Cardioameliorative effect of punicalagin against streptozotocin-induced apoptosis, redox imbalance, metabolic changes and inflammation

• Punicalagin ameliorates hyperglycemia and metabolic risk factors.
• Punicalagin ameliorates proinflammatory cytokines, oxidative stress and protected DNA integrity.
• It modulates apoptotic proteins to protect heart against diabetes-induced apoptosis.

The effect of punicalagin on metabolic risks, oxidative stress, inflammation, cardiac apoptosis and histopathological alterations in experimentally induced diabetes was addressed. Diabetes was induced in male rats by a single injection of streptozotocin (STZ; 40 mg/kg, i.p.), and then punicalagin (1 mg/kg) was i.p. administered every other day for 15 days. The diabetic rats treated with punicalagin exhibited ameliorated hyperglycemia and HbA1c; improved insulin levels, HOMA-IR levels and lipid profiles; and normalized levels of IL-1b, IL-6 and TNF-α. Punicalagin also reduced the increase in the MDA and H2O2 levels; normalized the levels of GSH, SOD and CAT in the heart; and improved serum markers of heart function including the levels of troponin T level and CK-MB and LDH activities. Histopathological examinations of heart sections match these results, confirming the beneficial effect of punicalagin. It also modulated cardiomyocyte apoptosis via enhanced Bcl-2 expression; blocked the increases in P53, Bax and caspases-3, 8 and 9; and ameliorated DNA damage in the heart. The current results suggest that punicalagin protected the heart against apoptosis, necrosis, inflammation and DNA damage by improving the redox state, suppressing caspases and P53 and increasing Bcl-2. In conclusion, punicalagin possesses strong therapeutic potential in treating and regulating diabetes and attenuating its associated complications in the heart.

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