Xiaoluowan exert anti-hepatic fibrosis effects by inhibiting the PI3K/Akt signaling pathway:based on network pharmacology and animal experiments

ZHU Chenghui; LI Junfei; JIANG Jianwei

doi:10.20227/j.cnki.2096-3610.2025.05.010

Abstract：Objective To investigate the mechanism of Xiaoluowan(XLW)against liver fibrosis based on network pharmacology and animal experiments.Methods The active components of XLW and their potential targets were screened using TCMSP and HERB databases.Liver fibrosis-related targets were obtained from GeneCards,DisGeNET,and OMIM databases.The overlapping targets were analyzed via protein-protein interaction(PPI)networks on the STRING platform,followed by Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis using Metascape.Visualization was performed with Cytoscape.For animal experiments,24 male C57BL/6 mice(6-8 weeks old)were randomly divided into control,model,and XLW groups(n=8 per group).Liver fibrosis was induced by carbon tetrachloride(CCl4)for 8 weeks.From the 5th week onward,the XLW group received daily oral gavage of XLW decoction(5.4 mL/kg),while control and model groups received equal volume saline.After 8 weeks,mice were sacrificed to assess liver-to-body weight ratio,serum ALT/AST levels,liver pathology(histological staining),and hepatic PI3K/Akt pathway protein expression(Western blot).Results A total of 388 XLW-related targets and 3 943 liver fibrosis-related targets were identified,with 242 overlapping targets.Core targets included AKT1,TNF,TP53,and PTGS2.KEGG enrichment analysis revealed that the PI3K/Akt signaling pathway and pathways in cancer as the most significantly enriched.XLW treatment markedly reduced the liver-to-body weight ratio,improved liver function,attenuated collagen deposition,and downregulated PI3K and Akt protein expression(P<0.05).Conclusion XLW exerts anti-fibrotic effects by modulating AKT1 core targets and inhibiting the PI3K/Akt signaling pathway.