To investigate the mechanism of action of glabridin in the treatment of castration-resistant prostate cancer (CRPC),we combined network pharmacology,molecular docking and in vitro cellular assays.A total of 248 drug targets were screened by HERB,TCMIO,TCMSP,PharmMapper and Batmant-TCM,Swiss Target Prediction database,and 683 disease targets were collected by DisGeNET database. Fifty-five drug-disease targets were obtained through the Venn diagram tool.Through PPI analysis and topological analysis,ten core target proteins such as AKT1,TP53,ESR1 and EGFR were obtained.The "clusterProfiler" package of R Studio software was used for GO functional enrichment analysis and KEGG pathway enrichment analysis.These targets are involved 847 GO items(P<0.01),involving response to steroid hormone,protein kinase B signaling,response to nutrient levels,etc.KEGG enrichment analysis revealed 105 signaling pathways related to PI3K/AKT signaling pathway,Proteoglycans in cancer,prostate cancer and other signaling pathways(P<0.01).The results of molecular docking using AutoDock software showed that glabridin had good binding ability with the core target.CCK8 assay showed that glabridin could inhibit PC-3 cell proliferation(P<0.01),flow cytometry and DAPI staining showed that glabridin could promote cell apoptosis(P<0.01),and Western blot showed that glabridin could inhibit the phosphorylation of AKT(P<0.01).In conclusion,our initial findings show that Glabridin may regulate AKT1,TP53,ESR1,EGFR and other proteins and through some important signaling pathways such as PI3K/AKT signaling pathway exerted anti-castration-resistant prostate cancer effects.