To Explore The Mechanism Evolution Of Xiaochaihu Decoction In The Treatment Of Hepatitis-cirrhosis-hepatocellular Carcinoma Based On Network Pharmacology Combined With Gene Chip Data

Objectives:Based on the network pharmacology combined with gene chip data set to explore the mechanism evolution of Xiao Chaihu decoction in the treatment of hepatitis,cirrhosis and liver cancer,vided ideas and clues for subsequent experiments to verify the mechanism of Xiao Chaihu decoction in the treatment of liver diseases.Methods:1.In the network pharmacological study of the action mechanism of Xiao Chaihu decoction in treating HB,relying on TCMSP database and SwissTarget Prediction data platform predicting Xiao Chaihu decoction active ingredient target genes.The chip data set GSE114783 related to HB was downloaded from GEO database,and DEGs was screened after analysis and processing by GEO2R plug-in.The target genes of the active ingredient of Xiao Chaihu decoction was intersected with DEGs of HB.The target genes of Xiao Chaihu decoction in treating HB were entered into the STRING database,and the Xiao Chaihu decoction-HB histone interaction network was constructed,and then imported into Cytoscape 3.7.2 software to analyze and screen the core target genes.Use DAVID 6.8 and Omicshare platform to carry out GO function enrichment and KEGG pathway enrichment for core target genes.2.In the network pharmacological study of the action mechanism of Xiao Chaihu decoction in treating LC,relying on TCMSP database and SwissTarget Prediction data platform predicting Xiao Chaihu decoction active ingredient target genes.The chip data set GSE114783 and GSE77627 related to LC was downloaded from GEO database,and DEGs was screened after analysis and processing by GEO2R plug-in.The target genes of the active ingredient of Xiao Chaihu decoction was intersected with DEGs of LC.The target genes of Xiao Chaihu decoction in treating LC were entered into the STRING database,and the Xiao Chaihu decoction-LC histone interaction network was constructed,and then imported into Cytoscape 3.7.2 software to analyze and screen the core target genes.Use DAVID 6.8 and Omicshare platform to carry out GO function enrichment and KEGG pathway enrichment for core target genes.3.In the network pharmacological study of the action mechanism of Xiao Chaihu decoction in treating HCC,relying on TCMSP database and SwissTarget Prediction data platform predicting Xiao Chaihu decoction active ingredient target genes.The chip data set GSE101685 and GSE25097 related to HCC was downloaded from GEO database,and DEGs was screened after analysis and processing by GEO2R plug-in.The target genes of the active ingredient of Xiao Chaihu decoction was intersected with DEGs of HCC.The target genes of Xiao Chaihu decoction in treating HCC were entered into the STRING database,and the Xiao Chaihu decoction-HCC histone interaction network was constructed,and then imported into Cytoscape 3.7.2 software to analyze and screen the core target genes;.Kaplan-Meier Plotter and GEPIA databases were used to identify the prognostic information of core target genes and gene expression level online.Use DAVID 6.8 and Omicshare platform to carry out GO function enrichment and KEGG pathway enrichment for core target genes.Results:1.In the network pharmacological study of the action mechanism of Xiao Chaihu decoction in treating HB.Through the core target genes such as TNF,Akt1,MAPK3,F2,mTOR and CAV1,the active ingredients of Xiao Chaihu decoction participate in biological processes such as cell proliferation,angiogenesis,platelet activation,T cell synergistic stimulation,liver regeneration,and protein serine/threonine kinase activity.Regulation thethe signaling pathways of hepatitis B,hepatitis C,hepatocellular carcinoma,NAFLD,TNF,T cell receptor,B cell receptor,NF-κB,PI3K-Akt,Jak/Stat,et al.2.In the network pharmacological study of the action mechanism of Xiao Chaihu decoction in treating LC,The active ingredients of Xiao Chaihu decoction affect the molecular functions of fiberectin binding,lysophospholipase activity and phospholipase A2 activity through core target genes such as VEGFA,AKT1,CYP2C9,PTGS1 and CXC12.Regulation of inflammatory response,cell proliferation,vascular endothelial cell migration regulation,phosphatidylcholine acyl chain remodeling,glucose metabolism and other biological processes.Regulation the signaling pathways of hepatitis B,TNF,Toll-like receptor,IL-17,chemokines,MAPK,RAS,NF-κB,arachidonic acid metabolism,linoleic acid metabolism,adipocyte lipolysis signaling pathway,VEGF signaling pathway,platelet activation,et al.3.In the network pharmacological study of the action mechanism of Xiao Chaihu decoction in treating HCC,Through the core target genes such as MYC,ESR1 and CDKN2A,PTGS2,FOS,TLR4 and CCL2,the active ingredients of Xiao Chaihu decoction participate in biological processes such as inflammation,estradiol reaction,oxidation-reduction process,lipid metabolism and organ regeneration,liver regeneration,angiogenesis.Regulation the signaling pathways of p53,cancer pathways,hepatitis B,liver cell carcinoma,TNF,T cell receptors,toll-like receptors,MAPK,NF-κB,et al.Among them,the core target genes CDKN2A,CCNB1,CDK1,EZH2,CCNA2,G6PD and NQO1 were significantly expressed in cancer of the liver tissue,and were associated with poor prognosis of patients.Conclusion:In this study,a comprehensive application of network pharmacology combined with bioinformatics analysis methods,the active ingredients,potential target genes and signal pathways of Xiao Chaihu decoction were systematically analyzed.It is preliminarily expounded that Xiao Chaihu decoction can inhibit the inflammatory response in hepatitis,cirrhosis and liver cancer.In the stage of hepatitis,it mainly regulates hepatitis B signaling pathway,hepatitis C signaling pathway,TNF and other signaling pathways,and has a strong role in inhibiting inflammation and regulating cell proliferation.In cirrhosis stage,it mainly regulates NF-κB signaling pathway,arachidonic acid metabolism,linoleic acid metabolism,VEGF and other signaling pathways,which can play a therapeutic role by regulating glucose and lipid metabolism,immunity and angiogenesis.In the stage of liver cancer,multiple cancer-related pathways such as p53,hepatocellular carcinoma and liver regeneration can be regulated to inhibit tumor progression.CDKN2A,CCNB1,CDK1,EZH2,CCNA2,G6PD and NQO1 are significantly expressed in liver cancer tissues and are associated with poor prognosis of patients.Therefore,can be used as a starting point for subsequent experimental studies and a potential target for drug redevelopment.This study systematically elaborated the mechanism of Xiao Chaihu decoction in the treatment of hepatitis,cirrhosis and liver cancer,and provided theoretical basis and direction for further experimental research on Xiao Chaihu decoction in the treatment of liver diseases.