Fong Pedro, Tong Henry H Y
School of Health Sciences, Macao Polytechnic Institute, Macao, 999078, China.
Nat Prod Commun. 2012 Oct;7(10):1287-94.
The identification of tyrosinase inhibitors is important, not only for the treatment of skin hyperpigmentation disorders, such as melasma, but also for the production of cosmetic whitening effects. The aim of this study was the in silico prediction of the naturally occurring lead compounds in three commonly used skin-whitening herbs: Ampelopsis japonica, Lindera aggregata, and Ginkgo biloba. The active ingredients responsible for the whitening effect of these herbs remain largely unknown. The tyrosinase binding affinities and skin permeation, skin irritancy, and corrosive properties of43 natural constituents of the three herbs were predicted by docking simulations using Surflex-Dock and the QSAR-based Dermal Permeability Coefficient Program (DERMWIN) and Skin Irritation Corrosion Rules Estimation Tool (SICRET) implemented in Toxtree. Nine constituents of the three herbs were found to have more advanced binding energies than the gold standard whitening agents, arbutin and kojic acid, but 40 were indicative of at least one skin sensitization alert, and many exhibited poor skin permeability. Linderagalactone c and (+)-n-methyllaurotetanine were found to have the strongest prospects for use in topical formulations, as they achieved high predicted tyrosinase binding scores and displayed good skin permeation properties and minimal potential for skin sensitization and irritation.
鉴定酪氨酸酶抑制剂不仅对治疗皮肤色素沉着紊乱（如黄褐斑）很重要，而且对产生美白的美容效果也很重要。本研究的目的是对三种常用美白草药（日本蛇葡萄、乌药和银杏）中的天然先导化合物进行计算机模拟预测。这些草药美白效果的活性成分在很大程度上仍然未知。通过使用Surflex-Dock以及Toxtree中实施的基于定量构效关系的皮肤渗透系数程序（DERMWIN）和皮肤刺激腐蚀规则估计工具（SICRET）进行对接模拟，预测了这三种草药43种天然成分的酪氨酸酶结合亲和力、皮肤渗透性、皮肤刺激性和腐蚀性。发现这三种草药的九种成分具有比金标准美白剂熊果苷和曲酸更高的结合能，但40种成分显示至少有一个皮肤致敏警报，并且许多成分表现出较差的皮肤渗透性。发现乌药内酯c和（+）-N-甲基劳丹碱在局部制剂中的应用前景最强，因为它们获得了较高的预测酪氨酸酶结合分数，显示出良好的皮肤渗透性能，并且皮肤致敏和刺激的可能性最小。
