葛根芩连汤治疗腹泻型肠易激综合征的网络药理学研究  

A network pharmacological study of Gegen Qinlian decoction in the treatment of diarrheal irritable bowel syndrome

作　　者：殷梓钰 王一 柏皓戈 王业昊 王祥宇 王荣 孙闵[1] YIN Ziyu;WANG Yi;BAI Haoge;WANG Yehao;WANG Xiangyu;WANG Rong;SUN Min

机构地区：[1]济宁医学院,山东济宁272067

出　　处：《中医临床研究》2024年第9期48-53,共6页Clinical Journal Of Chinese Medicine

基　　金：济宁医学院大学生创新训练计划项目(cx2021144);济宁医学院大学生创新训练计划项目(cx2022069z);济宁医学院中西医结合治疗脾胃病创新团队项目(jy201918);山东省中医药管理局重点学科(方剂学)。

摘　　要：目的:运用网络药理学方法及分子对接技术探究葛根芩连汤治疗腹泻型肠易激综合征(Diarrhea Irritable Bowel Syndrome,IBS-D)的可能潜在作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)检索葛根芩连汤中4味中药的有效成分和对应靶点,通过GeneCards数据库等获取IBS-D的相关疾病靶点,将药物作用靶点和相关疾病靶点进行映射,得到该方治疗IBS-D的共同作用靶点。利用STRING数据库和Cytoscape 3.7.2软件构建蛋白质-蛋白质相互作用(Protein-protein Interaction,PPI)网络,并得到核心作用靶点。通过DAVID数据库对共同作用靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。利用分子对接技术进行初步验证。结果:葛根芩连汤有效活性成分包括槲皮素、葛根素等144个,葛根芩连汤与IBS-D共同作用靶点135个,核心作用靶点为丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、白细胞介素(Interleukin,IL)-6、血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)A、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、肿瘤蛋白p53(Tumor Protein p53,TP53)等。KEGG通路富集分析得出葛根芩连汤可能通过调节磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinases,PI3K)-蛋白激酶B(Akt)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)、TNF等信号通路而对IBS-D起治疗作用。分子对接验证结果提示核心成分与靶点之间有较强的结合活性。结论:葛根芩连汤中多种成分可通过多靶点、多通路机制治疗IBS-D,其可能通过PI3K-Akt、MAPK等信号通路降低炎症反应、改善内脏高敏感性,从而发挥治疗作用。Objective:To investigate the potential mechanism of Gegen Qinlian decoction(葛根芩连汤)in treating diarrheal irritable bowel syndrome(IBS-D)by network pharmacology and molecular docking technique.Methods:The effective components and corresponding targets of 4 herbs in Gegen Qinlian decoction were retrieved from TCM Systematic Pharmacology database and Analysis Platform(TCMSP),and the relevant disease targets of IBS-D were obtained through GeneCards and other databases,and the drug action targets and related disease targets were mapped.The common targets of IBS-D were obtained.The PPI network was constructed using String database and Cytoscape 3.7.2 software,and the core target was obtained.Genetic ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were conducted for the co-interacting targets through the DAVID database.Molecular docking technology was used for preliminary verification.Results:The 144 active ingredients Gegen Qinlian decoction included quercetin,puerarin,etc.There were 135 common targets of Gegen Qinlian decoction and IBS-D,and the core targets were AKT1,IL6,VEGFA,TNF,TP53,etc.The KEGG pathway enrichment analysis showed that Gegen Qinlian decoction may play a therapeutic role on IBS-D by regulating phosphatidylinositol-3-kinase-protein kinase B(PI3K-Akt),mitogen-activated protein kinase(MAPK),tumor necrosis factor(TNF)and other signaling pathways.The results of molecular docking showed that there was strong binding activity between the core components and the targets.Conclusion:Various components in Gegen Qinlian decoction can treat IBS-D through multi-target and multi-pathway mechanisms,which may reduce inflammatory response and relieve visceral hypersensitivity through signaling pathways such as PI3K-Akt and MAPK,thereby e xerting therapeutic effects.

关 键 词：葛根芩连汤 腹泻型肠易激综合征 网络药理学 作用机制 分子对接 

分 类 号：R256.3[医药卫生—中医内科学]