| ObjectiveThis study aimed to elucidate the characteristics of influenza differentially expressed gene and explore function of Lianhua Qingwen Granule in the treatment of influenza based on network pharmacology so that to identify key component and the hub target of Lianhua Qingwen Granule.Methods1.Based on the GEO Database of NCBI,key word "influenza,human" was used to select suitable datasets according to strict eligibility criteria.The differentially expressed gene of influenza were selected by the online tool called NetworkAnalyst(|Log2FC|>1,P<0.05).Based on STRING11.0 website,GO analysis and KEGG analysis of differentially expressed gene was performed.The PPI network of differentially expressed gene was constructed by using Cytoscape3.6.0 software,and then the PPI network was analyzed to screen the key gene of influenza.2.The active components of Lianhua Qingwen Granule were collected.The drug-like components were evaluated by FaF-Drugs4 online tool.The targets of components were predicted by Pharmmapper online tool.The network was constructed by Cytoscape3.6.0.The key components and targets of Lianhua Qingwen Granule in the treatment of influenza was identified.The main biological process and pathway of those targets were analyzed.The Vina1.1.2 software was used to perform virtual screening to select the effective components targeting to the hub gene.Molecular docking of key components and hub gene was conducted.The interaction between key components and hub gene was visualized by Pymoll.7 software.Results1.5 human influenza datasets met the eligibility criteria.After merging 5 datasets,26 up-regulated gene and 71 down-regulated gene were obtained.2.GO and KEGG analysis of human influenza differentially expressed gene revealed that influenza involves biological processes such as type I interferon signaling pathway,viral defense response,innate immune response,cytokine regulated signaling pathway,negative regulation of viral genome replication,ribosome assembly and so on.3.By analyzing the protein-protein interaction network of differentially expressed gene,7 key gene were identified,including ISG15、IFIT3、IRF7、MX1、IFIT1、OAS2、RSAD2.They are closely related to interferon-dependent innate immune processes.4.550 active components were collected from Lianhua Qingwen Granule and 433 targets were predicted.5.By analyzing the protein-protein interaction network of Lianhua Qingwen Granule targeting influenza,10 key targets were identified.They are ESR2,ESR1,STAT1,EGFR,HSP90AB1,RXRA,PPPlCC,PPARG,EP300,ERBB2.STAT1 is the gene closely associated with the key gene of influenza differentially expressed gene.6.STAT1 was regulated by 38 components.The molecular virtual screening indicated that Rheochrysin was the key component binding to STAT1.Conclusion1.In this study,7 key targets related to the biological process of type I interferon were identified by analyzing the characteristics of influenza gene expression.2.The key components are quercetin、kaempferol、apigenin.The key targets are EGFR、HSP90、STAT1.3.It is suggested that Rheochrysin in Lianhua Qingwen Granules may regulate the signal pathway of type I interferon by regulating the key target STAT1 and regulate the innate immunity. |