Baicalin mitigates polycystic ovary syndrome‑associated non‑alcoholic fatty liver disease by inhibiting the AR/SREBP1 axis.

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder frequently associated with metabolic disturbances, such as non‑alcoholic fatty liver disease (NAFLD), driven by hyperandrogenism‑induced lipogenesis. Baicalin (BA), a flavonoid derived from Scutellaria baicalensis, exhibits therapeutic potential in the treatment of PCOS; however, the specific mechanisms against PCOS‑associated NAFLD remain unclear. In the present study, a PCOS mouse model was established via subcutaneous implantation of dihydrotestosterone. Model validation confirmed irregular estrous cycles, ovarian histopathological abnormalities and altered serum hormone levels. Treatment with BA markedly alleviated NAFLD‑associated metabolic abnormalities, including central obesity, dyslipidemia and hepatic steatosis. Moreover, liver transcriptomics indicated that BA modulated lipid metabolism primarily through sterol regulatory element‑binding protein 1 (SREBP1)‑mediated lipogenesis. Results of western blot analysis confirmed that BA suppressed hepatic protein expression of SREBP1 and its downstream lipogenic enzymes, fatty acid synthase and acetyl‑CoA carboxylase, indicating inhibition of hepatic lipogenesis. As androgen receptor (AR) functions as an upstream transcriptional regulator of SREBP1, network pharmacological analysis highlighted AR as a potential target of BA. Molecular docking predicted the BA‑AR binding site, guiding purification of truncated AR protein for isothermal titration calorimetry (ITC). Subsequently ITC was used to confirm the specific BA‑AR binding affinity. Luciferase reporter assays in MDA‑kb2 cells demonstrated that BA inhibited AR transcriptional activity. Collectively, the results of the present study indicated that BA ameliorates PCOS‑associated NAFLD through targeting the AR/SREBP1 axis, highlighting its potential as a therapeutic strategy for managing lipid metabolism disorders in PCOS.