title: Oxyresveratrol and hydroxystilbene compounds. Inhibitory effect on tyrosinase and mechanism of action.
abstract: Tyrosinase is responsible for the molting process in insects, undesirable browning of fruits and vegetables, and coloring of skin, hair, and eyes in animals. To clarify the mechanism of the depigmenting property of hydroxystilbene compounds, inhibitory actions of oxyresveratrol and its analogs on tyrosinases from mushroom and murine melanoma B-16 have been elucidated in this study. Oxyresveratrol showed potent inhibitory effect with an IC(50) value of 1.2 microm on mushroom tyrosinase activity, which was 32-fold stronger inhibition than kojic acid, a depigmenting agent used as the cosmetic material with skin-whitening effect and the medical agent for hyperpigmentation disorders. Hydroxystilbene compounds of resveratrol, 3,5-dihydroxy-4'-methoxystilbene, and rhapontigenin also showed more than 50% inhibition at 100 microm on mushroom tyrosinase activity, but other methylated or glycosylated hydroxystilbenes of 3,4'-dimethoxy-5-hydroxystilbene, trimethylresveratrol, piceid, and rhaponticin did not inhibit significantly. None of the hydroxystilbene compounds except oxyresveratrol exhibited more than 50% inhibition at 100 microm on l-tyrosine oxidation by murine tyrosinase activity; oxyresveratrol showed an IC(50) value of 52.7 microm on the enzyme activity. The kinetics and mechanism for inhibition of mushroom tyrosinase exhibited the reversibility of oxyresveratrol as a noncompetitive inhibitor with l-tyrosine as the substrate. The interaction between oxyresveratrol and tyrosinase exhibited a high affinity reflected in a K(i) value of 3.2-4.2 x 10(-7) m. Oxyresveratrol did not affect the promoter activity of the tyrosinase gene in murine melanoma B-16 at 10 and 100 microm. Therefore, the depigmenting effect of oxyresveratrol works through reversible inhibition of tyrosinase activity rather than suppression of the expression and synthesis of the enzyme. The number and position of hydroxy substituents seem to play an important role in the inhibitory effects of hydroxystilbene compounds on tyrosinase activity.
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Korea.
authors.forename: Yeon Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Jieun
authors.initials: J
authors.lastname: Yun
authors.forename: Chong-Kil
authors.initials: CK
authors.lastname: Lee
authors.forename: Hwanghee
authors.initials: H
authors.lastname: Lee
authors.forename: Kyung Rak
authors.initials: KR
authors.lastname: Min
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000363:Agaricales / Q000201:enzymology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007700:Kinetics; D008546:Melanoma, Experimental; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D010936:Plant Extracts / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011753:Pyrones / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011753:Pyrones; D013267:Stilbenes; C034912:puag-haad; C011890:kojic acid; D014442:Monophenol Monooxygenase