基于网络药理学和分子对接探究寒喘祖帕颗粒抗甲型流感病毒机制

Mechanism of Hanchuan Zupa Granules in the treatment of Influenza A virus based on network pharmacology and molecular docking

目的探究寒喘祖帕颗粒抗甲型流感病毒的有效成分、作用靶点及作用机制。方法通过检索TCMSP、GeneCards、OMIM、PharmGKB、TTD、DrugBank数据库获取寒喘祖帕颗粒抗甲型流感病毒相关成分及靶点;采用R软件获取寒喘祖帕颗粒-甲型流感病毒交集靶点;采用Cytoscape构建"药物-成分-靶点"网络;采用String数据库和Cytoscape建立蛋白质-蛋白质相互作用网络,并进行拓扑分析;借助R软件对交集靶点进行GO和KEGG富集分析;运用Auto Dock Tools进行分子对接验证。结果获得寒喘祖帕颗粒抗甲型流感病毒有效成分111个,作用靶点131个;核心成分有槲皮素、芹菜素、木犀草素、山柰酚、汉黄芩素等;核心靶点有STAT3、MAPK1、MAPK3、AKT1、JUN等;交集靶点主要富集在IL-17信号通路、甲型流感、TNF信号通路等178条通路;核心成分与靶点具有较好的亲和力。结论寒喘祖帕颗粒可能通过多成分-多靶点-多通路共同作用实现抗甲型流感病毒作用,为后续其机制研究提供依据。

Objective To explore the ingredients,targets,and mechanisms of Hanchuan Zupa Granules in the treatiment of Influenza A virus.Methods By using Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform(TCMSP),GeneCards,Online Mendelian Inheritance in Man(OMIM),Pharmacogenomics Knowledgebase(PharmGkb),Therapeutic target database(TTD)and DrugBank database to obtain relevant components and targets of Hanchuan Zupa Granules in the treatment of Influenza A virus;R software was used for the obtain of Hanchuan Zupa Granules-Influenza A virus intersection targets;Cytoscape software was applied for the construction of"Hanchuan Zupa Granules-component-target"network;Protein-protein interaction network(PPI)and topological analysis were constructed by STRING database and Cytoscape software.Intersection targets for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were conducted by R software;Auto Dock Tools were used for molecular docking.Results All together 111 potential active ingredients,with corresponding 131 targetswere identified from Hanchuan Zupa Granules in the treatment of Influenza A virus.Quercetin,apigenin,luteolin,kaempferol,wogonin,etc.are included as core ingredients.STAT3,MAPK1,MAPK3,AKT1,JUN,etc.are included as core targets.Intersection targets were mainly enriched in 178 signal pathways such as IL-17 signal pathway,influenza A signal pathway,TNF signal pathway,etc;Molecular docking showed that core component had a good affinity with the target.Conclusion Hanchuan Zupa Granules could play the role of anti-Influenza A virus with multi-component-multi-target-multi-pathway,characteristics,and this syudy provide a basis for future experimental research on its mechanism.