Comparative analysis of fennel essential oil and manganese in PCOS rat model via modulating miR-145 expression and structure-based virtual screening of IGF2R protein to address insulin resistance and obesity

Polycystic Ovarian Syndrome (PCOS) is a prevalent endocrine disorder in reproductive-aged women, characterized by ovarian cysts and often complicated by metabolic issues like insulin resistance and obesity, which exacerbate disease progression. Due to limitations in current treatments, this study introduces a novel dual approach by comparing Fennel Essential Oil (FEO) and manganese (Mn) as alternative treatments for miR-145 modulation and ovarian function in a PCOS rat model, highlighting miR-145 as a therapeutic target in PCOS-related metabolic and reproductive dysfunctions. Additionally, virtual screening was conducted to assess the inhibitory potential of three FDA-approved drugs and trans-anethole, a main component of fennel, on IGF2R which is a hub protein linking PCOS to insulin resistance and obesity. This study, addressing the gap between miR-145 and IGF2R as PCOS targets, offers new insights for managing PCOS. The study involved 30 rats, divided into six groups (n = 5). Three control groups (sesame oil, FEO, and manganese for 14 days) and three experimental groups (PCOS-induced by estradiol valerate, FEO treatment, and manganese treatment for 14 days). miR-145 gene expression was evaluated using qRT-PCR, while ovarian changes were examined histologically. Virtual screening of FDA-approved compounds was carried out using molecular docking and ADMET profiling. The study found that EV caused ovarian cysts and reduced miR-145 expression, while FEO increased cyst formation and decreased gene expression in normal rats. However, in PCOS rats, FEO significantly reduced ovarian cysts and increased miR-145 expression, though manganese was more effective than fennel. Virtual screening identified three FDA-approved compounds including Ergotamine (−9.2 kcal/mol), Lomitapide (−9.1 kcal/mol), and Maraviroc (−8.6 kcal/mol), as the best IGF2R inhibitors, outperforming fennel's trans-anethole. These findings suggest that targeting IGF2R could complement miR-145 modulation by addressing associated metabolic disorders and providing alternative treatments in PCOS patients. This dual approach, combining experimental modulation of miR-145 and improving ovarian function through FEO and Mn with in silico targeting of IGF2R for the first time, offers a novel therapeutic angle by managing ovarian function as well as related metabolic disorders like obesity and insulin resistance in PCOS. Future research should explore the clinical potential of these compounds, focusing on the key therapeutic targets miR-145 and IGF2R in PCOS treatment.