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10.1371/journal.pone.0179174 http://scihub22266oqcxt.onion/10.1371/journal.pone.0179174 C5464642!5464642 !28594906     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28594906 &cmd=llinks): Failed to open stream: HTTP request failed! 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The anti-inflammatory and immunomodulatory potential of braylin: Pharmacological properties and mechanisms by in silico, in vitro and in vivo approaches |pdf=|usr=}}{{28594906 }} gab.com Text The anti-inflammatory and immunomodulatory potential of braylin: Pharmacological properties and mechanisms by in silico, in vitro and in vivo approaches JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28594906 #FOAvip Braylin belongs to the group of natural coumarins, a group of compounds with a wide range of pharmacological properties. Here we characterized the pharmacological properties of braylin in vitro, in silico and in vivo in models of inflammatory/immune responses. In in vitro assays, braylin exhibited concentration-dependent suppressive activity on activated macrophages. Braylin (10-40 ?M) reduced the production of nitrite, IL-1?, TNF-? and IL-6 by J774 cells or peritoneal exudate macrophages stimulated with LPS and IFN-?. Molecular docking calculations suggested that braylin present an interaction pose to act as a glucocorticoid receptor ligand. Corroborating this idea, the inhibitory effect of braylin on macrophages was prevented by RU486, a glucocorticoid receptor antagonist. Furthermore, treatment with braylin strongly reduced the NF-?B-dependent transcriptional activity on RAW 264.7 cells. Using the complete Freund's adjuvant (CFA)-induced paw inflammation model in mice, the pharmacological properties of braylin were demonstrated in vivo. Braylin (12.5-100 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on CFA model. Braylin did not produce antinociception on the tail flick and hot plate tests in mice, suggesting that braylin-induced antinociception is not a centrally-mediated action. Braylin exhibited immunomodulatory properties on the CFA model, inhibiting the production of pro-inflammatory cytokines IL-1?, TNF-? and IL-6, while increased the anti-inflammatory cytokine TGF-?. Our results show, for the first time, anti-inflammatory, antinociceptive and immunomodulatory effects of braylin, which possibly act through the glucocorticoid receptor activation and by inhibition of the transcriptional activity of NF-?B. Because braylin is a phosphodiesterase-4 inhibitor, this coumarin could represent an ideal prototype of glucocorticoid receptor ligand, able to induce synergic immunomodulatory effects. Twit Text FOAVip The anti-inflammatory and immunomodulatory potential of braylin: Pharmacological properties and mechanisms by in silico, in vitro and in vivo approaches ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28594906 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28594906 #FOAvip English Wikipedia <ref>{{Cite pmid|28594906 }}</ref> The anti-inflammatory and immunomodulatory potential of braylin: Pharmacological properties and mechanisms by in silico, in vitro and in vivo approaches #MMPMID28594906 Espírito-Santo RF ; Meira CS ; Costa RDS ; Souza Filho OP ; Evangelista AF ; Trossini GHG ; Ferreira GM ; Velozo EDS ; Villarreal CF ; Pereira Soares MB PLoS One 2017[]; 12 (6 ): e0179174 PMID28594906 show ga Braylin belongs to the group of natural coumarins, a group of compounds with a wide range of pharmacological properties. Here we characterized the pharmacological properties of braylin in vitro, in silico and in vivo in models of inflammatory/immune responses. In in vitro assays, braylin exhibited concentration-dependent suppressive activity on activated macrophages. Braylin (10-40 ?M) reduced the production of nitrite, IL-1?, TNF-? and IL-6 by J774 cells or peritoneal exudate macrophages stimulated with LPS and IFN-?. Molecular docking calculations suggested that braylin present an interaction pose to act as a glucocorticoid receptor ligand. Corroborating this idea, the inhibitory effect of braylin on macrophages was prevented by RU486, a glucocorticoid receptor antagonist. Furthermore, treatment with braylin strongly reduced the NF-?B-dependent transcriptional activity on RAW 264.7 cells. Using the complete Freund's adjuvant (CFA)-induced paw inflammation model in mice, the pharmacological properties of braylin were demonstrated in vivo. Braylin (12.5-100 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on CFA model. Braylin did not produce antinociception on the tail flick and hot plate tests in mice, suggesting that braylin-induced antinociception is not a centrally-mediated action. Braylin exhibited immunomodulatory properties on the CFA model, inhibiting the production of pro-inflammatory cytokines IL-1?, TNF-? and IL-6, while increased the anti-inflammatory cytokine TGF-?. Our results show, for the first time, anti-inflammatory, antinociceptive and immunomodulatory effects of braylin, which possibly act through the glucocorticoid receptor activation and by inhibition of the transcriptional activity of NF-?B. Because braylin is a phosphodiesterase-4 inhibitor, this coumarin could represent an ideal prototype of glucocorticoid receptor ligand, able to induce synergic immunomodulatory effects. |*Computer Simulation [MESH] |Adjuvants, Immunologic [MESH] |Animals [MESH] |Anti-Inflammatory Agents/chemistry/*pharmacology [MESH] |Cell Death/drug effects [MESH] |Cell Line [MESH] |Coumarins/chemistry/*pharmacology [MESH] |Cytokines/biosynthesis [MESH] |Immunologic Factors/chemistry/*pharmacology [MESH] |Inflammation/pathology [MESH] |Macrophages/drug effects/metabolism [MESH] |Male [MESH] |Mice [MESH] |Molecular Docking Simulation [MESH] |NF-kappa B/metabolism [MESH] |Nitric Oxide/biosynthesis [MESH] |Receptors, Glucocorticoid/metabolism [MESH]The anti-inflammatory and immunomodulatory potential of braylin: Pharm(epmc).pdf DeepDyve Pubget Overpricing