Flavonoids and platelet aggregation: A brief review

European Journal of Pharmacology

Volumn 807, Issue , 2017, Pages 91-101

  Faggio, Caterina ^a   Sureda, Antoni ^b,c   Morabito, Silvia ^a   Sanches Silva, Ana ^d,e   Mocan, Andrei ^f,g   Nabavi, Seyed Fazel ^h   Nabavi, Seyed Mohammad ^h  

^a UNIVERSITY OF MESSINA   (Italy)

^b UNIVERSITAT DE LES ILLES BALEARS   (Spain)

^c Instituto de Salud Carlos III   (Spain)

^d NATIONAL INSTITUTE OF HEALTH DR RICARDO JORGE   (Portugal)

^e UNIVERSITY OF PORTO   (Portugal)

^f IULIU HATIEGANU UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^g UNIVERSITY OF AGRICULTURAL SCIENCES AND VETERINARY MEDICINE   (Romania)

^h BAQIYATALLAH UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

Flavonoids; Phytochemical; Platelet aggregation; Polyphenols

Indexed keywords

ACETYLSALICYLIC ACID; ANTHOCYANIN; CAFFEIC ACID; EPICATECHIN; FLAVONE; FLAVONOID; FLAVONOL; GRAPE SEED EXTRACT; ISOFLAVONE; NITRIC OXIDE; POLYPHENOL; THROMBOXANE;

ABSORPTION; ANTIOXIDANT ACTIVITY; APPLE; ARACHIDONIC ACID METABOLISM; ATHEROSCLEROTIC PLAQUE; BEVERAGE; BIOAVAILABILITY; BIOTRANSFORMATION; CACAO; CARDIOVASCULAR DISEASE; CHOCOLATE; COFFEE; CYTOKINE RELEASE; DAIRY PRODUCT; DIET SUPPLEMENTATION; FRUIT; GRAPE; HERB; HUMAN; HYPERTENSION; LEGUME; LIPID METABOLISM; NONHUMAN; PRIORITY JOURNAL; REVIEW; SEX DIFFERENCE; SPICE; THROMBOCYTE ACTIVATION; THROMBOCYTE ADHESION; THROMBOCYTE AGGREGATION; THROMBOCYTE AGGREGATION INHIBITION; THROMBOSIS; VEGETABLE; WINE; CHEMISTRY; DRUG EFFECTS; METABOLISM;

BIOLOGICAL AVAILABILITY; FLAVONOIDS; HUMANS; PLATELET AGGREGATION;

EID: 85017423963     PISSN: 00142999     EISSN: 18790712     Source Type: Journal    
DOI: 10.1016/j.ejphar.2017.04.009     Document Type: Review

References (138)

