Exploring Mechanism of Modified Banxia Xiexintang in Ameliorating Metabolic Disorders and Reproductive Function in PCOS-IR Rats Based on Metabolomics and Transcriptomics
10.13422/j.cnki.syfjx.20260164
- VernacularTitle:基于代谢组学与转录组学探究加味半夏泻心汤改善PCOS-IR大鼠代谢紊乱与生殖功能的作用机制
- Author:
Donghan BAI
1
;
Ruying TANG
1
;
Longfei LIN
1
;
Yuling LIU
1
;
Dongxue ZHENG
2
;
Qiling ZHANG
1
;
Xinmin LIU
2
;
Hui LI
1
Author Information
1. Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences，Beijing 100700，China
2. Guang'anmen Hospital，China Academy of Chinese Medical Sciences，Beijing 100053，China
- Publication Type:Journal Article
- Keywords:
modified Banxia Xiexintang;
polycystic ovary syndrome;
insulin resistance;
metabolomics;
transcriptomics;
ferroptosis;
immunomodulation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(7):140-149
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo evaluate the therapeutic effects of modified Banxia Xiexintang（MBXT） on polycystic ovary syndrome with insulin resistance（PCOS-IR） rats and reveal its potential mechanisms based on the integrated analysis of transcriptomics and metabolomics. MethodsFemale SD rats were selected， and a PCOS-IR model was established by intragastric administration of letrozole combined with a high-fat diet for 21 days. The modeled rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg-1）， and metformin group（0.158 g·kg-1）， with a normal group set up separately. After 14 days of administration， the estrous cycle was observed， ovarian morphology was examined by hematoxylin-eosin（HE） staining， and the levels of testosterone（T）， estradiol（E2）， follicle-stimulating hormone（FSH）， and luteinizing hormone（LH） in serum were detected by enzyme-linked immunosorbent assay（ELISA）. Serum metabolites and ovarian tissue gene expression were detected using ultra-performance liquid chromatography-quadrupole-electrostatic orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS） and RNA-Seq technology， respectively， followed by multi-omics integrated analysis. ResultsPharmacodynamic findings revealed that all MBXT dose groups could reversed abnormal estrous cycles in PCOS-IR rats， improve polycystic ovarian lesions， and normalize dysregulated serum hormone levels（T， LH， E2， FS， P<0.05， P<0.01）. Metabolomic analysis revealed that compared with the model group， MBXT reversed 278 differential metabolites such as estrone and S-formylglutathione， mainly involving pathways such as steroid hormone biosynthesis， glutathione metabolism， and lipid peroxidation regulation. Transcriptomic analysis identified 434 differentially expressed genes， and enrichment analysis revealed that MBXT significantly regulated lipid peroxidation defense systems， including glutathione metabolism， peroxisome function， and fatty acid metabolism， thereby intervening in ferroptosis processes. It also engaged in inflammation-related pathways such as the chemokine signaling pathway. Integrated analysis revealed that both metabolomics and transcriptomics co-enriched metabolic pathways associated with ferroptosis and fatty acid metabolism. And key Hub genes［such as Ras-related C3 botulinum toxin substrate 2 gene（Rac2） and Fas ligand gene（Faslg）］ showed significant correlations with differential metabolites. ConclusionMBXT can effectively ameliorate reproductive dysfunction and metabolic disorders in PCOS-IR rats. Its mechanism may be related to remodeling the immune-metabolism network， particularly by regulating MHC-mediated immune responses， inhibiting local ovarian ferroptosis， and enhancing steroid hormone synthesis pathways.
