基于网络药理学及分子对接探讨复方柳菊片治疗肺结核的作用机制  

The action mechanism of compound Liuju tablets in the treatment of pulmonary tuberculosis based on network pharmacology and molecular docking

作　　者：周容 左代英[1] 杨明 ZHOU Rong;ZUO Daiying;YANG Ming

机构地区：[1]沈阳药科大学,辽宁沈阳110016 [2]江西国药有限责任公司,江西南昌330052

出　　处：《中医临床研究》2023年第33期102-110,共9页Clinical Journal Of Chinese Medicine

摘　　要：目的:基于网络药理学方法研究复方柳菊片抗肺结核的活性成分、靶点,初步探讨其作用机制。方法:通过文献收集、中药系统药理学数据库与分析平台(TCMSP)、SwissADME数据库,以口服生物利用度≥30%、类药性≥0.18、类药性五规则作为活性化合物的筛选条件,借助TCMSP、Swiss Target Predition数据库得到化合物的作用靶点;借助OMIM、Gene Cards、DisGeNet等数据库得到疾病靶点,取交集,筛选出化合物与疾病共有靶点。采用Cytoscape 3.9.1软件构建可视化的“药物-成分-靶点-疾病”网络,利用STRING数据库构建蛋白质-蛋白质相互作用(Protein-protein Interaction,PPI)网络,应用DAVID生物学信息资源对关键靶点进行基因本体论(GO)及京都基因与基因组百科全书(KEGG)通路分析。通过AutodockTools及Vina对活性成分与关键靶点进行半柔性分子对接。结果:预测筛选出复方柳菊片抗肺结核22个活性成分、126个作用靶点,PPI网络提示肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素(Interleukin,IL)-6、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、IL1B、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、肿瘤蛋白p53(Tumor Protein p53,TP53)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)3、白细胞介素-8(C-X-C Motif Chemokine Ligand 8,CXCL8)、前列素内环氧化物合成酶2(Prostaglandin-endoperoxide Synthase 2,PTGS2)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)可能是复方柳菊片抗肺结核的核心靶点。GO功能富集分析显示,差异表达基因富集在细胞间质、细胞表面、细胞质膜、胞质等,通过调控酶结合、细胞因子活性等,在基因表达正向调控、细胞对脂多糖的反应、药物反应、炎症反应等方面发挥作用。KEGG通路富集分析结果显示,复方柳菊片靶点主要富集在疾病信号通路(hsa05161:乙型肝炎、hsa05160:丙型肝炎、hsa05152:肺�Objective:To study the active components and targets of compound Liuju tablets(复方柳菊片)against pulmonary tuberculosis based on network pharmacology,and to discuss the mechanism of action preliminarily.Methods:Through literature collection from TCMSP and SwissADME databases,bioavailability≥30%,drug-like≥0.18 and five rules of drug-like drugs were used as screening conditions for active compounds,and the target of compounds was obtained by TCMSP and Swiss Target Predition database.Disease targets were obtained by OMIM,Gene Cards,DisGeNet and other databases,and the common targets of compounds and diseases were screened by intersection.Cytoscape 3.9.1 software was used to construct a visual“drug-composition-target-disease”network,STRING database was used to construct protein-protein interaction(PPI)network,and DAVID biological information resources were used to analyze the GO and KEGG pathways of key targets.AutodockTools and Vina were used for semi-flexible molecular docking of active components and key targets.Results:It was predicted that 22 active components and 126 targets of compound Liuju tablets were selected for anti-tuberculosis.The PPI network suggested that TNF,IL-6,AKT1,IL1B,VEGFA,TP53,MAPK3,CXCL8,PTGS2 and EGFR might be the core targets of compound Liuju tablets for anti-tuberculosis.GO functional enrichment analysis showed that differentially expressed gene enrichment played a role in the positive regulation of gene expression,cellular response to LPS,drug response,and inflammatory response by regulating enzyme binding and cytokine activity in the interstitium,cell surface,cell plasma membrane,and cytoplasm.The results of KEGG analysis showed that the targets of compound Liuju tablets were mainly concentrated in disease signaling pathway(hsa05161:Hepatitis B,hsa05160:Hepatitis C,hsa05152:Tuberculosis)and signal transduction pathway(hsa01521:EGFR tyrosine kinase inhibitor resistance,hsa04151:PI3K-Akt signaling pathway,hsa04066:HIF-1 signaling pathway),immune signaling pathway(hsa04668:T

关 键 词：复方柳菊片 活性成分 网络药理学 抗肺结核作用 靶点 

分 类 号：R256.1[医药卫生—中医内科学]