基于网络药理学和分子对接探讨胆木浸膏糖浆治疗流行性感冒的作用机制

Mechanism of Danmu extract syrup in the treatment of influenza based on network pharmacology and molecular docking

目的 运用网络药理学方法和分子对接技术探究胆木浸膏糖浆治疗流感可能的作用机制。方法 通过文献查找胆木浸膏活性成分,根据Swiss Target Prediction数据平台对胆木浸膏糖浆的活性成分的作用靶点进行预测,采用Cytoscape 3.6.1软件构建化合物-靶点网络。通过GeneCard数据库查找流感相关基因,通过Venny图将胆木浸膏糖浆活性成分靶点与流感疾病靶点取交集,得到胆木浸膏糖浆有效活性成分治疗流感的关键靶点,构建药物-活性成分-关键靶点-疾病网络。通过STRING数据库对共有靶点进行蛋白质相互作用分析。运用Cytoscape 3.6.1进行可视化,利用插件CytoNCA分析蛋白互作网络(PPI)中度中心性(DC)、中间中心性(BC)、紧密中心性(CC)、特征向量中心性(EC)、网络中心性(NC)和局部平均连通性(LAC)参数,筛选核心靶基因;通过R语言对共有靶点进行基因本体(GO)和基因组数据库(KEGG)通路富集分析。运用AutoDock vina 1.1.2软件对选取的胆木浸膏糖浆主要活性成分与靶点进行分子对接。结果 获得胆木浸膏糖浆对应靶点的活性成分28个,预测作用靶点544个,流感相关基因2 574个,胆木浸膏糖浆治疗流感的关键靶点189个,PPI分析筛选出54个关键靶点,包括苏氨酸蛋白激酶1(AKT1)、信号转导及转录激活因子(STAT3)、丝裂原活化蛋白激酶8(MAPK8)、表皮生长因子受体(EGFR)等;富集分析显示胆木浸膏糖浆和流感的共同生物学过程与炎症反应、细胞增殖与凋亡等相关,作用的主要通路为病毒感染通路、凋亡通路、Th17通路、肿瘤坏死因子通路、T细胞受体信号通路等。分子对接的结果显示主要活性成分与流感病毒神经氨酸酶具有较好结合活性。结论 胆木浸膏糖浆可能主要通过抑制神经氨酸酶活性、炎症反应及凋亡相关因子和通路,抗流感,减轻流感引起的炎症反应,从而达到治疗流感的目的。

Objective To explore the possible mechanism of Danmu extract syrup in the treatment of influenza by network pharmacology and molecular docking technology.Methods The active components of Danmu extract were searched forby literature,and the target of active components in Danmu extract syrup was predicted according to Swiss target prediction data platform.The compound-target network was constructed by using the software of Cytoscape 3.6.1.Search for influenza-related genes through GeneCard database;through the Venny diagram,the intersection of active component target of Danmu extract syrup and influenza disease target was obtained,the key target of effective active component of Danmu extract syrup in treating influenza was obtained,and the drug-active component-key target-disease network was constructed.The common targets were analyzed for protein interaction by string database.In order to screen for the core target genes,Cytoscape 3.6.1 was used for visualization,and the plug-in CytoNCA was used to analyze the parameters of degree centrality(DC),betweenness centrality(BC),compactness centrality(CC),eigenvector centrality(EC),network centrality(NC) and local average connectivity(LAC) of protein-protein interaction(PPI);R language was used to make enrichment analysis of the GO and Kyoto encyclopedia of genes and genomes(KEGG) pathway.AutoDock vina 1.1.2 software was used to conduct molecular docking between the main active components and the target of Danmu extract syrup.Results Totally 28 active components corresponding to the target of Danmu extract syrup were obtained,and 544 targets were predicted.There were 2 574 influenza-related genes,189 key targets of Danmu extract syrup in the treatment of influenza.A total of 54 key targets were screened out by PPI network analysis,including threonine protein kinase 1(AKT1),signal transducer and activator of transcription(STAT3),mitogen activated protein kinase 8(MAPK8),epidermal growth factor receptor(EGFR),etc..Enrichment analysis showed that the common biological process of Danmu extract syrup and influenza was related to inflammatory reaction,cell proliferation and apoptosis,and the main pathways of action were virus infection pathway,apoptosis pathway,Th17 pathway,tumor necrosis factor pathway and T cell receptor signaling pathway.The results of molecular docking showed that the main active components had good binding activity with influenza virus neuraminidase.Conclusion Danmu extract syrup can inhibit the activity of neuraminidase,inflammatory reaction and apoptosis-related factors and pathways,so as to reduce the inflammatory reaction caused by influenza and achieve the purpose of treating influenza.