基于网络药理学和分子对接技术研究“木香-枳壳”治疗便秘型肠易激综合征的作用机制  

Mechanism of Muxiang-Zhiqiao in the treatment of constipation-predominant irritable bowel syndrome based on network pharmacology and molecular docking

作　　者：肖俐敏 罗雯鹏 李克亚[1] 周佳敏 王真权[1] Xiao Limin;Luo Wenpeng;Li Keya;Zhou Jiamin;Wang Zhenquan(The Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha Hunan 410005)

机构地区：[1]湖南中医药大学第二附属医院,湖南长沙410005

出　　处：《山西中医药大学学报》2025年第2期209-216,共8页Journal of Shanxi University of Chinese Medicine

基　　金：2023年度湖南省自然科学基金青年基金项目(2023JJ40496);2022年度湖南省“十四五”中医药科技创新平台项目(湘中医药函[2022]93号);2021年度湖南省中医药管理局一般项目(2021063);2020年度湖南省中医药管理局项目(湘中医药函[2020]51);湖南省中医肛肠病学学科带头人(湘中医药函[2022]4号)。

摘　　要：目的:基于网络药理学方法和分子对接技术研究“木香-枳壳”治疗便秘型肠易激综合征(IBS-C)的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)分别检索木香、枳壳的活性成分和作用靶点,再将蛋白靶点输入UniProt数据库获得相应基因靶点;利用人类基因数据库(GeneCards)、人类孟德尔遗传综合数据库(OMIM)检索IBS-C的作用靶点,药物靶点和疾病作用靶点通过Venny取交集后,结合STRING平台获取蛋白-蛋白相互作用关系,构建PPI网络,挖掘潜在蛋白质,并借助Cytoscape 3.9.1绘制“药物-成分-疾病-靶点”网络图;利用富集分析在线工具(DAVID)对关键靶基因进行基因本体(GO)功能分析及京都基因与基因组百科全书(KEEG)通路富集分析。使用AutoDock Tool(v1.5.6)软件对核心靶点与核心活性成分进行分子对接验证。结果“:木香-枳壳”治疗IBS-C的有效活性成分共11种,主要成分有柚皮素、β-谷甾醇、豆甾醇、川陈皮素、香豆素;交集靶点共86个,其中核心靶点有丝氨酸/苏氨酸蛋白激酶(Akt1)、前列腺素内过氧化物合成酶2(PTGS2)、p53蛋白(TP53)、B淋巴细胞瘤-2(BCL2)、胱天蛋白酶3(CASP3)“;木香-枳壳”治疗IBS-C主要涉及胆固醇代谢、Th1/Th2细胞分化、FoxO信号通路、NF-κB信号通路、Wnt信号通路等,外源物质应激、雌二醇反应、低氧反应、凋亡调控等相关生物进程,线粒体、神经元投射、质膜、突触等相关细胞组分,酶联反应、蛋白泛素化、类固醇激素受体活性、雌激素反应等相关分子功能。分子对接显示香豆素与PTGS2,β-谷甾醇与Akt1、BCL2,柚皮素、川陈皮素与Akt1、PTGS2、CAPS3,豆甾醇与Akt1、BCL2、PTGS2、CAPS3具有稳固的结合效应。结论“:木香-枳壳”药对可通过多成分、多靶点、多通路发挥作用治疗IBSC,其具体药理基础及作用机制仍待深入发掘。Objective:To investigate the mechanism of Muxiang-Zhiqiao in the treatment of constipation-predominant irritable bowel syndrome(IBS-C)based on network pharmacology and molecular docking technology.Methods:The active ingredients and their targets of Muxiang and Zhiqiao were retrieved from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),and then the protein targets were input into UniProt database to obtain the corresponding gene targets.The targets of IBS-C were searched using the human Gene Database(GeneCards)and the Comprehensive Database of Human Mendelian Genetics(OMIM).The intersection of drug targets and disease targets was obtained by Venny,and proteinprotein interaction was obtained by STRING platform to construct PPI network and explore potential proteins.Cytoscape 3.9.1 was used to draw the“drug-component-disease-target”network diagram.Gene ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEEG)pathway enrichment analysis of key target genes were performed using the enrichment analysis online too(l DAVID).AutoDock Too(l v1.5.6)software was used to verify the molecular docking between core targets and core active ingredients.Results:There were 11 active ingredients of Muxiang-Zhiqiao in the treatment of IBS-C,including naringenin,β-sitosterol,stigmasterol,nobiletin and coumarin.There were 86 intersection targets,among which the core targets were serine/threonine protein kinase(Akt1),prostaglandin peroxidase synthetase 2(PTGS2),p53 protein(TP53),B lymphoblastoma-2(BCL2)and Caspase 3(CASP3).The treatment of IBS-C with Muxiang-Zhiqiao mainly involved cholesterol metabolism,Th1/Th2 cell differentiation,FoxO signaling pathway,NF-κB signaling pathway,Wnt signaling pathway,exogenous stress,estradiol response,hypoxia response,apoptosis regulation and other related biological processes,mitochondria,neuronal projections,plasma membrane,synapses and other related cell components,enzyme linked reaction,protein ubiquitination,steroid hormone rece

关 键 词：便秘型肠易激综合征 木香 枳壳 网络药理学 分子对接 信号通路 分子机制 

分 类 号：R259[医药卫生—中西医结合] R574.62[医药卫生—中医内科学]