Guishen-erxian Decoction can improve ovarian function in rats with premature ovarian failure by inhibiting oxidative stress and granulosa cell DNA fragmentation mediated by the PI3K/Akt/FOXO3a pathway.

The aim of this study was to establish a rat model of premature ovarian failure (POF) with cyclophosphamide (CTX), and explore the molecular basis of POF and the mechanism of Guishen-Erxian Decoction (GSEXD) to improve POF from the perspective of oxidative stress regulation of ovarian granulosa cell (OGC) DNA fragmentation. The study utilized SD rats to establish a POF model via CTX. Rats were divided into Control, POF group, three GSEXD dosage groups (low, medium, high), and a GSEXD+PI3K agonist group to assess GSEXD's therapeutic effects on oxidative stress, DNA fragmentation and ovarian damage. GSEXD can improve the body weight, ovarian index, pathological status, and hormone secretion of POF rats, and inhibit ovarian oxidative stress and DNA fragmentation. In addition, GSEXD inhibits the activation of the PI3K/Akt/FoxO3a pathway. PI3K agonist 740 Y-P can reverse the effects of GSEXD on ovarian function, ovarian antioxidant capacity, and granulosa cell DNA fragmentation in POF rats. Inhibition of oxidative stress damage and excessive DNA fragmentation of granulosa cells is a key pathway for GSEXD to promote follicle growth and development and alleviate ovarian function decline, which may be related to the inhibition of the PI3K/AKT/FOXO3a pathway by GSEXD.