-2, NO, TNF-?, and MDA in the ?-carrageenan-induced edema paws were reduced and the activities of SOD, GPx, and GRd in liver tissues were raised by FECA. These results suggested that FECA possessed anti-inflammatory activities and the anti-inflammatory mechanisms might be related to the decrease of the levels of COX-2, NO, and TNF-? in inflamed tissues and the increase in the MDA level by increasing the activities of SOD, GPx, and GRd. PMID:23887648

  3. Pro and anti-inflammatory cytokine gene polymorphism profiles in Bulgarian multiple sclerosis patients

    Microsoft Academic Search

    Snejina Mihailova; Milena Ivanova; Anastassia Mihaylova; Ludmila Quin; Olia Mikova; Elissaveta Naumova

    2005-01-01

    Dysregulation in the expression of pro- and anti-inflammatory cytokines is one of the milestones in multiple sclerosis (MS) development and progression. The aim of this study was to investigate the possible influence of TNF-? (?308), TGF-? (codons 10 and 25), IL-10 (?1082, ?819, ?592), IL-6 (?174) and IFN-? (+874) polymorphisms on susceptibility to multiple sclerosis (MS). Genotyping was performed by

  4. Can the anti-inflammatory activities of ?2-agonists be harnessed in the clinical setting?

    PubMed Central

    Theron, Annette J; Steel, Helen C; Tintinger, Gregory R; Feldman, Charles; Anderson, Ronald

    2013-01-01

    Beta2-adrenoreceptor agonists (?2-agonists) are primarily bronchodilators, targeting airway smooth muscle and providing critical symptomatic relief in conditions such as bronchial asthma and chronic obstructive pulmonary disease. These agents also possess broad-spectrum, secondary, anti-inflammatory properties. These are mediated largely, though not exclusively, via interactions with adenylyl cyclase-coupled ?2-adrenoreceptors on a range of immune and inflammatory cells involved in the immunopathogenesis of acute and chronic inflammatory disorders of the airways. The clinical relevance of the anti-inflammatory actions of ?2-agonists, although often effective in the experimental setting, remains contentious. The primary objectives of the current review are: firstly, to assess the mechanisms, both molecular and cell-associated, that may limit the anti-inflammatory efficacy of ?2-agonists; secondly, to evaluate pharmacological strategies, several of which are recent and innovative, that may overcome these limitations. These are preceded by a consideration of the various types of ?2-agonists, their clinical applications, and spectrum of anti-inflammatory activities, particularly those involving adenosine 3?,5?-cyclic adenosine monophosphate-activated protein kinase-mediated clearance of cytosolic calcium, and altered gene expression in immune and inflammatory cells. PMID:24285920

  5. Further evidence of the anti-inflammatory effects of silver nanoparticles.

    PubMed

    Wong, Kenneth K Y; Cheung, Stephanie O F; Huang, Liuming; Niu, Jun; Tao, Chang; Ho, Chi-Ming; Che, Chi-Ming; Tam, Paul K H

    2009-07-01

    The production of pure silver in nanoparticle size has opened new dimensions in the clinical use of this precious metal. We and others have demonstrated previously that silver nanoparticles (nAg) possess efficient antimicrobial activity. Herein we show they may also have significant anti-inflammatory effects in a postoperative peritoneal adhesion model. This finding provides further insight into the biological actions of nAg as well as a potentially novel therapy for peritoneal adhesions in clinical surgery.With the advent of nanoscience, pure silver can now be made into nanometer-sized particles. As a result, we are able to explore the potentially beneficial properties of pure silver. In our previous study using a burn wound model in mice, we demonstrated that besides antibacterial action, silver nanoparticles (nAg) appear to have anti-inflammatory properties. Herein we further confirm the anti-inflammatory effects of nAg and explore their potential clinical application through a postoperative peritoneal adhesion model. We also elucidate the potential mechanism of action of silver. Our in vitro and in vivo experimental findings show that nAg are effective at decreasing inflammation in peritoneal adhesions without significant toxic effects. This study thus provides further evidence for and contributes to the understanding of the anti-inflammatory properties of nAg and may also give a novel therapeutic direction for the prevention of postoperative adhesions. PMID:19405063

  6. Evidence of anti-inflammatory effects of Passiflora edulis in an inflammation model

    Microsoft Academic Search

    Ana Beatriz Montanher; Silvana Maria Zucolotto; Eloir Paulo Schenkel; Tânia Silvia Fröde

    2007-01-01

    The popular medicine Passiflora edulis has been used as a sedative, tranquilizer, against cutaneous inflammatory diseases and intermittent fever. Most of the pharmacological investigations of Passiflora edulis have been addressed to its Central Nervous System activities, such as anxiolytic, anticonvulsant and sedative actions. Otherwise, there are few reports about the anti-inflammatory activity of the Passiflora species. The aim of this

  7. Anti-Inflammatory Activity of Curcumin in Macrophages Stimulated by Lipopolysaccharides from Porphyromonas gingivalis

    Microsoft Academic Search

    Dong Chen; Min Nie; Ming-wen Fan; Zhuan Bian

    2008-01-01

    Background:Porphyromonas gingivalis, a major periodontopathic bacterium, is necessary for periodontitis to take place. The lipopolysaccharide (LPS) of P. gingivalis stimulates cytokine secretion in immune cells, and thereby initiates the inflammation related to periodontitis. Macrophages are the important ones of the immune cells that are prominent at inflammatory periodontal sites. Curcumin, a major curcumanoid found in the spice turmeric, exhibits anti-inflammatory

  8. Inhibition of phagocyte-endothelium interactions by oxidized fatty acids: A natural anti-inflammatory mechanism?

    Microsoft Academic Search

    Sanjeev Sethi; Allison Y. Eastman; John W. Eaton

    1996-01-01

    Diets rich in marine fish oil may protect against cardiovascular disease. Although the mechanisms involved in such protection are not known, fish oils have been reported to exert anti-inflammatory actions. For example, dietary fish oil supplementation was observed to profoundly decrease the numbers of monocytic cells adherent to endothelium overlying atherosclerotic lesions in pigs. We have therefore investigated the possibility

  9. Journal of Theoretical Biology 241 (2006) 276294 Requirement for multiple activation signals by anti-inflammatory

    E-print Network

    Kirschner, Denise

    2006-01-01

    by anti-inflammatory feedback in macrophages J. Christian J. Ray, Denise E. Kirschnerà Department effectors such as nitric oxide (NO) and involving other cellular machinery including iron regulatory; Nitric oxide; Iron regulation; Biochemical network 1. Introduction One of the primary roles

  10. Antimicrobial and anti-inflammatory activity of folklore: Mallotus peltatus leaf extract

    Microsoft Academic Search

    Debprasad Chattopadhyay; G Arunachalam; Asit B Mandal; Tapas K Sur; Subash C Mandal; S. K Bhattacharya

    2002-01-01

    Since ages Mallotus peltatus (Geist) Muell. Arg. var acuminatus (Euphorbiaceae) leaf and stem bark is used in folk medicine to cure intestinal ailments and skin infections. In several intestinal ailments, localized inflammation is of common occurrence and hence we have evaluated the antimicrobial as well as anti-inflammatory activity of M. peltatus leaf extract. The crude methanol extract of M. peltatus

  11. Anti-Inflammatory Lactobacillus rhamnosus CNCM I-3690 Strain Protects against Oxidative Stress and Increases

    E-print Network

    Paris-Sud XI, Université de

    Anti-Inflammatory Lactobacillus rhamnosus CNCM I-3690 Strain Protects against Oxidative Stress, identified as Lactobacillus rhamnosus CNCM I-3690, protected worms by increasing their viability by 30% and with HT-29 cells and DC in the presence of LPS. Finally, this Lactobacillus strain reduced inflammation

