Chlorogenic acid inhibits human platelet activation and thrombus formation

PLoS One. 2014 Mar 5;9(3):e90699. doi: 10.1371/journal.pone.0090699. eCollection 2014.

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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adenosine Triphosphate / metabolism
  • Animals
  • Binding Sites
  • Bleeding Time
  • Cell Communication / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Chlorogenic Acid / pharmacology*
  • Collagen / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Enzyme Activation / drug effects
  • Hemorheology / drug effects
  • Humans
  • Inflammation Mediators / metabolism
  • Leukocytes / cytology
  • Leukocytes / drug effects
  • Mice
  • Models, Molecular
  • P-Selectin / metabolism
  • Platelet Activation / drug effects*
  • Platelet Adhesiveness / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Receptor, Adenosine A2A / metabolism
  • Thrombosis / metabolism
  • Thrombosis / pathology
  • Thrombosis / prevention & control*
  • Triazines / pharmacology
  • Triazoles / pharmacology

Substances

  • Inflammation Mediators
  • P-Selectin
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptor, Adenosine A2A
  • Triazines
  • Triazoles
  • ZM 241385
  • 9-(tetrahydro-2-furyl)-adenine
  • Chlorogenic Acid
  • Adenosine Triphosphate
  • Collagen
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Adenine

Grants and funding

This work was funded by the CONICYT REGIONAL/GORE MAULE/CEAP/R09I2001, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI- ES), and supported by grant no. 1130216 (I.P., M.G., R.M., M.A., J.C.) from Fondecyt, Chile. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.