Mechanism of Astragalus membranaceus-Salvia miltiorrhiza in treatment of hepatic fibrosis based on network pharmacology and experimental verification
AIM To explore the mechanism of Astragalus membranaceus-Salvia miltiorrhiza in the treatment of liver fibrosis using network pharmacology and verified in vivo experiments in mice.METHODS The main active ingredients of Astragalus membranaceus-Salvia miltiorrhiza were screened and the main active targets against liver fibrosis were screened by network pharmacology.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were conducted.The phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/rapamycin target protein(mTOR)pathway was selected,and a network diagram of the core component,key target,and target pathways of Astragalus membranaceus-Salvia miltiorrhiza was constructed using Cytoscape 3.7.2 software.Fifty KM mice were randomly divided into control group,model group,and low,medium,and high dose(25,50 and 100 mg·kg-1,Astragalus membranaceus-Salvia miltiorrhiza raw drug mass ratio 1∶1)groups,10 mice in each group.The changes in body weight,liver weight,liver histopathology,and expression level of key target protein and mRNA in mice before and after the treatment were detected.RESULTS A total of 183 common targets were obtained by mapping the active targets of Astragalus membranaceus-Salvia miltiorrhiza and disease targets of liver fibrosis.Through the analysis of the network diagram of Astragalus membranaceus-Salvia miltiorrhiza core ingredients-key targets-target pathways,vascular endothelial growth factor alpha(VEGFA),basic fibroblast growth factor 2(FGF2),epidermal growth factor receptor(EGFR),mitogen activated protein kinase 1(MAPK1)and glycogen synthase kinase-3 beta(GSK-3β)are key targets.Compared with the model group,the liver fibrosis were effectively alleviated,the expression levels of EGFR,MAPK1,VEGFA and GSK-3β mRNA were significantly decreased(P＜0.05),and FGF2 mRNA expression level was obviously increased(P＜0.05)in Astragalus membranaceus-Salvia miltiorrhiza groups.The expression levels of AKT,p-PI3K in the high-dose group,p-AKT,PI3K in the medium-dose group,p-AKT and p-PI3K protein in the low-dose groups were significantly increased(P＜0.05).CONCLUSION The core ingredients of Astragalus membranaceus-Salvia miltiorrhiza may improve liver fibrosis to act on VEGFA,FGF2,EGFR,MAPK1 and GSK-3β by regulating the PI3K/AKT/mTOR pathway.
Astragalus membranaceusSalvia miltiorrhizahepatic fibrosisnetwork pharmacologyanimal experimentationmolecular mechanisms of pharmacological action
NETL
NSTL
万方数据
维普
