Mogroside-rich extract alleviates the inflammation state in polycystic ovary syndrome rats through modulating intestinal microbiota-metabolic axis and suppressing the NF-κB/NLRP3 pathway

Polycystic ovary syndrome (PCOS), a complex endocrine-metabolic disorder characterized by hyperandrogenism, polycystic ovarian morphology, and ovulatory dysfunction, is often associated with insulin resistance. Mogroside-rich extract (MGE) from Siraitia grosvenorii possesses significant anti-inflammatory and antioxidant properties. However, its potential to restore intestinal microbial homeostasis and metabolic balance in PCOS and the underlying mechanisms remain unexplored. This study investigated MGE's protective effects and mechanisms in a letrozole-induced PCOS rat model. MGE administration significantly ameliorated estrous cycle irregularities, attenuated body weight gain, reduced cystic follicle formation in ovaries, and lowered serum testosterone and insulin levels. Integrated 16S rRNA sequencing and non-targeted metabolomics revealed that MGE enriched beneficial intestinal microbiota (Akkermansia, Parasutterella), associated with anti-inflammatory effects and metabolic improvement, while suppressing pro-inflammatory Corynebacterium. Notably, MGE partially reversed letrozole-induced alterations in colonic metabolites, restoring levels of anti-inflammatory metabolites like butyric acid and gamma-tocotrienol. Furthermore, MGE significantly reduced ovarian pro-inflammatory cytokines and downregulated the expression of p-NF-κB and NLRP3 proteins. Collectively, these findings demonstrate that MGE ameliorates PCOS symptoms by coordinately regulating ovarian inflammation via suppressing the NF-κB/NLRP3 pathway and restoring intestinal microbiota-metabolic axis balance, highlighting its therapeutic potential for PCOS.