Evaluating the therapeutic potential of L-arginine and licorice extract in letrozole-induced polycystic ovary syndrome in rats: targeting interconnected molecular pathways

Abstract Polycystic Ovary Syndrome (PCOS) is a common disorder characterized by hyperandrogenism and ovarian dysfunction. L-arginine and licorice extract, known for their antioxidant properties, are used to manage infertility. This study aimed to evaluate the effects of licorice extract and L-arginine on ovarian morphology, oocyte maturation, and pregnancy rates in PCOS-induced rats. Female rats were randomly assigned into six groups (n = 12): Group I (Control) received no treatment; Group II (Licorice) received 150 mg/kg licorice extract for 21 days; Group III (L-Arginine) received 22.9 mg/kg L-arginine for 21 days; Group IV (PCOS Model) received 1 mg/kg letrozole for 21 days to induce PCOS; Group V (Licorice + PCOS) received 150 mg/kg licorice extract post-PCOS induction; Group VI (L-Arginine + PCOS) received 22.9 mg/kg L-arginine post-PCOS induction. The study analyzed ovarian morphology, serum lipid profiles, antioxidant markers, nitric oxide levels, inflammatory cytokines, reproductive hormones, and Amhr2 gene expression, in conjunction with ovarian histopathology and immunohistochemistry for PCNA and Ki-67. L-arginine and licorice extract significantly improved lipid profiles, reduced oxidative stress (MDA, NO), and enhanced antioxidant activity (SOD, Catalase). They also showed beneficial effects on ovarian function, inflammation, and reproductive hormones, suggesting their therapeutic potential in managing PCOS. Fertility success improved from 33.3% in PCOS rats to 100% in both treatment groups, with increased litter sizes (9.25 ± 0.63 and 8.25 ± 0.75, respectively).