Yougui Pills inhibit oxidative stress-induced damage of granulosa cells by regulating Keap1/Nrf2 signaling pathway via Serpina3k.
10.19540/j.cnki.cjcmm.20241023.501
- Author:
Bei-Bei JIAO
1
;
Tian LI
2
;
Bei-Bei ZHOU
3
;
Si CHEN
3
;
Yue CHEN
3
;
Jian ZHANG
3
;
Pei-Juan WANG
3
Author Information
1. Tonglu Hospital of Traditional Chinese Medicine Hangzhou 311500, China Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine Nanjing 210028, China.
2. Nanjing Lishui District Hospital of Traditional Chinese Medicine Nanjing 211200, China.
3. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine Nanjing 210028, China.
- Publication Type:Journal Article
- Keywords:
Keap1/Nrf2 signaling pathway;
Serpina3k;
Yougui Pills;
ovarian granulosa cell;
oxidative stress
- MeSH:
NF-E2-Related Factor 2/genetics*;
Kelch-Like ECH-Associated Protein 1/genetics*;
Humans;
Female;
Signal Transduction/drug effects*;
Oxidative Stress/drug effects*;
Granulosa Cells/cytology*;
Drugs, Chinese Herbal/pharmacology*;
Apoptosis/drug effects*;
Serpins/genetics*
- From:
China Journal of Chinese Materia Medica
2025;50(4):1111-1120
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the effects and mechanisms of Yougui Pills(YGP) on oxidative damage induced by hydrogen peroxide(H_2O_2) in human ovarian granulosa cells(KGN). The components in serum with low-and high-doses of YGP were analyzed and compared through ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap mass spectrometry(UHPLC-QEMS), and selected the serum containing YGP high-dose group to follow-up experiments. To stimulated KGN with 200 μmol·L~(-1) H_2O_2to establish an oxidative damage model, which was divided into normal group, model group, low-, medium-, and high-dose of YGP groups, and the efficacy was further verified on the basis of silencing or overexpressing serine protease inhibitor(Serpina3k), further validating the efficacy based on the silencing or overexpression of Serpina3k. TUNEL staining was used to detect cell apoptosis,enzyme-linked immunosorbent assay(ELISA) was employed to measure the secretion levels of estradiol(E_2) and 17β-E_2 in KGN, and Western blot was utilized to assess the expression of Serpina3k and proteins related to the Keap1/Nrf2 signaling pathway. The results show that compared to the model group, each dose group of YGP not only significantly reduces granulocyte apoptosis and upregulates the secretion levels of E_2 and 17β-E_2, but also significantly upregulates Serpina3k and Nrf2 pathway. Further research has found that overexpression of Serpina3k not only enhances the therapeutic effect of YGP but also increases the expression of Nrf2 and inhibits the expression of Keap1. Conversely, interfering with Serpina3k partially reverses the therapeutic effect of YGP, while also partially. The results indicate that the mechanism by which YGP improves oxidative stress in KGN may be related to its upregulation of Serpina3k expression, which affects the conduction of the Keap1/Nrf2 signaling pathway. This study reveals the mechanism by which YGP protects granular cells, providing a certain theoretical basis for its clinical application.
