基于网络药理学的五苓散治疗慢性心力衰竭的机制研究

Mechanism of Wuling Powder in treatment of chronic heart failure based on network pharmacology

目的通过网络药理学方法探讨五苓散(WLS)治疗慢性心力衰竭(CHF)的作用机制。方法运用中药系统药理数据库和分析平台(TCMSP)与文献挖掘获取五苓散的有效活性成分和对应的作用靶点,从而建立单味药-活性成分-靶点网络;在GeneCards、OMIM数据库获得CHF的靶点,采用Cytoscape 3.7.1软件构建药物活性成分-CHF-靶点网络模型并进行分析;运用STRING数据库构建蛋白质相互作用网络(PPI),借助DAVID在线工具对关键靶点进行基因本体功能注释(GO)和东京基因组百科全书(KEGG)通路富集分析,并用Surflex软件进行分子对接。结果通过筛选得到50个活性成分,29个潜在靶点,8243个CHF靶点,27个五苓散-CHF共同靶点。网络分析结果表明,五苓散治疗CHF的关键靶点包括CASP3、RELA、AR、ESR1、CHRM1、CASP8等,生物过程主要涉及信号转导、神经系统发育、RNA聚合酶II启动子的转录起始、对雌二醇的反应、胆碱能突触传递等,KEGG富集主要涉及调节神经活性配体-受体相互作用、PI3K-Akt信号通路、胆碱能突触等。分子对接结果显示五苓散中(+)-儿茶素、花旗松素等关键化合物与CASP8、CHRM1、NR3C1等关键靶点有较好的结合能力。结论从网络药理学角度初步揭示了五苓散治疗CHF的物质基础和作用机制,为五苓散的临床应用提供了一定的理论依据。

Objective To explore the mechanism of Wuling Powder in the treatment of chronic heart failure(CHF)based on network pharmacology.Methods Traditional Chinese Medicine Systems Pharmacology Database(TCMSP)and literature mining were used to search the chemical components and targets of Wuling Powder,and a single drug-active ingredients-target network was established.The related targets of chronic heart failure were collected through Genecards and OMIM databases,the network model of active components-CHF-targets was constructed and analyzed by Cytoscape 3.7.1 software.The protein-protein interaction(PPI)network was constructed by STRING database platform,and the gene oesthetics(GO)function annotation and Kyoto Encyclopedin of Genes and Genomes(KEGG)signal pathway enrichment analysis were performed by DAVID online tools.The molecular docking was performed using Surflex software.Results Fifty components,29 potential targets,8243 targets related to chronic heart failure,and 27 targets of Wuling Powder-CHF were obtained.The network analysis results showed that the key targets of Wuling Powder in the treatment of chronic heart failure included CASP3,RELA,AR,ESR1,CHRM1 and CASP8,etc.Biological processes mainly involved signal transduction,nervous system development,transcription initiation from RNA polymerase II promoter in response to estradiol,synaptic transmission,cholinergic synaptic transmission,etc.KEGG enrichment involved neuroactive ligand-receptor interaction,PI3K-Akt signaling pathway,cholinergic synapse,etc.The molecular docking results showed that(+)-catechin,taxifolin and other key compounds in Wuling Powder had better binding ability with key targets such as CASP8,CHRM1,and NR3C1.Conclusion The material basis and mechanism of Wuling Powder in the treatment of chronic heart failure were revealed based on network pharmacology,which provided a certain theoretical basis for the clinical application of Wuling Powder.