Anti-diabetic effect of cotreatment with resveratrol and pioglitazone in diabetic rats

L.N. Tamimi, Z. Zakaraya, M. Hailat, W. Abu Dayyih, E. Daoud, A. Abed, M.J. Saadh, B. Majeed, H. Abumansour, A. Aburumman, J.M. Majeed, M. Hamad

Faculty of Pharmacy, Zarqa University, Zarqa, Jordan. mjsaadh@yahoo.com

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• Diabetes
• Pharmacology

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.

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