1. Almeida, A.P., Côrtes, S.F., Ferreira, A.J., Lemos, V.N.S., Increase on the coronary flow induced by dioclein in isolated rat heart. Life Sci. 70 (2002), 1121–1128.
2. Alvarez, A.I., Real, R., Pérez, M., Mendoza, G., Prieto, J.G., Merino, G., Modulation of the activity of ABC transporters (P-glycoprotein, MRP2, BCRP) by flavonoids and drug response. J. Pharm. Sci. 99:2 (2010), 598–617.
3. Amaretti, A., Raimondi, S., Leonardi, A., Quartieri, A., Rossi, M., Hydrolysis of the rutinose-conjugates flavonoids rutin and hesperidin by the gut microbiota and bifidobacteria. Nutrients 7:4 (2015), 2788–2800.
4. Andrews, R.K., Berndt, M.C., Platelet adhesion: a game of catch and release. J. Clin. Investig. 118 (2008), 3009–3011.
5. Aszódi, A., Pfeifer, A., Ahmad, M., Glauner, M., Zhou, X.H., Ny, L., Andersson, K.E., Kehrel, B., Offermanns, S., Fässler, R., The vasodilator‐stimulated phosphoprotein (VASP) is involved in cGMP‐and cAMP‐mediated inhibition of agonist‐induced platelet aggregation, but is dispensable for smooth muscle function. EMBO J. 18 (1999), 37–48.
6. Benavente-Garcia, O., Castillo, J., Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. J. Agric. Food Chem. 56 (2008), 6185–6205.
7. Benavente-García, O., Castillo, J., Marin, F.R., Ortuño, A., Del Río, J.A., Uses and properties of citrus flavonoids. J. Agric. Food Chem. 45 (1997), 4505–4515.
8. Beretz, A., Stierle, A., Anton, R., Cazenave, J.P., Role of cyclic AMP in the inhibition of human platelet aggregation by quercetin, a flavonoid that potentiates the effect of prostacyclin. Biochem. Pharmacol. 31 (1982), 3597–3600.
9. Bhagwat, S., Haytowitz, D.B., Holden, J.M., USDA Database for the Isoflavone Content of Selected Foods Release 2.0. 2008, United States Department of Agriculture, Nutrient Data Laboratory.
10. Bhagwat, S., Haytowitz, D.B., Holden, J.M., USDA Database for the Flavonoid Content of Selected Foods, Release 3.1. 2011, US Department of Agriculture, Beltsville.
11. Bors, W., Heller, W., Michel, C., Saran, M., Flavonoids as antioxidant: determination of radical-scavenging efficiencies. Methods Enzymol. 186 (1990), 343–367.
12. Borst, O., Walker, B., Münzer, P., Russo, A., Schmid, E., Faggio, C., Bigalke, B., Laufer, S., Gawaz, M., Lang, F., Skepinone-L, a novel potent and highly selective inhibitor of p38 MAP kinase, effectively impairs platelet activation and thrombus formation. Cell. Physiol. Biochem. 31 (2013), 914–924.
13. Borst, O., Münzer, P., Schmid, E., Schmidt, E.M., Russo, A., Walker, B., Yang, W., Leibrock, C., Szteyn, K., Schmidt, S., 1, 25 (OH) 2 vitamin D3-dependent inhibition of platelet Ca2+ signaling and thrombus formation in klotho-deficient mice. FASEB J. 28 (2014), 2108–2119.
14. Brass, L.F., Joseph, S., A role for inositol triphosphate in intracellular Ca2+ mobilization and granule secretion in platelets. J. Biol. Chem. 260 (1985), 15172–15179.
15. Braune, A., Gütschow, M., Engst, W., Blaut, M., Degradation of quercetin and luteolin by Eubacterium ramulus. Appl. Environ. Microbiol. 67:12 (2001), 5558–5567.
16. Bunting, S., Moncada, S., Vane, J., The prostacyclin-thromboxane A2 balance: pathophysiological and therapeutic implications. Br. Med. Bull. 39 (1983), 271–276.
17. Calderwood, D.A., Integrin activation. J. Cell Sci. 117 (2004), 657–666.
18. Chen, Z., Zheng, S., Li, L., Jiang, H., Metabolism of flavonoids in human: a comprehensive review. Curr. Drug Metab. 15:1 (2014), 48–61.
