Therapeutic Effects of Biochanin A in Diabetic Myocardial Injury: Evidence from an Experimental Model

Objective Diabetic cardiomyopathy (DCM) is a diabetes-associated cardiovascular complication characterized by progressive myocardial structural remodeling and functional deterioration, representing a leading cause of diabetes-related morbidity and mortality. Biochanin A (BCA), a phytoestrogenic isoflavone derived from Trifolium pratense , exhibits pleiotropic biological activities including antidiabetic, anti-inflammatory, and antioxidant effects. This study evaluated the therapeutic effects of BCA in a streptozotocin (STZ)-induced rat model of diabetic myocardial injury. Methods Forty male Wistar albino rats were randomized into four groups: Control, BCA (20 mg/kg/day), STZ (45 mg/kg), and STZ + BCA, with BCA administered i.p. for 30 days post-induction. Cardiac stress markers (ANP, NT-proBNP), endoplasmic reticulum stress (GRP78), and apoptosis (caspase-3) were assessed via immunohistochemistry, alongside serum myocardial injury markers (CK-MB, hs-cTnT, LDH), oxidative stress parameters (SOD, CAT, MDA), and pro-inflammatory mediators (TNF-α, IL-6, NF-κB). Results BCA treatment significantly reduced hyperglycemia, increased SOD and CAT levels, decreased MDA, reduced circulating TNF-α, IL-6, and NF-κB, and lowered serum myocardial injury markers. Immunohistochemistry showed reduced ANP, NT-proBNP, GRP78, and caspase-3 immunoreactivity, accompanied by improved myocardial architecture on histopathology. Conclusion These findings suggest that BCA exerts multitarget therapeutic effects on diabetic myocardial injury, through modulation of glycemic, oxidative, inflammatory, and ER stress-related apoptotic pathways, highlighting it as a promising candidate for the management of diabetic cardiac complications.