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dc.contributor.authorMedeiros, Rodrigo
dc.contributor.authorOtuki, Michel F.
dc.contributor.authorAvellar, Maria Christina W.
dc.contributor.authorCalixto, Joao B.
dc.date.accessioned2016-01-24T12:41:59Z
dc.date.available2016-01-24T12:41:59Z
dc.date.issued2007-03-22
dc.identifierhttp://dx.doi.org/10.1016/j.ejphar.2006.12.005
dc.identifier.citationEuropean Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 559, n. 2-3, p. 227-235, 2007.
dc.identifier.issn0014-2999
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/29593
dc.description.abstractThe present study evaluated some of the mechanisms through which alpha-amyrin, a pentacyclic triterpene isolated from Protium Kleinii and other plants, exerts its effects against 12-O-tetradecanoylphorbol-acetate (TPA)-induced skin inflammation in mice. Topical application of a-amyrin (0.1-1 mg/ear) dose-dependently inhibited TPA-induced increase of prostaglandin E-2 (PGE(2)) levels. in contrast with the selective cyclooxygenase (COX)-1 SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole] or COX-2 rofecoxib inhibitors, alpha-amyfin failed to alter either COX-1 or COX-2 activities in vitro. Western blot analysis revealed that a-amyrin dose-dependently inhibited TPA-induced COX-2 expression in the mouse skin. the evaluation of nuclear factor-kappa B (NF-kappa B) pathway revealed that topical treatment with alpha-amyrin is able to prevent I kappa B alpha degradation, p65/RelA phosphorylation and NF-kappa B activation. Moreover, alpha-amyrin given topically dose-dependently inhibited the activation of upstream protein kinases, namely extracellular signal-regulated protein kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC)alpha, following topical TPA treatment. Collectively, present results suggest that topical skin application of alpha-amyrin exerts a strong and rapid onset inhibition of TPA-induced inflammation. These effects seem to be associated with the suppression of skin PGE(2) levels by mechanisms involving the suppression of COX-2 expression, via inhibition of upstream protein kinases - namely ERK, p38 MAPK and PKC alpha - and blocking of NF-kappa B activation. These results indicate that a-amyrin-derivative could be potentially relevant for the development of a topical agent for the management of inflammatory diseases. (c) 2006 Elsevier B.V. All rights reserved.en
dc.format.extent227-235
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofEuropean Journal of Pharmacology
dc.rightsAcesso restrito
dc.subjectalpha-amyrinen
dc.subjectskin inflammationen
dc.subjectPGE(2)en
dc.subjectNF-kappa KBen
dc.subjectTPAen
dc.subjectCOX-2en
dc.titleMechanisms underlying the inhibitory actions of the pentacyclic triterpene alpha-amyrin in the mouse skin inflammation induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetateen
dc.typeArtigo
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institutionUniversidade Federal de Santa Catarina (UFSC)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.description.affiliationUniv Fed Santa Catarina, Ctr Ciencias Biol, Dept Farmacol, BR-88049900 Florianopolis, SC, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Farmacol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Farmacol, São Paulo, Brazil
dc.identifier.doi10.1016/j.ejphar.2006.12.005
dc.description.sourceWeb of Science
dc.identifier.wosWOS:000244969800020


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