The Mechanism Of Bupleurum In Treating Cirrhosis Based On Network Pharmacology And Molecular Docking

ObjectiveCirrhosis is a chronic liver disease provoked by one or more etiologies and accompanied by many types of liver dysfunction.The clinical incidence of cirrhosis is high and the harm is great.Besides liver transplantation,western medicine has no practical way to treat cirrhosis,and often uses liver protection and antiviral therapy.However,the treatment cost is high,long-term medication is easy to produce resistance,will also damage the digestive system function,aggravate the burden of liver and kidney,the curative effect is poor.But traditional Chinese medicine treatment has a unique curative effect.In this study,network pharmacology method and molecular docking technology were used to explore the active site and target of liver cirrhosis,and to infer the mechanism of action.So as to provide a basis for the experimental and clinical research of bupleurum treatment of liver cirrhosis.MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)were used to select the chemical components and related targets,and then the targets were entered into the Uni Prot database for standardization.The disease targets of liver cirrhosis were selected from the Dis Ge Net and Gene Cards databases,and then the common targets were analyzed and exported by the online software Venny2.1.0.The Cytoscape3.8.2 software was used to establish the "bupleurum compound-target" reticulation map,the protein interaction network was generated from the STRING database,and the PPI network topology was analyzed and the core targets were identified.DAVID database for GO and KEGG enrichment analysis,and the results of GO and KEGG were visualized using R package(tidyr,stringr,ggpubr and ggplot2).The molecular docking of the core target and the bupleurum active ingredient was performed using the software Auto Dock Tool 1.5.6 to test the binding performance of the active ingredient and the core target.Results17 active ingredients of bupleurum were selected from the TCMSP database,including 3,5,6,7-tetramethoxy-2-(3,4,5trimethoxyphenyl)chromone,kaempferol,linoleyl acetate,quercetin,stigmasterol,areapillin,baicalin,isorhamnetin,saikosaponin c＿qt,longikaurin A,troxerutin,petunidin,α-spinasterol,(+)-Anomalin,octalupine,cubebin,sainfuran,and the 17 components acted on 194 targets.4,754 liver cirrhosis-related targets were selected from the Gene Cards and Dis Ge Net databases.159 common targets of bupleurum and liver cirrhosis were obtained based on Venny2.1.0.And 15 key targets were gained by PPI network screening,namely: AKT1,TP53,IL6,TNF,VEGFA,JUN,IL1 B,CASP3,HIF1 A,MYC,EGFR,PTGS2,EGF,MMP9,CCND1.The GO enrichment analysis yielded 615 biological processes such as cell surface receptor signaling pathway,65 cellular components such as focal adhesion,and 121 molecular functions such as protein dimerization activity.The KEGG analysis yielded 130 pathways,among which the highly related pathways included cancer pathway,hepatitis B,TNF signaling pathway,etc.Molecular docking results showed that linoleyl acetate bound well to PTGS2 and EGF,kaempferol to CASP3,JUN,and TNF,and quercetin to MYC,EGFR,and CCND1.ConclusionBupleurum can affect multiple targets of liver cirrhosis by linoleyl acetate,kaempferol,and quercetin,resulting in the treatment of liver cirrhosis,and its key targets may be PTGS2,EGF,CASP3,JUN,TNF,MYC,EGFR,CCND1.Related pathways are the hsa05200 cancer pathway,hsa05161 hepatitis B,and hsa04668 TNF signaling pathway.This study may provide a theoretical basis for further elucidating the mechanism of bupleurum treatment in liver cirrhosis.