益心健脾方“异病同治”冠心病和慢性心力衰竭网络药理学机制研究

Mechanisms of action of coronary heart disease and chronic heart failure by Yixin Jianpi prescription with the concept of“homotherapy for heteropathy”based on network pharmacology

目的应用网络药理学探究益心健脾方治疗冠心病及慢性心力衰竭的作用机制。方法借助中药系统药理学(traditional Chinese medicine systems pharmacology,TCMSP)数据库、中药综合数据库(traditional Chinese medicine integrated database,TCMID)等结合文献资料筛选益心健脾方的活性成分靶标,应用人类基因数据库(the human gene database,GeneCards)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)等检索疾病靶标。STRING平台结合Cytoscape软件构建“药物-成分-靶标-疾病”网络图和蛋白互作网络。使用DAVID数据库等进行基因本体(gene ontology,GO)功能和京都基因与基因组百科全书(kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。关键成分与关键靶标利用AutoDuck工具进行分子对接。结果得到益心健脾方潜在靶点265个,其“异病同治”的共同靶点106个;关键活性成分为槲皮素、山奈酚、β-谷甾醇等,核心靶点分别是SRC、AKT1、MAPK1、TP53等;生物过程涉及基因表达的正调控、凋亡过程的负调控、信号转导等方式,参与脂质和动脉粥样硬化、流体剪切应力与动脉粥样硬化及炎症反应等途径;分子对接验证关键成分槲皮素、山奈酚与SRC、AKT1、MAPK1靶点稳定对接。结论本研究揭示益心健脾方“异病同治”冠心病和慢性心力衰竭多成分、多靶点、多通路的作用机制,为探索其新的临床应用提供依据。

Objective Network pharmacology was used to explore the mechanism of action of Yixin Jianpi prescription in the treatment of coronary heart disease and chronic heart failure.Methods With the help of traditional Chinese medicine systems pharmacology(TCMSP),traditional Chinese medicine integrated database(TCMID)and other databases combined with literature data to screen the active ingredient targets of Yixin Jianpi prescription,the human gene database(GeneCards),online mendelian inheritance in man(OMIM)and other databases were used to search for disease targets.The STRING platform combines Cytoscape software to construct a“component-target-disease”network diagram and protein interaction network.Gene ontology(GO)functionality and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis using the DAVID database.The key components are taken and the target is molecularly docked with AutoDuck tools.Results 265 potential targets of Yixin Jianpi Prescription were obtained,and 106 of them were common targets of“homotherapy for heteropathy”;The key active ingredients were quercetin,kaempferol,β-sitosterol,etc.and the core targets were SRC,AKT1,MAPK1,TP53,etc.Biological processes involve positive regulation of gene expression,negative regulation of apoptosis,signal transduction,etc.involving lipid and atherosclerosis,fluid shear stress,atherosclerosis and inflammatory response.Molecular docking verified the stable docking of key components quercetin and kaempferol with SRC,AKT1 and MAPK1 targets.Conclusion The study reveals the multi-component,multi-target,and multi-pathway mechanism of“homotherapy for heteropathy”of coronary heart disease and chronic heart failure by Yixin Jianpi prescription,and provides a basis for exploring its new clinical applications.