19. Chen, Z.J., Dai, Y.Q., Kong, S.S., Song, F.F., Li, L.P., Ye, J.F., Wang, R.W., Zeng, S., Zhou, H., Jiang, H.D., Luteolin is a rare substrate of human catechol-O-methyltransferase favoring a para-methylation. Mol. Nutr. Food Res. 57:5 (2013), 877–885.
20. Cho, H.J., Cho, J.Y., Rhee, M.H., Lim, C.R., Park, H.J., Cordycepin (3 ‘‐deoxyadenosine) inhibits human platelet aggregation induced by U46619, a TXA2 analogue. J. Pharm. Pharmacol. 58 (2006), 1677–1682.
21. Choi, J.H., Park, S.E., Kim, S.J., Kim, S., Kaempferol inhibits thrombosis and platelet activation. Biochimie 115 (2015), 177–186.
22. Choi, J.H., Kim, K.J., Kim, S., Comparative effect of quercetin and quercetin-3-O-β-d-glucoside on fibrin polymers, blood clots, and in rodent models. J. Biochem. Mol. Toxicol. 30:11 (2016), 548–558.
23. Chuankhayan, P., Rimlumduan, T., Svasti, J., Cairns, J.R., Hydrolysis of soybean isoflavonoid glycosides by Dalbergia beta-glucosidases. J. Agric. Food Chem. 55:6 (2007), 2407–2412.
24. Ciferri, S., Emiliani, C., Guglielmini, G., Orlacchio, A., Nenci, G.G., Gresele, P., Platelets release their lysosomal content in vivo in humans upon activation. Thromb. Haemost. 83 (2000), 157–164.
25. Cook, N., Samman, S., Flavonoids—chemistry, metabolism, cardioprotective effects, and dietary sources. J. Nutr. Biochem. 7 (1996), 66–76.
26. Corona, G., Deiana, M., Incani, A., Vauzour, D., Dessì, M.A., Spencer, J.P., Hydroxytyrosol inhibits the proliferation of human colon adenocarcinoma cells through inhibition of ERK1/2 and cyclin D1. Mol. Nutr. Food Res. 53 (2009), 897–903.
27. Côrtes, S.F., Rezende, B.A., Corriu, C., Medeiros, I.A., Teixeira, M.M., Lopes, M.J., Lemos, V.S., Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries. Br. J. Pharmacol. 133 (2001), 849–858.
28. Corvazier, E., Maclouf, J., Interference of some flavonoids and non-steroidal anti-inflammatory drugs with oxidative metabolism of arachidonic acid by human platelets and neutrophils. Biochim. Biophys. Acta (BBA)-Lipids Lipid Metab. 835 (1985), 315–321.
29. Costa, D.C., Costa, H., Albuquerque, T.G., Ramos, F., Castilho, M.C., Sanches-Silva, A., Advances in phenolic compounds analysis of aromatic plants and their potential applications. Trends Food Sci. Technol. 45 (2015), 336–354.
30. Day, A.J., Cañada, F.J., Díaz, J.C., Kroon, P.A., Mclauchlan, R., Faulds, C.B., Plumb, G.W., Morgan, M.R., Williamson, G., Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett. 468:2–3 (2000), 166–170.
31. Ebbeling, L., Robertson, C., McNicol, A., Gerrard, J.M., Rapid ultrastructural changes in the dense tubular system following platelet activation. Blood 80 (1992), 718–723.
32. El Haouari, M., Rosado, J.A., Platelet signalling abnormalities in patients with type 2 diabetes mellitus: a review. Blood Cells Mol. Dis. 41 (2008), 119–123.
33. El Haouari, M., López, J.J., Mekhfi, H., Rosado, J.A., Salido, G.M., Antiaggregant effects of Arbutus unedo extracts in human platelets. J. Ethnopharmacol. 113 (2007), 325–331.
34. Elwood, P.C., Beswick, A.D., Sharp, D.S., Yarnell, J., Rogers, S., Renaud, S., Whole blood impedance platelet aggregometry and ischemic heart disease. The Caerphilly Collaborative Heart Disease Study. Arteriosclerosis 10 (1990), 1032–1036.
35. Erlund, I., Review of the flavonoids quercetin, hesperetin, and naringenin. dietary sources, bioactivities, bioavailability, and epidemiology. Nutr. Res. 24 (2004), 851–874.
36. Erlund, I., Marniemi, J., Hakala, P., Alfthan, G., Meririnne, E., Aro, A., Consumption of black currants, lingonberries and bilberries increases serum quercetin concentrations. Eur. J. Clin. Nutr. 57 (2003), 37–42.
