title: Coumestrol Down-Regulates Melanin Production in Melan-a Murine Melanocytes through Degradation of Tyrosinase.
abstract: Pigmentation reflects skin darkening caused by melanin production, but excessive melanin synthesis may cause problems, such as melasma, solar lentigo, dark spots, and freckles. Considerable effort has been devoted to alleviating these undesired symptoms through the development of safe and effective depigmenting agents. Coumestrol, a plant-derived natural isoflavone with an estrogen-like structure and actions, is known to have anti-aging ability, but its potential depigmenting efficacy has not been evaluated. In the present study, we investigated the effects of coumestrol on melanin synthesis in normal melan-a murine melanocytes. Coumestrol significantly reduced melanin synthesis in a concentration-dependent manner up to a concentration of 25 µM without causing cytotoxicity. It also brightened tissue in an artificial skin model (MelanoDerm) that incorporates both human keratinocytes and melanocytes. Interestingly, although coumestrol did not inhibit tyrosinase activity or transcript level in melan-a cells, it clearly decreased the expression level of tyrosinase protein at a concentration of 25 µM. This coumestrol-induced reduction in tyrosinase protein levels was prevented by pretreatment with the proteasome inhibitor MG-132 or the lysosomal proteolysis inhibitor chloroquine. Collectively, our findings indicate that coumestrol exerts an inhibitory effect on melanin synthesis in melan-a cells, at least in part, through degradation of tyrosinase. These findings suggest that coumestrol is a good candidate for use in depigmentary reagents from a cosmetic and clinical perspective.
authors.affiliation: Amorepacific R&D Corporation Center.
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Hwang
authors.forename: Nok Hyun
authors.initials: NH
authors.lastname: Park
authors.forename: Yong Joo
authors.initials: YJ
authors.lastname: Na
authors.forename: Hae Kwang
authors.initials: HK
authors.lastname: Lee
authors.forename: John Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Chang Seok
authors.initials: CS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003375:Coumestrol / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D007976:Leupeptins / Q000494:pharmacology; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D048789:Phytoestrogens / Q000494:pharmacology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D008543:Melanins; D048789:Phytoestrogens; D014442:Monophenol Monooxygenase; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D003375:Coumestrol