Chrysoeriol Enhances Melanogenesis in B16F10 Cells Through the Modulation of the MAPK, AKT, PKA, and Wnt/β-Catenin Signaling Pathways

Abstract

Chrysoeriol is a 3′-O-methoxy flavone, chemically a derivative of luteolin, which is commonly found across the plant kingdom. Chrysoeriol is of great scientific interest because of its promising anti-inflammatory, anti-cancer, antioxidative, anti-lipase, anti-xanthin oxidase, and antimicrobial activities against multidrug-resistant (MDR) bacterial pathogens; however, its effects on melanogenesis have not yet been elucidated. Here, we report a novel effect of chrysoeriol on melanogenesis in B16F10 cells. Chrysoeriol treatment significantly increased the expression of the melanogenic enzymes tyrosinase (TRY), tyrosinase-related protein-1 (TRP-1), and TRP-2 and upregulated the expression of microphthalmia-associated transcription factor (MITF) in a concentration-dependent manner. Furthermore, chrysoeriol suppressed the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in a concentration-dependent manner. In addition, chrysoeriol treatment increased the phosphorylation of p38 mitogen-activated protein kinase (MAPK), glycogen synthase kinase (GSK)-3β, β-catenin, and protein kinase A (PKA) and decreased the production of β-catenin, which is involved in the transcriptional activation of MITF in melanogenesis. Finally, the structure–activity relationship (SAR) of chrysoeriol and its derivatives, including luteolin and apigenin, with regard to their melanin inhibitory activity was also investigated; we identified the significance of the 4′-OH group and C-3′ methoxylation in melanogenesis. Together, these findings indicate that chrysoeriol promotes melanogenesis in B16F10 cells by upregulating the expression of melanogenic enzymes through the MAPK, phosphatidylinositol 3-kinase (PI3K)/AKT, PKA, and Wnt/β-catenin signaling pathways; thus, chrysoeriol may be used as a cosmetic ingredient to promote melanogenesis or as a therapeutic agent against hypopigmentation disorders.