37. Fabiani, R., De Bartolomeo, A., Rosignoli, P., Servili, M., Montedoro, G., Morozzi, G., Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. Eur. J. Cancer Prev. 11 (2002), 351–358.
38. Fauci, A.S., Harrison's principles of internal medicine. 2008, Medical Publishing Division, McGraw-Hill.
39. Ferreyra, M.L.F., Rius, S.P., Casati, P., Flavonoids: biosynthesis, biological functions, and biotechnological applications. Front. Plant Sci., 3, 2012, 222.
40. Fini, L., Hotchkiss, E., Fogliano, V., Graziani, G., Romano, M., Edward, B., Qin, H., Selgrad, M., Boland, C.R., Ricciardiello, L., Chemopreventive properties of pinoresinol-rich olive oil involve a selective activation of the ATM–p53 cascade in colon cancer cell lines. Carcinogenesis 29 (2008), 139–146.
41. Freese, R., Alfthan, G., Jauhiainen, M., Basu, S., Erlund, I., Salminen, I., Aro, A., Mutanen, M., High intakes of vegetables, berries, and apples combined with a high intake of linoleic or oleic acid only slightly affect markers of lipid peroxidation and lipoprotein metabolism in healthy subjects. Am. J. Clin. Nutr. 76 (2002), 950–960.
42. Fuhrman, B., Volkova, N., Coleman, R., Aviram, M., Grape powder polyphenols attenuate atherosclerosis development in apolipoprotein E deficient (E0) mice and reduce macrophage atherogenicity. J. Nutr. 135 (2005), 722–728.
43. Furie, B., Furie, B.C., Mechanisms of thrombus formation. N. Engl. J. Med. 359 (2008), 938–949.
44. Gasper, A., Hollands, W., Casgrain, A., Saha, S., Teucher, B., Dainty, J.R., Venema, D.P., Hollman, P.C., Rein, M.J., Nelson, R., Williamson, G., Kroon, P.A., Consumption of both low and high (-)-epicatechin apple puree attenuates platelet reactivity and increases plasma concentrations of nitric oxide metabolites: a randomized controlled trial. Arch. Biochem. Biophys. 559 (2014), 29–37.
45. George, J.N., Platelets. Lancet 355 (2000), 1531–1539.
46. Giovannelli, L., Pitozzi, V., Luceri, C., Giannini, L., Toti, S., Salvini, S., Sera, F., Souquet, J.M., Cheynier, V., Sofi, F., Mannini, L., Gori, A.M., Abbate, R., Palli, D., Dolara, P., Effects of de-alcoholised wines with different polyphenol content on DNA oxidative damage, gene expression of peripheral lymphocytes, and haemorheology: an intervention study in post-menopausal women. Eur. J. Nutr. 50:1 (2011), 19–29.
47. Golebiewska, E.M., Poole, A.W., Platelet secretion: from haemostasis to wound healing and beyond. Blood Rev. 29 (2015), 153–162.
48. Gonçalves, R.L., Lugnier, C., Keravis, T., Lopes, M.J., Fantini, F.A., Schmitt, M., Cortes, S.F., Lemos, V.S., The flavonoid dioclein is a selective inhibitor of cyclic nucleotide phosphodiesterase type 1 (PDE1) and a cGMP-dependent protein kinase (PKG) vasorelaxant in human vascular tissue. Eur. J. Pharmacol. 620 (2009), 78–83.
49. Gonzales, G.B., Smagghe, G., Grootaert, C., Zotti, M., Raes, K., Van Camp, J., Flavonoid interactions during digestion, absorption, distribution and metabolism: a sequential structure-activity/property relationship-based approach in the study of bioavailability and bioactivity. Drug Metab. Rev. 47:2 (2015), 175–190.
50. Guerrero, J.A., Lozano, M.L., Castillo, J., Benavente-García, O., Vicente, V., Rivera, J., Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor. J. Thromb. Haemost. 3:2 (2005), 369–376.
