虚拟筛选辅助揭示中药药效物质基础的思路与初步实践

Thinking and primary practice on discovery of pharmacodynamic material basis of Chinese materia medica assisted by virtual screening method

基于多数常用中药的化学成分研究已很深入这一前提,尝试运用虚拟筛选方法辅助揭示中药药效物质基础,即把待研究中药所含的所有已确证结构的化学成分构建为分子库,与根据其功效而确定的各种靶点模型进行虚拟对接,筛选出理论活性成分后,再以药理实验数据进行验证,从而较全面地揭示代表相应功效的化学成分群。在初步的实践研究中,将由桑类中药510个化学成分构成的分子库分别与治疗消渴和利尿的靶点进行对接,结果显示:(1)对α-葡萄糖苷酶和碳酸酐酶XII有理论活性的成分分别远多于胰岛素受体和盐皮质激素受体;(2)部分化学成分对于α-葡萄糖苷酶的预测结果得到了文献实验数据的支持;(3)部分成分对多个靶点均显示较强的理论活性。虚拟筛选方法为阐释中药药效物质基础提供了新的视角和快捷途径。

Given in-depth study on the numerous chemical constituents from commonly used Chinese materia medica（CMM） whose pharmacodynamic material basis have not been completely clear yet,the tested virtual screening method has been used to reveal the pharmacodynamic material basis.It would be an unimaginable thing to experimentally evaluate the activity of every compound on all interrelated biomacromolecule targets one by one.In this study,the attempt of applying high-throughput virtual screening method to discover the therapeutically effective components,which represented corresponding active components in the given CMM,was developed.For the Chinese herb Sang（Morus alba） including Mori Folium,Mori Fructus,Mori Ramulus,and Mori Cortex,a molecular library consisted of their 510 known chemical components was docked with four target models related to antidiabetic and diuretic activity using Molegro software,respectively.It was shown that the numbers of components with theoretical activity on α-glucosidase and carbonic anhydrase XII were far more than those on insulin receptor and mineralocorticoid receptor,and some components were observed to display potent theoretical activity on multiple targets.Besides,the forecast of activity of some components aiming at α-glucosidase was found to be supported by literature experimental data.On the basis of these results,we deduced that the antidiabetic and diuretic activity of Sang could be mainly due to the effects on α-glucosidase and carbonic anhydrase XII,rather than those on insulin receptor and mineralocorticoid receptor.Virtual screening method should help us to build a new open mind for clarifying CMM pharmacodynamic material basis.