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.

Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies

“…Foodstuffs containing coumestrol exert beneficial effects in cancer, menopause, osteoporosis, atherosclerosis, and cardiovascular disease [ 17 ]. In addition, it has been reported to exhibit anti-aging [ 18 ], neuroprotective [ 19 ], anti-adipogenic [ 20 ], and depigmenting activity [ 21 ]. With such diverse potential, further investigation of its neuroprotective properties is necessary.…”

Melasma: Tratamento E Suas Implicações Estéticas

“…Duas vias de degradação podem ser sinalizadas para a tirosinase: a primeira, associada ao reticulo endoplasmático, mediada por um sistema ubiquitina de proteassoma; a segunda via de degradação ocorre através de endossomos ou lisossomos (22).…”

“…Na investigação das ações anti-melanogénicas, os autores mostraram que o coumestrol suprime os níveis da tirosinase, ocasionando degradação da proteína em células melan-A, mediada por proteases e lisossoma. No entanto, foi observado que esse efeito ocorria em 25 µM (22).…”

Natural skin‑whitening compounds for the treatment of melanogenesis (Review)

“…of AKT-GSK3β signaling, leading to the degradation of MITF in B16 murine melanoma cells (93,94). A list of other recently discovered flavonoids that have been reported to inhibit the activity of TYR is shown in Table II (95)(96)(97)(98)(99)(100)(101)(102)(103)(104). Phenylpropanoids and olefinic unsaturated compounds, which include ferulic acid, benzaldehyde (105), astaxanthin, curcumin and cinnamic acid esters (106), have been revealed to exert inhibitory effects on TYR.…”