基于网络药理学和分子对接探究鸡骨草防治肝纤维化的研究

Exploring the protective effect of Abri Herba on liver fibrosis based on network pharmacology and molecular docking

目的基于网络药理学和分子对接技术探究鸡骨草防治肝纤维化的分子机制。方法通过TCMSP、ETCM、TCM Database@Taiwan数据库获取鸡骨草的主要化学成分,用SwissADME平台筛选出活性化合物,并用SwissTargetPrediction平台预测活性化合物的潜在靶点;通过GeneCards、OMIM数据库获取肝纤维化相关靶点,利用STRING数据库获得蛋白质互作(PPI)关系,用Cytoscape软件构建PPI网络。同时,用DAVID数据库进行基因本体(GO)、京都基因与基因百科全书(KEGG)基因富集分析,以便获得鸡骨草防治肝纤维化的潜在作用通路,并用Cytoscape软件构建成分-靶点-通路图;用AutodockTools、AutodockVina软件进行分子对接研究。结果共筛选出鸡骨草活性化合物21种及其肝纤维化作用潜在靶点333个。富集分析显示:鸡骨草可通过多个通路对肝纤维化产生治疗作用。分子对接结果显示:核心成分可较好地与核心靶点结合。结论鸡骨草通过5,7,8-三羟基-2-甲基-色酮、相思子皂醇F、紫铆素等多个主要活性成分作用于癌症信号通路、磷脂酰肌醇3激酶(PI3K)-丝/苏氨酸蛋白激酶(Akt)信号通路、内分泌抗性等通路发挥治疗肝纤维化的作用。

Objective To investigate the molecular mechanisms of Abri Herba in liver fibrosis treatment via the network pharmacology and molecular docking technologies.Methods The main chemical components of Abri Herba were obtained from TCMSP,ETCM and TCM Database@Taiwan databases.The SwissADME platform was used to screen out the active compounds,and the SwissTargetPrediction platform was used to predict their potential targets.Liver fibrosis-related targets were retrieved through GeneCards and OMIM databases.Protein-protein interaction(PPI)relationships were obtained using STRING database.and PPI network was constructed by Cytoscape software.The gene ontology(GO)bioprocess and Kyoto encyclopedia of genes and genomes(KEGG)signaling pathway enrichment analysis of intersection were performed using DAVID database to obtain the potential action pathways of Abri Herba in treating liver fibrosis.Cytoscape software was used to construct the component-target-pathway network.Molecular docking was performed using AutodockTools and AutodockVina softwares.Results A total of 21 active compounds of Abri Herba and their 333 potianl targets for liver fibrosis were screened out.Enrichment analysis revealed that Abri Herba could exert therapeutic effects on liver fibrosis through multiple pathways.Molecular docking results showed that the core components had good binding activities with the core targets.Conclusion Abri Herba has a therapeutic effect on liver fibrosis through multiple main active components including 5,7,8-trihydroxy-2-methyl-chromone,abrisapogenol F,and butin,acting on cancer signaling pathway,phosphatidylin ositol 3 kinase(PI3K)-Serine/threonine protein kinase(Akt)signaling pathway,endocrine resistance,etc.