基于网络药理学探讨葛根芩连汤治疗流行性感冒的分子机制

Study on the molecular mechanism of Gegen Qinlian decoction in the treatment of influenza based on network pharmacology

目的:基于网络药理学探讨葛根芩连汤治疗流行性感冒的分子机制。方法:检索TCMSP数据库得到葛根芩连汤中各药物的有效成分及靶基因,构建化合物-靶点网络;再检索OMIM数据库DisGeNET数据库获得疾病的基因,将药物作用基因与疾病基因取交集得到核心基因;然后采用STRING数据库构建基因功能关联网络,最后采用DAVID数据库对核心基因进行GO富集分析和通路富集分析。结果:通过TCMSP数据库共获得有效成分146种,靶点128个;检索疾病基因数据库共得到588个基因;采用Cytoscape构建药物有效成分-靶基因网络并对网络进行拓扑分析得到度值靠前靶基因分别是PTGS2、HSP90AA1、AR、CALM1、ESR1、NOS2、PRSS1、PPARG、PTGS1、NCOA2、SCN5A、CDK2、ESR2、GSK3B、CHEK1、CCNA2、DPP4、MAPK14;将药物基因与疾病基因取交集共得到46个核心基因,然后采用STRING数据库构建基因功能关联网络,将网络信息数据导入Cytoscape软件进行拓扑分析发现IL-6、MAPK8、CASP3、IL-1β、CCL2、PTGS2、JUN、IL-4、MAPK1、MMP9、MPO、CAT、MAPK14、STAT1、IL-2、EGFR、HMOX1、PPARG、FOS、RELA、CXCL10、NOS2、CASP8、SOD1、SERPINE1、CD40LG、CRP、IL-1A、CXCL2属于核心靶点;使用DAVID数据库进行GO富集分析共得到13个富集的生物过程聚类,通路富集分析共获得7个富集的通路聚类,然后再构建药物有效成分、药物靶点以及通路图。结论:本研究通过数据库分析初步得到了葛根芩连汤治疗流感的作用靶点以及作用通路,并结合公开发表的实验研究对本文研究结果进行验证,表明葛根芩连汤治疗流感不仅有理论依据,体外实验也支持这一结论。

Objective To explore the molecular mechanism of Gegen Qinlian decoction in the treatment of influenza based on network pharmacology.MethodsEffective components and target genes of Gegen Qinlian decoctionwere retrieved from TCMSP database in order toconstruct the compound target network,and then disease gene were retrieved from OMIM and DisGeNET database,and the core genes were obtained by intersection of drug action genes and disease genes.Then,string database was used to construct gene function association network.Finally,David database was used to analyze GO enrichment and pathway enrichment of core genes.Results A total of 146 active ingredients and 128 gene targets were obtained by TCMSP database,588 genes were obtained from disease gene database,and PTGS2,HSP90AA1,AR,CALM1,ESR1,NOS2,PRSS1,PPARG,PTGS1,NCOA2,SCN5A,CDK2,ESR2,GSK3B,CHEK1,CCNA2,DPP4,MAPK14 were identified after we used Cytoscape method to construct drug active ingredient target gene network and topological analysis.A total of 46 core genes were obtained by intersection of drug genes and disease genes,and then gene function association network was constructed by using string database,and network information data was imported into Cytoscape software for topology analysis.We indentifiedthat IL-6,MAPK8,CASP3,IL-1B,CCL2,PTGS2,JUN,IL-4,MAPK1,MMP9,MPO,CAT,MAPK14,STAT1,IL-2,EGFR,HMOX1,PPARG,FOS,RELA,CXCL10,NOS2,CASP8,SOD1,SERPINE1,CD40LG,CRP,IL-1A,CXCL2 were the core targets;13 enriched bioprocess clusters were obtained by GOenrichment and 7 enriched pathway clusters were obtained by pathway enrichment analysis.Based on the above mentioned results effective components,drug targets and pathway map of drugs were constructed.Conclusion The target and pathway that Gegen Qinlian decoction treating influenza have been preliminarily identified through database analysis which have been verified by published experimental studies indicating that the therapeutical effects of Gegen Qinlian decoction on influenza were supported not only by theoretical basis for the treatment of influenza,but also in vitro experiments.