51. Guerrero, J.A., Navarro‐Nuñez, L., Lozano, M.L., Martínez, C., Vicente, V., Gibbins, J.M., Rivera, J., Flavonoids inhibit the platelet TxA2 signalling pathway and antagonize TxA2 receptors (TP) in platelets and smooth muscle cells. Br. J. Clin. Pharmacol. 64 (2007), 133–144.
52. Guo, D.J., Li, F., Yu, P.H.F., Chan, S.W., Neuroprotective effects of luteolin against apoptosis induced by 6-hydroxydopamine on rat pheochromocytoma PC12 cells. Pharm. Biol. 51 (2013), 190–196.
53. Hallund, J., Bügel, S., Tholstrup, T., Ferrari, M., Talbot, D., Hall, W., Reimann, M., Williams, C., Wiinberg, N., Soya isoflavone-enriched cereal bars affect markers of endothelial function in postmenopausal women. Br. J. Nutr. 95 (2006), 1120–1126.
54. Hamed, M.S., Gambert, S., Bliden, K.P., Bailon, O., Singla, A., Antonino, M.J., Hamed, F., Tantry, U.S., Gurbel, P.A., Dark chocolate effect on platelet activity, C-reactive protein and lipid profile: a pilot study. South Med. J. 101:12 (2008), 1203–1208.
55. Hanske, L., Loh, G., Sczesny, S., Blaut, M., Braune, A., Recovery and metabolism of xanthohumol in germ-free and human microbiota-associated rats. Mol. Nutr. Food Res. 54:10 (2010), 1405–1413.
56. Hao, H.Z., He, A.D., Wang, D.C., Yin, Z., Zhou, Y.J., Liu, G., Liang, M.L., Da, X.W., Yao, G.Q., Xie, W., Xiang, J.Z., Ming, Z.Y., Antiplatelet activity of loureirin A by attenuating Akt phosphorylation: In vitro studies. Eur. J. Pharmacol. 746 (2015), 63–69.
57. Hathaway, D.R., Adelstein, R.S., Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin for activity. Proc. Natl. Acad. Sci. 76 (1979), 1653–1657.
58. Heijnen, H., van der Sluijs, P., Platelet secretory behaviour: as diverse as the granules … or not?. J. Thromb. Haemost. 13:12 (2015), 2141–2151.
59. Heim, K.E., Tagliaferro, A.R., Bobilya, D.J., Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J. Nutr. Biochem. 13 (2002), 572–584.
60. Heiss, C., Kleinbongard, P., Dejam, A., Perré, S., Schroeter, H., Sies, H., Kelm, M., Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J. Am. Coll. Cardiol. 46 (2005), 1276–1283.
61. Hollman, P.C., Absorption, bioavailability, and metabolism of flavonoids. Pharm. Biol. 42 (2004), 74–83.
62. Hubbard, G., Stevens, J., Cicmil, M., Sage, T., Jordan, P., Williams, C., Lovegrove, J., Gibbins, J., Quercetin inhibits collagen‐stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway. J. Thromb. Haemost. 1 (2003), 1079–1088.
63. Hung, C.C., Tsai, W.J., Kuo, L.M., Kuo, Y.H., Evaluation of caffeic acid amide analogues as anti-platelet aggregation and anti-oxidative agents. Bioorg. Med. Chem., 13(5), 2005 (1791-1717).
64. Jackson, S.P., The growing complexity of platelet aggregation. Blood 109 (2007), 5087–5095.
65. Jeong, Y.J., Choi, Y.J., Kwon, H.M., Kang, S.W., Park, H.S., Lee, M., Kang, Y.H., Differential inhibition of oxidized LDL-induced apoptosis in human endothelial cells treated with different flavonoids. Br. J. Nutr. 93 (2005), 581–591.
66. Karuppagounder, S., Madathil, S., Pandey, M., Haobam, R., Rajamma, U., Mohanakumar, K., Quercetin up-regulates mitochondrial complex-I activity to protect against programmed cell death in rotenone model of Parkinson's disease in rats. Neuroscience 236 (2013), 136–148.
67. Kim, D.H., Jung, E.A., Sohng, I.S., Han, J.A., Kim, T.H., Han, M.J., Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Arch. Pharm. Res. 21:1 (1998), 17–23.
68. Kim, J.M., Yun-Choi, H.S., Anti-platelet effects of flavonoids and flavonoid-glycosides from Sophora japonica. Arch. Pharm. Res. 31 (2008), 886–890.
