Ye Xiaomin, Chen Miao, Zhong Jiajing, Chen Haofan, Lin Xinmiao
Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, 524045, China.
Department of Obstetrics and Reproductive Health and Infertility, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, 524045, China.
Reprod Sci. 2025 Aug 11. doi: 10.1007/s43032-025-01949-w.
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.
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.
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.
KTC ameliorates POF by inhibiting excessive ovarian autophagy through AMPK/mTOR pathway activation, providing a mechanistic basis for its clinical use.
卵巢早衰（POF）是一种妇科内分泌疾病，目前的治疗方法存在局限性。坤泰胶囊（KTC）是一种中药制剂，被认为对POF有益，但其作用机制尚不清楚。网络药理学有助于探索药物作用机制。
使用环磷酰胺（CTX）建立POF大鼠模型。大鼠接受低剂量KTC（0.6 g/kg/d）、高剂量KTC（1.8 g/kg/d）或脱氢表雄酮（DHEA，阳性对照）。通过组织病理学、激素测定（ELISA）、细胞凋亡（TUNEL/流式细胞术）、自噬标志物（蛋白质免疫印迹法）和网络药理学评估卵巢功能。
KTC治疗（尤其是高剂量）改善了CTX处理大鼠的POF，表现为卵巢重量增加、发情周期恢复和卵泡发育改善。KTC治疗后，血清雌二醇（E2）、抗苗勒管激素（AMH）和超氧化物歧化酶（SOD）水平升高，而促卵泡生成素（FSH）、丙二醛（MDA）和活性氧（ROS）水平降低。KTC还减轻了卵巢细胞凋亡和自噬，高剂量KTC更有效。网络药理学预测AMPK/mTOR通路参与其中。蛋白质免疫印迹法证实KTC激活了AMPK/mTOR信号，下调了自噬标志物（LC3B-II/I、Beclin1），并上调了P62。自噬抑制（通过3-MA）反映了KTC的作用，而mTOR阻断（雷帕霉素）则逆转了这些作用。
KTC通过激活AMPK/mTOR通路抑制卵巢过度自噬来改善POF，为其临床应用提供了机制基础。
