Oxyresveratrol and Hydroxystilbene Compounds

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 M 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 M 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 M on L-tyrosine oxidation by murine tyrosinase activity; oxyresveratrol showed an IC 50 value of 52.7 M 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 ؋ 10 ؊7 M. Oxyresveratrol did not affect the promoter activity of the tyrosinase gene in murine melanoma B-16 at 10 and 100 M. 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.Tyrosinase catalyzes two distinct reactions of the conversion of tyrosine to Dopa 1 (tyrosine hydroxylase activity (EC 1.14.18.1); tyrosine, 3,4-dihydroxyphenylalanine, oxygen, and oxidoreductase) and the oxidation of the resultant Dopa (Dopa oxidase activity (EC 1.10.3.1); Dopa, oxygen, and oxidoreductase) (1, 2). The enzyme oxidizes phenols and diphenols using a catalytic mechanism that depends on the presence of copper atoms at the active site (3, 4). Dopaquinone produced by tyrosinase is nonenzymatically converted to dopachrome, which is acted upon by an isomerase producing dihydroxyindoles (5, 6). Melanin pigments are eventually produced by further oxidation and polymerization of the indoles (7).Tyrosinase, an enzyme catalyzing the rate-limiting step for the biosynthetic pathway of melanin pigments, is widely distributed in nature. It exists in many organisms with slightly different forms. The enzyme participates in several important reactions of host defense, wound healing, and sclerotization in insects and other arthropods (8 -10). E...

Syntheses of Resveratrol and its Hydroxylated Derivatives as Radical Scavenger and Tyrosinase Inhibitor

“…Remaining stilbenes which had resorcinol moiety (1-3) and/or destroyed catechol moiety (6)(7)(8) had lower ABTS radical scavenging activity than catecholic stilbenes (4 and 5) (Table 1). Fortunately, almost all synthetic stilbenes 1-8 showed (4) 4.1 ± 1.1 (4.8) 95.7 ± 1.4 8.6 trans -3',4'-Dihydroxy -3,5-dimethoxystilbene (5) 10.3 ± 0.7 (1.9) 40.6 ± 0.8 > 100 trans-4'-Hydroxy -3, 3',5-trimethoxystilbene (6) 17.4 ± 0.9 (1.1) 14.5 ± 2.5 > 100 trans-3'-Hydroxy -3, 4',5-trimethoxystilbene (7)…”

“…5 This enzyme is responsible for browning of fruits and coloring of skin in animals including human being. 6 Inhibitors of tyrosinase is important molecular tools for food quality and skin whitening in human. The strong tyrosinase inhibitor, such as piceatannol, has potential applications as whitening agent in cosmetic preparations or anti-browning agent for food products.…”

Gnetol as a Potent Tyrosinase Inhibitor from GenusGnetum

“…It was also demonstrated that oxyresveratrol inhibited tyrosinase activity more than resveratorol (3,4?,5-trihydroxystilbene). 13) We have also observed that resveratrol inhibited tyrosinase activity, but was less eŠective than gnetol (data not shown). Therefore, the number of hydroxy substituents seems to play an important role in the inhibitory potency of hydroxystilbene compounds for tyrosinase activity.…”

“…Recently, Kim et al 13) have demonstrated that oxyresveratrol (2,3?,4,5?-tetrahydroxystilbene) from Morus alba Linne was a potent inhibitor of tyrosinase activity. Gnetol is chemically related to oxyresveratrol, which is a tetrahydroxystilbene.…”

Karakteristik Mutu Fisikokimia Jamur Merang (Volvarella Volvacea) Selama Penyimpanan Dalam Berbagai Jenis Larutan Dan Kemasan

“…Proses pencoklatan menyebabkan terjadinya perubahan nutrisi dan organoleptik sehingga menyebabkan perubahan mutu yang tidak dikehendaki 28,29 . Banyak faktor yang dapat menyebabkan terjadinya proses pencoklatan antara lain kondisi penyimpanan, waktu penyimpanan serta terjadinya oksidasi senyawa fenolik menjadi quinon yang dikatalisis oleh polyphenol oxidase (PPO) 30 .…”