8-Methoxycoumarin enhances melanogenesis the MAPKase signaling pathway.

8-Methoxycoumarin (8-methoxy-chromen-2-one), isolated from L., is able to alleviate arthritis by inhibition of proinflammatory cytokines. However, its effects on melanogenesis have largely remained unreported. The present study examined the effects of 8-methoxycoumarin on melanogenesis in B16F10 murine cells, together with its effect on the mechanism of melanin synthesis. The cells were treated with different concentrations of 8-methoxycoumarin; -MSH was used as the positive control. We found 8-methoxycoumarin to significantly increase the melanin content of the cells without exerting any cytotoxicity. In addition, it significantly upregulated the expression of tyrosinase and tyrosinase-related protein-1 and 2 inducing the expression of microphthalmia-associated transcription factor. Furthermore, we demonstrated the involvement of mitogen-activated protein kinase (MAPK) pathway-mediated phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and inhibition of phosphorylation of extracellular signal-regulated kinase (ERK) to be responsible for enhanced melanin production. Use of SB203580 (p38 inhibitor) and SP600125 (p-JNK inhibitor) corroborated these findings. Additionally, we investigated the effects of 8-methoxycoumarin on protein kinase B (AKT) phosphorylation and protein kinase A (PKA) signaling pathway (using H89, a PKA inhibitor). These results suggested that 8-methoxycoumarin increases melanogenesis the MAPK signaling pathway. Based on these findings, we conclude that 8-methoxycoumarin could serve as a potential compound for treating hypopigmentation disorders. It could also serve as a promising chemical for hair depigmentation treatment in the cosmetic industry.