基于网络药理学方法研究枳实薤白桂枝汤治疗冠心病的作用机制

A Network Pharmacology Approach to Explore Mechanisms of Zhishi Xiebai Guizhi Decoction for Treatment of Coronary Heart Disease

目的通过网络药理学方法,对枳实薤白桂枝汤治疗冠心病的作用机制进行研究。方法收集枳实薤白桂枝汤中5味药的有效化合物,预测这些化合物对冠心病的作用靶点,对这些靶点进行蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络图构建、基因本体(gene ontology,GO)富集分析和KEGG通路注释分析,将这些化合物与靶点进行分子对接。结果枳实薤白桂枝汤共收集到51个有效化合物,作用于31个冠心病相关靶点,PPI网络图显示ALB、ACE、REN、F2、NOS3、MAPK1、MMP9、MMP2、PPARG、SELE为10个联系最多的靶点,联系最密切的3组靶点为凝血组、斑块稳定组、其他保护组。GO富集分析显示出76个生物过程、26个分子功能、14个细胞成分,通路注释分析显示出19条通路,155组分子对接结果显示91组具有较好的结合活性。结论枳实薤白桂枝汤治疗冠心病具有多成分、多靶点的特点,可能通过抗凝血、稳斑块、抗氧化、抗炎症、降血脂、抑制RASS系统、增加NO保护、促进雌激素保护8个方面发挥治疗冠心病的作用。

Objective To investigate mechanisms of Zhishi Xiebai Guizhi decoction for treatment of coronary heart disease by using a network pharmacology approach. Methods Collect the effective compounds of 5 herbs contained Zhishi Xiebai Guizhi decoction and predict the potential targets about coronary heart disease of the effective compounds,and then structure the targets by protein-protein interaction(PPI) network picture and analyse the targets by gene ontology(GO) and KEGG pathway analysis. At last dock these compounds and targets with molecular. Results The 51 effective compounds of Zhishi Xiebai Guizhi decoction are obtained which act on 31 targets of coronary heart disease. 10 maximum connecting targets are displayed by PPI network are ALB、ACE、REN、F2、NOS3、MAPK1、MMP9、MMP2、PPARG and SELE. 3 groups of targets which are closest contacted are coagulation, stabilizing plaque and other protection. The 76 biological processes, 26 molecular functions and 14 cellular components are obtained by GO analysis.155 groups of molecular docking results show that 91 groups have good binding activities. Conclusion The Zhishi Xiebai Guizhi decoction treatment on coronary heart disease has the characteristics of multi-component and multitarget. It maybe play the treatment role by 8 aspects of anticoagulation, stabilizing plaque, antioxidant, suppressing coronary artery inflammation, reducing fat, suppressing RAAS system, adding NO protection and promoting estrogen secretion.