基于网络药理学及分子对接技术探讨红花治疗肺动脉高压的作用机制

Study on the Action Mechanism of Honghua in the Treatment of Pulmonary Hypertension Based on Network Pharmacology and Molecular Docking Technology

目的:基于网络药理学及分子对接技术探讨红花治疗肺动脉高压(pulmonary hypertension,PH)的作用机制。方法:应用中药系统药理学数据库与分析平台、本草组鉴数据库、中医综合数据库、中国知网检索红花的活性成分,并采用Swiss Target Prediction数据库预测相关靶标。在GeneCards数据库、DrugBank数据库、TTD数据库、在线人类孟德尔遗传数据库、DisGeNET数据库中检索PH疾病靶标。采用STRING数据库构建红花活性成分靶点及PH疾病靶标的蛋白相互作用(protein-protein interaction,PPI)网络,并利用Cytoscape3.7.2软件获得红花治疗PH的潜在靶点的PPI网络,拓扑分析筛选红花治疗PH的潜在核心靶点。应用DAVID数据库及Metascape数据库对潜在核心靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析,并构建“红花-活性成分-靶点-通路-PH”网络。采用AutoDock Vina 4.6.2软件对核心活性成分和靶点进行分子对接。结果:红花活性成分20种,相关靶点607个,PH相关靶点1613个。潜在靶点PPI网络拓扑分析得到红花治疗PH的潜在核心靶点48个。GO功能富集分析共获得54个条目,包括生物过程20条、细胞组分14条及分子功能20条。KEGG信号通路富集分析共得到信号通路144条。分子对接显示,红花核心活性成分与靶点有较强结合能力。结论:红花可通过多成分-多靶点-多通路发挥治疗PH的作用。

Objective:To study the action mechanism of Honghua(Flos Carthami)in the treatment of pulmonary hypertension(PH)based on network pharmacology and molecular docking technology.Methods:The active ingredients of Honghua were retrieved by using the systematic pharmacology database and analysis platform of traditional Chinese medicine,the pharmacognosy database of herbal medicine,the comprehensive database of traditional Chinese medicine,and the CNKI,and the Swiss Target Prediction database was used to predict the relevant targets.PH disease targets were searched in GeneCards database,DrugBank database,TTD database,online human Mendel genetic database and DisGeNET database.The STRING database was used to construct the protein-protein interaction(PPI)network of Honghua active ingredient targets and PH disease targets,and the PPI network of the potential target of Honghua for treating PH was obtained by using Cytoscape 3.7.2 software.The potential core targets of Honghua for treating PH was screened by using the topology analysis.DAVID database and Metascape database were used to perform gene ontology(GO)function enrichment analysis and Kyoto Encyclopedia of genes and genomes(KEGG)signal pathway enrichment analysis of potential core targets,and to construct a"Honghua-active ingredient-target-pathway-PH"network.AutoDock Vina 4.6.2 software was used for molecular docking of core active components and targets.Results:There were 20 kinds of active ingredients in Honghua,607 related targets and 1,613 PH related targets.The potential target PPI network topology analysis obtained 48 potential core targets for Honghua treatment of PH.A total of 54 items were obtained from GO functional analysis,including 20 biological processes,14 cell components and 20 molecular functions.A total of 144 signal pathways were obtained by KEGG enrichment analysis.Molecular docking showed that the core active components of Honghua have strong binding ability with the targets.Conclusion:Honghua can play a role in PH treatment through multi-component,multi-target,and multi-pathway.