  12. New insights into the mode of action of anti-inflammatory drugs

    Microsoft Academic Search

    J. R. Vane; R. M. Botting

    1995-01-01

    The discovery of a second cyclooxygenase has provided fresh impetus to the search for new anti-inflammatory drugs. The second enzyme is effectively absent from healthy tissues but its levels rise dramatically during inflammation. It can be induced in migratory cells by bacterial lipopolysaccharide, cytokines and growth factors. The constitutive cyclooxygenase-1 (COX-1) can thus be considered a “housekeeping” enzyme, in contrast

  13. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice

    Microsoft Academic Search

    Hossein Hosseinzadeh; Hani M Younesi

    2002-01-01

    BACKGROUND: Crocus sativus L. (saffron) is used in folk medicine, for example as an antiedematogenic agent. We aimed to evaluate the antinociceptive and anti-inflammatory activity of saffron extracts in mice. RESULTS: We used aqueous and ethanolic maceration extracts of Crocus sativus L. stigma and petals. Antinociceptive activity was examined using the hot plate and writhing tests. The effect of extracts

  14. Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation

    Microsoft Academic Search

    Mohamed El Gazzar; Rabab El Mezayen; John C. Marecki; Mark R. Nicolls; Andrew Canastar; Stephen C. Dreskin

    2006-01-01

    Thymoquinone (TQ), the main active constituent of the volatile oil extracted from Nigella sativa's seeds, has been reported to have an anti-inflammatory and immune stimulatory effect on bronchial asthma and inflammation. However, little is known about the factors and mechanisms underlying these effects. In the present study, we examined the effect of TQ on airway inflammation in a mouse model

  15. Anti-inflammatory effects of recombinant human manganese superoxide dismutase on adjuvant arthritis in rats

    Microsoft Academic Search

    M. Shingu; S. Takahashi; M. Ito; N. Hamamatu; Y. Suenaga; Y. Ichibangase; M. Nobunaga

    1994-01-01

    The anti-inflammatory effects of recombinant human manganese superoxide dismutase on adjuvant arthritis was investigated. Local application of this manganese superoxide dismutase given every 2 days not only significantly reduced foot swelling but also retarded radiological bone destruction in adjuvant arthritis. Copper zinc superoxide dismutase had little effect on foot swelling.

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

    Microsoft Academic Search

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

    2005-01-01

    Jojoba [Simmondsia chinensis (Link 1822) Schneider 1907] is an arid perennial shrub grown in several American and African countries. Jojoba seeds, which are rich in liquid wax, were used in folk medicine for diverse ailments. In the current study, the potential anti-inflammatory activity of jojoba liquid wax (JLW) was evaluated in a number of experimental models. Results showed that JLW

  17. Phytochemical compounds involved in the anti-inflammatory effect of propolis extract

    Microsoft Academic Search

    F. Borrelli; P. Maffia; L. Pinto; A. Ianaro; A. Russo; F. Capasso; A. Ialenti

    2002-01-01

    Two ethanolic propolis extracts (EPE) with and without the caffeic acid phenethyl ester (CAPE), CAPE and galangin (major components of propolis) were investigated for anti-inflammatory activity in rats using carrageenin foot oedema, carrageenin pleurisy and adjuvant arthritis. In our experiments, EPE with CAPE and CAPE alone significantly inhibited carrageenin oedema, carrageenin pleurisy and adjuvant arthritis. In contrast EPE without CAPE

  18. Broad-spectrum chemokine inhibitors (BSCIs) and their anti-inflammatory effects in vivo

    Microsoft Academic Search

    David J. Grainger; Jill Reckless

    2003-01-01

    Inappropriate inflammation is a component of a wide range of human diseases, including autoimmune disease, atherosclerosis, osteoporosis and Alzheimer’s disease. Chemokines play an important role in orchestrating leukocyte recruitment during inflammation, and therefore represent an important target for anti-inflammatory therapies. Unfortunately, the chemokine system is complex, with about 50 ligands and 20 receptors, often acting with redundancy, making selection of

  19. Anti-inflammatory effects of crude methanolic extract and fractions of Alchornea cordifolia leaves

    Microsoft Academic Search

    P. O Osadebe; F. B. C Okoye

    2003-01-01

    The leaves of Alchornea cordifolia were collected, identified, dried, and reduced to coarse powder and extracted with aqueous methanol. Using various solvent treatments, the powdered dried leaf was fractionated into five fractions, A1, A2, B, C, D and E. The fractions were subjected to phytochemical analysis to identify the biologically active constituents. The anti-inflammatory effects of crude methanolic extract (ME)

  20. Systemic anti-inflammatory effect induced by antidromic stimulation of the dorsal roots in the rat

    Microsoft Academic Search

    Erika Pintér; János Szolcsányi

    1996-01-01

    Neurogenic inflammation and other local efferent functions of the capsaicin-sensitive nerve endings is well established. Here, we describe evidence for a systemic neurogenic anti-inflammatory effect initiated in the rat by this local response. A preceding local neurogenic inflammatory induced by antidromic stimulation of lumbar dorsal roots inhibited a subsequent inflammatory response due to antidromic stimulation of the contralateral dorsal roots

  1. Anti-inflammatory effects of ethanolic extract and alkamides-derived from Heliopsis longipes roots

    Microsoft Academic Search

    Ivones Hernández; Lucía Márquez; Ioanna Martínez; Rodrigo Dieguez; Carla Delporte; Sylvia Prieto; Jorge Molina-Torres; Gabino Garrido

    2009-01-01

    Ethnopharmacological relevanceHeliopsis longipes (A. Gray) Blake (Asteraceae) is a broadly used species in the Mexican, Central and South American Traditional Medicine for its anaesthetic, analgesic, anti-inflammatory and anti-ulcerative properties. The ethanolic extract contains alkamides, mainly affinin (spilanthol). This family of compounds exerts an in vitro inhibitory action on the cyclooxygenase and lipoxygenase enzymes.

  2. In vitro antimicrobial and anti-inflammatory effects of herbs against Propionibacterium acnes

    Microsoft Academic Search

    Tsung-Hsien Tsai; Tzung-Hsun Tsai; Wen-Huey Wu; Jonathon Te-Peng Tseng; Po-Jung Tsai

    2010-01-01

    Propionibacterium acnes play an important role in the pathogenesis of acne by inducing certain inflammatory mediators and comedogenesis. The objective of this study was to evaluate the antimicrobial and anti-inflammatory effects of herbal extracts against P. acnes. Among the ten tested herbs, methanolic extracts of rose (Rosa damascene), duzhong (Eucommia ulmoides Oliv.), and yerba mate (Ilex paraguariensis) were found to

  3. Antinociceptive and Anti-Inflammatory Effects of Solvent Extracts of Tagetes erectus Linn ( Asteraceae)

    Microsoft Academic Search

    NV Shinde; KG Kanase

    Purpose: Traditionally, the leaves of Tagetes erectus L. are used in India for the alleviation of pain and inflammation. The objective of this study was to investigate the antinociceptive and anti-inflammatory activities of this plant material in an animal model. Methods: The chloroform, methanol and ether extracts of the leaves of Tagetes erectus L. (family: Asteraceae) were tested against acetic

  4. Physalis angulata extract exerts anti-inflammatory effects in rats by inhibiting different pathways

    Microsoft Academic Search

    G. N. T. Bastos; A. J. A. Silveira; C. G. Salgado; D. L. W. Picanço-Diniz; J. L. M. do Nascimento

    2008-01-01

    Physalis angulata is a popular medicine used in Brazil due to its anti-inflammatory effects, but the pharmacological mechanisms underlying these actions remain to be better understood. In the present work, lyophilized aqueous extract from the roots of Physalis angulata Linneu (AEPa) was used to control the inflammatory response induced by the injection of 1% carrageenan into subcutaneous rat's air pouches.

