Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and its treatment remains a significant challenge. This study investigated the mechanism of Jujuboside A (JuA) in the treatment of PCOS through mitophagy. Granulosa cells (GCs) were collected from follicular fluid derived from PCOS women. The effects of JuA on PCOS were determined by measuring body weight, ovarian weight, estrous cycle, glucose level, insulin tolerance, and ovarian morphology in dehydroepiandrosterone-induced mice. SIRT3 expression levels were quantified in GCs, KGN cells, and mouse ovaries. The effects of JuA on SIRT3-related oxidative stress and mitochondrial damage were investigated in KGN cells and mice. Transmission electron microscopy was used to observe mitochondrial damage and mitophagy in GCs. The expression of mitophagy-related proteins (PINK1 and Parkin) was analyzed. JuA significantly improved body weight, estrous cycle, ovarian morphology, glucose tolerance, and insulin resistance, partially restoring ovarian function in PCOS mice. Moreover, JuA significantly activated SIRT3 expression and alleviated SIRT3-related oxidative stress and mitochondrial damage in mouse ovaries, GCs, and KGN cells. Mechanistically, JuA upregulated SIRT3 and inhibited excessive activation of the PINK1/Parkin pathway to reduce mitophagy. These findings demonstrated JuA protected GCs from mitochondrial damage by activating SIRT3 and inhibiting PINK1/Parkin-mediated mitophagy.
