Ginsenoside Rg1 alleviates dehydroepiandrosterone-induced polycystic ovary syndrome by regulating granulosa cell glycolysis, proliferative activity, and apoptosis through the PI3K/Akt/mTOR pathway.

Abstract

Polycystic ovary syndrome (PCOS) represents a common endocrine-metabolic disorder. Mounting evidence has demonstrated that Korean red ginseng confers therapeutic advantages in PCOS; accordingly, this investigation sought to elucidate the therapeutic potential of its bioactive constituent, ginsenoside Rg1, in this pathological condition. A DHEA-induced murine PCOS model was generated for in vivo experiments. Serum hormonal profiles and insulin sensitivity were assessed. Ovarian histomorphological alterations were evaluated through hematoxylin and eosin staining. For in vitro studies, a PCOS-mimicking cellular model was constructed by exposing KGN cells to dihydrotestosterone (DHT, 500nM) for 24h. Cell viability was quantified using the CCK-8 assay. Apoptotic events were characterized through flow cytometric analysis and immunoblotting of Bax and Bcl-2. Expression patterns of glycolytic enzymes, alongside the proliferation marker PCNA, were examined. Rg1 administration ameliorated PCOS-associated phenotypes in mice, manifesting as reduced body mass, partly restored serum hormone concentrations, enhanced insulin responsiveness, and improved ovarian architecture. Rg1 potentiated glycolytic and proliferative activities while suppressing apoptotic processes in both PCOS mice and DHT-challenged KGN cells. Mechanistically, Rg1 triggered PI3K/Akt/mTOR cascade activation, evidenced by elevated p-Akt and p-mTOR expression, effects that were partially reversed by LY294002, a pharmacological antagonist of this pathway. Furthermore, LY294002 co-administration attenuated the protective actions of Rg1 against PCOS in both experimental paradigms. In conclusion, ginsenoside Rg1 exerts beneficial effects on PCOS by enhancing glycolysis and proliferative activity while attenuating apoptosis in ovarian granulosa KGN cells via PI3K/Akt/mTOR pathway activation. These findings position Rg1 as a promising therapeutic candidate for PCOS management.