Naringenin improves ovarian health by reducing the serum androgen and eliminating follicular cysts in letrozole‐induced polycystic ovary syndrome in the Sprague Dawley rats

Abstract

Polycystic ovary syndrome (PCOS) is most common in women of reproductive age, giving rise to androgen excess and anovulation, leading to infertility and non‐reproductive complications. We explored the ameliorating effect of naringenin in PCOS using the Sprague Dawley (SD) rat model and human granulosa cells. Letrozole‐induced PCOS rats were given either naringenin (50 mg/kg/day) alone or in combination with metformin (300 mg/kg/day), followed by the estrous cycle, hormonal analysis, and glucose sensitivity test. To evaluate the effect of naringenin on granulosa cell (hGC) steroidogenesis, we treated cells with naringenin (2.5 μM) alone or in combination with metformin (1 mM) in the presence of forskolin (10 μM). To determine the steroidogenesis of CYP‐17A1, ‐19A1, and 3βHSD2, the protein expression levels were examined. Treatment with naringenin in the PCOS animal groups increased ovulation potential and decreased cystic follicles and levels of androgens. The expression levels of CYP‐17A1, ‐19A1, and 3βHSD2, were seen restored in the ovary of PCOS SD rats' model and in the human ovarian cells in response to the naringenin. We found an increased expression level of phosphorylated‐AKT in the ovary and hGCs by naringenin. Naringenin improves ovulation and suppress androgens and cystic follicles, involving AKT activation.

Naringenin modulates the NO‑cGMP‑PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs

“…Previous studies have reported that NAR promotes AKT phosphorylation to regulate apoptosis and enhances the cellular cholesterol efflux process in prostate cancer cells ( 46 , 47 ). Notably, NAR-promoted AKT phosphorylation regulates various cellular biological functions such as inducing prostate cancer apoptosis, supporting migration of cells, improving ovulation and suppressing androgens and cystic follicles ( 46 , 48 , 49 ). In the present study, NAR gavage significantly promoted the repair and regeneration of alveolar bone defects in a bone defect model.…”

Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature

“…Furthermore, naringenin has a protective effect on the ovary and can alleviate polycystic ovary syndrome. In vivo naringin treatment in rats inhibits steroidogenic enzymes and consequently controls ovulation, thereby restoring ovarian morphology and cystic follicle levels in patients with polycystic ovary syndrome [ 243 ].…”

“…Virus-induced gonadal damage [235] Coagulation abnormalities and endothelial damage [236] Decreased testosterone [238] Decrease in sperm quality caused by inflammatory response [240] Inhibition of oxidative stress and mitochondrial apoptosis in testes [241] Preserved the structure of the testes and sperm viability [242] Inhibited steroidogenic enzymes and controlled ovulation [243] Thrombus Formation Endothelial damage and dysfunction [244] Formation of fibrin-like microclots that are difficult to hydrolyze [249] Inflammatory factor storm activated exogenous coagulation pathways [250] Formation of autoantibodies and chronic hypoxia [251] Upregulated NO bioavailability [253] Decreasing levels of inflammatory factors [254] Inhibited excessive autophagy in endothelial cells [255] Inhibited platelet activation [256,257] Inhibited thrombin activity [258,259]…”