  5. Shikonin extracted from medicinal Chinese herbs exerts anti-inflammatory effect via proteasome inhibition

    Microsoft Academic Search

    Li Lu; Aiping Qin; Hongbiao Huang; Ping Zhou; Chuanyin Zhang; Ningning Liu; Shujue Li; Guanmei Wen; Change Zhang; Weihua Dong; Xuejun Wang; Q. Ping Dou; Jinbao Liu

    2011-01-01

    Shikonin, extracted from medicinal Chinese herb (Lithospermum erythrorhizo), was reported to exert anti-inflammatory and anti-cancer effects both in vitro and in vivo. We have found that proteasome was a molecular target of shikonin in tumor cells, but whether shikonin targets macrophage proteasome needs to be investigated. In the current study, we report that shikonin inhibited inflammation in mouse models as

  6. Anti-Inflammatory and Immunomodulatory Mechanism of Tanshinone IIA for Atherosclerosis

    PubMed Central

    Chen, Zhuo

    2014-01-01

    Tanshinone IIA (Tan II A) is widely used in the treatment of cardiovascular diseases as an active component of Salvia miltiorrhiza Bunge. It has been demonstrated to have pleiotropic effects for atherosclerosis. From the anti-inflammatory and immunomodulatory mechanism perspective, this paper reviewed major progresses of Tan IIA in antiatherosclerosis research, including immune cells, antigens, cytokines, and cell signaling pathways. PMID:25525444

  7. A gastroprotective anti-inflammatory agent: the ? -morpholinoethyl ester of niflumic acid (morniflumate)

    Microsoft Academic Search

    P. Schiantarelli; S. Cadel; D. Acerbi

    1984-01-01

    In several animal models orally administered morniflumate, the ?-morpholinoethyl ester of niflumic acid, proved almost equal to the parent compound in anti-inflammatory, analgesic and antipyretic activity with the advantage of complete freedom from the ulcerogenic effects of the acidic parent compound. Further, it was 5 times less active in intestinal perforation experiments and 10 times less toxic in acute toxicity

  8. In vivo anti-inflammatory and in vitro antioxidant activities of Mediterranean dietary plants

    Microsoft Academic Search

    Filomena Conforti; Silvio Sosa; Mariangela Marrelli; Federica Menichini; Giancarlo A. Statti; Dimitar Uzunov; Aurelia Tubaro; Francesco Menichini; Roberto Della Loggia

    2008-01-01

    Five hydroalcoholic extracts of edible plants from Calabria region (Italy) used in local traditional medicine for the treatment of inflammatory diseases were evaluated for their in vivo topical anti-inflammatory activity (inhibition of croton oil-induced ear oedema in mice) and in vitro antioxidant and antiradical properties (inhibition of linoleic acid oxidation and bovine brain liposomes peroxidation, DPPH radical scavenging). All the

  9. Interobserver variation in assessment of gastroduodenal lesions associated with non-steroidal anti-inflammatory drugs.

    PubMed Central

    Hudson, N; Everitt, S; Hawkey, C J

    1994-01-01

    Video endoscopic images were used to investigate whether gastroenterologists could agree on the definition of lesions within the stomach seen at endoscopy, with particular reference to those seen in patients taking non-steroidal anti-inflammatory drugs. Seven experienced endoscopists, unaware of the patients' clinical history or drug consumption, recorded their classification for 93 randomised video images of gastric lesions. There was complete agreement in the diagnosis of ulceration for nine images from patients who were not taking non-steroidal anti-inflammatory drugs; eight of nine were classified as deep ulcers, with 86% agreement for this subclassification. By contrast, the overall agreement for lesions in patients taking non-steroidal anti-inflammatory drugs was only 55%. Only nine of 44 ulcers were subclassified as deep, and there was considerable cross classification of non-haemorrhagic erosions and ulcers. In conclusion, ulcers that occur in patients taking non-steroidal anti-inflammatory drugs differ from those in patients who are not taking these drugs in that they are often more superficial and difficult to distinguish from erosions. The prognostic importance of these lesions is, therefore, uncertain. PMID:7926900

  10. Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway

    Microsoft Academic Search

    Leah M Flick; Kiwon W Park; Samir Softic; Todd M Greer; Raquel Keledjian; Rong Yang; Jasim Uddin; William B Guggino; Sowsan F Atabani; Yasmine Belkaid; Yan Xu; Jeffrey A Whitsett; Frank J Accurso; Marsha Wills-Karp; Nicos A Petasis; Christopher L Karp

    2004-01-01

    In cystic fibrosis, dysregulated neutrophilic inflammation and chronic infection lead to progressive destruction of the airways. The underlying mechanisms have remained unclear. Lipoxins are anti-inflammatory lipid mediators that modulate neutrophilic inflammation. We report here that lipoxin concentrations in airway fluid were significantly suppressed in patients with cystic fibrosis compared to patients with other inflammatory lung conditions. We also show that

  11. Analgesic, anti-inflammatory and venotonic effects of Cissus quadrangularis Linn

    Microsoft Academic Search

    Ampai Panthong; Wanicha Supraditaporn; Duangta Kanjanapothi; Tawat Taesotikul; Vichai Reutrakul

    2007-01-01

    Cissus quadrangularis, a medicinal plant indigenous to Asia and Africa, is used for many ailments, especially for the treatment of hemorrhoid. The effects associated with hemorrhoid, i.e. analgesic and anti-inflammatory activities as well as the venotonic effect of the methanol extract of C. quadrangularis (CQ) were assessed in comparison with reference drugs. In the analgesic test, CQ provoked a significant

  12. In vivo Antinociceptive and Anti-inflammatory Activities of Dried and Fermented Processed Virgin Coconut Oil

    Microsoft Academic Search

    Z. A. Zakaria; M. N. Somchit; A. M. Mat Jais; L. K. Teh; M. Z. Salleh; K. Long

    2011-01-01

    Objective: The present study was carried out to investigate the antinociceptive and anti-inflammatory activities of virgin coconut oil (VCO) produced by theMalaysian Agriculture Research and Development Institute (MARDI) using various in vivo models. Materials and Methods: Two types of VCOs, produced via standard drying (VCOA) and fermentation (VCOB) processes were used in this study. Both VCOA and VCOB were serially

  13. Structural investigation of chitosan-based microspheres with some anti-inflammatory drugs

    NASA Astrophysics Data System (ADS)

    Dreve, Simina; Kacso, Iren; Popa, Adriana; Raita, Oana; Dragan, Felicia; Bende, A.; Borodi, Gh.; Bratu, I.

    2011-06-01

    The use of chitosan as an excipient in oral formulations, as a drug delivery vehicle for ulcerogenic anti-inflammatory drugs and as base in polyelectrolyte complex systems, to prepare solid release systems as sponges was investigated. The preparation by double emulsification of chitosan hydrogels carrying diclofenac, acetyl-salycilic acid and hydrocortisone acetate as anti-inflammatory drugs is reported. The concentration of anti-inflammatory drug in the chitosan hydrogel generating the sponges was 0.08 mmol. Chitosan-drug loaded sponges with anti-inflammatory drugs were prepared by freeze-drying at -60 °C and 0.009 atm. Structural investigations of the solid formulations were done by Fourier-transformed infrared and ultraviolet-visible spectroscopy, spectrofluorimetry, differential scanning calorimetry and X-ray diffractometry. The results indicated that the drug molecules are forming temporary chelates in chitosan hydrogels and sponges. Electron paramagnetic resonance demonstrates the presence of free radicals in a wide range and the antioxidant activity for chitosan-drug supramolecular cross-linked assemblies.

