Therapeutic potential of 3-acetyl coumarin against polycystic ovarian syndrome induced by letrozole using female rats

Polycystic ovarian syndrome is a heterogeneous endocrine disorder characterized by ovarian cysts, anovulation, endocrine variations, which includes oligo-amenorrhea along with associated subfertility and hyperandrogenism manifested as acne, hirsutism, and male-pattern alopecia. Coumarins are fused benzene and pyrone ring systems that exhibit a wide spectrum of bioactivities. This study aimed to investigate the effects of 3-acetyl coumarin (3-AC) on polycystic ovarian syndrome in female rats. Acute oral toxicity conducted according to OECD guidelines 425 (a test conducted in scenarios where there is information indicating that the test material is non-toxic) exhibited no mortality. In vitro DPPH assay demonstrated anti-oxidant potential of 3-AC. Letrozole, a nonsteroidal aromatase inhibitor was used to induce PCOS (1 mg/kg-21 days). Normal and PCOS control rats were administered a vehicle solution (0.5% CMC), whereas 3-AC (10, 20, and 30 mg/kg) and metformin (300 mg/kg) was administered to treatment groups for 15 days. Vaginal smears were taken to assess estrous cycle. Rats were euthanized at day 37. In vivo analysis included measurement of fasting blood glucose, total-cholesterol, triglycerides, FSH, LH, and testosterone levels. ELISA was used for measurement of inflammatory markers (IL-1β, IL-6, and TNF-α). Oxidative stress markers (SOD, CAT, GSH, MDA, NO) were also evaluated. Expression levels of NF-κB and LHCGR were detected by RT-qPCR. Molecular docking was also performed. One-way analysis of variance was employed followed by Tukey's test for statistical analysis. Treatment with 3-AC led to favorable effects in PCOS rats. Specifically, inflammatory levels, antioxidant status, lipid profile, and glucose concentrations were all improved. These findings suggest that 3-acetyl coumarin (3-AC) may serve as a promising therapeutic agent for alleviating symptoms of PCOS in this animal model.