Network pharmacological analysis and experimental verification for anti-liver fibrosis effects of Mori fructus
AIM To explore the main active components,targets and pathways of anti-liver fibrosis of Mori fructus by network pharmacology and animal experiment,and to explore its potential mechanism of Mori fructus against liver fibrosis.METHODS The main active components and corresponding targets of Mori fructus were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and the target information was converted into target gene by Uniprot database.The targets of inflammatory disease were predicted in OMIM database and GeneCards database,and the targets of inflammatory genes were obtained.The network diagram of component-target-pathway was constructed using Cytoscape 3.7.2 software.Protein protein interaction(PPI)network was constructed using the String database and Cytoscape 3.7.2 software,and Gene Ontology(GO)biological process analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed.Fifty Kunming mice were randomly divided into six groups,including normal group,model group and low,medium and high dose of total flavonoids from Mori fructus(75,150,300 mg·kg-1)groups.The liver fibrosis model of mice was induced by carbon tetrachloride,and the serum biochemical indexes and predicted inflammatory indexes were detected.The histopathological changes of liver were observed,and the expression of matrix metalloproteinase 9(MMP9)protein in liver tissue was detected by immunohistochemical method.RESULTS The main anti-inflammation components of Mori fructus include cyanin,quercetin,morin and β-carotene.There were 80 potential anti-inflammatory targets,and the PPI network mainly includes interleukin(IL)-6,tumor necrosis factor(TNF),protein kinase B(AKT)1,albumin(ALB),vascular endothelial growth factor(VEGFA)and MMP9 and other core targets.The pathways involved mainly include fluid shear stress and atherosclerosis,pathways in cancer,lipid and atherosclerosis,Janus kinase/signal transducer and activator of transcription(JAK-STAT),etc.Animal experimental results showed that compared with the normal group,the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum,the contents of IL-6 and TNF-α in liver tissue as well as the expression of MMP9 protein in the model group were significantly increased(P＜0.01).Compared with the model group,the levels of ALT and AST in serum,the contents of IL-6 and TNF-α and the protein expression of MMP9 protein in liver tissue were decreased(P＜0.05)and the degree of liver injury was alleviated in different doses of total flavonoids from Mori fructus.CONCLUSION Mori fructus has anti-liver fibrosis effects on IL-6,TNF-α,MMP9 and other targets through active components such as anthocyanin and quercetin,which are mainly related to phosphoinositide 3 kinase(P13K)/AKT,JAK-STAT,and other signaling pathways.Its mechanism of liver protection may be related to the reduction of inflammatory reaction and the down-regulation of the protein expression of MMP9.
Mori fructusinflammatoryimmunityliver fibrosisnetwork pharmacologycarborn tetrachloride
万方数据
维普
