Curcumin inhibits GPVI-mediated platelet activation by interfering with the kinase activity of Syk and the subsequent activation of PLCgamma2.
Turmeric (Curcuma longa), a herbal remedy and culinary spice, has been used in traditional Indian culture for millennia. An active ingredient found in turmeric is curcumin (diferuloylmethane). In the current study, we investigated the antiplatelet properties of this naturally occurring compound. Curcumin inhibited human platelet aggregation and dense granule secretion induced by GPVI agonist convulxin in a concentration-dependent manner. At 50 microM, it effectively inhibited the maximal extent of aggregation and dense granule secretion to as much as 75%. It also dramatically inhibited the activation-dependent tyrosine phosphorylation of Y753 and Y759 on PLCgamma2, but did not affect the phosphorylation of Y145 residue on the cytosolic adaptor protein SLP-76. Interestingly, curcumin had no significant effect on the phosphorylation of Y525/Y526 present on the activation loop of Syk (spleen tyrosine kinase), but had a significant inhibitory effect on in vitro Syk kinase activity. Moreover, the inhibitory action of curcumin is not due to an inhibition of thromboxane generation because all our studies were performed using aspirin-treated platelets. We conclude that curcumin inhibits platelet activation induced by GPVI agonists through interfering with the kinase activity of Syk and the subsequent activation of PLCgamma2.
Mayanglambam
Azad
A
Department of Physiology, Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Dangelmaier
Carol A
CA
Thomas
Dafydd
D
Damodar Reddy
C
C
Daniel
James L
JL
Kunapuli
Satya P
SP
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D000072377:Syk Kinase
D003435:Crotalid Venoms; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; C028890:convulxin; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D051966:Phospholipase C gamma; D003474:Curcumin