Homoisoflavanone inhibits UVB-induced skin inflammation through reduced cyclooxygenase-2 expression and NF-κB nuclear localization

Abstract

Since the generation of reactive oxygen species (ROS) and release of inflammatory mediators play a major role in UVB-induced inflammation, vigorous attempts have been made for the pharmacological management of these molecules as well as for uncovering the molecular signaling pathways. Homoisoflavanone (5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-chroman-4-one, HIF) extracted from Cremastra appendiculata has anti-angiogenic activities, but its effect on inflammation was unknown. To investigate the anti-inflammatory effects of HIF on the skin and the underlying molecular mechanisms. HaCaT cells were irradiated by UVB (10 mJ/cm(2)) with or without HIF. Prostaglandin E(2) (PGE(2)) level was measured by enzyme immunoassay. Activation of MAPK and production of cyclooxygenase-2 (COX-2) were determined by Western blot analysis. Localization of nuclear factor kappa B (NF-kappaB) was assessed by immunofluorescence microscopy. Hairless mice were stimulated with UVB or chemical stimulants to induce inflammatory responses in skin. Pretreatment with HIF inhibited the production of intracellular ROS induced by UVB irradiation in HaCaT cells. Further analysis revealed a decrease in the level of MAPK activation and down-regulation of COX-2 expression. In addition, HIF attenuated the nuclear localization of NF-kappaB, resulting in the suppression of inflammatory molecules such as IL-6, IL-8, and TNF-alpha. Finally, topical treatment with HIF inhibited ear edema induced by UVB, 12-O-tetradecanoylphorbol-13-acetate (TPA), arachidonic acid (AA), or croton oil. HIF has a strong protective effect against proinflammatory responses, implying the possibility of preventive application for inflammatory skin diseases.