69. Kozlowska, A., Szostak-Wegierek, D., Flavonoids-food sources and health benefits. Rocz. Państwowego Zakładu Hig., 2014, 65.
70. Kumar, S., Pandey, A.K., Chemistry and biological activities of flavonoids: an overview. Sci. World J., 2013, 2013, 162750.
71. Lemos, V.S., Freitas, M.R., Muller, B., Lino, Y.D., Queiroga, C.E., Côrtes, S.F., Dioclein, a new nitric oxide-and endothelium-dependent vasodilator flavonoid. Eur. J. Pharmacol. 386 (1999), 41–46.
72. Li, N., Platelet–lymphocyte cross-talk. J. Leukoc. Biol. 83 (2008), 1069–1078.
73. Liang, M.L., Da, X.W., He, A.D., Yao, G.Q., Xie, W., Liu, G., Xiang, J.Z., Ming, Z.Y., Pentamethylquercetin (PMQ) reduces thrombus formation by inhibiting platelet function. Sci. Rep., 5, 2015, 11142.
74. Lindahl, M., Tagesson, C., Flavonoids as phospholipase A2 inhibitors: importance of their structure for selective inhibition of group II phospholipase A2. Inflammation 21 (1997), 347–356.
75. Ludwig, A., Lorenz, M., Grimbo, N., Steinle, F., Meiners, S., Bartsch, C., Stangl, K., Baumann, G., Stangl, V., The tea flavonoid epigallocatechin-3-gallate reduces cytokine-induced VCAM-1 expression and monocyte adhesion to endothelial cells. Biochem. Biophys. Res. Commun. 316 (2004), 659–665.
76. Luzak, B., Kassassir, H., Rój, E., Stanczyk, L., Watala, C., Golanski, J., Xanthohumol from hop cones (Humulus lupulus L.) prevents ADP-induced platelet reactivity. Arch. Physiol. Biochem. 123:1 (2017), 54–60.
77. Maheswaraiah, A., Rao, L.J., Naidu, K.A., Anti-platelet activity of water dispersible curcuminoids in rat platelets. Phytother. Res. 29:3 (2015), 450–458.
78. Mantena, S.K., Baliga, M.S., Katiyar, S.K., Grape seed proanthocyanidins induce apoptosis and inhibit metastasis of highly metastatic breast carcinoma cells. Carcinogenesis 27 (2006), 1682–1691.
79. Maynard, D., Heijnen, H., Horne, M., White, J., Gahl, W., Proteomic analysis of platelet α‐granules using mass spectrometry. J. Thromb. Haemost. 5 (2007), 1945–1955.
80. Mazereeuw, G., Herrmann, N., Bennett, S.A., Swardfager, W., Xu, H., Valenzuela, N., Fai, S., Lanctôt, K.L., Platelet activating factors in depression and coronary artery disease: a potential biomarker related to inflammatory mechanisms and neurodegeneration. Neurosci. Biobehav. Rev. 37:8 (2013), 1611–1621.
81. Meng, S., Wu, B., Singh, R., Yin, T., Morrow, J.K., Zhang, S., Hu, M., SULT1A3-mediated regiospecific 7-O-sulfation of flavonoids in Caco-2 cells can be explained by the relevant molecular docking studies., 9(4), 2012, 862.
82. Messina, F., Guglielmini, G., Curini, M., Orsini, S., Gresele, P., Marcotullio, M.C., Effect of substituted stilbenes on platelet function. Fitoterapia 105 (2015), 228–233.
83. Mitchelmore, C., Troelsen, J.T., Spodsberg, N., Sjöström, H., Norén, O., Interaction between the homeodomain proteins Cdx2 and HNF1alpha mediates expression of the lactase-phlorizin hydrolase gene. Biochem. J. 346:Pt 2 (2000), 529–535.
84. Mladěnka, P., Zatloukalová, L., Filipský, T., Hrdina, R., Cardiovascular effects of flavonoids are not caused only by direct antioxidant activity. Free Radic. Biol. Med. 49 (2010), 963–975.
85. Mower, R.L., Landolfi, R., Steiner, M., Inhibition in vitro of platelet aggregation and arachidonic acid metabolism by flavone. Biochem. Pharmacol. 33 (1984), 357–363.
86. Muñoz, Y., Garrido, A., Valladares, L., Equol is more active than soy isoflavone itself to compete for binding to thromboxane A(2) receptor in human platelets. Thromb. Res. 123:5 (2009), 740–744.
