Mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance in rats via metabolomics and proteomics.
10.19540/j.cnki.cjcmm.20250304.401
- Author:
Cong-Hui ZHANG
1
;
Hai-Xin XIANG
2
;
Xiu-Wen WANG
1
;
He XIAO
3
;
Fang-Jiao WEI
2
;
Jing-Chun YAO
4
;
En-Li WANG
2
Author Information
1. School of Pharmacy, Shandong University of Traditional Chinese Medicine Ji'nan 250355, China.
2. State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd. Linyi 273400, China.
3. Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine, Lunan Pharmaceutical Group Co., Ltd. Linyi 273400, China.
4. School of Pharmacy, Shandong University of Traditional Chinese Medicine Ji'nan 250355, China State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd. Linyi 273400, China.
- Publication Type:Journal Article
- Keywords:
AMPK/mTOR/FoxO/GLUT signaling pathway;
Yuzhi Zhixue Granules;
insulin resistance;
polycystic ovary syndrome
- MeSH:
Animals;
Female;
Insulin Resistance;
Polycystic Ovary Syndrome/genetics*;
Drugs, Chinese Herbal/administration & dosage*;
Rats;
Metabolomics;
Proteomics;
Rats, Sprague-Dawley;
Humans;
Ovary/metabolism*;
Signal Transduction/drug effects*
- From:
China Journal of Chinese Materia Medica
2025;50(12):3368-3376
- CountryChina
- Language:Chinese
-
Abstract:
Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
