Hesperetin-supplemented soybean and ginger hydroalcoholic extracts alleviate diabetic cardiomyopathy in streptozotocin induced diabetic rats by modulating NF-κB/MMP-9/TIMPs pathway

Abstract

Prolonged hyperglycemia is a major driver of microvascular and macrovascular complications in diabetes mellitus, including diabetic cardiomyopathy (DC). Polyphenolic flavonoids, found abundantly in fruits, vegetables, and medicinal plants, have shown therapeutic potential against diabetes-related complications. This study evaluates the effects of a combination of hesperetin, soy extract, and ginger extract on DC in a Type II diabetic rat model. Diabetes was induced in neonatal rats by a single intraperitoneal injection of streptozotocin (STZ) (90 mg/kg) on postnatal day 5. Six weeks post-induction, rats were divided into a diabetic control group and a treatment group, with the latter receiving daily oral administration of a combination of soy extract (300 mg/kg), ginger extract (75 mg/kg), and hesperetin (100 mg/kg) for 24 weeks.

At the end of the treatment period, biochemical, physiological, hemodynamic, electrocardiographic (ECG), echocardiographic (ECHO), molecular, and zymographic parameters were analyzed. The treatment significantly reduced blood glucose, CK-MB, LDH, hsCRP, the area under the curve (AUC) in the oral glucose tolerance test (OGTT), and HOMA-IR. It also alleviated diabetes-induced abnormalities in hemodynamic, ECG, and ECHO parameters. Furthermore, the combination demonstrated anti-inflammatory effects by downregulating the expression of NF-κB and attenuating cardiac remodeling through the inhibition of TGF-β and MMP-9 pathways.

These findings highlight the potential cardioprotective effects of hesperetin-supplemented soy and ginger hydroalcoholic extracts. By modulating key inflammatory and extracellular matrix remodeling pathways, this combination effectively mitigated diabetes-induced cardiac dysfunction. This study provides evidence supporting the use of this herbal combination as an adjunctive therapy for managing diabetic cardiomyopathy, warranting further exploration in clinical settings.