title: The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide.
abstract: BACKGROUND
  Epidemiologic studies have shown an inverse relation between moderate consumption of red wine and cardiovascular disease. Studies have shown that red wine and its component flavonoids inhibit in vivo platelet activation, but the underlying mechanism has not yet been identified.
  
  
  OBJECTIVE
  Because we showed previously that collagen-induced platelet aggregation is associated with a burst of hydrogen peroxide, which in turn contributes to stimulating the phospholipase C pathway, the aim of this study was to investigate whether flavonoids synergize in inhibiting platelet function and interfere with platelet function by virtue of their antioxidant effect.
  
  
  METHODS
  We tested the effect of 2 flavonoids, quercetin and catechin, on collagen-induced platelet aggregation and hydrogen peroxide and on platelet adhesion to collagen.
  
  
  RESULTS
  Catechin (50-100 micromol/L) and quercetin (10-20 micromol/L) inhibited collagen-induced platelet aggregation and platelet adhesion to collagen. The combination of 25 micromol catechin/L and 5 micromol quercetin/L, neither of which had any effect on platelet function when used alone, significantly inhibited collagen-induced platelet aggregation and platelet adhesion to collagen. Such a combination strongly inhibited collagen-induced hydrogen peroxide production, calcium mobilization, and 1,3,4-inositol triphosphate formation.
  
  
  CONCLUSIONS
  These data indicate that flavonoids inhibit platelet function by blunting hydrogen peroxide production and, in turn, phospholipase C activation and suggest that the synergism among flavonoids could contribute to an understanding of the relation between the moderate consumption of red wine and the decreased risk of cardiovascular disease.
authors.affiliation: Department of Experimental Medicine and Pathology, Institute of 1st Clinical Medicine, University La Sapienza, National Institute for Nutrition, Rome, Italy. gazzaniga@uniroma1.it
authors.forename: P
authors.initials: P
authors.lastname: Pignatelli
authors.forename: F M
authors.initials: FM
authors.lastname: Pulcinelli
authors.forename: A
authors.initials: A
authors.lastname: Celestini
authors.forename: L
authors.initials: L
authors.lastname: Lenti
authors.forename: A
authors.initials: A
authors.lastname: Ghiselli
authors.forename: P P
authors.initials: PP
authors.lastname: Gazzaniga
authors.forename: F
authors.initials: F
authors.lastname: Violi
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D002118:Calcium / Q000097:blood; D002392:Catechin / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood*; D007295:Inositol Phosphates / Q000097:blood; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000097:blood
chemical_list: D007295:Inositol Phosphates; D002392:Catechin; D003094:Collagen; D011794:Quercetin; D006861:Hydrogen Peroxide; D010738:Type C Phospholipases; D002118:Calcium