Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population

Food Funct. 2016 Aug 10;7(8):3609-16. doi: 10.1039/c6fo00927a. Epub 2016 Aug 2.


This ex vivo study was performed to evaluate the anti-platelet and anti-thrombogenic potential of shikimic acid (SA), a plant phenolic metabolite. Fasting blood samples were collected from 22 sedentary participants to analyse the effect of varying concentrations of SA (0.1 mM, 0.2 mM, 0.5 mM, 1 mM and 2 mM) on platelet surface-marker expression, platelet aggregation and biomarkers of thrombogenesis. Monocyte-platelet aggregates (CD14/CD42b) and platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31), effective indicators of thrombus formation were evaluated. Procaspase-activating compound 1 (PAC-1) and P-selectin or CD62P were used to assess platelet activation-related thrombogenesis. Adenosine diphosphate (ADP) was used to stimulate the P2Y1/P2Y12 pathway of platelet activation to mimic the in vivo thrombogenic pathway. Platelet aggregation studies utilised both ADP and collagen as exogenous platelet agonists to target both P2Y1/P2Y12 and GPVI pathways of thrombus formation. It was observed with flow cytometry that SA produced a significant antiplatelet effect on PAC-1 (p = 0.03 at 2 mM) and CD62P (p = 0.017, p = 0.036 at 1 mM and 2 mM respectively) expression in addition to lowering monocyte-platelet aggregate formation (p = 0.013, p < 0.01 and p < 0.01 at 0.5 mM, 1 mM and 2 mM respectively). SA at 1 mM concentration reduced PECAM-1 expression (p = 0.035), signifying a reduction to endothelial leucocyte migration during thrombus growth. SA did not demonstrate a platelet aggregation inhibitory effect by targeting the GPVI collagen pathway but reduced ADP induced platelet aggregation at 2 mM concentration (p < 0.01 at 2 mM). The results suggest that SA, an active metabolite of polyphenol-rich food intake, could play an important role in reducing platelet activation, aggregation related thrombus formation and biomarkers of thrombogenesis in sedentary individuals.

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adult
  • Antithrombins / pharmacology*
  • Biomarkers / blood
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Body Mass Index
  • Female
  • Humans
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / metabolism
  • P-Selectin / genetics
  • P-Selectin / metabolism
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Platelet Membrane Glycoproteins / genetics
  • Platelet Membrane Glycoproteins / metabolism
  • Receptors, Purinergic P2Y12 / genetics
  • Receptors, Purinergic P2Y12 / metabolism
  • Sedentary Behavior*
  • Shikimic Acid / blood
  • Shikimic Acid / pharmacology*
  • Young Adult


  • Antithrombins
  • Biomarkers
  • P-Selectin
  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Platelet Membrane Glycoproteins
  • Receptors, Purinergic P2Y12
  • SELP protein, human
  • platelet membrane glycoprotein VI
  • Shikimic Acid
  • Adenosine Diphosphate