基于网络药理学及分子对接方法研究黄芪治疗血管性痴呆的机制

Mechanism of Astragalus membranaceus in treatment for vascular dementia based on network pharmacology and molecular docking

目的利用网络药理学和分子对接方法研究黄芪治疗血管性痴呆(vascular dementia,VD)的机制。方法利用TCMSP数据库搜集黄芪活性成分,根据各成分的SMILES式在TargetNet数据库预测各成分的靶点;在GeneCards数据库搜集VD靶点,求黄芪活性成分靶点与VD靶点的交集,得到黄芪治疗VD的潜在靶点,利用Cytoscape 3.9.1软件构建活性成分-靶点网络;将黄芪治疗VD的潜在靶点导入STRING数据库构建蛋白-蛋白交互作用(protein-protein interaction,PPI)网络,并分析获得核心靶点;将核心靶点导入DAVID数据库进行基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析;利用AutoDock软件对黄芪主要活性成分与VD核心靶点进行分子对接。结果共搜集到黄芪活性成分20个,包括华良姜素、异桔梗素、异黄酮烷、山奈酚和槲皮素等,得到预测靶点102个。收集并筛选得到VD靶点3556个,得到黄芪与VD共同靶点71个,经PPI分析获得36个核心靶点,包括SLC6A4、ESR1、PTGS2、ABCB1、AR等。36个核心靶点富集到187个GO条目和32条KEGG通路,主要集中于神经功能、激素信号和血管生成方面。分子对接显示黄芪主要活性成分与VD核心靶点具有良好亲和力。结论黄芪可能主要通过调节神经功能、激素水平和血管生成治疗VD。

Objective To investigate the mechanism of Astragalus membranaceus(AM)in the treatment of vascular dementia(VD)by network pharmacology and molecular docking.Methods The active components of AM were collected from TCMSP database,and the targets of active components were predicted in TargetNet database according to the SMILES.The VD targets were collected by GeneCards database,and the common targets of active components and VD was calculated to obtain the potential targets of AM in the treatment of VD.The active components-target network was constructed by Cytoscape 3.9.1 software.The potential targets of AM in the treatment of VD were imported into STRING database to construct protein-protein interaction(PPI)network,which was analyzed to obtain core targets.The core targets were imported into DAVID database to perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The molecular docking was performed to assess the affinity of main active components of AM and the corresponding VD core targets via AutoDock software.Results A total of 20 active components of AM were collected,including jaranol,isorhamnetin,isoflavanone,kaempferol and quercetin,and a total of 102 predicted targets were obtained.A total of 3556 VD targets were screened,71 common targets of AM and VD were calculated,and 36 core targets were obtained by PPI analysis,including SLC6A4,ESR1,PTGS2,ABCB1 and AR.A total of 187 GO items and 32 KEGG pathways were enriched,mainly focusing on neurological function,hormone signal and angiogenesis.Molecular docking showed good affinity between the main active components of AM and VD core targets.Conclusion AM treats VD mainly by regulating neurological function,hormone signal and angiogenesis.