期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 698, 期 1-3, 页码 413-420出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2012.10.019
关键词
Euphol; TPA; Inflammation; PKC; MAPK; COX-2
资金
- Grants from Amazonia Fitomedicamentos, Brazil
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Programa de Apoio aos Nucleos de Excelencia (PRONEX)
- Fundacao de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC)
Inflammation underlies the development and progression of a number of skin disorders including psoriasis, atopic dermatitis and cancer. Therefore, novel antiinflammatory agents are of great clinical interest for prevention and treatment of these conditions. Herein, we demonstrated the underlying molecular mechanisms of the antiinflammatory activity of euphol, a tetracyclic triterpene isolated from the sap of Euphorbia tirucalli, in skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mice. Topical application of euphol (100 mu g/ear) significantly inhibited TPA-induced ear edema and leukocyte influx through the reduction of keratinocyte-derived chemokine (CXCL1/KC) and macrophage inflammatory protein (MIP)-2 levels. At the intracellular level, euphol reduced TPA-induced extracellular signal-regulated protein kinase (ERK) activation and cyclooxygenase-2 (COX-2) upregulation. These effects were associated with euphol's ability to prevent TPA-induced protein kinase C (PKC) activation, namely PKC alpha and PKC delta isozymes. Our data indicate that topical application of euphol markedly inhibits the inflammatory response induced by TPA. Thus, euphol represents a promising agent for the management of skin diseases with an inflammatory component. (c) 2012 Elsevier B.V. All rights reserved.
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