  14. An investigation of antioxidant and anti-inflammatory activities from blood components of Crocodile (Crocodylus siamensis).

    PubMed

    Phosri, Santi; Mahakunakorn, Pramote; Lueangsakulthai, Jiraporn; Jangpromma, Nisachon; Swatsitang, Prasan; Daduang, Sakda; Dhiravisit, Apisak; Thammasirirak, Sompong

    2014-10-01

    Antioxidant and anti-inflammatory activities were found from Crocodylus siamensis (C. siamensis) blood. The 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, nitric oxide scavenging, hydroxyl radical scavenging and linoleic peroxidation assays were used to investigate the antioxidant activities of the crocodile blood. Results show that crocodile blood components had antioxidant activity, especially hemoglobin (40.58 % nitric oxide radical inhibition), crude leukocyte extract (78 % linoleic peroxidation inhibition) and plasma (57.27 % hydroxyl radical inhibition). Additionally, the anti-inflammatory activity of the crocodile blood was studied using murine macrophage (RAW 264.7) as a model. The results show that hemoglobin, crude leukocyte extract and plasma were not toxic to RAW 264.7 cells. Also they showed anti-inflammatory activity by reduced nitric oxide (NO) and interleukin 6 (IL-6) productions from lipopolysaccharide (LPS)-stimulated cells. The NO inhibition percentages of hemoglobin, crude leukocyte extract and plasma were 31.9, 48.24 and 44.27 %, respectively. However, only crude leukocyte extract could inhibit IL-6 production. So, the results of this research directly indicate that hemoglobin, crude leukocyte extract and plasma of C. siamensis blood provide both antioxidant and anti-inflammatory activities, which could be used as a supplementary agent in pharmaceutical products. PMID:25216803

  15. Comparative Evaluation of Anti-Inflammatory Activity of Curcuminoids, Turmerones, and Aqueous Extract of Curcuma longa

    PubMed Central

    Bagad, Ashish Subhash; Bhaskaran, Natarajan; Agarwal, Amit

    2013-01-01

    Curcuma longa is widely known for its anti-inflammatory activity in traditional system of medicine for centuries and has been scientifically validated extensively. The present study was conducted to evaluate the anti-inflammatory activity of curcuminoids and oil-free aqueous extract (COFAE) of C. longa and compare it with that of curcuminoids and turmerones (volatile oil), the bioactive components of C. longa that are proven for the anti-inflammatory potential. The activity against inflammation was evaluated in xylene-induced ear edema, cotton pellet granuloma models in albino Swiss mice and albino Wistar rats, respectively. The results showed that COFAE of C. longa at three dose levels significantly (P ? 0.05) inhibited inflammation in both models, as evidenced by reduction in ear weight and decrease in wet as well as dry weights of cotton pellets, when compared to the vehicle control. The COFAE of C. longa showed considerable anti-inflammatory effects against acute and chronic inflammation and the effects were comparable to those of curcuminoids and turmerones. PMID:24454348

  16. Experimental evaluation of analgesic and anti-inflammatory activity of simvastatin and atorvastatin

    PubMed Central

    Jaiswal, Swapnil R.; Sontakke, Smita D.

    2012-01-01

    Aim: The aim of this study is to evaluate the analgesic and anti-inflammatory activities of atorvastatin and simvastatin in different experimental models in mice and rats. Materials and Methods: Analgesic activity of simvastatin and atorvastatin was assessed in tail flick model in rats (n = 6), where it was compared with aspirin and tramadol and in acetic acid induced writhing in mice (n = 6), where it was compared with aspirin. Anti-inflammatory activity of statins was evaluated using carrageenin induced paw edema and formalin induced arthritis in rats. Results: In the tail flick method, analgesic effect of tramadol was significantly more than the other drugs except at two observation times, when it was comparable to simvastatin and atorvastatin. Effect of simvastatin was found to be comparable to aspirin. In acetic acid induced writhing method, analgesic activity of simvastatin was comparable to that of aspirin while that of atorvastatin was significantly less. In carrageenin induced paw edema in rats, both simvastatin and atorvastatin showed anti-inflammatory activity which was comparable to aspirin. Both the statins exhibited significant anti-inflammatory activity (P < 0.01) in formalin induced arthritis model though less than aspirin (P < 0.05). Conclusion: The results of this study if substantiated by further experimental and clinical research suggest that simvastatin and atorvastatin may play an adjuvant role, which may be particularly beneficial in the treatment of inflammatory disorders, especially when there is coexisting dyslipidemia. PMID:23087508

  17. Abstract. Soluble epoxide hydrolase (sEH) hydrolyses/ inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs)

    E-print Network

    Hammock, Bruce D.

    the development of many types of cancers (1, 2). A typical example is inflammatory bowel disease (IBD) that comes active inflammatory process in the gut and includes two diseases: ulcerative colitis (UC) and CrohnAbstract. Soluble epoxide hydrolase (sEH) hydrolyses/ inactivates anti-inflammatory

  18. In vitro anti-inflammatory, mutagenic and antimutagenic activities of ethanolic extract of Clerodendrum paniculatum root

    PubMed Central

    Phuneerub, Pravaree; Limpanasithikul, Wacharee; Palanuvej, Chanida; Ruangrungsi, Nijsiri

    2015-01-01

    Clerodendrum paniculatum L. (Family Verbenaceae) has been used as an antipyretic and anti-inflammatory drug in traditional Thai medicine. This present study investigated the in vitro anti-inflammatory, mutagenic and antimutagenic activities of the ethanolic extract of C. paniculatum (CPE) dried root collected from Sa Kaeo Province of Thailand. Murine macrophage J774A.1 cells were stimulated by lipopolysaccharide (LPS) to evaluate nitric oxide (NO), tumor necrosis factor-? (TNF-?) and prostaglandin E2 (PGE2) production in the anti-inflammatory test while the mutagenic and antimutagenic potential was performed by the Ames test. The outcome of this study displayed that the CPE root significantly inhibited LPS-induced NO, TNF-?, and PGE2 production in macrophage cell line. In addition, the CPE root was not mutagenic toward Salmonella typhimurium strain TA98 and TA100 with and without nitrite treatment. Moreover, it inhibited the mutagenicity of nitrite treated 1-aminopyrene on both strains. The findings suggested the anti-inflammatory and antimutagenic potentials of CPE root. PMID:25878973

  19. Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble

    E-print Network

    Hammock, Bruce D.

    Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs-inflammatory drugs (NSAIDs) and previously undescribed soluble epoxide hydrolase inhibitors (sEHIs) in lipo that these drug combinations (NSAIDs and sEHIs) produce a valuable beneficial analgesic and anti-inflamma- tory

  20. Analgesic and anti-inflammatory effects of essential oils of Eucalyptus

    Microsoft Academic Search

    Jeane Silva; Worku Abebe; S. M Sousa; V. G Duarte; M. I. L Machado; F. J. A Matos

    2003-01-01

    Many species of the genus Eucalyptus from the Myrtaceae family are used in Brazilian folk medicine for the treatment of various medical conditions such as cold, flue, fever, and bronchial infections. In the current investigation, we evaluated the analgesic and anti-inflammatory effects of essential oil extracts from three species of Eucalyptus employing various standard experimental test models. Using acetic acid-induced

  1. Antinociceptive and anti-inflammatory effects of Satureja hortensis L . extracts and essential oil

    Microsoft Academic Search

    Valiollah Hajhashemi; Alireza Ghannadi; Sayed Karim Pezeshkian

    2002-01-01

    Satureja hortensis L. (Lamiaceae) is a medicinal plant used in Iranian folk medicine as muscle and bone pain reliever. In the present study, hydroalcoholic extract, polyphenolic fraction and essential oil of the aerial parts of the herb were prepared and evaluated for the analgesic activity using light tail flick, formalin and acetic acid-induced writhing in mice. Also, the anti-inflammatory effects

  2. Peripheral muscarinic receptors mediate the anti-inflammatory effects of auricular acupuncture

    Microsoft Academic Search

    Wai Yeung Chung; Hong Qi Zhang; Shi Ping Zhang

    2011-01-01

    BACKGROUND: The cholinergic and opioid systems play important roles in modulating inflammation. This study tests whether auricular acupuncture (AA) produces anti-inflammatory effects via opioid and peripheral cholinergic receptors in a rat model. METHODS: Rats were anesthetized with chloral hydrate and inflammation was induced by intraplantar injection of carrageenan. Electroacupuncture was performed at auricular points bilaterally. The severity of inflammation was

  3. Rosuvastatin displays anti-atherothrombotic and anti-inflammatory properties in apoE-deficient mice

    Microsoft Academic Search

    M. Monetti; M. Canavesi; M. Camera; R. Parente; R. Paoletti; E. Tremoli; A. Corsini; S. Bellosta

    2007-01-01

    Inflammation contributes importantly to all stages of atherosclerosis, including the onset of acute thrombotic complications. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. Moreover, statins have been shown to possess several pleiotropic properties independent of cholesterol lowering in experimental settings. Based on these premises, we investigated the anti-inflammatory and anti-atherothrombotic properties of

  4. Antioxidant and anti-inflammatory effects of selected natural compounds contained in a dietary supplement on two human immortalized keratinocyte lines.

    PubMed

    Fasano, Elena; Serini, Simona; Mondella, Nadia; Trombino, Sonia; Celleno, Leonardo; Lanza, Paola; Cittadini, Achille; Calviello, Gabriella

    2014-01-01

    Several advantages may derive from the use of dietary supplements containing multiple natural antioxidants and/or anti-inflammatory agents. At present, however, there is scarce information on the properties and potential of combined supplements. To fill the gap, the antioxidant and anti-inflammatory activities exerted by a combination of seven natural components (coenzyme Q10, krill oil, lipoic acid, resveratrol, grape seed oil, ?-tocopherol, and selenium) contained in a dietary supplement used for the prevention of skin disorders were investigated in vitro. Each component was administered, alone or in combination, to human keratinocytes, and the inhibition of Reactive Oxygen Species production and lipid peroxidation as well as the ability to reduce inflammatory cytokine secretion and to modulate Nuclear Factor-?B pathway was evaluated. The combination exhibited high antioxidant activity and in specific conditions the combination's efficiency was higher than that of the most powerful components administered individually. Moreover, the combination showed remarkable anti-inflammatory properties. It reduced more efficiently than each component the secretion of Monocyte Chemoattractant Protein-1, a crucial cytokine for the development of chronic inflammation in skin, and inhibited Nuclear Factor-?B molecular pathway. Overall, our findings suggest that the combined formulation may have the potential to powerfully inhibit oxidative stress and inflammation at skin level. PMID:25197638

  5. Kaposi's Sarcoma-Associated Herpesvirus Subversion of the Anti-Inflammatory Response in Human Skin Cells Reveals Correlates of Latency and Disease Pathogenesis

    PubMed Central

    Fontana, Judith M.; Mygatt, Justin G.; Conant, Katelyn L.; Parsons, Chris H.; Kaleeba, Johnan A. R.

    2014-01-01

    KSHV is the etiologic agent for Kaposi's sarcoma (KS), a neoplasm that manifests most aggressively as multifocal lesions on parts of human skin with a propensity for inflammatory reactivity. However, mechanisms that control evolution of KS from a benign hyperplasia to the histologically complex cutaneous lesion remain unknown. In this study, we found that KSHV induces proteomic and morphological changes in melanocytes and melanoma-derived cell lines, accompanied by deregulation of the endogenous anti-inflammatory responses anchored by the MC1-R/?-MSH signaling axis. We also identified two skin-derived cell lines that displayed differences in ability to support long-term KSHV infection and mapped this dichotomy to differences in (a) NF-?B activation status, (b) processing and expression of KSHV latency-associated nuclear antigen isoforms putatively associated with the viral lytic cycle, and (c) susceptibility to virus-induced changes in expression of key anti-inflammatory response genes that antagonize NF-?B, including MC1-R, POMC, TRP-1, and xCT. Viral subversion of molecules that control the balance between latency and lytic replication represents a novel correlate of KSHV pathogenesis and tropism in skin and underscores the potential benefit of harnessing the endogenous anti-inflammatory processes as a therapeutic option for attenuating cutaneous KS and other proinflammatory outcomes of KSHV infection in high-risk individuals. PMID:24701351

  6. Sucrose Counteracts the Anti-Inflammatory Effect of Fish Oil in Adipose Tissue and Increases Obesity Development in Mice

    PubMed Central

    Ma, Tao; Liaset, Bjørn; Hao, Qin; Petersen, Rasmus Koefoed; Fjære, Even; Ngo, Ha Thi; Lillefosse, Haldis Haukås; Ringholm, Stine; Sonne, Si Brask; Treebak, Jonas Thue; Pilegaard, Henriette; Frøyland, Livar; Kristiansen, Karsten; Madsen, Lise

    2011-01-01

    Background Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance. Methodology/Principal Findings We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein?sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state. Conclusions/Significance The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice. PMID:21738749

  7. [Effect of a non-steroidal anti-inflammatory agent, tolmetin sodium on exudative inflammation in experimental animals (author's transl)].

    PubMed

    Nakamura, H; Yokoyama, Y; Motoyoshi, S; Ishii, K; Shimizu, M

    1979-07-01

    Effect of tolmetin sodium(Tol) on acute and subacute exudative inflammation was tested in experimental animals. Tol had a potent inhibitory activity (ED50 = 0.75 mg/kg, p.o.) on the increased vascular permeability induced by acetic acid in mice, and the potency was about 0.4 times that of indomethacin (Ind), and 6-93 times that of ibuprofen (Ibu), phenylbutazone(Phe) and aspirin(Asp). The inhibitory activity of Tol(ED50 = 18.2 mg/kg, p.o.) on UV-induced erythema in guinea pigs was about 0.3 times that of Ind. A recovery of the hind paw edema of rats, produced by a mixture of kaolin and carrageenin, was promoted by oral administration of Tol(2.5 approximately 20 mg/kg x 5/2 days). Tol(80 mg/kg/day, p.o.) showed a significant activity in inhibiting the exudation caused by croton oil in rats, and the activity was about 0.025 times that of Ind and greater than that of Ibu, Phe and Asp. Tol(100-800 microgram/ml) inhibited in a dose-dependent manner the phytohemagglutinin-induced blast transformation of cultured lymphocytes from rat thymus, as did salicylic acid. In vitro, Tol showed a potent activity similar to that of Ibu and Phe in preventing the denaturation of bovine serum albumin and the lysis of rat erythrocytes. From these results, it is suggested that Tol has a particularly potent inhibitory activity on acute exudative inflammation, and the mode of action may be attributed to a mechanism similar to that seen with other acidic non-steroidal anti-inflammatory drugs. PMID:540878

