Biol. Pharm. Bull. 30(11) 2007—2011 (2007)

skin and hair, and is synthesized in melanosomes transferred from melanocytes. Although melanin plays an important protective role against UV light, over production and accumulation of melanin pigment it could create serious skin problems such as freckles, age spots, and melasma. Thus, the inhibition of melanogenesis has been the focus of medicinal and cosmetic treatments for skin depigmenting and lightening. Melanogenesis that is regulated by the key enzyme, tyrosinase, is also affected by other non-enzymatic factors such as ultraviolet rays and a-melanocyte-stimulating hormone (a-MSH). Tyrosinase (monophenol monooxygenase, EC 1.14.18.1), also known as polyphenol oxidase is an enzyme that catalyzes the oxidation of monohydric phenols (e.g. such as tyrosine). During melanogenesis, if free radicals are improperly processed, hydrogen peroxide is produced, causing production of more damaging hydroxyl radicals and other reactive oxygen species. It has been reported that antioxidants or compounds with redox properties can inhibit or delay hyperpigmentation, and that reduced glutathione (GSH), an important biological reductant, is involved in regulation of melanin synthesis. Our recent study characterized the antimelanogenic action of 4,4 -dihydroxybiphenyl, which is likely carried out by a combined effect of its antioxidative property and ability to increase intracellular GSH levels. In the past, many depigmenting substances, including phenolic compounds and stilbene derivatives, have been reported to have skin whitening effects. Piceatannol (PICE; 3,5,3 ,4 -tetrahydroxy-trans-stilbene) and resveratrol (RES; trans-3,5,4 -tridydroxystilbene) are phenolic compounds that occur naturally in grapes and red wine. RES is known to have antioxidative, estrogenic, and anti-cancer properties. Its natural metabolite, the RES analogue, piceatannal (PICE) is reported to possess antioxidative, anti-tumorigenic, and apoptosis-inducing effects. However, PICE’s inhibitory effect on melanogenesis has not been reported to date. This study compares the inhibitory effect between PICE and RES against melanogenesis. The effect of PICE on the inhibition of mushroom tyrosinase was evaluated. Additionally, tyrosinase inhibiting activity and melanin content were assessed in B16F10 melanoma cells (B16 cells). To elucidate the underlying process by which PICE inhibits tyrosinase activity and melanogenesis, PICE’s effect on reactive species (RS) generation and GSH and oxidized glutathione (GSSG) ratio were assessed.