山慈菇调控TLR4/AKT/mTOR信号通路抗肝纤维化的研究OA

Objective:To examine the mechanism of Shancigu(山慈菇)on hepatic fibrosis based on network phar-macology combined with experimental validation.Methods:The potential targets and signaling pathways for Shancigu's anti-fibrotic effect were identified by searching databases and literature.Then,the targets were imported into Cytoscape to construct a protein-protein interaction network,from which core targets were screened.Additionally,the binding capabili-ty between the active compounds and the key targets of the Shancigu was simulated and validated by molecular docking technology.Finally,the results of network pharmacology and molecular binding were verified by experiment on the hepat-ic fibrosis rat model induced by pig serum.Results:Based on network pharmacology analysis,53 active components of Shancigu and 58 anti-hepatic fibrosis therapeutic targets were identified.The main active ingredients such as quercetin and hesperetin,as well as key targets such as serine/threonine-protein kinase 1(AKT1),Toll-like receptor 4(TLR4),and mammalian target of rapamycin(MTOR),were screened.The gene ontology(GO)function enrichment analysis found that the biological processes were mainly related to cellular response to oxidative stress.The cellular components were mainly related to membrane rafts and the extracellular matrix.The molecular functions were mainly related to pro-tein kinase activity.Kyoto encyclopedia of genes and genomes(KEGG)analysis revealed that important pathways in-cluded phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT).The molecular docking results showed that the main active ingredients had ideal binding activities with the TLR4,AKT1,and MTOR core targets.Animal experiments validated that Shancigu exhibited anti-hepatic fibrosis properties in rats.Compared with those in the normal control group,the content levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),hydraulic acid(HA),laminin(LN),procollagen type Ⅲ(PC Ⅲ),and collagen Ⅳ(Col Ⅳ),as well as the expressions of TLR4,p-AKT,and p-MTOR were significantly increased in the model control group(P<0.01).In contrast,compared with the model con-trol group,the content levels of ALT,AST,HA,LN,PC Ⅲ,and Col Ⅳ,as well as the expressions of TLR4,p-AKT,and p-MTOR,were significantly reduced in Shancigu 2.10 g/kg and 1.05 g/kg groups(P<0.01 or P<0.05).Conclusion:The study suggests that Shancigu has an anti-hepatic fibrosis effect,and the mechanism may be related to regulating the TLR4/AKT/MTOR signaling axis.