title: Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population.
abstract: 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.
authors.affiliation: School of Medical and Applied Sciences, Central Queensland University, North Rockhampton, Queensland 4702, Australia. a.santhakumar@cqu.edu.au sabishekbommannan@gmail.com daniel.veach@cqumail.com.au holly.hosking@cqumail.com.au k.r.thompson@cqu.edu.au.
authors.forename: Daniel
authors.initials: D
authors.lastname: Veach
authors.forename: Holly
authors.initials: H
authors.lastname: Hosking
authors.forename: Kiara
authors.initials: K
authors.lastname: Thompson
authors.forename: Abishek Bommannan
authors.initials: AB
authors.lastname: Santhakumar
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000328:Adult; D000991:Antithrombins / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics / Q000378:metabolism; D057185:Sedentary Behavior; D012765:Shikimic Acid / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000991:Antithrombins; D015415:Biomarkers; D019007:P-Selectin; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010980:Platelet Membrane Glycoproteins; D058925:Receptors, Purinergic P2Y12; C546937:SELP protein, human; C098341:platelet membrane glycoprotein VI; D012765:Shikimic Acid; D000244:Adenosine Diphosphate