Ursolic acid, a pentacyclic triterpene from Ochrosia elliptica Labill leaves and its role in the management of polycystic ovary syndrome (PCOS)

Abstract

Ursolic Acid (UA), a naturally occurring pentacyclic triterpene, was isolated from Ochrosia elliptica. Polycystic Ovary Syndrome (PCOS) a prevalent endocrine disorder characterized by hyperandrogenism, insulin resistance, and chronic inflammation. In this study, we investigate the role of UA in alleviating the symptoms of PCOS, focusing on its biochemical, hormonal, and histopathological effects in a rat model. Using adult female Wistar Albino rats, PCOS was induced through letrozole administration. The rats were then treated with UA at two different doses (25 and 50 mg/kg), alongside a control group and a standard ovulation-inducing medication, clomiphene citrate (1 mg/kg). Biochemical analyses showed that PCOS induction significantly increased serum malondialdehyde (MDA) levels by approximately 1.21-fold, while markedly reducing superoxide dismutase (SOD) and catalase (CAT) activities (p ≤ 0.05) by approximately 0.48-fold, relative to negative control. Treatment with UA (50 mg/kg) dose-dependently restored oxidative balance, reducing MDA (~ 0.82-fold) and elevating SOD (~ 2.39-fold) and CAT (~ 2.11-fold) activities toward PCOS values (p ≤ 0.05). Hormonally, PCOS rats exhibited elevated luteinizing hormone (LH) and testosterone levels by approximately 1.70-fold, compared to the negative control (p ≤ 0.05). Both doses of UA significantly lowered LH and testosterone, with the 50 mg/kg dose achieving reductions comparable to clomiphene citrate (p ≤ 0.05). Histopathological examination showed improved ovarian morphology with reduced cystic follicles and increased corpus lutea in UA-treated groups. Furthermore, UA downregulated key genes involved in steroidogenesis and oxidative stress response, suggesting a multifaceted mechanism of action. The findings highlight UA's potential as a novel therapeutic option for managing PCOS symptoms, emphasizing the need for further research into its efficacy and safety in clinical applications.