基于网络药理学探讨真武汤治疗慢性心力衰竭作用机制

Study on the Mechanism of Zhenwu Decoction in Treating Chronic Heart Failure Based on Network Pharmacology

目的基于网络药理学探讨真武汤治疗慢性心力衰竭(Chronic Heart Failure,CHF)的作用机制。方法通过中药系统药理学数据库(TCMSP)筛选出真武汤的有效成分及作用靶点的相关信息;使用Genecard查找与CHF相关的疾病靶点;使用R及Venn Diagram得到药物与疾病相互作用的靶点;使用Cytoscape 3.6.1软件构建"药物-成分-靶点-疾病"网络图;用String构建PPI蛋白网络互作图;对预测靶点进行基因本体(GO)功能富集分析、京都基因与基因组百科全书(KEGG)通路富集分析。结果真武汤的药物有效成分59种,作用于CHF的分子24个,靶标48个,富集到92个基因功能,代谢通路85条。结论真武汤中治疗慢性心力衰竭的主要成分包括甾醇类、芍药苷类、常春藤苷、山奈酚及儿茶酚胺等。主要作用于IL-6、MAPK8、CASP3、Re LA、ESR1等靶点,主要通过辅因子结合(cofactor binding)、核受体活性(nuclear receptor activity)、类固醇激素受体(steroid hormone receptor activity)、神经递质受体活性(neurotransmitter receptor activity)、类固醇结合(steroid binding)等功能作用于流体剪切力与动脉粥样硬化、肿瘤坏死因子信号通路、细胞凋亡、白介素-17、NF-κB、p53、卵巢类固醇生成等相关通路。真武汤通过多有效成分、多靶点、多生物途径及多通路方式协同抗心力衰竭。其结果需要通过实验进一步论证。

Objective To explore the mechanism of Zhenwu Decoction(ZWD)in treating chronic heart failure(CHF)based on network pharmacology.Methods The effective ingredients and target information of ZWD were screened out by TCMSP;the disease targets related to CHF were searched by Genecard;and the disease targets related to CHF were searched by R and Venn D.Iagram obtains the target of drug-disease interaction;uses Cytoscape 3.6.1 software to construct"drug-component-target-disease"network;uses String to construct PPI protein network interaction map;carries out gene ontology(GO)functional enrichment analysis for predicted target;Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results There are 59 active ingredients in Zhenwu Decoction,24 molecules acting on CHF,48 targets in the drug-disease interaction,and 92 gene functions,85 metabolic pathways.Conclusion The main components of Zhenwu Decoction in treating chronic heart failure include sterols,paeoniflorins,ivy glycosides,kaempferol and catecholamines.It mainly acts on IL-6,MAPK8,CASP3,Re LA,ESR1 and other targets,and it mainly through cofactor binding,nuclear receptor activity,steroid hormone receptor activity,neurotransmitter receptor activity,and steroid receptor activity act on fluid shear force atherosclerosis,tumor necrosis factor signaling pathway,apoptosis,interleukin-17,NF-kappa B,p53,ovarian steroid production and other related pathways.Therefore,Zhenwu Decoction is synergistic against heart failure through multiple active ingredients,multiple targets,multiple biological pathways and multiple pathways,but he results need to be further demonstrated by experiments.