Effect of ginsenoside Rg3 on polycystic ovary syndrome in rats via regulation of the Nrf2/HO-1-mediated endoplasmic reticulum stress pathway
10.3760/cma.j.cn311282-20250219-00081
- VernacularTitle:人参皂苷Rg3调控Nrf2/HO-1介导的内质网应激途径对多囊卵巢综合征大鼠的影响
- Author:
Wei GUO
1
;
Hui WANG
1
;
Ling GENG
1
Author Information
1. 驻马店市中心医院生殖医学科，驻马店 463000
- Publication Type:Journal Article
- Keywords:
Polycystic ovary syndrome;
Ginsenoside Rg3;
Ovarian injury;
Endoplasmic reticulum stress;
Nrf2/HO-1 pathway
- From:
Chinese Journal of Endocrinology and Metabolism
2025;41(8):681-690
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of ginsenoside Rg3(G-Rg3) on ovarian injury in polycystic ovary syndrome(PCOS) rats and its mechanism.Methods:(1)SD rats were divided into Control group, PCOS group, G-Rg3 low-dose group(G-Rg3-L, 5 mg/kg), G-Rg3 high-dose group(G-Rg3-H, 20 mg/kg), and positive control metformin group(Met, 100 mg/kg), with 12 rats per group.(2)SD rats were divided into Control group, PCOS group, G-Rg3-H group, Nrf2 inhibitor group(ML385, 30 mg/kg), G-Rg3-H+ Nrf2 inhibitor group(G-Rg3-H+ ML385), with 12 rats per group. Except the Control group, other groups were established as PCOS models using letrozole gavage. After successful model establishment, rats received the respective interventions once daily for 21 consecutive days. The body weight, uterine weight, ovarian weight, fasting blood glucose(FBG) and fasting insulin(FINS) levels in rats were measured. Serum levels of follicle stimulating hormone(FSH), luteinizing hormone(LH), progesterone(P), testosterone(T), estradiol(E 2), as well as inflammatory cytokines IL-17, IL-6, TNF-α, IL-18 levels were detected by ELISA method. HE staining observed ovarian histopathological changes. The ultrastructural changes of ovarian tissue were observed by transmission electron microscopy. Western blot and immunohistochemistry were used to detect endoplasmic reticulum stress-related proteins and Nrf2/HO-1 pathway proteins expression. Results:Compared with Control group, PCOS group showed abnormal estrous cycles, increased body weight, ovarian weight, FBG and FINS levels, decreased uterine weight, marked histopathological damage in the ovaries, decreased FSH, E 2, P, increased LH, T, IL-17, IL-6, TNF-α, IL-18, elevated GRP78, CHOP, p-IRE1α and p-eIF2α proteins expression, and decreased Nrf2 and HO-1 proteins expression. Compared with the PCOS group, all medication-treated groups showed significant improvement in the aforementioned parameter alterations, while the ML385 group showed further deterioration in these parameters. In contrast to the G-Rg3-H group, G-Rg3-H+ ML385 combination treatment was found to inhibit the activation of the Nrf2/HO-1 pathway and reverse the protective effects of G-Rg3 on ovarian histopathological damage in PCOS rats. Conclusion:G-Rg3 alleviates ovarian injury in PCOS rats by activating the Nrf2/HO-1 pathway, suppressing endoplasmic reticulum stress, reducing inflammation, and modulating hormone secretion.
