Therapeutic Potential of <i>Asparagus racemosus</i> and <i>Vitex negundo</i> Against Polycystic Ovarian Syndrome in Wistar Rats: Exploring an Oxidative Stress Independent Mechanism

Abstract Polycystic ovarian syndrome (PCOS) is the most predominant endocrine disorder responsible for female infertility. The clinical treatment strategies of PCOS only provide symptomatic relief but are often unsatisfactory. Asparagus racemosus and Vitex negundo have long been used as traditional herbal intervention in treating various metabolic and reproductive issues. Therefore, a pressing need for a better alternative approach is essential. The study aimed to assess the effect of A. racemosus (ARA) and V. negundo (VNA) aqueous extract on treating PCOS-like symptoms in female rats. Letrozole (1.0 mg/kg BW) was used to induce PCOS in rats which were then treated with ARA and VNA in a dose of 250 mg/kg BW orally for 21 consecutive days. These herbs improved the estrous cycle after being perturbed by letrozole. ARA and VNA significantly increased the level of estradiol and estradiol receptor ( ESR1 ) in PCOS rats, which further prevented uterine shrinkage. Post treatment of these herbs also revealed a notable decline in serum glucose and triglyceride levels in letrozole-induced PCOS rats. Letrozole caused reproductive and metabolic alterations without inducing oxidative stress, evidenced by higher activity of SOD and catalase in PCOS group. However, both supplemented groups showed baseline level of SOD and catalase similar to the vehicle-treated control. Moreover, ARA and VNA administration decreased the appearance of cystic follicles in histomorphological study by regulating ovarian folliculogenesis. Hence, this is the first time we reported that restoration of normal reproductive and metabolic function in letrozole induced PCOS by ARA and VNA were independent of oxidative stress.