Zaragozá Cristina, Monserrat Jorge, Mantecón Carolina, Villaescusa Lucinda, Zaragozá Francisco, Álvarez-Mon Melchor
Biomedical Sciences Department, Pharmacology Unit, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
Laboratory of Immune System Diseases and Oncology, Department of Medicine and Medical Specialties, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain.
Vascul Pharmacol. 2016 Dec;87:139-149. doi: 10.1016/j.vph.2016.09.002. Epub 2016 Sep 9.
Polyphenols are used as phlebotonic drugs, but their mechanism of action remains unknown. Since platelet activity and platelet-endothelial cell interactions are involved in the pathogenesis of cardiovascular disease, this work examines whether different flavonoid and coumarin drugs are able to inhibit platelet aggregation. This specific case of coumarins, the antiplatelet effect is not linked with a possible interaction over blood coagulation since this effect only dicoumarols have it. The antiplatelet capacity of polyphenols was assayed using peripheral blood platelets from healthy controls. The distribution of the different platelets subsets was quantified by flow cytometry, using the calcium ionophore as a pro-aggregant. The number of GPIIb/IIIa receptors occupied by the drugs was assayed by flow cytometry using two CD61 surface fluorescein antibodies. All the polyphenols tested inhibited platelet aggregation. A percentage antiplatelet activity of 88.91±7.98% was recorded for naringin, 48.43±8.84% for naringenin, 53.83±7.87% for esculetin, 54.65±6.91% for fraxetin, and 25.75±4.12% for coumarin. Naringin showed significantly greater percentage occupation of GPIIb/IIIa receptors than did naringenin (14.82±0.81% vs. 3.90±0.55%), and esculetin returned significantly higher values than fraxetin and coumarin (12.47±0.97 vs. 7.53±0.49 and 7.90±0.69 respectively). All drugs show important antiplatelet activity. Naringin was the best antiplatelet compound, showing the greatest antiplatelet activity and the highest percentage binding of GPIIb/IIIa receptors. However, any of the compounds used could be used in the prevention of cardiovascular disease.
多酚类物质被用作静脉活性药物，但其作用机制尚不清楚。由于血小板活性和血小板-内皮细胞相互作用参与了心血管疾病的发病机制，因此本研究探讨了不同的黄酮类和香豆素类药物是否能够抑制血小板聚集。在香豆素类药物的这种特定情况下，抗血小板作用与对血液凝固的可能相互作用无关，因为只有双香豆素才有这种作用。使用健康对照者的外周血血小板测定多酚类物质的抗血小板能力。使用钙离子载体作为促聚集剂，通过流式细胞术对不同血小板亚群的分布进行定量。使用两种CD61表面荧光素抗体，通过流式细胞术测定药物占据的GPIIb/IIIa受体数量。所有测试的多酚类物质均能抑制血小板聚集。柚皮苷的抗血小板活性百分比为88.91±7.98%，柚皮素为48.43±8.84%，七叶亭为53.83±7.87%，秦皮素为54.65±6.91%，香豆素为25.75±4.12%。柚皮苷占据GPIIb/IIIa受体的百分比显著高于柚皮素（14.82±0.81%对3.90±0.55%），七叶亭的值显著高于秦皮素和香豆素（分别为12.47±0.97对7.53±0.49和7.90±0.69）。所有药物均显示出重要的抗血小板活性。柚皮苷是最佳的抗血小板化合物，具有最大的抗血小板活性和最高的GPIIb/IIIa受体结合百分比。然而，所使用的任何一种化合物都可用于预防心血管疾病。
