基于网络药理学与分子对接探析三七-白及药对治疗反流性食管炎的作用机制

Mechanism of action of Panax notoginseng-Bletilla striata herb pair in the treatment of reflux esophagitis based on network pharmacology and molecular docking

[目的]探析三七-白及药对治疗反流性食管炎(RE)的作用机制.[方法]运用TCMSP网络药理学分析平台筛选三七、白及的活性成分及靶点,通过UniProt数据库提取作用靶点的基因名称,采用Cytoscape3.9.0软件构建药物-成分-靶点网络.以reflux esophagitis为关键词检索OMIM、GeneCards数据库中与RE相关的靶点.借助Venny2.1在线作图网站筛选出药物与疾病的共同作用靶点.通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,利用Cytoscape3.9.0软件插件Cytohubba的Degree拓扑分析法筛选出PPI网络中排名前5的基因作为核心基因.采用DAVID数据库对核心基因进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,并研究作用机制.使用AutoDock软件对药对关键成分槲皮素与核心靶点进行分子对接.[结果]在三七-白及药对中共筛选出17个活性成分、192个作用靶点,共获得RE相关靶点2692个,其中120个为三七-白及药对的作用靶点,AKT1、TP53、IL-6、TNF、VEGFA为PPI网络图中的核心基因.GO功能和KEGG通路富集分析涉及81个生物学过程(BP)、3个细胞组成(CC)、7个分子功能(MF)及82条信号通路.[结论]三七-白及药对通过影响AKT1、TP53、IL-6、TNF、VEGFA靶点蛋白的表达调控PI3K-Akt、MAPK、糖尿病并发症的AGE-RAGE、Toll样受体及TNF信号通路等,进而抑制炎症及细胞过度增殖以发挥治疗RE的作用.

OBJECTIVE To explore the mechanism of action of Panax notoginseng-Bletilla striata herb pair in the treatment of reflux esophagitis(RE).METHODS TCMSP network pharmacology analysis platform was used to screen the active ingredients and targets of Panax notoginseng and Bletilla striata,and the gene names of the targets were extracted through Uniprot database,and the herbs-component-targets network was constructed with Cytoscape 3.9.0 software.The RE-related targets were retrieved in OMIM and GeneCards databases with reflux esophagitis as key words.The combined action targets of herbs and diseases were screened by Venny2.1 online mapping website.Protein protein interaction(PPI)network was constructed by STRING database,and the top 5 genes in PPI network were selected as core genes by Degree topology analysis of Cytohubba,a software plug-in of Cytoscape 3.9.0.DAVID database was used for gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of core genes,and the mechanism of action was studied.AutoDock software was used to conduct molecular docking between quercetin,a key component of herb pair,and the core target.RESULTS A total of 17 active components and 192 targets of Panax notoginseng-Bletilla striata herb pair were screened out,and 2692 targets related to reflux esophagitis were obtained,among which 120 targets were targets of herb pair.AKT1,TP53,IL-6,TNF and VEGFA,were the core genes in the PPI network.Enrichment analysis of GO function and KEGG pathway involved 81 biological process(BP),3 celluar component(CC),7 molecular functions(MF),and 82 signaling pathways.CONCLUSION Panax notoginseng-Bletilla striata herb pair can regulate PI3K-Akt signaling pathway,MAPK signaling pathway,AGE-RAGE signaling pathway in diabetic complications,Toll-like receptor signaling pathway,TNF signaling pathway and other signaling pathways by affecting the expressions of AKT1,TP53,IL-6,TNF,and VEGFA target proteins,thus inhibiting inflammation and hyperproliferation of cells to play a role in the treatment of RE.