title: Chlorogenic acid inhibits human platelet activation and thrombus formation.
abstract: BACKGROUND
  Chlorogenic acid is a potent phenolic antioxidant. However, its effect on platelet aggregation, a critical factor in arterial thrombosis, remains unclear. Consequently, chlorogenic acid-action mechanisms in preventing platelet activation and thrombus formation were examined.
  
  
  RESULTS
  Chlorogenic acid in a dose-dependent manner (0.1 to 1 mmol/L) inhibited platelet secretion and aggregation induced by ADP, collagen, arachidonic acid and TRAP-6, and diminished platelet firm adhesion/aggregation and platelet-leukocyte interactions under flow conditions. At these concentrations chlorogenic acid significantly decreased platelet inflammatory mediators (sP-selectin, sCD40L, CCL5 and IL-1β) and increased intraplatelet cAMP levels/PKA activation. Interestingly, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent A2A receptor antagonist) attenuated the antiplatelet effect of chlorogenic acid. Chlorogenic acid is compatible to the active site of the adenosine A2A receptor as revealed through molecular modeling. In addition, chlorogenic acid had a significantly lower effect on mouse bleeding time when compared to the same dose of aspirin.
  
  
  CONCLUSIONS
  Antiplatelet and antithrombotic effects of chlorogenic acid are associated with the A2A receptor/adenylate cyclase/cAMP/PKA signaling pathway.
authors.affiliation: Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile; Centro de Estudios en Alimentos Procesados (CEAP), CONICYT-Regional, Gore Maule, Talca, Chile.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fuentes
authors.affiliation: Center for Bioinformatics and Molecular Simulations, Faculty of Engineering in Bioinformatics, Universidad de Talca, Talca, Chile.
authors.forename: Julio
authors.initials: J
authors.lastname: Caballero
authors.affiliation: Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile; Centro de Estudios en Alimentos Procesados (CEAP), CONICYT-Regional, Gore Maule, Talca, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Alarcón
authors.affiliation: Biomedical Research Laboratories, Medicine Faculty, Catholic University of Maule, Talca, Chile.
authors.forename: Armando
authors.initials: A
authors.lastname: Rojas
authors.affiliation: Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca, Chile; Centro de Estudios en Alimentos Procesados (CEAP), CONICYT-Regional, Gore Maule, Talca, Chile.
authors.forename: Iván
authors.initials: I
authors.lastname: Palomo
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001760:Bleeding Time; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002726:Chlorogenic Acid / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D018056:Hemorheology / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008958:Models, Molecular; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D018836:Inflammation Mediators; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C017759:9-(tetrahydro-2-furyl)-adenine; D002726:Chlorogenic Acid; D000255:Adenosine Triphosphate; D003094:Collagen; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000225:Adenine