Curcumin by activation of adenosine A2A receptor stimulates protein kinase a and potentiates inhibitory effect of cangrelor on platelets

Biochem Biophys Res Commun. 2022 Jan 1:586:20-26. doi: 10.1016/j.bbrc.2021.11.006. Epub 2021 Nov 4.

Abstract

Curcumin is a natural polyphenol derived from the turmeric plant (Curcuma longa) which exhibits numerous beneficial effects on different cell types. Inhibition of platelet activation by curcumin is well known, however molecular mechanisms of its action on platelets are not fully defined. In this study, we used laser diffraction method for analysis of platelet aggregation and Western blot for analysis of intracellular signaling mechanisms of curcumin effects on platelets. We identified two new molecular mechanisms involved in the inhibitory effects of curcumin on platelet activation. Firstly, curcumin by activation of adenosine A2A receptor stimulated protein kinase A activation and phosphorylation of Vasodilator-stimulated phosphoprotein. Secondly, we demonstrated that curcumin even at low doses, which did not inhibit platelet aggregation, potentiated inhibitory effect of ADP receptor P2Y12 antagonist cangrelor which partly could be explained by activation of adenosine A2A receptor.

Keywords: A(2A) receptor; Adenosine; Curcumin; Platelets; Protein kinase A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / pharmacology
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Curcuma / chemistry
  • Curcumin / isolation & purification
  • Curcumin / pharmacology*
  • Cyclic AMP-Dependent Protein Kinases / genetics*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Drug Synergism
  • Gene Expression Regulation
  • Humans
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Plant Extracts / chemistry
  • Platelet Activation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology
  • Primary Cell Culture
  • Purinergic P2Y Receptor Antagonists / pharmacology
  • Receptor, Adenosine A2A / genetics*
  • Receptor, Adenosine A2A / metabolism
  • Receptors, Purinergic P2Y12 / genetics
  • Receptors, Purinergic P2Y12 / metabolism
  • Signal Transduction

Substances

  • Cell Adhesion Molecules
  • Microfilament Proteins
  • P2RY12 protein, human
  • Phosphoproteins
  • Plant Extracts
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P2Y12
  • vasodilator-stimulated phosphoprotein
  • Adenosine Monophosphate
  • Adenosine Diphosphate
  • cangrelor
  • turmeric extract
  • Cyclic AMP-Dependent Protein Kinases
  • Curcumin