Ginsenoside Rb2 improves diminished ovarian reserve through regulation of gonadal hormones and apoptosis via SIRT1

Diminished ovarian reserve (DOR), a leading cause of female infertility, can result in premature reproductive senescence. Ginsenoside Rb2, an active component of ginseng, exhibits various physiological activities, including anticancer and anti-inflammatory effects. Our study was designed to explore the effect of ginsenoside Rb2 on ovarian function in DOR rats and to elucidate its underlying mechanisms. A single injection of 90 mg/kg cyclophosphamide was administered to establish a DOR rat model; 4 d after the injection, the rats were treated with ginsenoside Rb2/EX-527 for 32 d. Body weight and ovarian index were calculated. Ovarian histopathological changes were evaluated by hematoxylin and eosin staining; the numbers of primordial, mature, and atretic follicles were calculated. Serum levels of follicle-stimulating hormone, luteinizing hormone, and estradiol were determined by ELISA. Apoptosis of ovarian cells was detected using a TUNEL assay. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses were performed to detect Bcl-2 and Bax protein expression and their corresponding mRNA levels, respectively. Furthermore, SIRT1 expression in rat ovaries was detected using immunohistochemistry and RT-qPCR. After intragastric administration, ginsenoside Rb2 improved body weight and ovarian index in DOR rats. Moreover, compared with the control group, the number of primordial and mature follicles decreased; the number of atretic follicles increased in DOR rats. We also observed increased follicle-stimulating hormone and luteinizing hormone levels and reduced estradiol levels in the serum of DOR rats compared with those of the control group. Relative to the control group, the number of apoptotic ovarian cells in the model group was markedly increased, and the level of Bcl-2 in the model group was dramatically reduced, whereas Bax levels were significantly elevated. Immunohistochemistry and RT-qPCR results revealed that SIRT1 was downregulated in the ovarian tissues of the model group compared with that of the control group. Opposite effects were observed in ginsenoside Rb2-treated rats; these findings were partly reversed by EX-527 treatment. Ginsenoside Rb2 modulated gonadal hormones and reduced ovarian cell apoptosis by regulating SIRT1, thereby improving ovarian function in DOR rats. Our findings highlight the potential role of ginsenoside Rb2 in the treatment of DOR.