基于网络药理学探讨葛根治疗动脉粥样硬化效应机制

Mechanism of Puerariae Radix in Treatment of Atherosclerosis Based on Network Pharmacology

目的:探索葛根治疗动脉粥样硬化(atherosclerosis,AS)的效应机制。方法:通过中药系统药理学分析平台(TCMSP)来检索葛根的化学成分和作用的靶点。并在TTD、OMIM、Drugbank、Digsee等多种数据库查询与AS相关的基因。同时基于UniProt数据库分析出靶点多对应的基因,并通过Cytoscape 3.2.1软件构建出葛根的化合物-靶点网络、蛋白质相互作用(PPI)网络筛选出核心靶点,最后使用DAVID数据库进行基因本体(GO)功能富集分析和京都基因和基因组百科全书(KEGG)通路富集分析,得出其可能存在的作用机制。结果:预测得到葛根治疗AS的化合物-靶点网络中有效成分为2个,有效靶点46个,并因此得出其作用机制可能与细胞凋亡、肿瘤坏死因子(TNF)信号通路、钙通道受体信号通路、PI3K-Akt信号通路等有关,并且可能JUN、MAPK14、CASP3、AR、ESPR1、PTGS2等靶点基因起着重要作用。结论:通过网络药理学探讨了葛根治疗AS的多成分-多靶点-多通路的作用机制特点,为进一步揭示葛根治疗AS的作用机制的科研探索提供了新的思路和新的方法。

Objective:To explore the effect mechanism of Puerariae Radix on atherosclerosis(AS).Methods:The chemical constituents and targets of Puerariae Radix were retrieved by Traditional Chinese Medcine Systems Platform(TCMSP).In addition,genes related to AS were searched in various databases such as TTD,OMIM,Drugbank,Digsee,etc.At the same time,the multi-target genes were analyzed based on UniProt database,and the compound-target network and protein-protein interaction(PPI)network of Puerariae Radix were constructed through Cytoscape 3.2.1 to screen out the core targets.Finally,the Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out by using DAVID database to obtain the possible mechanism of action.Results:It is predicted that there are 2 effective components and 46 effective targets in the compound-target network of Puerariae Radix in treating AS.Therefore,it is concluded that its mechanism of action may be related to cell death,Tumor Necrosis Factor(TNF)signal pathway,Calcium channel receptor signal pathway,PI3K-Akt signal pathway,etc,and it may play an important role in target genes such as JUN,MAPK14,CASP3,AR,ESPR1,PTGS2,etc.Conclusion:Through network pharmacology,the characteristics of multi-component multi-target multi-pathway mechanism of Puerariae Radix in treating AS were discussed,which provided new ideas and new methods for scientific research and exploration to further reveal the mechanism of Puerariae Radix in treating AS.