基于网络药理学和分子对接探究桑菊感冒颗粒抗甲型H1N1流感的活性成分及作用机制

The component and mechanism of Sangjuganmao Granules against influenza A(H1N1)based on network pharmacology and molecular docking

目的基于网络药理学和分子对接技术探寻桑菊感冒颗粒抗甲型H1N1流感的核心成分和作用机制。方法利用TCMSP、BATMAN-TCM和SwissTargetPrediction数据库并查阅文献收集和预测桑菊感冒颗粒的活性成分及作用靶点;通过GeneCards、OMIM、DisGeNET等数据库收集甲型H1N1流感的疾病靶点;绘制Venny图获得二者交集靶点。将交集靶点通过DAVID数据库进行GO功能以及KEGG通路富集分析;将交集靶点导入STRING数据库构建蛋白互作网络,利用Cytoscape 3.9.1软件MCC算法确定关键核心靶点并反向筛选核心活性成分,绘制中药-成分-靶点-疾病网络关系图。最后利用分子对接软件验证核心活性成分和关键核心治疗靶点之间的相互作用。结果筛选得到桑菊感冒颗粒活性成分153个及潜在作用靶点336个,甲型H1N1流感疾病靶点765个,共有58个交集靶点。GO功能分析得到GO条目414个,生物过程主要涉及RNA聚合酶Ⅱ启动子转录的正向调节、基因表达的正调控以及细胞凋亡;细胞组分主要涉及胞外区、外泌体以及线粒体;分子功能主要涉及蛋白质结合、细胞因子活性。KEGG通路富集分析筛选到126条结果,主要涉及IL-17、TNF、C型凝集素受体信号通路。进一步筛选得到核心活性成分槲皮素、木犀草素、山奈酚等,关键核心靶点涉及IL-6、IL-1B、TNF、JUN、TP53、PTGS2、VEGFA、ALB、MMP9、IL-10等。分子对接结果表明桑菊感冒颗粒核心活性成分与抗甲型H1N1流感关键核心靶点之间具有良好的结合活性。结论桑菊感冒颗粒可能主要通过槲皮素、木犀草素、山奈酚等核心活性成分作用IL-6、IL-1B、TNF、JUN、TP53、PTGS2、VEGFA、ALB、MMP9、IL-10等关键核心靶点,通过参与IL-17、TNF、C型凝集素受体多种信号通路协同发挥抗甲型H1N1流感的作用。

Objective To explore the active ingredients and mechanism of Sangjuganmao Granules against influenza A(H1N1)based on network pharmacology and molecular docking technology.Methods The active ingredients and related targets of Sangjuganmao Granules were collected by TCMSP,BATMAN-TCM,SwissTargetPrediction databases and literature review.The related targets of influenza A(H1N1)were collected from GeneCards,OMIM,DisGeNET and other databases.Venny diagram was drawn in order to obtain the intersection targets.Then the intersection targets were input into DAVID database for GO function and KEGG pathway enrichment analysis,and were imported into the STRING database to construct the protein intersection(PPI)network.The core targets and the main active ingredients were captured by the MCC algorithm of Cytoscape 3.9.1 software.This software was also used to draw the traditional Chinese medicine-component-target-disease network diagram.Finally,molecular docking software was used to verify the interaction between main active ingredients and core targets.Results A total of 153 active ingredients and 336 potential targets were obtained from Sangjuganmao Granules,and 765 targets of influenza A(H1N1)were identified,with a total of 58 intersection targets.GO functional analysis abtained 414 GO entries,the biological processes were mainly involved in the positive tegulation of RNA polymeraseⅡpromoter transcription,positive regulation of gene expression and apoptosis.The cellular components were mainly involved extracellular regions,exosomes and mitochondria.The molecular functions were mainly involved in protein binding and cytokine activity.KEGG pathway enrichment analysis obtained 126 results,which mainly involved in IL-17,TNF and C-type lectin receptor signaling pathways.The core active ingredients such as quercetin,luteolin,and kaempferol were captured by further analysis,and the core targets were involved in IL-6,IL-1B,TNF,JUN,TP53,PTGS2,VEGFA,ALB,MMP9,IL-10,etc.Molecular docking results showed that the core active ingredients of Sangjuganmao Granules had good binding activity with the core targets of anti-influenza A(H1N1).Conclusions Sangjuganmao Granules mainly acts on core targets IL-6,IL1-B,TNF,JUN,TP53,PTGS2,VEGFA,ALB,MMP9 and IL-10 through quercetin,luteolin,kaferol and other active ingredients,and plays an important role in anti-influenza A(H1N1)by participating in multiple signaling pathways such as IL-17,TNF and C-type lectin receptor.