Tangeretin, a polymethoxylated flavone, modulates lipid homeostasis and decreases oxidative stress by inhibiting NF-κB activation and proinflammatory cytokines in cardiac tissue of streptozotocin-induced diabetic rats

The cardioprotective nature of tangeretin, a polymethoxylated flavone present in citrus fruits, was investigated by assessing the key markers of heart, lipid profiles, oxidative stress, proinflammatory cytokines and ultrastructural alterations in streptozotocin-induced diabetic rats. Oral administration of tangeretin (100 mg/kg body weight/day) for 30 days to diabetic rats reversed the body weight and heart weight changes by its insulinotropic action which in turn decreased the plasma and cardiac lipid profiles through modification activities of key enzymes of lipid metabolism in liver and increased the GLUT4 expression in the heart of diabetic rat. Moreover, tangeretin treatment increased the activities of antioxidant enzymes by decreasing the levels of lipid peroxidation and extent of inflammatory cytokines and cardiac marker enzymes in both plasma and heart of diabetic rats. Further, tangeretin blunted the rise in cardiac [Ca2+] and [Na+] whereas it increased the activities of Ca2+-ATPase and Na+/K+-ATPase in diabetic rats. The results of biochemical tests together with histological observations suggest that tangeretin treatment plays a beneficial role in regulating diabetes and its associated complications in the heart. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide an antidiabetic drug. (C) 2015 Elsevier Ltd. All rights reserved.