In this study, the authors investigated the anti-melanogenic effects of 3,8-dihydroxyquinoline (jineol) isolated from Scolopendra subspinipes mutilans, the mechanisms responsible for its inhibition of melanogenesis in melan-a cells, and its antioxidant efficacy. Mushroom tyrosinase activities and melanin contents were determined in melan-a cells, and the protein and mRNA levels of MITF, tyrosinase, TYRP-1, and TYRP-2 were assessed. Jineol exhibited significant, concentration-dependent antioxidant effects as determined by DPPH, ABTS, CUPRAC, and FRAP assays. Jineol significantly inhibited mushroom tyrosinase activity by functioning as an uncompetitive inhibitor, and markedly inhibited melanin production and intracellular tyrosinase activity in melan-a cells. In addition, jineol abolished the expressions of tyrosinase, TYRP-1, TYRP-2, and MITF, thereby blocking melanin production and interfering with the phosphorylations of ERK1/2 and p38. Furthermore, specific inhibitors of ERK1/2 and p38 prevented melanogenesis inhibition by jineol, and the proteasome inhibitor (MG-132) prevented jineol-induced reductions in cellular tyrosinase levels. Taken together, jineol was found to stimulate MAP-kinase (ERK1/2 and p38) phosphorylation and the proteolytic degradation pathway, which led to the degradations of MITF and tyrosinase, and to suppress the productions of melanin.

Melanin has been reported to be the key factor for skin homeostasis. Besides defining an important human phenotypic trait, melanin overproduction may cause various disorders such as vitiligo, Addison's disease, Cushing's syndrome, and melasma. In this study, we aimed to investigate the anti-melanogenic potential of dried spike extract of chestnut. The extract inhibited tyrosinase (TYR) activity in a dose-dependent manner. Cellular melanin content decreased markedly after treatment with the extract. The spike extract inhibited microphthalmia-associated transcription factor (MITF) expression and downregulated TYR, TYRP-1, and TYRP-2 protein expression by increasing the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 signalling pathway in melan-a cells. In addition, treatment with U0126, a specific inhibitor of ERK, restored melanin content. Collectively, these results suggest that the chestnut spike extract attenuated melanogenesis by inhibiting MITF expression and downregulating TYR, TYRP-1, and TYRP-2 protein expressions via activation of ERK1/2 pathway.