In Silico and Experimental Evaluation of Myricetin in Insulin Resistance‐Associated PCOS in Rats

Polycystic ovary syndrome (PCOS) is a prevalent endocrinal disease characterized by hyperandrogenism, insulin resistance, cardiometabolic dysfunction, and hormonal disturbances, often leading to infertility. IR, a hallmark feature of PCOS, is observed in 30%–95% of women with PCOS. Current therapies are associated with potential side effects, necessitating exploration of alternative strategies. The present study aimed to identify and evaluate natural phytoconstituents targeting insulin receptor substrate‐1 (IRS‐1), a critical mediator in insulin signaling. In silico molecular docking of 22 phytoconstituents against IRS‐1 revealed myricetin (MYR) has a binding energy of −9.3 kcal/mol, and favorable ADMET characteristics. MYR also showed significant binding affinity against PI3K and NF‐κB (−8.6 and −7.0 kcal/mol, respectively), indicating its potential to improve insulin sensitivity. Subsequently, the therapeutic efficacy of MYR was assessed in a high‐fat diet and letrozole induced PCOS in rats. MYR treatment at varying doses significantly ( p < 0.001) reversed PCOS associated with metabolic and reproductive abnormalities. MYR (300 mg/kg) demonstrated substantial improvements in body weight, BMI, estrous cycle, restored hormonal balance, and improved IR. MYR significantly improved β‐cell functions, serum lipid profile, oxidative stress, and histology in ovarian tissues. The findings of the study underscore the potential of MYR as safe and effective candidate for PCOS management.