Gengnianchun formula ameliorates insulin resistance-induced diminished ovarian reserve via the estrogen signaling pathway: evidence from network pharmacology and experimental validation

• DOI: 10.1186/s13048-025-01632-3
• Publication Date: 2025-03-11T12:40:48Z
• Authors: Yanqiu Rao; Jun Li; Ting Xu; Lingyun Gao; Wenjun Wang

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 function by improving IR and regulating hormonal balance. Despite GNC's demonstrated efficacy, its precise therapeutic mechanisms remain unclear. This study aims elucidate which GNC ameliorates IR-induced DOR through comprehensive pharmacological experimental validation. The combined Liquid chromatograph mass spectrometer (LC-MS), ultra-performance liquid chromatography (UPLC-TOF-MS/MS), network pharmacology, molecular docking identify active components key targets GNC. Functional enrichment analyses (GO KEGG) studies were performed. A high-fat diet-induced mouse model IR-DOR was established, followed treatment at varying doses. Therapeutic effects evaluated via qRT-PCR, western blot, immunofluorescence, histological analysis. contains 219 ingredients targeting 53 genes associated with DOR. KEGG analysis revealed estrogen signaling pathway mechanism. High-dose significantly improved increasing AKT1, ESR1, ESR2 expression, confirmed blot immunofluorescence These findings indicate that enhances sensitivity, promotes follicular development, restores function. demonstrates for first time alleviates modulating activating targets. results provide foundation clinical research development novel strategies Not applicable