Therapeutic Effects of Cichorium intybus L. Extract in an Experimentally Induced Insulin Resistance Model in Rats

Introduction: Insulin resistance (IR) is a central metabolic feature of polycystic ovary syndrome (PCOS). Althou gh metformin improves insulin sensitivity, its adverse effects limit long-term use, prompting interest in herbal alternatives. The present study aimed to investigate the effects of Cichorium intybus L. ethanolic extract on PCOS-associated IR in a letrozole-induced rat model, compared with metformin. Materials and Methods: A total of twenty-four female Sprague–Dawley rats were allocated into four groups: healthy control (H), PCOS-associated insulin resistance (IR), metformin-treated (MET), and Cichorium intybus ethanolic extract–treated (C.I). PCOS was induced by oral letrozole administration (1 mg/kg/day) for 21 days. Following confirmation of IR by estrous cycle disruption and oral gl ucose tolerance test (OGTT), treatments were administered orally for 15 da ys. Metabolic parameters, serum insulin, glucose, lipid profile, sex hormones, and HOMA-IR index were evaluated. Skeletal muscle tissues were examined histopathologically and by immunohistochemical analysis of insulin receptor (INSR), insulin receptor subsrate 1 (IRS1), and insulin receptor subsrate 2 (IRS2) expression. Results: PCOS-associated IR rats showed impaired glucose tolerance, hyperinsulinemia, increased HOMA-IR, dyslipidemia, and hormonal imbalance. C. intybus ethanolic extract treatment significantly improved glucose tolerance, insulin levels, HOMA-IR, and lipid profile, with effects comparable to metformin. While metformin markedly restored INSR, IRS1, and IRS2 expression in skeletal muscle, C. intybus produced only moderate improvements. Conclusion: C. intybus ethanolic extract improved metabolic, hormonal, and biochemical paramete rs in PCOS-associated IR. However, its effects on skeletal muscle insulin signaling markers were less pronounced than metformin, suggesting a complementary therapeu tic role mainly through systemic metabolic regulation. © 2026, Yuzuncu Yil Universitesi Tip Fakultesi. All rights reserved.