Isorhamnetin as a promising agent for reducing diabetes-induced cardiac damage: insights into antioxidant and enzyme regulatory mechanisms

Purpose
This study assessed the protective effect of Isorhamnetin in diabetic rats induced by streptozotocin (STZ).

Methods
Male Wistar rats were randomly divided into five groups. Normal control, Diabetic control, Low dose of Isorhamnetin – 50 mg/kg, High dose of Isorhamnetin – 150 mg/kg, and Metformin – 200 mg/kg. Diabetes was induced by a single intraperitoneal injection of STZ and treatment was given orally for a period of 21 days. The parameters that were observed in this study were oxidative markers, ATPase and phosphatase activities, p53 and VCAM-1gene expression, myocardial injury markers and histopathology.

Result
Diabetic rats increased the level of MDA, decreased antioxidant enzyme catalase, SOD, GPx, and GST activity, decreased ATPase activities of Na+/ K+-ATPase, Ca2+/Mg2+- ATPase, and Mg2+-ATPase, increased the expression of p53 and VCAM-1 gene compared to normal control. Low and High dose of Isorhamnetin significantly decreased the MDA level, increased the antioxidant enzyme activity, ATPase, and Na+/K+-ATPase activity compared to diabetic rats and this activity was similar to metformin. Isorhamntenin decreased the p53 and VCAM gene concisely to the diabetic group, increased AST and ALTand reduced the CK-MB and cardiac troponins. Histopathological study showed that reduced the muscle fiber degeneration and congestion pattern of heart congestion.

Conclusion
Isorhamnetin plays a cardioprotective effect in diabetic rats by reducing oxidative stress, increased antioxidant defense, restored and enzyme activity of ATPase and reduced inflammation and apoptosis. Hence, Isorhamnetin can be used as a promising multi-target drug for diabetes-induced cardiac and injury.