Mechanisms underlying the inhibitory actions of the pentacyclic triterpene alpha-amyrin in the mouse skin inflammation induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetate

Mechanisms underlying the inhibitory actions of the pentacyclic triterpene alpha-amyrin in the mouse skin inflammation induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetate

Author Medeiros, Rodrigo Google Scholar
Otuki, Michel F. Google Scholar
Avellar, Maria Christina W. Google Scholar
Calixto, Joao B. Google Scholar
Institution Universidade Federal de Santa Catarina (UFSC)
Universidade Federal de São Paulo (UNIFESP)
Abstract The 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.
Keywords alpha-amyrin
skin inflammation
PGE(2)
NF-kappa KB
TPA
COX-2
Language English
Date 2007-03-22
Published in European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 559, n. 2-3, p. 227-235, 2007.
ISSN 0014-2999 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 227-235
Origin http://dx.doi.org/10.1016/j.ejphar.2006.12.005
Access rights Closed access
Type Article
Web of Science ID WOS:000244969800020
URI http://repositorio.unifesp.br/handle/11600/29593

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