Homoisoflavanone, an extract of Cremastra appendiculata Makino, inhibits UVB-induced skin inflammation

Abstract

Ultraviolet B (UVB) irradiation on skin induces an acute inflammation, by the generation of reactive oxygen species (ROS) and release of cytokines via activating cyclooxygenase-2 (COX-2). In this study, we investigated an anti-inflammatory action and underlying molecular mechanisms of homoisoflavanone in UVB-induced inflammation. Pretreatment of homoisoflavonone inhibited the production of intracellular ROS by UVB irradiation in HaCaT cells. Simultaneously, homoisoflavanone also inhibited UVB-induced matrix metalloproteinase (MMP-1) expression and production of prostaglandin E2 in human dermal fibroblast (HDF). Analysis of UVB-irradiated keratinocytes showed decrease in COX-2 level, cytosolic phospholipase A2 (cPLA2) and p38 activation by homoisoflavonone. The expression of pro-inflammatory cytokines, IL-6, IL-8 and TNF-alpha, was concurrently decreased by homoisoflavanone, which is associated with inhibition of NF-kB nuclear translocation. Moreover, topical treatment of homoisoflavanone inhibited ear edema in response to different agents including phorbol 12-myristate 13-acetate (TPA), arachdonic acid, UVB, and croton oil over 50 % in mice. These data demonstrates that homoisoflavanone has a strong protective effect against inflammatory response via down-regulation of COX-2, cPLA2, p38 and NF-kB, providing the possibility of therapeutic application in skin inflammatory diseases.