Antiaggregant effects of Arbutus unedo extracts in human platelets

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• 作者：Mohammed El Haouari ; José ; J. Ló ; pez ; Hassane Mekhfi ; Juan A. Rosado ; Giné ; s M. Salido
• 关键词：Thrombin ; Platelets ; Aggregation ; Calcium mobilization ; Tyrosine phosphorylation ; Antioxidants ; Arbutus unedo
• 刊名：Journal of Ethnopharmacology
• 出版年：2007
• 期刊代码：26_03788741
• 类别：pha
• 出版时间：5 September 2007
• 卷：113
• 期：2
• 页码：325-331
• 文件大小：618 K

摘要

Platelet hyperaggregability plays a pivotal role in the pathogenesis of cardiovascular diseases. Thrombin evokes aggregation through Ca²⁺ mobilization, tyrosine phosphorylation and generation of reactive oxygen species (ROS). We have investigated the antiaggregant properties of Arbutus unedo extracts in human platelets. Changes in cytosolic Ca²⁺ concentration and intracellular oxidants production were registered by espectrofluorimetry using fura-2 and dichlorodihydrofluorescein, respectively, platelet aggregation was assessed by aggregometry and protein tyrosine phosphorylation was detected by Western blotting. Platelet treatment with increasing concentrations (0.015–1.5 mg/mL) of crude aqueous, ethyl acetate or diethyl ether extracts reduced platelet aggregation evoked by thrombin (0.5 U/mL) and show a potent ROS scavenger activity, preventing thrombin-evoked endogenous generation of ROS. Treatment with Arbutus unedo extracts did not alter thrombin-evoked Ca²⁺ release from the intracellular stores but reduced store-operated Ca²⁺ entry induced by thrombin or by selective depletion of the two Ca²⁺ stores in platelets, the dense tubular system and the acidic stores. In addition, platelet treatment with extracts reduced both basal and thrombin-stimulated protein tyrosine phosphorylation. We conclude that Arbutus unedo extracts show antiaggregant actions due to attenuation of Ca²⁺ mobilization, ROS production and protein tyrosine phosphorylation and might be used for the treatment and/or prevention of cardiovascular diseases.