Vinpocetine attenuates diabetic cardiomyopathy by downregulating transforming growth factor-1 and phosphodiesterase-1 expression in rats

Abstract

Diabetic cardiomyopathy is one of the serious secondary complications of diabetes mellitus in humans. Existing therapy affords symptomatic relief without halting disease progression. Vinpocetine is an alkaloid having pleiotropic pharmacological effects. Present study is designed to investigate the effect of vinpocetine in diabetic cardiomyopathy in rats. Rats were fed with high fat diet (HFD) for nine weeks along with streptozotocin (35 mg/kg, intraperitoneal) after second week to induce diabetic cardiomyopathy. At the end of protocol, echocardiography of rats was done. Morphological parameters including body weight, heart weight was noted. Rat heart were evaluated for functional status (left ventricular developed pressure, dp/dtmax, dp/dtmin) using Biopac system. Cardiac biochemical (creatine kinase-MB, lactate dehydrogenase, aspartate aminotransferase) oxidative stress parameters (malondialdehyde, superoxide dismutase, reduced glutathione, catalase) and inflammatory cytokine (tumor necrosis factor-α, interleukin-6) level, were analysed in addition to haematoxylin eosin and picrosirius red staining to study histological changes, cardiomyocyte diameter and fibrosis, respectively. Phosphodiesterase-1 (PDE-1) and transforming growth factor-β (TGF-β) expression in cardiac tissues was quantified using western blot and RT-PCR. Vinpocetine treatment and its combination with enalapril decreased glucose levels as compared to diabetic control rats. Vinpocetine improved echocardiographic parameters and cardiac functional status revealed by Biopac study. Vinpocetine decreased cardiac biochemical parameters, oxidative stress, inflammatory cytokines levels, cardiomyocyte diameters and fibrosis in rats. Interestingly, expressions of TGF-β and PDE-1 were ameliorated by vinpocetine alone and its combination with enalapril. Vinpocetine ameliorates diabetic cardiomyopathy by its anti-oxidant, anti-inflammatory, hypoglycaemic property and by inhibiting PDE-1 and TGF-β in rats.