Rao Yanqiu, Li Jun, Xu Ting, Gao Lingyun, Wang Wenjun
Department of Integrated Traditional & Western Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Department of Integrated Traditional & Western Medicine, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China.
J Ovarian Res. 2025 Mar 11;18(1):51. doi: 10.1186/s13048-025-01632-3.
Diminished ovarian reserve (DOR), a major cause of female infertility, is closely linked to insulin resistance (IR). Traditional Chinese Medicine (TCM) approaches, such as the Gengnianchun (GNC) formula, focus on restoring ovarian function by improving IR and regulating hormonal balance. Despite GNC's demonstrated efficacy, its precise therapeutic mechanisms remain unclear.
This study aims to elucidate the mechanisms by which GNC ameliorates IR-induced DOR through comprehensive pharmacological and experimental validation.
The study combined Liquid chromatograph mass spectrometer (LC-MS), ultra-performance liquid chromatography (UPLC-TOF-MS/MS), network pharmacology, and molecular docking to identify active components and key therapeutic targets of GNC. Functional enrichment analyses (GO and KEGG) and molecular docking studies were performed. A high-fat diet-induced mouse model of IR-DOR was established, followed by GNC treatment at varying doses. Therapeutic effects were evaluated via qRT-PCR, western blot, immunofluorescence, and histological analysis.
GNC contains 219 active ingredients targeting 53 genes associated with IR-induced DOR. KEGG analysis revealed the estrogen signaling pathway as a key mechanism. High-dose GNC significantly improved IR and ovarian reserve by increasing AKT1, ESR1, and ESR2 expression, as confirmed by qRT-PCR, western blot and immunofluorescence analysis. These findings indicate that GNC enhances insulin sensitivity, promotes follicular development, and restores ovarian function.
This study demonstrates for the first time that GNC alleviates IR-induced DOR by modulating the estrogen signaling pathway and activating key molecular targets. These results provide a foundation for clinical research and the development of novel therapeutic strategies for DOR.
Not applicable.
卵巢储备功能减退（DOR）是女性不孕的主要原因，与胰岛素抵抗（IR）密切相关。中医方法，如更年春（GNC）配方，专注于通过改善IR和调节激素平衡来恢复卵巢功能。尽管GNC已显示出疗效，但其确切的治疗机制仍不清楚。
本研究旨在通过全面的药理学和实验验证阐明GNC改善IR诱导的DOR的机制。
该研究结合液相色谱 - 质谱仪（LC-MS）、超高效液相色谱（UPLC-TOF-MS/MS）、网络药理学和分子对接来鉴定GNC的活性成分和关键治疗靶点。进行了功能富集分析（GO和KEGG）和分子对接研究。建立了高脂饮食诱导的IR-DOR小鼠模型，然后用不同剂量的GNC进行治疗。通过qRT-PCR、蛋白质免疫印迹、免疫荧光和组织学分析评估治疗效果。
GNC含有219种活性成分，靶向与IR诱导的DOR相关的53个基因。KEGG分析显示雌激素信号通路是关键机制。qRT-PCR、蛋白质免疫印迹和免疫荧光分析证实，高剂量GNC通过增加AKT1、ESR1和ESR2的表达显著改善IR和卵巢储备。这些发现表明GNC增强胰岛素敏感性，促进卵泡发育，并恢复卵巢功能。
本研究首次证明GNC通过调节雌激素信号通路和激活关键分子靶点来减轻IR诱导的DOR。这些结果为DOR的临床研究和新治疗策略的开发提供了基础。
不适用。
