Effect of ajoene, the major antiplatelet compound from garlic, on platelet thrombus formation.
Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic (Allium sativum). Ajoene reversibly inhibits in vitro platelet aggregation as well as release reaction induced by all known agonists. We used a well characterized cylindrical perfusion chamber to study the effect of ajoene on platelet deposition onto physiological substrates such as pig aortic subendothelium and tunica media as a model of mildly and severely damaged vessel wall respectively. Experiments were performed under flow conditions of high and low shear rate that mimic laminar blood flow in small and medium size arteries (1690 sec-1 and 212 sec-1). Our results indicate that ajoene prevents thrombus formation both at low and high shear rate in citrated whole blood. The inhibitory effect of ajoene on platelet-thrombus formation seems to be dependent on its inhibition of fibrinogen binding, since significantly higher concentrations of ajoene are needed to affect von Willebrand factor binding to GPIIb/IIIa receptors. Further, ajoene does not impair Ristocetin-induced platelet agglutination, mediated by GPIb. Our results suggest that ajoene may be useful for the acute prevention of thrombus formation induced by vascular damage.
Apitz-Castro
R
R
Lab. Trombosis Experimental, IVIC, Caracas, Venezuela.
Badimon
J J
JJ
Badimon
L
L
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005737:Garlic; D007205:Indium Radioisotopes; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011485:Protein Binding; D012212:Rheology; D013314:Stress, Mechanical; D013454:Sulfoxides; D013552:Swine; D013927:Thrombosis / Q000517:prevention & control*; D014841:von Willebrand Factor / Q000302:isolation & purification / Q000378:metabolism
D004220:Disulfides; D007205:Indium Radioisotopes; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D013454:Sulfoxides; D014841:von Willebrand Factor; D000244:Adenosine Diphosphate; C048980:ajoene