基于组分配伍探讨黄连 黄芩保肝的物质基础

Investigation of Material Basis for Protecting Liver in Coptis chinensis and Scutellaria baicalensis Based on Component Compatibility

目的:采用分子E对接技术研究黄连、黄芩保肝的物质基础。方法:依据口服利用度、类似药、化合物的分子量等筛选黄连、黄芩的化学成分,采用i GEMDOCK软件对黄连、黄芩中28个化学成分与CYP1A2、CYP2E1、CYP2D6、CYP2C9、CYP3A4进行能量匹配,通过Cytoscape软件构建黄连、黄芩有效成分-CYP450网络模型。结果:28个化合物与CYP1A2、CYP2E1、CYP2D6、CYP2C9结合稳定,与CYP3A4结合较不稳定。黄连、黄芩共有10个化学成分同时与CYP1A2结合,3个成分与CYP2C9结合,抑制其活性。而黄芩还可以抑制CYP2E1、CYP2D6的活性。配伍比单味用药可能保肝效果更好。结论:发现CYP450酶系可能是黄连、黄芩保肝的作用靶点,尤其是CYP1A2和CYP2C9,抑制其活性,减少毒物N-乙酸-对苯醌亚胺生成,降低肝细胞损伤,达到保肝作用,为进一步研究黄连、黄芩保肝的分子机制提供理论依据。

Objective: To study the material basis for protecting liver in Coptis chinensis and Scutellaria baicalensis based on molecular docking. Methods: The chemical constituents of Coptidis Rhizoma and Radix Scutellariae were screened based on oral availability,similar drugs and molecular weight of compounds,energy matching of 28 chemical constituents from Coptidis Rhizoma and Radix Scutellariae with CYP2 D6,CYP2 C9 and CYP3 A4 were carried out by using i GEMDOCK Software,the network model of effective components of Coptidis Rhizoma and Radix Scutellariae was constructed by Cytoscape. Results: The combination of 28 compounds was stable with CYP1 A2,CYP2 E1,CYP2 D6,CYP2 C9,and instable with CYP3 A4,there were 11 chemical constituents of Coptidis Rhizoma and Radix Scutellariae combined with CYP1 A2 at the same time,three constituents of them bound to CYP2 C9 to inhibit their activity. Radix Scutellariae also inhibited the activities of CYP2 E1 and CYP2 D6. Conclusion: It was found that the enzyme system of CYP450 might be the target of protecting liver of Coptidis Rhizoma and Radix Scutellariae,especially CYP1 A2 and CYP2 C9,which inhibited its activity and reduced the production of N-acetic acid-p-benzoquinone imine,reduced the damage of hepatocytes to protect the liver. It provides theoretical basis for further study of the molecular mechanism of Coptidis Rhizoma and Radix Scutellariae.