Anti-Melanogenic Effects of Bergamottin via Mitogen-Activated Protein Kinases and Protein Kinase B Signaling Pathways

In this study, we examined the inhibitory effects of bergamottin on melanogenesis in B16F10 murine melanoma cells, together with its effects on the mechanism of melanin synthesis. alpha-Melanocyte stimulating hormone-stimulated B16F10 cells were treated with various concentrations of bergamottin, with arbutin as a positive control. Bergamottin significantly decreased the melanin content and tyrosinase activity without showing any cytotoxicity. In addition, bergamottin treatment significantly downregulated the expression of tyrosinase-related protein-1,2 and tyrosinase by suppressing the expression of microphthalmia-associated transcription factor. The phosphorylation status of mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) was examined to determine the mechanism underlying the antimelanogenic effects of bergamottin. Bergamottin treatment increased the phosphorylation of extracellular signal-regulated kinase (ERK) and AKT, but decreased the phosphorylation of p38 and c-Jun N-terminal kinase in the B16F10 cells. Moreover, the use of PD98059 (ERK inhibitor) and LY294002 (AKT inhibitor) corroborated these findings, indicating that bergamottin inhibits melanogenesis via the MAPKase and AKT signaling pathway. Thus, bergamottin has potential for treating hyperpigmentation disorders and can be a promising chemical for skin-whitening in the cosmetic industry.