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

    PubMed

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

    2014-03-01

    The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 ?g/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors. PMID:24318481

  9. Analgesic and anti-inflammatory activities of methanol extract from Desmodium triflorum DC in mice.

    PubMed

    Lai, Shang-Chih; Peng, Wen-Huang; Huang, Shun-Chieh; Ho, Yu-Ling; Huang, Tai-Hung; Lai, Zhen-Rung; Chang, Yuan-Shiun

    2009-01-01

    In this study, we evaluated the analgesic effect of methanol extract from Desmodium triflorum DC (MDT) by using animal models of acetic acid-induced writhing response and formalin test. The anti-inflammatory effect of MDT was investigated by lambda-carrageenan-induced paw edema in mice. In order to study the anti-inflammatory mechanism of MDT, we detected the activities of glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver, the levels of interleukin-1beta (IL-1beta), tumor necrosis factor (TNF-alpha), malondialdehyde (MDA) and nitric oxide (NO) in the edema paw tissue. In the analgesic test, MDT (0.5 and 1.0 g/kg) decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test. In the anti-inflammatory test, MDT (0.5 and 1.0 g/kg) decreased the paw edema at the 3rd, 4th, 5th and 6th hour after lambda-carrageenan administration. On the other hand, MDT increased the activities of SOD and GRd in liver tissues and decreased the MDA level in the edema paw at the 3rd hour after lambda-carrageenan-induced inflammation. MDT also affected the levels of interleukin-1beta, tumor necrosis factor-alpha, NO and MDA which were induced by lambda-carrageenan. The results suggested that MDT possessed analgesic and anti-inflammatory effects. The anti-inflammatory mechanism of MDT might be related to the decreases in the level of MDA in the edema paw via increasing the activities of SOD and GRd in the liver, and the NO level via regulating the IL-1beta production and the level of TNF-alpha in the inflamed tissues. PMID:19606516

  10. Analgesic, anti-inflammatory and anti-pyretic activities of Caesalpinia decapetala

    PubMed Central

    Parveen, Amna; Sajid Hamid Akash, Muhammad; Rehman, Kanwal; Mahmood, Qaisar; Qadir, Muhammad Imran

    2014-01-01

    Introduction: In many pathological conditions, pain, inflammation and fever are interdependent to each other. Due to the use of synthetic drugs, many unwanted effects usually appear. Various studies have been conducted on Caesalpinia decapetala (C. decapetala) to evaluate its effects in the treatment of various diseases but no sufficient scientific literature is available online to prove its analgesic, anti-inflammatory and anti-pyretic activities. Methods: The analgesic, anti-inflammatory and anti-pyretic activities of 70% aqueous methanolic and n-hexane extracts of C. decapetala was evaluated using Swiss albino mice (20-30 g). Results: The results showed that aqueous methanolic extract of C. decapetala at the dose of 100 mg/kg exhibited significant (p< 0.05) activities in various pain models including acetic acid-induced writhing (18.4 ± 0.53), formalin-induced licking (275 ± 4.18) and hot plate method (2.3 ± 0.0328); whereas,  n-hexane extract showed its effects in acetic acid-induced writhing (20 ± 0.31), formalin-induced licking (293 ± 1.20) and hot plate method (2.224 ± 0.029) compared to the effects observed in control group animals. Similarly, the aqueous methanolic extract of C. decapetala after 2 h of treatment exhibited more significant anti-inflammatory (0.66 ± 0.06) and anti-pyretic (38.81 ± 0.05) activities compared to the control group animals. Conclusion: From the findings of our present study, we concluded that the aqueous methanolic extract of C. decapetala has stronger analgesic, anti-inflammatory and anti-pyretic effects than its n-hexane extract. Further studies are required to investigate the active constituents of C. decapetala that exhibit analgesic, anti-inflammatory and anti-pyretic activities. PMID:24790898

  11. Caveolae control the anti-inflammatory phenotype of senescent endothelial cells

    PubMed Central

    Powter, Elizabeth E; Coleman, Paul R; Tran, Mai H; Lay, Angelina J; Bertolino, Patrick; Parton, Robert G; Vadas, Mathew A; Gamble, Jennifer R

    2015-01-01

    Senescent endothelial cells (EC) have been identified in cardiovascular disease, in angiogenic tumour associated vessels and in aged individuals. We have previously identified a novel anti-inflammatory senescent phenotype of EC. We show here that caveolae are critical in the induction of this anti-inflammatory senescent state. Senescent EC induced by either the overexpression of ARHGAP18/SENEX or by H2O2 showed significantly increased numbers of caveolae and associated proteins Caveolin-1, cavin-1 and cavin-2. Depletion of these proteins by RNA interference decreased senescence induced by ARHGAP18 and by H2O2. ARHGAP18 overexpression induced a predominantly anti-inflammatory senescent population and depletion of the caveolae-associated proteins resulted in the preferential reduction in this senescent population as measured by neutrophil adhesion and adhesion protein expression after TNF? treatment. In confirmation, EC isolated from the aortas of CAV-1?/? mice failed to induce this anti-inflammatory senescent cell population upon expression of ARHGAP18, whereas EC from wild-type mice showed a significant increase. NF-?B is one of the major transcription factors mediating the induction of E-selectin and VCAM-1 expression, adhesion molecules responsible for leucocyte attachment to EC. TNF?-induced activation of NF-?B was suppressed in ARHGAP18-induced senescent EC, and this inhibition was reversed by Caveolin-1 knock-down. Thus, out results demonstrate that an increase in caveolae and its component proteins in senescent ECs is associated with inhibition of the NF-kB signalling pathway and promotion of the anti-inflammatory senescent pathway. PMID:25407919

  12. Caveolae control the anti-inflammatory phenotype of senescent endothelial cells.

    PubMed

    Powter, Elizabeth E; Coleman, Paul R; Tran, Mai H; Lay, Angelina J; Bertolino, Patrick; Parton, Robert G; Vadas, Mathew A; Gamble, Jennifer R

    2015-02-01

    Senescent endothelial cells (EC) have been identified in cardiovascular disease, in angiogenic tumour associated vessels and in aged individuals. We have previously identified a novel anti-inflammatory senescent phenotype of EC. We show here that caveolae are critical in the induction of this anti-inflammatory senescent state. Senescent EC induced by either the overexpression of ARHGAP18/SENEX or by H?O? showed significantly increased numbers of caveolae and associated proteins Caveolin-1, cavin-1 and cavin-2. Depletion of these proteins by RNA interference decreased senescence induced by ARHGAP18 and by H?O?. ARHGAP18 overexpression induced a predominantly anti-inflammatory senescent population and depletion of the caveolae-associated proteins resulted in the preferential reduction in this senescent population as measured by neutrophil adhesion and adhesion protein expression after TNF? treatment. In confirmation, EC isolated from the aortas of CAV-1(-/-) mice failed to induce this anti-inflammatory senescent cell population upon expression of ARHGAP18, whereas EC from wild-type mice showed a significant increase. NF-?B is one of the major transcription factors mediating the induction of E-selectin and VCAM-1 expression, adhesion molecules responsible for leucocyte attachment to EC. TNF?-induced activation of NF-?B was suppressed in ARHGAP18-induced senescent EC, and this inhibition was reversed by Caveolin-1 knock-down. Thus, out results demonstrate that an increase in caveolae and its component proteins in senescent ECs is associated with inhibition of the NF-kB signalling pathway and promotion of the anti-inflammatory senescent pathway. PMID:25407919

  13. Anti-inflammatory effect of a novel food Cordyceps guangdongensis on experimental rats with chronic bronchitis induced by tobacco smoking.

