Quercetin 3-O-(6″-O-E-caffeoyl)-β-D-glucopyranoside, a Flavonoid Compound, Promotes Melanogenesis through the Upregulation of MAPKs and Akt/GSK3β/β-Catenin Signaling Pathways.

Quercetin 3-O-(6″-O-E-caffeoyl)-β-D-glucopyranoside is a flavonoid compound produced by various plants with reported antiprotozoal potential against and ; however, its effects on skin pigment regulation have not been studied in detail. In this investigation, we discovered that quercetin 3-O-(6″-O-E-caffeoyl)-D-glucopyranoside (coded as ) demonstrated a more increased melanogenesis effect in B16 cells. exhibited no cytotoxicity or effective stimulating melanin content or intracellular tyrosinase activity. This melanogenic-promoting effect was accompanied by activated expression levels of microphthalmia-associated transcription factor (MITF), a key melanogenic regulatory factor, melanogenic enzymes, and tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1) and 2 (TRP-2) in the -treated cells. Mechanistically, we found that exerted melanogenic effects by upregulating the phosphorylation of stress-regulated protein kinase (p38) and c-Jun N-terminal kinase (JNK). Moreover, the upregulation of phosphor-protein kinase B (Akt) and Glycogen synthase kinase-3 beta (GSK-3β) increased the content of β-catenin in the cell cytoplasm, and subsequently, it translocated into the nucleus, resulting in melanogenesis. Specific inhibitors of P38, JNK, and Akt validated that promotes melanin synthesis and tyrosinase activity by regulating the GSK3β/β-catenin signaling pathways. Our results support that the regulation of melanogenesis involves MAPKs and Akt/GSK3β/β-catenin signaling pathways.