Ginsenoside Rg1 improves pathological damages by activating the p21-p53-STK pathway in ovary and Bax-Bcl2 in the uterus in premature ovarian insufficiency mouse models

The aim of the present study was to investigate the effects of the ginsenoside Rg1 on D-galactose (D-gal)-induced mouse models of premature ovarian insufficiency (POI) and the related mechanisms. C57BL/6 female mice were randomly grouped into the following: i) D-gal [subcutaneously (s.c.) 200 mg/kg/d D-gal for 42 days]; ii) Rg1 [intraperitoneally (i.p.) 20 mg/kg/d Rg1 for 28 days]; iii) D-gal + Rg1 (s.c. 200 mg/kg/d D-gal for 42 days followed by i.p. 20 mg/kg/d Rg1 for 28 days); and iv) saline groups (equivalent volume of saline s.c. and i.p.). Hematoxylin and eosin staining and electron microscopy were used to analyze uterine and ovarian morphology. Expression levels of senescence factors (p21, p53 and serine/threonine kinase), secretion of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and IL-1 beta] and the activities of oxidation biomarkers [superoxide dismutase (T-SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-px)] were analyzed. The results showed that mice in the Rg1 + D-gal group had significantly higher uterine and ovarian weight compared with those in the D-gal group. Uterus morphology was also improved, based on the comparison between the D-gal group and the Rg1 + D-gal group. In addition, the Rg1 treatment after D-gal administration significantly decreased the expression of senescence-associated factors, enhanced the activities of anti-oxidant enzymes total T-SOD and GSH-px in addition to reducing TNF-alpha, IL-1 beta, MDA and IL-6 (based on the comparison between the D-gal group and the Rg1 + D-gal group). In conclusion, the present study suggested that the ginsenoside Rg1 improved pathological damages in the ovary and uterus by increasing anti-oxidant and anti-inflammatory abilities whilst reducing the expression of senescence signaling pathways in POI mouse models.

Automated summary

The study demonstrated that ginsenoside Rg1 had significant effects on D-gal-induced POI mouse models by increasing uterine and ovarian weight, improving uterine morphology, reducing the expression of senescence factors, and enhancing anti-oxidant and anti-inflammatory abilities.