通脉逐瘀汤治疗动脉粥样硬化的网络药理学和分子对接研究

Network Pharmacology and Molecular Docking Study of Tongmai Zhuyu Decoction(通脉逐瘀汤)in Treatment of Atherosclerosis

目的:采用网络药理学与分子对接技术探讨通脉逐瘀汤治疗动脉粥样硬化(AS)的潜在作用机制。方法:利用中药系统药理学数据库(TCMSP)、分子机制的生物信息学(BATMAN)数据库、通用蛋白质资源(Uniprot)数据库获得通脉逐瘀汤的活性成分及其作用靶点;通过在线人类孟德尔遗传(OMIM)数据库、基因卡片(Gene Cards)数据库、基因疾病关联(DisGeNET)数据库和毒性与基因比较(CTD)数据库获取AS的相关靶点并与通脉逐瘀汤作用靶点取交集;基于Cytoscape软件构建通脉逐瘀汤治疗AS的化合物-靶点-疾病网络并进行网络拓扑学分析;通过检索交互基因搜索工具(STRING)数据库构建靶点蛋白质交互作用(PPI)关系网络并进行网络拓扑学分析;利用AutoDock_Vina软件进行分子对接模拟;最终利用Bioconductor中的R包Clusterprofile version 3.12.0对交集靶点进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:共筛选到279种活性成分和586个靶点;分子对接模拟发现,川陈皮素、(+)-儿茶素、黄芩素等活性成分与关键靶点的结合活性较好;GO富集分析结果共有1749个GO条目,其中1627个生物过程条目、30个细胞组分条目和92个分子功能条目;KEGG通路富集分析结果共有94条通路,主要有低氧诱导因子-1(HIF-1)信号通路、肿瘤坏死因子(TNF)信号通路、钙离子信号通路等通路。结论:通脉逐瘀汤可通过多成分、多靶点、多通路参与治疗AS。

Objective:Network pharmacology and molecular docking technique were used to explore the potential mechanism of Tongmai Zhuyu Decoction(通脉逐瘀汤)in the treatment of atherosclerosis(AS).Methods:The active components and action targets of Tongmai Zhuyu Decoction were obtained by using Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN)and Universal Protein Resource(Uniprot).The related targets of AS were obtained through the Online Mendelian Inheritance in Man(OMIM),Gene Cards Database,DisGeNet and Comparative Toxicogenomics Database(CTD),and intersected with the action targets of Tongmai Zhuyu Decoction.Based on Cytoscape software,the compound-target-disease network of Tongmai Zhuyu Decoction in the treatment of AS was constructed and the network topology was analyzed.The relationship network of Protein–protein Interactions(PPI)was constructed by using Search Tool for the Retrieval of Interacting Genes(STRING)and analyzed by the network topology analysis.AutoDock_Vina software was used for molecular docking simulation.Finally,the R package Clusterprofile version 3.12.0 in Bioconductor was used to analyze the intersection targets for Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results:Total 279 active components and 586 targets were screened.Molecular docking simulation showed that the active components such as nobiletin,(+)-catechin,and baicalein had good binding activity to the key targets.The results of GO enrichment analysis showed that there were total 1749 GO items,including 1627 biological process items,30 cell component items and 92 molecular function items.KEGG pathway enrichment analysis showed that there were total 94 pathways,including hypoxia-inducible factor(HIF-1)signaling pathway,tumor necrosis factor(TNF)signaling pathway,calcium signaling pathway and so on.Conclusions:Tongmai Zhuyu Decoction can participate in the treatment of AS through multi-components,multi-targets and multi-pathways.