Abstract
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.
Highlights
Melanin, the major skin color determining factor, provides defense against the harmful effects of ultraviolet (UV)-induced skin damage[1]
Ultra-violet radiation (UV) generates reactive oxygen species (ROS), including hydrogen peroxide (H2O2) and the hydroxyl (HO), and superoxide (O2−) -radicals in melanocytes and induces melanin biosynthesis, which primarily results in the production of pheomelanin[1,5]
To elucidate the mechanism of melanogenesis, we examined the expressions of tyrosinase, TYRP-1, tyrosinase-related protein 2 (TYRP-2), and microphthalamia-associated transcription factor (MITF) in melan-a cells after jineol treatment (12.5, 25, or 50 μM) for 4 days
Summary
The major skin color determining factor, provides defense against the harmful effects of ultraviolet (UV)-induced skin damage[1]. Nitric oxide (NO) has been reported to up-regulate melanin production in melanocytes by activating the α-melanocyte stimulating hormone/melanocortin 1 receptor (α-MSH/MC1R) or MITF signaling pathway[7,8] These observations suggest that the antioxidant-defense system might play a beneficial role by mitigating the detrimental effect of excessive melanin production induced by oxidant formation. Whitening products based on tyrosinase inhibitors have severe side effects, which include cellular toxicity, and poor stability in the presence of oxygen and water Because they are considered safe and largely free from side effects, natural materials are viewed as being suitable for the development of effective and safe skin depigmenting agents in the cosmetic research and development field
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