Abstract
Fisetin is a flavonoid found in plants and has been reported to be effective in various human diseases. However, the effective mechanisms of ultraviolet-A (UVA)-mediated skin damage are not yet clear. In this study, we investigated the protective mechanisms of fisetin regarding UVA-induced human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) damages. Fisetin showed a cytoprotective effect against UVA irradiation and suppressed matrix metalloproteinases (MMPs), MMP-1, and MMP-3 expression. In addition, fisetin was rescued, which decreased mRNA levels of pro-inflammatory cytokines, reactive oxygen species production, and the downregulation of MAPK/AP-1 related protein and NADPH oxidase (NOX) mRNA levels. Furthermore, UVA-induced MMP-1 and MMP-3 were effectively inhibited by siRNAs to NOX 1 to 5 in HDFs and HEKs. These results indicate that fisetin suppresses UVA-induced damage through the NOX/ROS/MAPK pathway in HDFs and HEKs.