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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Ethnopharmacology

Yangjing Shugan Decoction targets the Sirt1/Nrf2 antioxidant pathway and gut microbiota-metabolite axis to protect against premature ovarian failure

Provisionally accepted
Ling  YangLing Yang1Li  LiuLi Liu1Junbo  LiuJunbo Liu1Meng  Ran XuMeng Ran Xu2Jing  RenJing Ren2Bo  LiBo Li2Lili  JiaoLili Jiao2Yunyan  WeiYunyan Wei2Jing  WangJing Wang3*Yi  GuoYi Guo3
  • 1Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
  • 2Changchun University of Chinese Medicine, Changchun, China
  • 3The Third Affiliated Clinical Hospital of Changchun University of Chinese Medicine, Changchun, China

The final, formatted version of the article will be published soon.

Objective: This study aimed to assess the therapeutic potential of Yangjing shugan decoction (YJSGD) in D-galactose (D-gal)-induced Premature Ovarian Failure (POF) mice and to elucidate its underlying mechanisms. Methods: The main metabolites in YJSGD were characterized. A D-gal-induced POF mouse model was established and intervened with YJSGD at doses of 25, 50, and 100 mg/kg. A comprehensive analysis encompassing ovarian function, oxidative stress, inflammation, the Sirt1/Nrf2 pathway, gut microbiota, short-chain fatty acids (SCFAs), and serum metabolomics was conducted. Results: The results demonstrated that YJSGD effectively restored estrous cyclicity, normalized serum estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels, and improved ovarian follicular development. YJSGD treatment also enhanced systemic antioxidant capacity and attenuated inflammation. Mechanistically, the therapeutic effects were associated with the upregulation of the Sirt1/Nrf2 signaling pathway in the ovary, as evidenced by increased protein expression of Sirt1, Nrf2, and HO-1, and suppressed Keap1. Furthermore, YJSGD ameliorated gut microbiota dysbiosis, promoted beneficial SCFAs production, and rectified serum metabolic disturbances involved in amino acid, lipid, and energy metabolism. Conclusion: The results indicate that YJSGD is a promising multi-target agent for POF treatment, and its synergistic effects on reproductive, oxidative, and gut microbiota homeostasis provide a solid basis for its clinical application.

Keywords: Yangjing Shugan Decoction, SIRT1/NRF2, premature ovarian failure, antioxidant, Gut Microbiota

Received: 11 Oct 2025; Accepted: 25 Nov 2025.

Copyright: © 2025 Yang, Liu, Liu, Xu, Ren, Li, Jiao, Wei, Wang and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jing Wang

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