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. 2025 Aug 11.
doi: 10.1007/s43032-025-01949-w. Online ahead of print.

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

Xiaomin Ye #  1 , Miao Chen #  1 , Jiajing Zhong  1 , Haofan Chen  1 , Xinmiao Lin  2
Affiliations

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

Xiaomin Ye et al. Reprod Sci. .

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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Conflict of interest statement

Declarations. Ethics Approval and Consent to Participate: All animal procedures were approved by the Animal Ethical and Welfare Committee of Guangzhou Miles Biosciences Co. Ltd (No. IACUC-MIS20230069; title: Kuntai capsule improves premature ovarian failure; date of approval: Sept 2, 2024). The manuscript was reported in accordance with the ARRIVE guidelines for the reporting of animal experiments. Consent for Publication: Not applicable. Competing Interests: The authors declare that they have no competing interests.

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