    PubMed

    Yan, Wenjuan; Li, Taihui; Zhong, Zhiyong

    2014-10-01

    Cordyceps guangdongensis T. H. Li, Q. Y. Lin & B. Song (Cordycipitaceae) is a novel food approved by the Ministry of Public Health of China in 2013. Preliminary studies revealed that this novel food has multiple pharmacological activities such as anti-fatigue effect, antioxidant ability, prolonging life, anti-avian influenza virus activity, and therapeutic effect on chronic renal failure. However, the anti-inflammatory effect on chronic bronchitis and the effective constituent are still unknown. The purpose of this study was to investigate both the anti-inflammatory effect of the edible fungus on experimental rats with chronic bronchitis induced by tobacco smoking, and the pilot effective constituent. Test rats were intragastrically administered with 3 doses of hot-water extract from C. guangdongensis (0.325, 0.65 and 1.30 g kg(-1) bw daily for low, middle and high dose, respectively) for 26 days. Biochemical indices and histological examinations in rats with chronic bronchitis induced by tobacco smoking were determined. The content and molecular weights of the polysaccharide from the hot-water extract were detected by the phenol-sulfuric acid method and gel permeation chromatography, respectively. Biochemical indices in the low, middle and high-dose groups with the hot-water extract of C. guangdongensis were only 53.4%, 46.0% and 40.4% of those in the model control group (total leukocytes), respectively; 70.7%, 60.3% and 58.1% (macrophages); 33.0%, 26.8% and 16.1% (neutrophils); and 22.2%, 23.5% and 13.6% (lymphocytes) of those in the model control group. The bronchial lesions and inflammatory cell infiltration were significantly alleviated in all groups with hot-water extract of C. guangdongensis. This study indicates that the hot-water extract from C. guangdongensis has a significant anti-inflammatory effect on chronic bronchitis. The content of the polysaccharide was 6.92%; the molecular weights of the 3 polysaccharide components were respectively 1.28 × 10(6), 2.36 × 10(4) and 5.21 × 10(3) Da. PMID:25135295

  14. Polyphenolic Profile, Antioxidant and Anti-Inflammatory Activity of Eastern Teaberry (Gaultheria procumbens L.) Leaf Extracts.

    PubMed

    Michel, Piotr; Dobrowolska, Anna; Kicel, Agnieszka; Owczarek, Aleksandra; Bazylko, Agnieszka; Granica, Sebastian; Piwowarski, Jakub P; Olszewska, Monika A

    2014-01-01

    Dry leaf extracts of eastern teaberry (Gaultheria procumbens L.) were evaluated as a source of bioactive phytocompounds through systematic activity testing and phytochemical profiling. The antioxidant efficiency was tested using five complementary in vitro models (DPPH; FRAP; linoleic acid (LA) peroxidation assay; O2•- and H2O2 scavenging tests) in parallel with standard antioxidants. The 75% methanol extract and its diethyl ether, ethyl acetate (EAF), n-butanol and water fractions exhibited the dose-dependent responses in all assays, with the highest capacities found for EAF (DPPH EC50 = 2.9 ?g/mL; FRAP = 12.8 mmol Fe2+/g; IC50 for LA-peroxidation = 123.9 ?g/mL; O2•- SC50 = 3.9 ?g/mL; H2O2 SC50 = 7.2 ?g/mL). The EAF had also the highest anti-inflammatory activity in the inhibition tests of lipoxygenase and hyaluronidase (60.14% and 21.83% effects, respectively, at the concentration of 100 ?g/mL). Activity parameters of the extracts correlated strongly with the levels of total phenolics (72.4-270.7 mg GAE/g), procyanidins, and phenolic acids, whereas for flavonoids only moderate effects were observed. Comprehensive UHPLC-PDA-ESI-MS3 and HPLC-PDA studies led to the identification of 35 polyphenols with a procyanidin A-type trimer, quercetin 3-O-glucuronide, isomers of caffeoylquinic acids, and (?)-epicatechin being the dominant components. Significant activity levels, high phenolic contents and high extraction yields (39.4%-42.5% DW for defatted and crude methanol extracts, respectively) indicate the value of eastern teaberry leaves as bioactive products. PMID:25493634

  15. Nitroxide derivatives of non-steroidal anti-inflammatory drugs exert anti-inflammatory and superoxide dismutase scavenging properties in A459 cells

    PubMed Central

    Flores-Santana, Wilmarie; Moody, Terry; Chen, Weibin; Gorczynski, Michael J; Shoman, Mai E; Velázquez, Carlos; Thetford, Angela; Mitchell, James B; Cherukuri, Murali K; King, S Bruce; Wink, David A

    2012-01-01

    BACKGROUND AND PURPOSE Inflammation and reactive oxygen species are associated with the promotion of various cancers. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in cancer prevention treatments has been promising in numerous cancers. We report the evaluation of NSAIDs chemically modified by the addition of a redox-active nitroxide group. TEMPO-aspirin (TEMPO-ASA) and TEMPO-indomethacin (TEMPO-IND) were synthesized and evaluated in the lung cancer cell line A549. EXPERIMENTAL APPROACHES We evaluated physico-chemical properties of TEMPO-ASA and TEMPO-IND by electron paramagnetic resonance and cyclic voltammetry. Superoxide dismutase-like properties was assayed by measuring cytochrome c reduction and anti-inflammatory effects were assayed by measuring production of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). MTT proliferation assay and clonogenic assay were evaluated in the A549 lung carcinoma cell line. Maximum tolerated doses (MTD) and acute ulcerogenic index were also evaluated in in vivo. KEY RESULTS MTD were: TEMPO (140 mg·kg?1), ASA (100 mg·kg?1), indomethacin (5 mg·kg?1), TEMPO-ASA (100 mg·kg?1) and TEMPO-IND (40 mg·kg?1). While TEMPO-ASA was as well tolerated as ASA, TEMPO-IND showed an eightfold improvement over indomethacin. TEMPO-IND showed markedly less gastric toxicity than the parent NSAID. Both TEMPO-ASA and TEMPO-IND inhibited production of PGE2 and LTB4 in A549 cells with maximum effects at 100 µg·mL?1 or 10 µg·mL?1 respectively. CONCLUSIONS AND IMPLICATIONS The nitroxide-NSAIDs retained superoxide scavenging capacity of the parent nitroxide and anti-inflammatory effects, inhibiting cyclooxygenase and 5-lipoxygenase enzymes. These redox-modified NSAIDs might be potential drug candidates, as they exhibit the pharmacological properties of the parent NSAID with antioxidant activity decreasing NSAID-associated toxicity. PMID:21658022

  16. Anti-Inflammatory Properties of the Medicinal Mushroom Cordyceps militaris Might Be Related to Its Linear (1?3)-?-D-Glucan

    PubMed Central

    Smiderle, Fhernanda R.; Baggio, Cristiane H.; Borato, Débora G.; Santana-Filho, Arquimedes P.; Sassaki, Guilherme L.; Iacomini, Marcello; Van Griensven, Leo J. L. D.

