Therapeutic mechanism of Polygonum multiflorum Thunb. in premature ovarian insufficiency: an integration of network pharmacology, molecular docking, and experimental validation.

Premature ovarian insufficiency (POI) often leads to infertility and long-term health complications. Processed Polygonum multiflorum Thunb. (PM) is a traditional medicinal and edible plant widely used in health supplements and herbal medicine. It has shown potential in mitigating ovarian aging but its mechanisms against POI remain unclear. This study integrated network pharmacology, molecular docking, and experimental validation to explore the therapeutic mechanism of PM in POI. Bioactive compounds in PM were identified by liquid chromatography-mass spectrometry and literature screening, yielding 91 compounds targeting 320 POI-related genes. Core targets included AKT1, PIK3CA, and PIK3R1, with pathway enrichment highlighting the PI3K/AKT signaling pathway, which was further supported by molecular docking. In a rat model of POI, treatment with either low- or high-dose PM restored estrous cyclicity, improved serum follicle-stimulating hormone (FSH) and estradiol (E2) levels, improved follicular development, and increased the expression of bone morphogenetic protein 15 (BMP-15), growth differentiation factor 9 (GDF-9), and key PI3K/AKT proteins. Polygonum multiflorum Thunb. may alleviate POI by activating the PI3K/AKT pathway, restoring hormonal balance, reducing follicular atresia, and preserving ovarian reserve. These findings underscore the potential of PM as a natural therapeutic resource for POI management. © 2026 Society of Chemical Industry.