基于双心医学理论和分子对接技术探讨柴胡-黄芩药对治疗冠心病的作用机制

Research on the Mechanism of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)Drug Pair in Treating Coronary Heart Disease Based on Double Heart Medicine and Molecular Docking

目的从双心理论角度出发,应用网络药理学的研究方法及分子对接技术,探讨柴胡-黄芩药对对冠心病的疗效机制。方法应用中药系统药理学数据库与分析平台将柴胡、黄芩两味中药的有效成分及作用靶点进行查询及筛选,再利用TCMID、TCM-MESH、BATMAN-TCM、SymMap数据库对结果进行补充。从GeneCards数据库检索冠心病的疾病靶点,利用Venney 2.1.0在线程序绘制柴胡-黄芩-冠心病交集靶点韦恩图,再用Cytoscape软件进行可视化处理。用enrichGO、enrichKEGG函数分别进行GO注释和KEGG通路富集分析,AutoDock vina将柴胡-黄芩的有效成分与重要蛋白受体进行分子对接。结果筛选出柴胡-黄芩药对治疗冠心病作用的共同靶点112个,GO注释生物过程1776条,细胞组成63条、分子功能132条。KEGG富集分析显示柴胡-黄芩药对主要通过PTGS1、PTGS2、PPARG、NOS、NCOA2、GSK3B、ADRB1、ADRA2A、HTR2A等靶点及流体剪应力与动脉粥样硬化、IL-17、雌激素、松弛素、HIF-1、TNF等信号通路发挥作用。分子对接结果显示柴胡-黄芩有效化合物配体小分子与受体蛋白对接结果均<-5.0 kcal/moL,并通过氢键作用、疏水作用、Pi-Pi共轭作用维持稳定构象。结论文章揭示了柴胡-黄芩药对治疗冠心病的潜在机制,进一步印证了中药多途径、多靶点的治疗特点,为临床基于“双心医学”论治冠心病提供理论依据。

Objective To explore the potential therapeutic effects of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)drug pair on coronary heart disease from the perspective of doubleheart medicine theory by using network pharmacology research methods and molecular docking technology.Methods Through the TCMSP query and screen Chaihu(Bupleuri Radix)and Huangqin(Scutellariae Radix),and through TCMID,TCM-MESH,BATMAN-TCM and SymMap databases supplement the results of TCMSP.The disease targets of coronary heart disease were retrieved from the GeneCards database,and the Venn diagram of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)-coronary heart disease intersection targets was drawn using the online program of Venney 2.1.0,and then visualized by Cytoscape software.Using enrichGO and enrichKEGG functions to perform GO annotation and KEGG pathway enrichment analysis,respectively,AutoDock vina to molecularly dock the active ingredients of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)and important protein receptors.Results We screened out 112 common targets of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)baicalensis for the treatment of coronary heart disease,1776 GO-annotated biological processes,63 cell composition,132 molecular functions,mainly related to cell response to drugs,response to nutritional levels.The reaction to oxidative stress,the metabolic process of reactive oxygen species,and the response to steroid hormones.KEGG enrichment analysis showed that Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)baicalensis drug pair mainly through PTGS1,PTGS2,PPARG,NOS,NCOA2,GSK3B,ADRB1,ADRA2A,HTR2A and other targets and fluid shear stress and atherosclerosis,IL-17,estrogen,signal pathways such as relaxin,HIF-1 and TNF play a role.The molecular docking results showed that the docking results of the small molecules of the effective compound ligand of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)and the receptor protein were less than-5.0 kcal/mol,and the stable conformation was maintained through hydrogen bonding,hydrophobic interaction,and Pi-Pi conjugation.Conclusion This article reveals the potential mechanism of Chaihu(Bupleuri Radix)-Huangqin(Scutellariae Radix)baicalensis for the treatment of coronary heart disease,further confirms the multi-channel and multi-target treatment characteristics of traditional Chinese medicine,and provides a theoretical basis for the clinical treatment of coronary heart disease based on“double heart medicine”.