    2014-01-01

    The Ascomycete Cordyceps militaris, an entomopathogenic fungus, is one of the most important traditional Chinese medicines. Studies related to its pharmacological properties suggest that this mushroom can exert interesting biological activities. Aqueous (CW and HW) and alkaline (K5) extracts containing polysaccharides were prepared from this mushroom, and a ?-D-glucan was purified. This polymer was analysed by GC-MS and NMR spectrometry, showing a linear chain composed of ?-D-Glcp (1?3)-linked. The six main signals in the 13C-NMR spectrum were assigned by comparison to reported data. The aqueous (CW, HW) extracts stimulated the expression of IL-1?, TNF-?, and COX-2 by THP-1 macrophages, while the alkaline (K5) extract did not show any effect. However, when the extracts were added to the cells in the presence of LPS, K5 showed the highest inhibition of the pro-inflammatory genes expression. This inhibitory effect was also observed for the purified ?-(1?3)-D-glucan, that seems to be the most potent anti-inflammatory compound present in the polysaccharide extracts of C. militaris. In vivo, ?-(1?3)-D-glucan also inhibited significantly the inflammatory phase of formalin-induced nociceptive response, and, in addition, it reduced the migration of total leukocytes but not the neutrophils induced by LPS. In conclusion, this study clearly demonstrates the anti-inflammatory effect of ?-(1?3)-D-glucan. PMID:25330371

  17. Anti-Inflammatory Effect of Procyanidins from Wild Grape (Vitis amurensis) Seeds in LPS-Induced RAW 264.7 Cells

    PubMed Central

    Bak, Min-Ji; Truong, Van Long; Kang, Hey-Sook; Jun, Mira; Jeong, Woo-Sik

    2013-01-01

    In the present study, the anti-inflammatory effect and underlying mechanisms of wild grape seeds procyanidins (WGP) were examined using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells. We used nitric oxide (NO) and prostaglandin E2 (PGE2) and reactive oxygen species (ROS) assays to examine inhibitory effect of WGP and further investigated the mechanisms of WGP suppressed LPS-mediated genes and upstream expression by Western blot and confocal microscopy analysis. Our data indicate that WGP significantly reduced NO, PGE2, and ROS production and also inhibited the expression of proinflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions. Consistently, WGP significantly reduced LPS-stimulated expression of proinflammatory cytokines such as tumor necrosis factor ? (TNF-?) and interleukin- (IL-) 1?. Moreover, WGP prevented nuclear translocation of nuclear factor-?B (NF?B) p65 subunit by reducing inhibitory ?B-? (I?B?) and NF?B phosphorylation. Furthermore, we found that WGP inhibited LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). Taken together, our results demonstrated that WGP exerts potent anti-inflammatory activity through the inhibition of iNOS and COX-2 by regulating NF?B and p38 MAPK pathway. PMID:24260615

  18. Anti-inflammatory effect of ginsenoside Rb1 contributes to the recovery of gastrointestinal motility in the rat model of postoperative ileus.

    PubMed

    Tan, Shanjun; Yu, Wenkui; Lin, Zhiliang; Chen, Qiyi; Shi, Jialiang; Dong, Yi; Duan, Kaipeng; Bai, Xiaowu; Xu, Lin; Li, Jieshou; Li, Ning

    2014-01-01

    Ginsenoside Rb1 (GRb1), one of the principle active components of Panax ginseng, has been reported to reduce inflammation in various diseases. In the present study, we investigated whether GRb1 has an anti-inflammatory effect on postoperative ileus (POI) and further contributes to the recovery of gastrointestinal motility. POI was induced in rats by intestinal manipulation. The POI rats received 5, 10 and 20?mg/kg GRb1 orally via gavage four times before and after surgery. Gastrointestinal motility was assessed by charcoal transport. Systemic inflammation was assessed by serum tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6 and IL-10 concentrations, whereas intestinal inflammation was assessed by the activity of myeloperoxidase, and concentrations and gene expression of TNF-?, IL-1?, IL-6 and IL-10 in the ileum tissue. The results revealed that GRb1 increased rat gastrointestinal transit with POI. The increased levels of systemic and intestinal inflammatory parameters in POI rats were also reduced by GRb1. In addition, GRb1 reduced systemic and intestinal inflammation and increased the gastrointestinal transit of POI rats in a dose-dependent manner, and with signi?cance at doses of 10 and 20?mg/kg. These results suggest that GRb1 has a potent anti-inflammatory effect on POI and further contributes to the recovery of gastrointestinal motility. GRb1 may be a promising treatment for POI prophylaxis. PMID:25177041

  19. Arzanol, an anti-inflammatory and anti-HIV-1 phloroglucinol alpha-Pyrone from Helichrysum italicum ssp. microphyllum.

    PubMed

    Appendino, Giovanni; Ottino, Michela; Marquez, Nieves; Bianchi, Federica; Giana, Anna; Ballero, Mauro; Sterner, Olov; Fiebich, Bernd L; Munoz, Eduardo

    2007-04-01

    An acetone extract of Helichrysum italicum ssp. microphyllum afforded the phloroglucinol alpha-pyrone arzanol (1a) as a potent NF-kappaB inhibitor. Arzanol is identical with homoarenol (2a), whose structure should be revised. The phloroglucinol-type structure of arzanol and the 1,2,4-trihydroxyphenyl-type structure of the base-induced fragmentation product of homoarenol could be reconciled in light of a retro-Fries-type fragmentation that triggers a change of the hydroxylation pattern of the aromatic moiety. On the basis of these findings, the structure of arenol, the major constituent of the clinically useful antibiotic arenarin, should be revised from 2b to 1b, solving a long-standing puzzle over its biogenetic derivation. An alpha-pyrone (micropyrone, 7), the monoterpene rac-E-omega-oleoyloxylinalol (10), four known tremetones (9a-d), and the dimeric pyrone helipyrone (8) were also obtained. Arzanol inhibited HIV-1 replication in T cells and the release of pro-inflammatory cytokines in LPS-stimulated primary monocytes, qualifying as a novel plant-derived anti-inflammatory and antiviral chemotype worth further investigation. PMID:17315926

  20. In vitro anti-inflammatory and pro-aggregative effects of a lipid compound, petrocortyne A, from marine sponges.

    PubMed

    Hong, Sungyoul; Kim, Sung Hwan; Rhee, Man Hee; Kim, Ae Ra; Jung, Jee H; Chun, Taehoon; Yoo, Eun Sook; Cho, Jae Youl

    2003-12-01

    (3 S,14 S)-Petrocortyne A, a lipid compound (a C(46) polyacetylenic alcohol), from marine sponges ( Petrosia sp.) is potently cytotoxic against several solid tumour cells. In this study, we investigated in vitro anti-inflammatory and pro-aggregative effects of petrocortyne A at non-cytotoxic concentrations on various cellular inflammatory phenomena using the macrophage and monocytic cell lines RAW264.7 and U937. Petrocortyne A blocked tumour necrosis factor-alpha (TNF-alpha) production strongly and concentration-dependently in lipopolysaccharide (LPS)-activated RAW264.7 cells and phorbol 12-myristate 13-acetate (PMA)/LPS-treated U937 cells. It also blocked NO production concentration-dependently in LPS- or interferon (IFN)-gamma-treated RAW264.7 cells. Among the migration factors tested, the compound selectively blocked the expression of hepatocyte growth factor/scatter factor (HGF/SF). On the other hand, as assessed by a cell-cell adhesion assay, petrocortyne A did not block the activation of adhesion molecules induced by aggregative antibodies to adhesion molecules, but suppressed PMA-induced cell-cell adhesion significantly. Intriguingly, petrocortyne A induced U937 homotypic aggregation following long exposure (2 and 3 days), accompanied by weak induction of pro-aggregative signals such as tyrosine phosphorylation of p132 and phosphorylation of extracellular signal-related kinase 1 and 2 (ERK 1/2). Petrocortyne A may thus inhibit cellular inflammatory processes and immune cell migration to inflamed tissue. PMID:14615882