基于网络药理学和分子对接探讨柴胡-大黄药对防治胆石症的作用机制  

Study on the Mechanism of Bupleurum-rhubarb in the Prevention and Treatment of Cholelithiasis Based on Network Pharmacology and Molecular Docking

作　　者：高云霄 李泽 杨柳[1] 郭榆西 郭彤 李博林 杨倩[2] GAO Yunxiao;LI Ze;YANG Liu;GUO Yuxi;GUO Tong;LI Bolin;YANG Qian(Graduate School of Hebei University of Chinese Medicine,Shijiazhuang 050090,China;The First Affiliated Hospital of Hebei University of Chinese Medicine,Shijiazhuang 050011,China)

机构地区：[1]河北中医学院研究生院,石家庄050090 [2]河北中医学院第一附属医院,石家庄050011

出　　处：《世界中医药》2022年第4期447-454,共8页World Chinese Medicine

基　　金：河北省中医药管理局科研计划项目(2020080)。

摘　　要：目的:基于网络药理学和分子对接技术初步探讨柴胡-大黄药对治疗胆石症的有效物质基础及作用机制。方法:借助中药系统药理学数据库与分析平台(TCMSP)检索柴胡、大黄的有效活性成分及潜在作用靶点;通过GeneCards、CTD、TTD数据库得出胆石症相关作用靶点。利用Cytoscape 3.7.2软件及STRING数据库构造药物与疾病共同靶蛋白质-蛋白质相互作用(PPI)网络、中药-成分-疾病-靶点PPI网络。采用DAVID 6.8数据库及R 4.0.3软件对药物与疾病共同靶点进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析。运用AutoDockTools 1.5.6软件进行分子对接验证。结果:经过筛选柴胡-大黄药对共得出有效活性成分23个,成分靶点91,和936个胆石症相关靶点取交集共得到35个共同靶点。通过GO分析显示核心靶点具有一氧化氮生物合成过程的正调控、细胞对脂多糖的反应、平滑肌细胞增殖的正调控等生物学过程。KEGG通路分析发现核心靶点可能和癌症信号通路、HIF-1信号通路、TNF信号通路等相关。分子对接结果提示豆甾醇与TNF靶点有强烈的结合活性(-7.79 kcal/mol),豆甾醇与JUN靶点有较好的结合活性(-5.71 kcal/mol),豆甾醇与TP53靶点有一定的结合活性(-4.34 kcal/mol)。结论:柴胡-大黄药对中的豆甾醇、槲皮素、山柰酚等有效活性成分可能通过TNF、JUN、TP53等核心靶点调控炎症介质及细胞缺氧反应信号转导通路联合治疗胆石症。Objective:To explore the effective material basis and mechanism of bupleurum-rhubarb in the treatment of cholelithiasis based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to retrieve the active ingredients and potential targets of bupleuri and radix;GeneCards,CTD and TTD databases were used to find the targets related to cholelithiasis.The interaction networks of PPI and Chinese medicine-components-disease-target were constructed with Cytoscape 3.7.2 software and STRING database.DAVID 6.8 database and R 4.0.3 software were used for enrichment analysis of GO and KEGG on mutual targets of drug and disease.AutoDockTools 1.5.6 software was used to verify molecular docking.Results:A total of 23 major active compounds and 91 component targets were screened from the bupleurum-rhubarb pair,and 35 common targets were obtained by crossing 936 cholelithiasis related targets.GO analysis showed that the core targets had biological processes,such as positive regulation of nitric oxide biosynthesis,cellular response to lipopolysaccharide,and positive regulation of smooth muscle cell proliferation.KEGG pathway analysis found that the core target may be related to cancer signaling pathway,HIF-1 signaling pathway and TNF signaling pathway.Molecular docking results showed that stigmasterol had a strong binding activity to TNF(-7.79 kcal/mol),a good binding activity to Jun(-5.71 kcal/mol),and a mild binding activity to TP53(-4.34 kcal/mol).Conclusion:Stigmasterol,quercetin,kaempferol and other active components in bupleurum-rhubarb pair may regulate inflammatory cytokines and hypoxia signal transduction pathway through TNF,Jun,TP53 and other core targets in the treatment of cholelithiasis.

关 键 词：网络药理学 分子对接 柴胡-大黄 胆石症 作用机制 

分 类 号：R285[医药卫生—中药学]