Understanding the Activation of Platelets in Diabetes and Its Modulation by Allyl Methyl Sulfide, an Active Metabolite of Garlic

Abstract

Background. Diabetes mellitus (DM) is a chronic metabolic disorder associated with higher risk of having cardiovascular disease. Platelets play a promising role in the pathogenesis of cardiovascular complications in diabetes. Since last several decades, garlic and its bioactive components are extensively studied in diabetes and its complications. Our aim was to explore the antiplatelet property of allyl methyl sulfide (AMS) focusing on ameliorating platelet activation in diabetes. Method. We used streptozotocin- (STZ-) induced diabetic rats as model for type 1 diabetes. We have evaluated the effect of allyl methyl sulfide on platelet activation by administrating AMS to diabetic rats for 10 weeks. Flow cytometry-based analysis was used to evaluate the platelet activation, platelet aggregation, platelet macrophage interaction, and endogenous ROS generation in the platelets obtained from control, diabetes, and AMS- and aspirin-treated diabetic rats. Results. AMS treatment for 10 weeks effectively reduced the blood glucose levels in diabetic rats. Three weeks of AMS (50 mg/kg/day) treatment did not reduce the activation of platelets but a significant (p<0.05) decrease was observed after 10 weeks of treatment. Oral administration of AMS significantly (p<0.05) reduced the baseline and also reduced ADP-induced aggregation of platelets after 3 and 10 weeks of treatment. Furthermore, 10 weeks of AMS treatment in diabetic rats attenuated the endogenous ROS content (p<0.05) of platelets and platelet macrophage interactions. The inhibition of platelet activation in diabetic rats after AMS treatment was comparable with aspirin treatment (30 mg/kg/day). Conclusion. We observed an inhibitory effect of allyl methyl sulfide on platelet aggregation, platelet activation, platelet macrophage interaction, and increased ROS levels in type 1 diabetes. Our data suggests that AMS can be useful to control cardiovascular complication in diabetes via inhibition of platelet activation.