Aged garlic extract inhibits platelet activation by increasing intracellular cAMP and reducing the interaction of GPIIb/IIIa receptor with fibrinogen

Aims: Increased platelet aggregation plays an important role in the etiology of cardiovascular disease. Garlic inhibits platelet aggregation; however, the mechanisms involved have not clearly been defined. This study was undertaken to investigate the mechanisms by which an aged garlic extract (AGE) inhibits both the activation and aggregation of human platelets. Main methods: Isolated human platelets were stimulated with ADP and their adhesion to fibrinogen was assessed using Rose Bengal or Cr-51 uptake. Activation of platelets was assessed using fluorescence activated cell sorting (FACS) analysis along with measurement of intracellular cAMP. Key findings: AGE at concentrations in the range of 3.12 to 12.5% (v/v) inhibited the binding of platelets to fibrinogen by approximately 40% when compared to control values in the Rose Bengal assay (P<0.05). In the Cr-51 experiments AGE significantly inhibited the binding of ADP-activated platelets to immobilized fibrinogen by 61.5% at 1.56% and 6.25% (v/v) of AGE respectively. At a concentration of 12.5% (v/v) the inhibition was 70.4% and at 25% (v/v) it was 64.5% respectively (P<0.05). In the fluorescence activated cell sorting (FACS) analysis, AGE significantly decreased the amount of PAC-1 binding to GPIIb/IIIa by approximately 72% compared with PBS control. In conjunction to these observations, AGE also increased platelet cAMP (P<0.01) levels. Significance: These findings suggest that AGE inhibits platelet aggregation via inhibition of the GPIIb/IIIa receptor and an increase in cAMP. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.