基于网络药理学和分子对接探讨黄芪治疗糖尿病周围血管疾病的分子机制  

Exploring the Molecular Mechanism of Huangqi in Treating Diabetic Peripheral Vascular Diseases Based on Network Pharmacology and Molecular Docking

作　　者：严仕梦 闫少庆[1] 杨晓[1] 王丽翔[1] 柳国斌[1] YAN Shimeng;YAN Shaoqing;YANG Xiao;WANG Lixiang;LIU Guobin(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai China 200021)

机构地区：[1]上海中医药大学附属曙光医院,上海200021

出　　处：《中医学报》2021年第12期2661-2666,共6页Acta Chinese Medicine

基　　金：国家自然科学基金青年项目(81804095);国家自然科学基金面上项目(81774310)。

摘　　要：目的:通过网络药理学方法和分子对接技术研究黄芪治疗糖尿病周围血管疾病(diabetic peripheral vascular disease,DPVD)的作用靶点及分子机制,并推测可能的关键作用成分。方法:通过TCMSP数据库筛选黄芪的活性成分及对应的分子靶点。以关键词"Diabetic Peripheral Vascular Disease"在GeneCards和OMIM数据库中寻找疾病的对应靶点,与药物靶点取交集获得黄芪治疗DPVD的主要靶标。构建"药物-疾病-靶点"的可视化网络图与蛋白互作网络图,运用MCODE插件进行核心靶点基因筛选。运用R语言数据包对主要靶标进行GO功能和KEGG富集分析。通过TCMSP网站下载黄芪主要成分的mol2结构式,通过蛋白质结构数据库PDB网站下载核心靶点蛋白PDB结构式,通过Autodock Tools对药物和基因靶点结构式进行加氢,计算电荷,合并非极氢操作,运用Autodock vina进行分子对接操作。结果:经过筛选,共获得黄芪有效成分20个,其中主要作用成分16个,DPVD的分子靶点共7 469个,黄芪与DPVD的共同靶点98个。通过MCODE插件筛选获得蛋白互作网络10个核心基因。富集得到GO主要生物信号20个,提示黄芪在治疗DPVD中主要涉及肽结合活性,酰胺结合活性,丝氨酸水解酶活性等。富集得到KEGG主要信号通路20条,主要涉及G蛋白耦联受体活性,肾上腺素能受体活性,类固醇激素受体活性,抗氧化活性等。分子对接结果提示黄芪核心成分大部分能够与核心靶点产生稳定结合,其中黄芪异黄烷苷、白桦脂酸、叶酸与DPVD核心靶点产生强烈结合活性,提示其可能是黄芪治疗DPVD的核心组分。结论:黄芪可以通过多靶点调控DPVD的多条信号通路,黄芪异黄烷苷、白桦脂酸、叶酸可能是黄芪治疗DPVD的关键组分。Objective:To study the target and molecular mechanism of Huangqi(Radix Astragali seu Hedysari) in treating diabetic peripheral vascular disease(DPVD) through network pharmacology and molecular docking technology,and to speculate its possible key components.Methods:The active components and corresponding molecular targets of Huangqi were screened by TCMSP database.The key word "Diabetic Peripheral Vascular Disease" is used to find the corresponding target of diseases in GeneCards and OMIM databases,and the main target of Huangqi for treating DPVD is obtained by crossing with the drug target.The visual network diagram of "drug-disease-target" and protein interaction network diagram are constructed,and MCODE plug-in is used to screen core target genes.And the main targets were analyzed for gene ontology(GO) function and KEGG enrichment with R language data packets.Mol2 structural formula of Huangqi main components is downloaded through TCMSP website,PDB structural formula of core target protein is downloaded through PDB website of protein structure database.Using Autodock Tools to hydrogenate the structural formulas of drugs and gene targets,calculate the charge,and combine non-polar hydrogen operations,and carrying out molecular docking operation with Autodock vina.Results:After screening,20 active ingredients of Huangqi were obtained,including 16 main active ingredients.And there are 7469 DPBD molecular targets,and 98 common targets for Huangqi and DPVD.10 core genes of protein interaction network were obtained through screening of MCODE plug-in.The enrichment obtained 20 main biological signals of GO,suggesting that Huangqi mainly involves peptide binding activity,amide binding activity,serine hydrolase activity,etc.in DPVD treatment.And 20 major signal pathways of KEGG were obtained by the enrichment,mainly involving G protein coupled receptor activity,adrenergic receptor activity,steroid hormone receptor activity,antioxidant activity,etc.Molecular docking results indicate that most of the core components of Hua

关 键 词：黄芪 糖尿病周围血管疾病 网络药理学 分子对接 

分 类 号：R284.2[医药卫生—中药学]