Flavonoid-rich cranberry extract alleviates endometrial thinning in PCOS mice and modulates gut microbiota

Cranberries, rich in flavonoids and exhibiting antioxidant properties, are gaining increasing attention for their potential benefits in female reproductive health. This study demonstrates that cranberry extract (CBE) can restore endometrial thinning associated with polycystic ovary syndrome (PCOS) and improve endocrine and metabolic disturbances. Firstly, the bioactive compounds in CBE were analyzed and identified using widely targeted metabolomic techniques. In vivo experiments showed that CBE restored endometrial thickness, regulated the estrous cycle, reduced serum testosterone and estradiol levels, and improved dyslipidemia. Network pharmacology analysis revealed that key active components, such as kaempferol, myricetin, and quercetin, exert their effects by modulating critical pathways, including endocrine resistance, estrogen signaling, and the PI3K-AKT pathway. Furthermore, CBE enhanced gut microbiota diversity and increased the abundance of beneficial bacteria in mice with PCOS. These results suggest that CBE promotes endometrial repair through multi-target, multifaceted mechanisms, highlighting its potential as a non-hormonal, functional food-based intervention for managing endometrial thinning in PCOS. • CBE improved endometrial thickness in PCOS mice. • Network pharmacology identified the targets of CBE intervention in the TE of PCOS. • PI3KR1 may serve as a crucial link in the pharmacological action pathway of CBE. • CBE intervention treatments improved gut microbiota diversity.