The mechanism of Astragalus on hepatocellular carcinoma was explored from the perspectives of cell experiment and network pharmacology.Methods:Relevant gene targets and active components of Astragalus and hepatocellular carcinoma were searched through CNKI,PubMed,TCMSP,GeneCards,and OMIM.The networks of protein-protein interaction(PPI) and Astragalus-hepatocellular carcinoma interaction were constructed by the STRING database and Cytoscape software.KEGG and GO enrichment analysis was performed with the DAVID database,and molecular docking was performed with the CB-DOCK platform.Cell experiments were performed by MTT assay and Western blot assay to detect cell proliferation and protein expression.Results:Nineteen active ingredients and 250 targets of Astragalus were screened out.GO and KEGG enrichment analysis obtained 549 entries and 145 signaling pathways,mainly involved in regulating DNA transcription,cell proliferation,and apoptosis.The pathway of action mainly involved tumor-related pathways,such as cancer pathway,lipid and atherosclerosis,Kaposi's sarcoma infection,and PI3K-AKT signaling pathway.Molecular docking results showed that formononetin,isoflavones,and astragaloside IV,the core components of for anti-hepatocellular carcinoma of Astragalus,had good binding ability to proteins in the PI3K/AKT signaling pathway.Based on the results of network pharmacology analysis,further cell experiments confirmed that water extract of Astragalus can effectively inhibit the proliferation of HepG2 cells and down-regulate the protein expression levels of AKT1,PI3K p110,and p-AKT1.Conclusion:Astragalus can inhibit the PI3K/AKT signaling pathway,exert an inhibitory effect on HepG2 cells,and provide theoretical support for its application in the clinical treatment of hepatocellular carcinoma.