Biochanin A Mitigates Oxidative Stress and Inflammation in Diabetic Myocardial Infarction: Insights From a Streptozotocin and Isoproterenol Rat Model.

INTRODUCTION

Diabetes mellitus (DM) significantly increases the risk and severity of myocardial infarction (MI), contributing to poor cardiovascular outcomes through oxidative stress, inflammation, and endothelial dysfunction.

METHODS

This study evaluates the cardioprotective potential of biochanin A (BCA), a naturally occurring isoflavonoid with antioxidant and anti-inflammatory properties, in a streptozotocin (STZ) and isoproterenol (ISO)-induced model of diabetic myocardial infarction (DMI) in rats. Male Wistar rats were divided into five groups, including normal controls, STZ+ISO, and three BCA-treated groups (5, 10, and 20 mg/kg).

Results

BCA administration significantly improved electrocardiographic parameters by reducing ST height and QT interval prolongation (p < 0.05). It also reduced myocardial injury markers (lactate dehydrogenase (LDH), creatinine kinase on myocardial bundle (CK-MB), aspartate transaminase (AST), and cardiac troponin-T (cTn-T)) in a dose-dependent manner (p < 0.001). BCA normalized blood pressure, heart rate, and left ventricular function, improving maximum and minimum rate of ventricular contraction (+dP/dt, -dP/dt) (p < 0.01). Furthermore, BCA significantly decreased blood glucose levels and improved lipid profiles by lowering total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) while increasing high-density lipoprotein (HDL) levels (p < 0.001). It suppressed inflammation by reducing tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β levels (p < 0.01). Oxidative stress markers, including malondialdehyde (MDA), were reduced, while antioxidant markers such as glutathione (GSH), superoxide dismutase (SOD), and catalase were increased (p < 0.001). BCA enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) expression, promoting antioxidant defense. Histopathological analysis confirmed reduced myocardial injury and improved cardiac architecture.

Conclusion

These findings highlight BCA's potential as a therapeutic agent for managing DMI through its dual antioxidant and anti-inflammatory actions.