Polygonum multiflorum Thunb. Extract Stimulates Melanogenesis by Induction of COX2 Expression through the Activation of p38 MAPK in B16F10 Mouse Melanoma Cells

Polygonum multiflorum Thunb. (PM) root extracts have been used for treating graying hair in Oriental medicine; however, the molecular mechanisms underlying the melanogenic effects of PM root have not been fully understood. In the present study, we investigated the melanogenic effects of an ethanolic extract of PM root (PME) and the mechanisms involved. We examined the effects of PME on cell viability, cellular melanin content, and tyrosinase activity in B16F10 cells. The melanogenic mechanism of PME was explored using signaling inhibitors and examining the expression of melanogenic genes and signaling molecules by western blot and RT-qPCR analyses. PME did not exhibit any cytotoxicity in B16F10 cells compared to that in control cells. PME treatment significantly increased melanin production and tyrosinase activity. In addition, PME induced the expression of cyclooxygenase-2 (COX2) as well as that of melanogenic genes, such as microphthalmia-associated transcription factor (MiTF), tyrosinase-related protein (Trp) 1, Trp2, and tyrosinase, in B16F10 cells. PME treatment increased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK), and pretreatment with SB 203580, a p38 MAPK inhibitor, significantly suppressed this PME-induced increase in the expression of COX2 and melanogenic genes. These results indicate that PME induced the expression of melanogenic genes by inducing COX2 expression via the activation of the p38 MAPK pathway, thereby contributing to the enhancement of melanogenesis.