Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) poses significant health risks for women of reproductive age, and conventional treatments typically involve anti-hormonal interventions or surgical procedures, which often lead to lifelong medication cycles and potential side effects. Bile acids have been applied in the treatment of PCOS-related conditions, including obesity and type 2 diabetes. This study aimed to investigate the effects of bile acids on a PCOS rat model and explore the underlying mechanisms involved. METHODS: Morphological index evaluation, histopathological examination, and hormonal profiling were employed to assess the therapeutic effects of eight bile acids. A targeted proteomics was utilized to characterize and quantify highly homologous chemerin isoforms in rat serum. Network pharmacology analysis was conducted to identify potential targets and molecular mechanisms involved. Molecular docking was performed to evaluate the affinity between bile acids and farnesoid X receptor (FXR). RESULTS: Five of the eight bile acids markedly restored morphological indices, histopathological manifestations, hormonal imbalances, and chemerin isoform dysregulation. Notably, the therapeutic effects of TDCA and GUDCA on PCOS were reported for the first time. As the severity of the disease decreased, chemerin-157S was negatively correlated with progesterone (P4), estradiol (E2), antral follicles, and corpus luteum, respectively. Several chemerin-associated pathways have been identified via network pharmacology analysis. Additionally, a 7β-hydroxy group carried on the steroid skeleton of bile acids has been found to exhibit positive therapeutic efficacy in PCOS. CONCLUSIONS: Downregulating chemerin levels via specific bile acids may be a promising therapeutic strategy for PCOS patients.