Our study demonstrated that gallic acid inhibited platelet aggregation, P-selectin expression and PLA stimulated by ADP or U46619 possibly through decreasing
intracellular Ca2+ mobilization. And the inhibition of phosphorylation of PKCα/p38 MAPK and Akt/GSK3β in stimulated platelets after gallic acid pre-treatment is the
suggestive mechanisms of action. This is the first report about the properties of gallic acid on platelet inhibition and its mechanisms. These findings of gallic acid suggest a possible therapeutic application of this agent in the diseases associated with atherosclerosis.
REFERENCE
1. Ruggeri, Z.M. Platelets in atherothrombosis. Nature medicine 8, 1227-1234 (2002).
2. Jennings, L.K. Role of platelets in atherothrombosis. The American journal of cardiology 103, 4A-10A (2009).
3. Davi, G. & Patrono, C. Platelet activation and atherothrombosis. N Engl J Med 357, 2482-2494 (2007).
4. Gawaz, M., Langer, H. & May, A.E. Platelets in inflammation and atherogenesis.
Journal of Clinical Investigation 115, 3378 (2005).
5. Ridker, P., Buring, J. & Rifai, N. Soluble P-selectin and the risk of future cardiovascular events. Circulation 103, 491 (2001).
6. Renaud, S.C., Gueguen, R., Schenker, J. & d'Houtaud, A. Alcohol and mortality in middle-aged men from eastern France. Epidemiology 9, 184-188 (1998).
7. Hayek, T., et al. Reduced Progression of Atherosclerosis in Apolipoprotein E Deficient Mice Following Consumption of Red Wine, or Its Polyphenols Quercetin or Catechin, Is Associated With Reduced Susceptibility of LDL to Oxidation and
Aggregation. Arterioscler Thromb Vasc Biol 17, 2744-2752 (1997).
8. Rimm EB, W.P., Fosher K, Criqui M, Stampfer MJ. Alcohol lowers risk of heart disease through effect on lipids and haemostatic factors. BMJ 319(1999).
9. Frankel En Fau - Kanner, J., Kanner J Fau - German, J.B., German Jb Fau - Parks, E., Parks E Fau - Kinsella, J.E. & Kinsella, J.E. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet, 1152–1159 (1994).
10. Wang, Z., et al. Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. International journal of molecular medicine 9, 77-80 (2002).
11. Feng, A.N., Chen, Y.L., Chen, Y.T., Ding, Y.Z. & Lin, S.J. Red wine inhibits
monocyte chemotactic protein-1 expression and modestly reduces neointimal hyperplasia after balloon injury in cholesterol-fed rabbits. Circulation 100, 2254 (1999).
12. Cabrera, C., Artacho, R. & Giménez, R. Beneficial Effects of Green Tea, - A Review. Journal of the American College of Nutrition 25, 79-99 (2006).
13. Rietveld, A. & Wiseman, S. Antioxidant Effects of Tea: Evidence from Human Clinical Trials. The Journal of nutrition 133, 3285S-3292S (2003).
14. Priscilla, D.H. & Prince, P. Cardioprotective effect of gallic acid on cardiac troponin-T, cardiac marker enzymes, lipid peroxidation products and antioxidants in experimentally induced myocardial infarction in Wistar rats. Chemico-biological interactions 179, 118-124 (2009).
15. Kroes, B., Van den Berg, A., Van Ufford, H.C.Q., Van Dijk, H. & Labadie, R. Anti-inflammatory activity of gallic acid. Planta medica 58, 499-499 (1992).
16. Hsu, C.L. & Yen, G.C. Effect of gallic acid on high fat diet-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats. Br J Nutr 98, 727-735 (2007).
17. Clarke, R. & Armitage, J. Antioxidant vitamins and risk of cardiovascular disease.
Review of large-scale randomised trials. Cardiovascular drugs and therapy 16, 411-415 (2002).
18. Rink, T. & Sage, S. Calcium signaling in human platelets. Annual review of physiology 52, 431-449 (1990).
19. Saklatvala, J., et al. Role for p38 Mitogen-activated Protein Kinase in Platelet Aggregation Caused by Collagen or a Thromboxane Analogue. Journal of Biological Chemistry 271, 6586-6589 (1996).
20. Coulon, L., Calzada, C., Moulin, P., Vericel, E. & Lagarde, M. Activation of p38 mitogen-activated protein kinase/cytosolic phospholipase A2 cascade in hydroperoxide-stressed platelets. Free Radical Biology and Medicine 35, 616-625 (2003).
21. Kroner, C., Eybrechts, K. & Akkerman, J. Dual regulation of platelet protein kinase B. J Biol Chem 275, 27790-27798 (2000).
