Ginsenoside Rg1 attenuates premature ovarian failure of D-gal induced POF mice through downregulating p16INK4a and upregulating SIRT1 expression.

Abstract

BACKGROUND\nPremature ovarian failure (POF) refers to pathological amenorrhea before 40 years.\n\n\nAIM/OBJECTIVE\nTo explore regulatory effect of Rg1 on POF and clarify associated mechanisms.\n\n\nMATERIALS AND METHODS\nPOF mice were induced by injecting with D-galactose (D-gal, 200 mg/kg/day). Mice were divided into phosphate buffered saline (PBS), D-gal (POF mice), D-gal/Rg1 group (POF mice administrating D-gal/Rg1). Weight growth rate and ovarian weight coefficient were measured. Serum estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), catalase (CAT) levels were examined using ELISA. Status of follicle and corpus luteum was determined using hematoxylin-eosin (HE) staining. P16INK4a and silent-mating type information regulation-2 homolog-1 (SIRT1) was determined using western blotting and RT-PCR.\n\n\nFINDINGS\nWeight growth rate and ovarian weight coefficient of mice in D-gal group were significantly decreased than PBS group (p<0.05). Serum E2, LH, SOD, CAT levels were significantly decreased, FSH levels were remarkably increased in D-gal group than PBS group (p<0.05). Rg1 (D-gal/Rg1 group) significantly increased weight growth rate and ovarian weight coefficient, enhanced E2, LH, SOD, CAT levels and decreased FSH levels than D-gal group (p<0.05). HE staining demonstrated normal follicle morphology/structure of mice in PBS group and decreased number of follicles, obvious vacuolation of corpus luteum and increased atretic follicles of mice in D-gal group. Compared with D-gal group, number of follicles was increased, luteal follicles was decreased of mice in D-gal/Rg1 group (p<0.05). Rg1 significantly (D-gal/Rg1) downregulated p16INK4a and upregulated SIRT1 expression in ovarian tissues of mice compared to D-gal group (p<0.05).\n\n\nCONCLUSIONS\nRg1 could delay premature ovarian failure in D-gal induced POF mouse model through downregulating p16INK4a and upregulating SIRT1 expression.