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

BACKGROUND: 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.

RESULTS: 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.

CONCLUSION: 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.