22. Barry, F.A., Graham, G.J., Fry, M.J. & Gibbins, J.M. Regulation of glycogen synthase kinase 3 in human platelets: a possible role in platelet function? . FEBS letters 553, 173-178 (2003).
23. Aruoma, O.I., Murcia, A., Butler, J. & Halliwell, B. Evaluation of the antioxidant and prooxidant actions of gallic acid and its derivatives. Journal of agricultural and food chemistry 41, 1880-1885 (1993).
24. Krotz, F., Sohn, H.Y. & Pohl, U. Reactive oxygen species: players in the platelet game. Arteriosclerosis, thrombosis, and vascular biology 24, 1988 (2004).
25. Gawaz, M., Langer, H. & May, A.E. Platelets in inflammation and atherogenesis.
The Journal of Clinical Investigation 115, 3378-3384 (2005).
26. Chapado, L., et al. Synthesis and evaluation of the platelet antiaggregant properties of phenolic antioxidants structurally related to rosmarinic acid. Bioorganic Chemistry 38, 108-114 (2010).
27. Bertelli, A., et al. Antiplatelet activity of cis-resveratrol. Drugs under experimental and clinical research 22, 61 (1996).
28. de Lange, D.W. & van de Wiel, A. Drink to prevent: review on the cardioprotective mechanisms of alcohol and red wine polyphenols. Vol. 4 173-186 (2004).
29. Pace-Asciak, C.R., Rounova, O., Hahn, S.E., Diamandis, E.P. & Goldberg, D.M.
Wines and grape juices as modulators of platelet aggregation in healthy human subjects.
Clinica chimica acta 246, 163-182 (1996).
30. Sarma, J., et al. Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 105, 2166-2171 (2002).
31. Rinder, C.S., et al. Cardiopulmonary bypass induces leukocyte-platelet adhesion.
Blood 79, 1201 (1992).
32. Gawaz, M.P., Mujais, S.K., Schmidt, B. & Gurland, H.J. Platelet-leukocyte aggregation during hemodialysis. Kidney international 46, 489-495 (1994).
33. Ogura, H., et al. Activated platelets enhance microparticle formation and platelet-leukocyte interaction in severe trauma and sepsis. The Journal of trauma 50, 801 (2001).
34. May, A.E., et al. Platelet-leukocyte interactions in inflammation and
atherothrombosis. Vol. 33 123-127 (New York: Stratton Intercontinental Medical Book Corporation, c1974-, 2007).
35. Yokoyama, S., et al. Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates. Journal of the American College of Cardiology 45, 1280-1286 (2005).
36. McGregor, L., Martin, J. & McGregor, J.L. Platelet-leukocyte aggregates and
derived microparticles in inflammation, vascular remodelling and thrombosis. Front Biosci 11, 830-837 (2006).
37. Appeldoorn, C., et al. Gallic acid antagonizes P-selectin-mediated platelet-leukocyte interactions: implications for the French paradox. Circulation 111, 106 (2005).
38. Redondo, P.C., Salido, G.M., Pariente, J.A. & Rosado, J.A. Dual effect of hydrogen peroxide on store-mediated calcium entry in human platelets. Biochemical pharmacology 67, 1065-1076 (2004).
39. Kim, S.H., et al. Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells. Toxicological Sciences 91, 123 (2006).
40. Nishizuka, Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258, 607-614 (1992).
41. Mangin, P., et al. Signaling role for phospholipase Ca2+ in platelet glycoprotein Ib calcium flux and cytoskeletal reorganization. Journal of Biological Chemistry 278, 32880 (2003).
42. Bugaud, F., Nadal-Wollbold, F., Levy-Toledano, S., Rosa, J.-P. & Bryckaert, M.
Regulation of c-Jun-NH2 Terminal Kinase and Extracellular-Signal Regulated Kinase in Human Platelets. Blood 94, 3800-3805 (1999).
43. Kim, S., Jin, J. & Kunapuli, S.P. Relative contribution of G-protein-coupled
pathways to protease-activated receptor-mediated Akt phosphorylation in platelets. Blood 107, 947 (2006).
44. Andre, P., et al. P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries. Journal of Clinical Investigation 112, 398-406
(2003).
45. Chen, J., et al. Impaired platelet responses to thrombin and collagen in AKT-1 deficient mice. Blood 104, 1703 (2004).
46. Li, D., August, S. & Woulfe, D.S. GSK3β is a negative regulator of platelet function and thrombosis. Blood 111, 3522 (2008).
47. Cross, D.A.E., Alessi, D.R., Cohen, P., Andjelkovich, M. & Hemmings, B.A.
Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378, 785-789 (1995).
48. Aviram, M., Hayek, T. & Fuhrman, B. Red wine consumption inhibits LDL
oxidation and aggregation in humans and in atherosclerotic mice. BioFactors 6, 415-419 (1997).