Natural dipeptidyl peptidase-4 inhibitor Terminalia arjunamitigates myocardial infarction co-existing with diabetes in experimental rats

Abstract

Diabetes mellitus (DM) and ensuing cardiovascular (CV) complications have arisen as the epidemic of the early 21st century. Diabetes mellitus remains a profound risk factor for cardiovascular disease. Excess mortality in type 2 DM is largely related to an increased incidence of CV disease with approximately 75% of deaths in people with diabetes attributable to stroke, myocardial infarction (MI) and peripheral arterial disease.1,2 Management of cardiovascular risk is an essential aspect of diabetes care and acceptable CV risk is a requirement for Antidiabetes medications. DPP-4 inhibitors are a novel class of oral hypoglycemic agents, widely used for the treatment of type 2 diabetes mellitus (T2DM). Besides established ant diabetic effects, several studies have reported the cardioprotective benefits of DPP-4 inhibitors via GLP-1 dependent and independent pathways. Studies documented that, DPP-4 inhibitors improve several cardiovascular risk factors: they improve glucose control (by reducing the risk of post prandial and fasting hyperglycemia), weight neutral, lower blood pressure, improve dyslipemia, reduce inflammatory markers, diminish oxidative stress, improve endothelial functions and reduce platelet aggregation in patients with T2DM.3,4 In Zucker diabetic fatty rats, a genetic rodent model for type 2 diabetes, the inhibition of DPP-4 corrected glycemic dysmetabolism, hypertriglyceridemia, inflammation and hypertension.5 Since a large pool of diabetic patients have co-existing cardiovascular diseases, DPP-4 inhibitors may represent novel and promising ant diabetic agents with potential cardiovascular benefits. Thus, DPP-4 inhibitors are a promising new therapeutic approach for the management of type 2 diabetes. However they are expensive drugs and recently have been associated with a number of unacceptable adverse effects.6–9