Antiaggregant effects of Arbutus unedo extracts in human platelets

• Published in: Journal of ethnopharmacology 2007-09, Vol.113 (2), p.325-331
• Main Authors: El Haouari, Mohammed, López, José J., Mekhfi, Hassane, Rosado, Juan A., Salido, Ginés M.
• Format: Article
• Language: English
• Subjects: Aggregation; anticoagulant activity; anticoagulants; Antioxidants; Antioxidants - pharmacology; Arbutus unedo; bioassays; Biological and medical sciences; blood platelets; Blood Platelets - cytology; Blood Platelets - drug effects; Blood Platelets - metabolism; Blotting, Western; Calcium - metabolism; Calcium mobilization; Calcium Signaling - drug effects; cardiovascular diseases; chemical constituents of plants; Enzyme Inhibitors - pharmacology; Ericaceae - chemistry; Fluoresceins - chemistry; Fluoresceins - metabolism; Fluorescence; General pharmacology; human cell lines; Humans; Hydroquinones - pharmacology; Medical sciences; medicinal plants; medicinal properties; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phosphorylation - drug effects; Phosphotyrosine - metabolism; plant extracts; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Leaves - chemistry; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - isolation & purification; Platelet Aggregation Inhibitors - pharmacology; Platelets; Reactive Oxygen Species - metabolism; Temperature; Thapsigargin - pharmacology; Thrombin; Thrombin - pharmacology; Time Factors; Tyrosine phosphorylation
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2007.06.016

Platelet hyperaggregability plays a pivotal role in the pathogenesis of cardiovascular diseases. Thrombin evokes aggregation through Ca 2+ 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 Ca 2+ 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 Ca 2+ release from the intracellular stores but reduced store-operated Ca 2+ entry induced by thrombin or by selective depletion of the two Ca 2+ 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 Ca 2+ mobilization, ROS production and protein tyrosine phosphorylation and might be used for the treatment and/or prevention of cardiovascular diseases.