基于网络药理学和分子对接探讨心脉安片“异病同治”心律失常和心力衰竭的作用机制

Study on theMechanismof Xinmai'an Tablets in Treating Arrhythmia and Heart Failure with Concept of"Treating Different Diseases with Same Method"Based on Network Pharmacology and Molecular Docking

应用网络药理学方法和分子对接技术揭示心脉安片治疗心律失常和心力衰竭的作用机制。通过TCMSP、BATMAN-TCM、Swiss Target Prediction和Stitch数据库收集心脉安片化学成分及其相关靶点,并结合GeneCards、TTD、OMIM和DrugBank数据库获取心律失常和心力衰竭疾病靶点。采用Cytoscape软件获得心脉安片“异病同治”的共同靶点,并绘制中药有效成分共同靶点疾病网络图,利用STRING数据库对疾病成分靶点构建蛋白蛋白互作(PPI)分析,通过Cytoscape软件分析PPI网络的核心靶点,并运用DAVID数据库对核心靶点进行GO功能富集分析和KEGG通路富集分析。同时将核心靶点与关键活性成分进行分子对接验证。本研究从心脉安片中筛选出146个活性化合物,其“异病同治”的共同靶点178个,核心靶点11个,分别是STAT3、AKT1、IL-6、TNF、MAPK3、TP53、EGFR、HSP90AA1、VEGFA、EDN1和PPARA。关键活性成分有槲皮素、山柰酚、木犀草素、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1和毛蕊异黄酮葡萄糖苷等成分。关键生物通路包括HIF-1信号通路和TNF信号通路等。分子对接结果显示,槲皮素、山柰酚、木犀草素、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1和毛蕊异黄酮葡萄糖苷等成分与STAT3、TNF、IL-6和VEGFA等靶点稳定对接。心脉安片“异病同治”心律失常和心力衰竭多成分、多靶点、多通路的作用机制,为进一步研究心脉安片效应机制,探索其新的临床应用提供科学依据。

The study aimed to explore the mechanismof Xinmai'an tablets in the treatment of arrhythmia and heart failure based on network pharmacology and molecular docking.The effective components and the corresponding targets of Xinmai'an tablets were collected by TCMSP,BATMAN-TCM,Swiss Target Prediction and Stitch databases.Targets of arrhythmia and heart failure were found by GeneCards,TTD,OMIMand DrugBank databases.The common targets of targets of Xinmai'an tablets and targets of arrhythmia and heart failure were founded by Cytoscape software.The"active components of traditional Chinese medicine-common targets-diseases"network map of Xinmai'an tablets in treating arrhythmia and heart failure was also constructed using Cytoscape software.The protein-protein interactions network(PPI)of common targets of dieases and effective components was constructed using STRING database,and core targets were obtained by analyzing PPI network with Cytoscape software.GO functional enrichment analysis and KEGG pathway enrichment analysis of core targets were conducted by DAVID.The key targets and effective components were verified by molecular docking.Atotal of 146 active components of Xinmai'an tablets were screened.178 common targets of Xinmai'an tablets in treatment of arrhythmia and heart failure were founded.11 core targets were STAT3,AKT1,IL-6,TNF,MAPK3,TP53,EGFR,HSP90AA1,VEGFA,EDN1 and PPARA,respectively.Key active components were quercetin,kaempferol,luteolin,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and calycosin-7-O-beta-Dglucoside,etc.Key pathway analysis were HIF-1 signaling pathway,TNF signaling pathway and so on.Molecular docking results showed that quercetin,kaempferol,luteolin,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,calycosin-7--beta--glucoside and other components could be stably docked with STAT3,TNF,IL-6,VEGFA and other targets.Xinmai'an tablets in the treatment of arrhythmia and heart failure with concept of"treating different diseases with same method"was by multi-components,multi-targets and multi-pathways.It provides scientific basis for further study on the effect mechanismof Xinmai'an tablets and exploration of its new clinical application.