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


METHODS
Isolated human platelets were stimulated with ADP and their adhesion to fibrinogen was assessed using Rose Bengal or (51)Cr uptake. Activation of platelets was assessed using fluorescence activated cell sorting (FACS) analysis along with measurement of intracellular cAMP.


RESULTS
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 (51)Cr 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.


CONCLUSIONS
These findings suggest that AGE inhibits platelet aggregation via inhibition of the GPIIb/IIIa receptor and an increase in cAMP.
School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, Eric Williams Medical Sciences Complex, Champ Fleurs, Trinidad and Tobago.
Gillian L
GL
Allison
Gordon M
GM
Lowe
Khalid
K
Rahman
D000244:Adenosine Diphosphate / Q000008:administration & dosage; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism*; D005434:Flow Cytometry; D005737:Garlic / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*
D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D000242:Cyclic AMP