School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, Eric Williams Medical Sciences Complex, Champ Fleurs, Trinidad and Tobago.
Life Sci. 2012 Dec 17;91(25-26):1275-80. doi: 10.1016/j.lfs.2012.09.019. Epub 2012 Oct 13.
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.
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.
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.
These findings suggest that AGE inhibits platelet aggregation via inhibition of the GPIIb/IIIa receptor and an increase in cAMP.
血小板聚集增加在心血管疾病的病因学中起着重要作用。大蒜抑制血小板聚集；然而，涉及的机制尚未明确界定。本研究旨在探讨一种陈蒜提取物（AGE）抑制人血小板激活和聚集的机制。
用 ADP 刺激分离的人血小板，并使用 Rose Bengal 或（51）Cr 摄取评估其与纤维蛋白原的粘附。通过荧光激活细胞分选（FACS）分析以及测量细胞内 cAMP 来评估血小板的激活。
AGE 在 3.12%至 12.5%（v/v）的浓度范围内，与 Rose Bengal 测定中的对照值相比，抑制血小板与纤维蛋白原的结合约 40%（P<0.05）。在（51）Cr 实验中，AGE 分别在 1.56%和 6.25%（v/v）时显著抑制 ADP 激活的血小板与固定化纤维蛋白原的结合，抑制率分别为 61.5%。在 12.5%（v/v）的浓度下，抑制率为 70.4%，在 25%（v/v）时为 64.5%（P<0.05）。在荧光激活细胞分选（FACS）分析中，AGE 与 PBS 对照相比，显著降低了 PAC-1 与 GPIIb/IIIa 的结合量，约为 72%。结合这些观察结果，AGE 还增加了血小板 cAMP（P<0.01）水平。
这些发现表明，AGE 通过抑制 GPIIb/IIIa 受体和增加 cAMP 来抑制血小板聚集。
