Antiaggregant effects of Arbutus unedo extracts in human platelets.
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 (0.015-1.5mg/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.
El Haouari
Mohammed
M
Laboratoire de Physiologie et Pharmacologie Cellulaire, Département de Biologie, Université Mohamed 1er, Faculté des Sciences, Bd. Mohamed VI, BP 717, Oujda 60000, Morocco.
López
José J
JJ
Mekhfi
Hassane
H
Rosado
Juan A
JA
Salido
Ginés M
GM
D000975:Antioxidants / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D029791:Ericaceae / Q000737:chemistry*; D005452:Fluoresceins / Q000737:chemistry / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013696:Temperature; D019284:Thapsigargin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors
D000975:Antioxidants; D004791:Enzyme Inhibitors; D005452:Fluoresceins; D006873:Hydroquinones; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; C029569:diacetyldichlorofluorescein; D019000:Phosphotyrosine; D019284:Thapsigargin; C018855:2-tert-butylhydroquinone; D013917:Thrombin; D002118:Calcium