Kuntai Capsules Improve Premature Ovarian Failure by Regulating AMPK-Mediated Autophagy

  • Reprod Sci. 2025 Aug 11. doi: 10.1007/s43032-025-01949-w.
Xiaomin Ye  #  1 ,  Miao Chen  #  1 ,  Jiajing Zhong  1 ,  Haofan Chen  1 ,  Xinmiao Lin  2
Affiliations
  • 1. Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, 524045, China.
  • 2. Department of Obstetrics and Reproductive Health and Infertility, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, 524045, China. [email protected].
  • # Contributed equally.
PMID: 40789984 DOI: 10.1007/s43032-025-01949-w
Abstract

Background: Premature ovarian failure (POF) is a gynecological endocrine disorder with current treatments having limitations. Kuntai capsule (KTC), a traditional Chinese medicine formulation, is thought to be beneficial for POF, but its mechanism is unclear. Network pharmacology can help explore drug mechanisms.

Methods: A POF rat model was established using cyclophosphamide (CTX). Rats received low-dose KTC (0.6 g/kg/d), high-dose KTC (1.8 g/kg/d), or dehydroepiandrosterone (DHEA, positive control). Ovarian function was evaluated via histopathology, hormone assays (ELISA), Apoptosis (TUNEL/flow cytometry), Autophagy markers (Western blot), and network pharmacology.

Results: KTC treatment (especially high-dose) ameliorated POF in CTX-treated rats, as shown by increased ovarian weight, restored estrus cycle, and improved follicle development. The serum estradiol (E2), anti-mullerian hormone (AMH), and superoxide dismutase (SOD) levels increased, whereas the follicle-stimulating hormone (FSH), malondialdehyde (MDA), and Reactive Oxygen Species (ROS) levels decreased following KTC treatment. KTC also alleviated ovarian cell Apoptosis and Autophagy, with higher-dose KTC being more effective. Network pharmacology predicted AMPK/mTOR pathway involvement. Western blot confirmed KTC activated the AMPK/mTOR signaling, downregulated Autophagy markers (LC3B-II/I, Beclin1), and upregulated p62. Autophagy inhibition (via 3-MA) mirrored KTC effects, while mTOR blockade (rapamycin) reversed them.

Conclusions: KTC ameliorates POF by inhibiting excessive ovarian Autophagy through AMPK/mTOR pathway activation, providing a mechanistic basis for its clinical use.

Keywords
AMPK/mTOR signaling pathway; Autophagy; Follicular granulosa cell; Kuntai capsule; Premature ovarian failure.
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