Analysis of the Potential Mechanismof Sanhua Decoction in Treating Ischemic Stroke Based on Network Pharmacology and Molecular Docking Technology  

基于网络药理学和分子对接技术分析三化汤治疗缺血性脑卒中的潜在作用机制

作　　者：Wei Zhao Dan Li Min Yue Cheng Yan Feng Li Yonghua Qi 赵威;李丹;岳敏;闫诚;李峰;齐永华(新乡学院药学院,河南新乡453003)

机构地区：[1]School of Pharmacy,Xinxiang College,Xinxiang,Henan,China

出　　处：《Chinese Medicine and Natural Products》2024年第4期161-172,共12页中医学报(英文)

基　　金：funded by Key Scientific Research Project of Higher Education in Henan Province(22B230010);National College Student Innovation and Entrepreneurship Training Program(202111071002).

摘　　要：Objective The aim of this study was to explore the action mechanism of Sanhua decoction in treating ischemic stroke through network pharmacology and molecular docking technology.Methods Active components and related targets of Sanhua decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.A“drug-active component-target”network was constructed,and core components were selected throughtopological analysis.Disease targets related to ischemic stroke were screened based on the Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),GeneCards,DrugBank,and PharmGKB databases.The intersection of active component–related targets and ischemic stroke disease targets was identified to obtain potential targets of Sanhua decoction for treating ischemic stroke,represented using a Venn diagram.The STRING database was used to construct a protein–protein interaction(PPI)network of potential targets and filter for core targets.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of core targets were performed using the DAVID database and Metascape platform.Molecular docking verification of core targets and core components was conducted using AutoDock.Results A total of 52 active components and 142 related targets were screened from Sanhua decoction,with core active components including luteolin,nobiletin,β-sitosterol,eucalyptol,and aloe-emodin.There were 2,991 ischemic stroke–related targets,with 98 potential targets identified in the intersection with active component–related targets.An analysis of the PPI network analysis revealed 23 core targets,including serine/threonine-protein kinase 1(AKT1),tumor protein p53(TP53),and mitogen-activated protein kinase 3(MAPK3).Enrichment analysis obtained 35 GO results and 41 signaling pathways.Molecular docking results indicated good binding between core components and core targets.Conclusion Multiple components in the classic formu目的:本研究旨在通过网络药理学与分子对接技术探讨三化汤治疗缺血性脑卒中的作用机制。方法:通过中药系统药理学数据库与分析平台获取三化汤的活性成分及相关靶点,构建“药物-活性成分-靶点”网络,拓扑分析筛选核心成分。基于在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、治疗靶标数据库(therapeutic target database,TTD)、Genecards、Drugbank及Pharm GKB数据库筛选缺血性脑卒中疾病靶点。取活性成分相关靶点及缺血性脑卒中疾病靶点的交集,得到三化汤治疗缺血性脑卒中的潜在靶点,用Veen图表示。利用STRING数据库构建潜在靶点的蛋白质-蛋白质相互作用网络(protein-protein interaction network,PPI)并筛选得到核心靶点。通过DAVID数据库和Metascape平台对核心靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。运用Auto Dock对核心靶点和核心成分进行分子对接验证。结果:从三化汤中筛选得到52种活性成分及142个相关靶点,其中核心活性成分为木犀草素(Luteolin)、川陈皮素(Nobiletin)、β-谷固醇(Beta-sitosterol)、桉叶油素(Eucalyptol)和芦荟大黄素(Aloe-emodin)等。缺血性脑卒中相关靶点2991个,与活性成分相关靶点取交集共得到98个潜在靶点。PPI网络分析得到丝氨酸/苏氨酸蛋白激酶1(Serine/threonine-protein kinase 1,AKT1)、肿瘤蛋白p53(tumor protein p53,TP53)和丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAPK3)等23个核心靶点。富集分析共得到35项GO富集分析结果和41条信号通路。分子对接结果表明,核心成分与核心靶点结合良好。结论:经典名方三化汤中的木犀草素、川陈皮素等多个成分可能通过调控AKT1、TP53、MAPK3等核心靶点参与多条信号通路发挥治疗缺血性脑卒中的作用。

关 键 词：Sanhua decoction ischemic stroke network pharmacology molecular docking technology 

分 类 号：R74[医药卫生—神经病学与精神病学]