Antiaggregant effects of Arbutus unedo extracts in human platelets

J Ethnopharmacol. 2007 Sep 5;113(2):325-31. doi: 10.1016/j.jep.2007.06.016. Epub 2007 Jul 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Blotting, Western
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Enzyme Inhibitors / pharmacology
  • Ericaceae / chemistry*
  • Fluoresceins / chemistry
  • Fluoresceins / metabolism
  • Fluorescence
  • Humans
  • Hydroquinones / pharmacology
  • Phosphorylation / drug effects
  • Phosphotyrosine / metabolism
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / isolation & purification
  • Platelet Aggregation Inhibitors / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Temperature
  • Thapsigargin / pharmacology
  • Thrombin / pharmacology
  • Time Factors

Substances

  • Antioxidants
  • Enzyme Inhibitors
  • Fluoresceins
  • Hydroquinones
  • Plant Extracts
  • Platelet Aggregation Inhibitors
  • Reactive Oxygen Species
  • diacetyldichlorofluorescein
  • Phosphotyrosine
  • Thapsigargin
  • 2-tert-butylhydroquinone
  • Thrombin
  • Calcium