ABSTRACT
OBJECTIVE: Limitations and side effects associated with current anti-diabetic treatments have necessitated the search for new therapeutic alternatives. This study aimed to explore the combined use of resveratrol (RVT) and established anti-diabetic drug pioglitazone (PGZ) against streptozotocin (STZ)-induced diabetes mellitus (DM). MATERIALS AND METHODS: STZ was supplemented daily to Sprague-Dawley rats to induce DM. The synergistic effect of the RVT (20 mg/kg) and PGZ (0.65 mg/kg) on DM complications was evaluated after 8 weeks of treatment. Biochemical analyses were performed to evaluate the effectiveness of our treatment on glucose level, insulin sensitivity, lipid disturbances, oxidative mediators and inflammatory markers. RESULTS: STZ induced DM onset that is accompanied with elevated diabetic markers, lipid disturbances, remarkable oxidative damage and hyper-inflammation. The PGZ+RVT combination has the best effect as illustrated by significant (p < 0.05) decreases in fasting blood glucose, insulin, HbA1c and HOMA-IR levels. This combination attenuated (p < 0.05) lipid disturbances and their associated elevated atherogenic biomarkers. At the same time, treatments with PGZ+RVT exhibited an anti-inflammatory effect as it attenuated the increase in inflammatory parameters (CRP, TNF-α, IL-6). Also, it restored total antioxidant capacity and peroxisome proliferator-activated receptor (PPARg) levels that decreased by STZ-DM induction. CONCLUSIONS: This study provides PGZ+RVT as promising DM therapeutic alternative. This synergistic combination alleviates most of DM-related complications and insulin resistance.
