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Endocrine, Metabolic & Immune Disorders - Drug Targets

Author(s): Xiao-Hu Liu, Shi-Zhong Cai, Yue Zhou*, Ya-Ping Wang*, Yan-Jun Han, Cui-Li Wang and Wen Zhou

DOI: 10.2174/1871523020666210830164152

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Ginsenoside Rg1 Attenuates Premature Ovarian Failure of D-gal Induced POF Mice Through Downregulating p16INK4a and Upregulating SIRT1 Expression

Page: [318 - 327] Pages: 10

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Abstract

Background: Premature ovarian failure (POF) refers to pathological amenorrhea before 40 years.

Objective: To explore the regulatory effect of Rg1 on POF and clarify associated mechanisms.

Materials and Methods: POF 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. The status of follicle and corpus luteum was determined using hematoxylin-eosin (HE) staining. P16INK4a and silent- mating type information regulation-2 homolog-1 (SIRT1) were determined using western blotting and RT-PCR.

Results: Weight 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 the number of follicles, obvious vacuolation of corpus luteum and increased atretic follicles of mice in D-gal group. Compared with D-gal group, the number of follicles was increased, luteal follicles were decreased in 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 the D-gal group (p<0.05).

Conclusion: Rg1 could delay premature ovarian failure in D-gal induced POF mouse model through downregulating p16INK4a and upregulating SIRT1 expression.

Keywords: Ginsenoside Rg1, premature ovarian failure, SIRT1, D-gal, aging, chinese medicine.

Graphical Abstract

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