基于网络药理学与分子对接的“鬼箭羽-白花蛇舌草”治疗子宫内膜异位症的作用机制研究  

A Study on the Mechanism of"Winged Euonymus Branchlet and Spreading Hedyotis Herb"in the Treatment of Endometriosis Based on Network Pharmacology and Molecular Docking

作　　者：王珺 徐传花[2] WANG Jun;XU Chuan-hua(Graduate School of Nanjing University of Traditional Chinese Medicine,Nanjing 210023,Jiangsu,China;Department of Gynaecology,Changzhou Hospital of Traditional Chinese Medicine Affiiated to Nanjing University of Traditional Chinese Medicine,Changzhou 213000,Jiangsu,China)

机构地区：[1]南京中医药大学研究生院,江苏南京210023 [2]南京中医药大学附属常州市中医医院妇科,江苏常州213000

出　　处：《医学信息》2023年第9期21-29,共9页Journal of Medical Information

基　　金：第五批全国中医临床优秀人才研修项目(编号:国中医药人教函〔2022〕1号)。

摘　　要：目的应用网络药理学与分子对接技术揭示“鬼箭羽-白花蛇舌草”药对治疗子宫内膜异位症的分子机制,为其临床应用提供新的理论依据及研究思路。方法从中药系统药理学数据库与分析平台(TCMSP)获取“鬼箭羽-白花蛇舌草”药对主要活性成分,利用PubChem及SwissTargetPrediction数据库获取主要活性成分的药物靶点;利用GeneCards、TTD、人类孟德尔遗传数据库(OMIM)获取子宫内膜异位症相关靶点,与药物靶点进行交集获得共有靶点。利用DAVID 2021在线数据库对共有靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,应用STRING11.5在线数据库构建共有靶点蛋白互作网络(PPI),通过Discovery Studio2019对靶点蛋白与关键化合物进行分子对接评价。结果共筛选出13个“鬼箭羽-白花蛇舌草”主要活性成分,药物靶点366个,与疾病靶点取交集得到130个共有靶点,其中核心靶点有STAT3、SRC、EGFR、AKT1、MAPK3等。GO富集分析显示:生物学过程(BP)共富集到493个条目,主要为凋亡过程的负调控、蛋白质磷酸化、基因表达的负调控、炎症反应、对药物的反应等;细胞组分(CC)共富集到63个条目,主要为细胞质、胞质溶胶、质膜、细胞外空间、质膜的组成部分等;分子功能(MF)共富集到126个条目,主要为相同蛋白质结合、ATP结合、酶结合、蛋白激酶活性、血红素结合等。KEGG富集分析得到129个条目,主要为癌症通路、AGE-RAGE信号通路在糖尿病并发症中的作用、EGFR酪氨酸激酶抑制剂耐药、化学致癌-受体激活、脂质和动脉粥样硬化、化学致癌-活性氧等。通过PPI互作网络并拓扑分析得出度值排名靠前的靶点有STAT3、SRC、EGFR、AKT1、MAPK3等,这些蛋白靶点是其治疗EMT的关键靶点。分子对接结果显示,MAPK3与5,7-二羟基-2-(3-羟基-4-甲氧基苯基)色满-4-酮、山柰酚、槲皮素,AKT1与5,7-二羟基-2-(3-羟基-4-甲氧基�Objective To reveal the molecular mechanism of"Winged Euonymus Branchlet and Spreading Hedyotis herb"in the treatment of endometriosis by network pharmacology and molecular docking technology,and to provide new theoretical basis and research ideas for its clinical application.Methods The main active components of"Winged Euonymus Branchlet and Spreading Hedyotis Herb"were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the drug targets of the main active components were obtained by PubChem and SwissTargetPrediction databases.GeneCards,TTD and human Mendelian genetic database(OMIM)were used to obtain endometriosis-related targets,which were intersected with drug targets to obtain common targets.DAVID 2021 online database was used to perform gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis on common targets.STRING11.5 online database was used to construct a common target protein interaction network(PPI).Discovery Studio 2019 was used to evaluate the molecular docking of target proteins and key compounds.Results A total of 13 main active components of"Winged Euonymus Branchlet and Spreading Hedyotis Herb"and 366 drug targets were screened out,and 130 common targets were obtained by intersecting with disease targets,among which the core targets were STAT3,SRC,EGFR,AKT1,MAPK3,etc.GO enrichment analysis showed that biological process(BP)was enriched to 493 items,mainly including negative regulation of apoptosis process,protein phosphorylation,negative regulation of gene expression,inflammatory response,response to drugs,etc.The cellular component(CC)was enriched to 63 items,mainly including cytoplasm,cytosol,plasma membrane,extracellular space,components of plasma membrane,etc.Molecular function(MF)was enriched to 126 items,mainly including the same protein binding,ATP binding,enzyme binding,protein kinase activity,heme binding,etc.KEGG enrichment analysis obtained 129 items,mainly including cancer pathways,the role of AGE

关 键 词：鬼箭羽-白花蛇舌草 子宫内膜异位症 网络药理学 分子对接 

分 类 号：R711.71[医药卫生—妇产科学]