Maeda K, Fukuda M
Shiseido Research Center, Yokohama, Japan.
J Pharmacol Exp Ther. 1996 Feb;276(2):765-9.
Arbutin, a naturally occurring beta-D-glucopyranoside of hydroquinone, is effective in the topical treatment of various cutaneous hyperpigmentations characterized by hyperactive melanocyte function. We examined the mechanism of its depigmenting action in human melanocyte cultures. Arbutin inhibited the tyrosinase activity of cultured human melanocytes at noncytotoxic concentrations. It did not affect the expression of tyrosinase mRNA. Melanin production was inhibited significantly by arbutin, as determined by measuring eumelanin radicals with an electron spin resonance spectrometer. The study of the kinetics and mechanism for inhibition of tyrosinase confirms the reversibility of arbutin as a competitive inhibitor of this enzyme. The utilization of L-tyrosine or L-dopa as the substrate suggests a mechanism involving competition with arbutin for the L-tyrosine binding site at the active site of tyrosinase. These results suggest that the depigmenting mechanism of arbutin in humans involves inhibition of melanosomal tyrosinase activity, rather than suppression of the expression and synthesis of tyrosinase.
熊果苷是对苯二酚的一种天然存在的β-D-吡喃葡萄糖苷，对以黑素细胞功能活跃为特征的各种皮肤色素沉着具有有效的局部治疗作用。我们在人黑素细胞培养物中研究了其色素脱失作用的机制。熊果苷在无细胞毒性浓度下抑制培养的人黑素细胞的酪氨酸酶活性。它不影响酪氨酸酶mRNA的表达。通过电子自旋共振光谱仪测量真黑素自由基确定，熊果苷显著抑制黑色素生成。对酪氨酸酶抑制动力学和机制的研究证实了熊果苷作为该酶竞争性抑制剂的可逆性。以L-酪氨酸或L-多巴作为底物表明其机制涉及熊果苷与酪氨酸酶活性位点上的L-酪氨酸结合位点竞争。这些结果表明，熊果苷在人体内的色素脱失机制涉及抑制黑素小体酪氨酸酶活性，而不是抑制酪氨酸酶的表达和合成。
