基于网络药理学和分子对接探讨石吊兰治疗结核的作用机制  

Action mechanism of Lysionotus pauciflorus in the treatment of tuberculosis based on network pharmacology and molecular docking

作　　者：舒燕霞 刘趣 徐文芬 孙庆文 李云超 陈亮 SHU Yanxia;LIU Qu;XU Wenfen;SUN Qingwen;LI Yunchao;CHEN Liang(School of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Department of Pharmacy,the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)

机构地区：[1]贵州中医药大学药学院,贵州贵阳550025 [2]贵州中医药大学第一附属医院药学部,贵州贵阳550025

出　　处：《贵州科学》2023年第5期23-32,共10页Guizhou Science

基　　金：贵州中医药大学研究生创新项目(GNYL〔2017〕008号-7-Y);贵州省优秀青年科技人才项目(黔科合平台人才〔2019〕5658)。

摘　　要：目的:探讨石吊兰治疗结核病的潜在活性成分及其作用机制。方法:借助Swiss ADME、PubChem、Swiss Target Prediction、SEA Search Server、UniProt等数据库检索石吊兰活性成分及其对应靶点,通过GeneCards、OMIM及Drugbank数据库检索结核疾病相关靶点,并经Venny 2.1.0获取成分-疾病交集靶点。采用Cytoscape 3.9.1软件和String数据库进行“药物-成分-靶点”网络和蛋白质相互作用(PPI)网络的构建与分析,并筛选PPI网络中的核心靶点。运用Metascape数据库对交集靶点进行基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析,并通过Cytoscape 3.9.1软件构建“成分-靶点-通路”网络。最后,利用AutoDock Tools 1.5.7软件将潜在成分与核心靶点进行分子对接。结果:共筛选出石吊兰的活性成分30个、对应靶点510个、结核疾病相关靶点1050个、活性成分与结核病的交集靶点119个。PPI网络共筛选得核心靶点36个,包括STAT3、MAPK1、AKT1、TNF、SRC等。GO功能富集条目共558个(P<0.05),其中生物过程353个、分子功能114个、细胞组分91个;KEGG通路富集分析共得到156个条目(P<0.05),主要涉及癌症、甲型流感、糖尿病中AGE-RAGE、乙型肝炎、结核等信号通路。分子对接结果显示,石吊兰中石吊兰素、去甲氧基苏打基亭、5,7,3′-二羟基-6,8,4′-三甲氧基黄酮、槲皮素等活性成分与STAT3、MAPK1、AKT1等蛋白的结合能均小于-5 kcal·mol^(-1),均具有较强的结合活性。结论:本研究初步探讨了石吊兰抗结核的活性成分及相关信号通路,其作用机制涉及多个靶点基因及通路,与中药多成分、多靶点、多通路协同作用的治病特点不谋而合,为石吊兰抗结核的进一步研究提供了理论依据。This paper investigates the potential active components and action mechanism of Lysionotus pauciflorus in the treatment of tuberculosis.Based on Swiss ADME,PubChem,Swiss Target Prediction,SEA Search Server,UniProt and other databases,the active components of Lysionotus pauciflorus and their corresponding targets were screened out.The targets related to tuberculosis were searched through GeneCards,OMIM and Drugbank databases,and the component-disease intersection targets were obtained by Venny 2.1.0.Cytoscape 3.9.1 software and String database were used to construct and analyze the drug-component-target network and the protein interaction(PPI)network,and the core targets in the PPI network were screened out.Gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the intersection targets using Metascape database,and the component-target-pathway network was constructed by Cytoscape 3.9.1 software.Finally,the potential components were molecularly docked with the core targets by AutoDock Tools 1.5.7 software.A total of 30 active components and 510 corresponding targets of Lysionotus pauciflorus,1050 targets related to tuberculosis,and 119 intersection targets of the active components and tuberculosis were screened out.A total of 36 core targets were screened in the PPI network,including STAT3,MAPK1,AKT1,TNF,SRC,etc.There were 558 GO enrichment items(P<0.05),including 353 biological processes,114 molecular functions and 91 cell components.A total of 156 KEGG pathway enrichment analysis items were obtained(P<0.05),mainly involving cancer,influenza A,AGE-RAGE signaling pathway in diabetic complications,hepatitis B,tuberculosis and other signaling pathways.The results of molecular docking showed that the affinity of the active components,such as nevadensin,desmethoxysudachitin,3′,5,7-trihydroxy-4′,6,8-trimethoxyflavone and quercetin,with STAT3,MAPK1 and AKT1 proteins were all less than-5 kcal/mol,showing strong affinity.In conclusion,the act

关 键 词：石吊兰 结核病 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]