Shoutai Pill synergistically inhibits internal reproductive organ apoptosis: coordinated EGFR/PI3K/AKT modulation in primary ovarian insufficiency

作者：Yi-Piao Zhang, Si-Mei Dong, Zhiyuan Li, Chengliang Zhou, Yun-Long Qiao, Wanfeng Xu, Bo Li, Chu Chu, Guiyuan Lv, Suhong Chen · 发表于：Journal of Ethnopharmacology · 年份：2025 · DOI：10.1016/j.jep.2025.120247 · 被引用次数：6 · 研究领域：Reproductive Biology and Fertility、Natural Compounds in Disease Treatment、Ovarian function and disorders

ETHNOPHARMACOLOGICAL RELEVANCE: Primary ovarian insufficiency (POI), which affects 3.7 % of women under age 40, is characterized by reduced ovarian function and infertility. Although Shoutai Pill (STW) is used for endocrine regulation, its mechanism in treating POI is unclear. Existing studies of POI have focused on ovarian damage, while the pathological changes in the uterus and its interactions with the ovary have not been clarified. AIM OF THE STUDY: To uncover the mechanism by which STW alleviates POI through the regulation of internal reproductive organs (ovary-uterus axis). MATERIALS AND METHODS: We combined chemical profiling (UHPLC-Q-Exactive-MS/MS) with network pharmacology to identify STW's active ingredients and targets. A POI model was established in mice using tripterygium glycosides (TG). Mice were treated with STW (1.2, 2.4, or 3.6 g/kg) or a hormone-based positive control consisting of sequential administration of estradiol (0.15 mg/kg) and progesterone (1.5 mg/kg). Serum hormone levels (E2, FSH, LH), estrous cycles, and ovarian and uterine pathology were assessed. Proteomic changes were analyzed using data-independent acquisition (DIA) mass spectrometry, and the key findings were validated through molecular docking, immunohistochemistry, TUNEL, and western blotting. RESULTS: STW contains 72 active compounds with good oral bioavailability (OB > 28 %). Key ingredients like luteolin and kaempferol were predicted to interact with POI-related genes (e.g., ESR1/2, ...