Abstract

Background Polycystic ovary syndrome (PCOS), characterized by imbalances in female sex hormones, leads to ovarian cyst formation in secondary follicles and anovulatory infertility, having become epidemic in recent years. Baicalin (BAL), a flavonoid compound isolated from the root of the traditional Chinese medicine Scutellaria baicalensis Georgi, has been shown in numerous studies to regulate the PI3K/AKT/mTOR signaling pathway and the NLRP3 inflammasome in various pathological models, thereby influencing critical biological processes such as autophagy and pyroptosis, and demonstrating significant anti-inflammatory, antioxidant, and cytoprotective activities. However, it remains unclear whether BAL can concurrently target both the PI3K/AKT/mTOR pathway and the NLRP3 inflammasome to affect downstream autophagy and pyroptosis in PCOS. Objective The study aims to investigate whether BAL ameliorates PCOS by modulating the PI3K/AKT/mTOR signaling pathway and NLRP3 inflammasome-mediated autophagy and pyroptosis. Results In a PCOS rat model, BAL administration significantly improved ovarian tissue morphology, restored sex hormone balance, and reduced systemic pro-inflammatory cytokine levels. Treatment with BAL also mitigated ovarian autophagy dysregulation, evidenced by decreased microtubule-associated protein 1 light chain 3 (LC3-II) accumulation and increased p62 levels, while suppressing pyroptosis, as shown by reduced expression of NLRP3 and cleaved Caspase-1 p20. Mechanistically, BAL activated the PI3K/AKT/mTOR signaling pathway and inhibited NLRP3 inflammasome assembly. In vitro experiments using KGN cells confirmed that BAL effectively inhibited both autophagy and pyroptosis. These effects were pathway specific: the PI3K inhibitor LY294002 blocked BAL-induced activation of the PI3K/AKT/mTOR pathway and its subsequent inhibition of autophagy, whereas the NLRP3 agoni