87. Nabavi, S.F., Nabavi, S.M., Mirzaei, M., Moghaddam, A.H., Protective effect of quercetin against sodium fluoride induced oxidative stress in rat's heart. Food Funct. 3 (2012), 437–441.
88. Nabavi, S.F., Russo, G.L., Daglia, M., Nabavi, S.M., Role of quercetin as an alternative for obesity treatment: you are what you eat!. Food Chem. 179 (2015), 305–310.
89. Navarro-Nunez, L., Castillo, J., Lozano, M.L., Martinez, C., Benavente-García, O., Vicente, V., Rivera, J., Thromboxane A2 receptor antagonism by flavonoids: structure− activity relationships. J. Agric. Food Chem. 57 (2009), 1589–1594.
90. Németh, K., Plumb, G.W., Berrin, J.G., Juge, N., Jacob, R., Naim, H.Y., Williamson, G., Swallow, D.M., Kroon, P.A., Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur. J. Nutr. 42:1 (2003), 29–42.
91. Nurden, A.T., Nurden, P., Sanchez, M., Andia, I., Anitua, E., Platelets and wound healing. Front. Biosci. 13 (2007), 3532–3548.
92. Ostertag, L.M., Kroon, P.A., Wood, S., Horgan, G.W., Cienfuegos-Jovellanos, E., Saha, S., Duthie, G.G., de Roos, B., Flavan-3-ol-enriched dark chocolate and white chocolate improve acute measures of platelet function in a gender-specific way-a randomized-controlled human intervention trial. Mol. Nutr. Food Res. 57:2 (2013), 191–202.
93. Ottaviani, J.I., Balz, M., Kimball, J., Ensunsa, J.L., Fong, R., Momma, T.Y., Kwik-Uribe, C., Schroeter, H., Keen, C.L., Safety and efficacy of cocoa flavanol intake in healthy adults: a randomized, controlled, double-masked trial. Am. J. Clin. Nutr. 102:6 (2015), 1425–1435.
94. Peterson, J., Dwyer, J., Flavonoids: dietary occurrence and biochemical activity. Nutr. Res. 18 (1998), 1995–2018.
95. Piao, M., Mori, D., Satoh, T., Sugita, Y., Tokunaga, O., Inhibition of endothelial cell proliferation, in vitro angiogenesis, and the down-regulation of cell adhesion–related genes by genistein combined with a cdna microarray analysis. Endothelium 13 (2006), 249–266.
96. Pignatelli, P., Pulcinelli, F.M., Lenti, L., Gazzaniga, P.P., Violi, F., Hydrogen peroxide is involved in collagen-induced platelet activation. Blood 91:2 (1998), 484–490.
97. Pignatelli, P., Pulcinelli, F.M., Celestini, A., Lenti, L., Ghiselli, A., Gazzaniga, P.P., Violi, F., The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide. Am. J. Clin. Nutr. 72:5 (2000), 1150–1155.
98. Pignatelli, P., Di Santo, S., Buchetti, B., Sanguigni, V., Brunelli, A., Violi, F., Polyphenols enhance platelet nitric oxide by inhibiting protein kinase C-dependent NADPH oxidase activation: effect on platelet recruitment. FASEB J. 20:8 (2006), 1082–1089.
99. Ras, R.T., Zock, P.L., Zebregs, Y.E., Johnston, N.R., Webb, D.J., Draijer, R., Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension. Br. J. Nutr. 110:12 (2013), 2234–2241.
100. Rendu, F., Brohard-Bohn, B., The platelet release reaction: granules' constituents, secretion and functions. Platelets 12 (2001), 261–273.
101. Rezende, B.A., Cortes, S.F., Lemos, V.S., Mechanisms involved in the vasodilator effect of the flavanol floranol in rat small mesenteric arteries. Planta Med. 70 (2004), 465–467.
102. Rezende, B.A., Cortes, S.F., De Sousa, F.B., Lula, I.S., Schmitt, M., Sinisterra, R.D., Lemos, V.S., Complexation with β-cyclodextrin confers oral activity on the flavonoid dioclein. Int. J. Pharm. 367 (2009), 133–139.
103. Ribeiro-Santos, R., Carvalho-Costa, D., Cavaleiro, C., Costa, H.S., Albuquerque, T.G., Castilho, M.C., Ramos, F., Melo, N.R., Sanches-Silva, A., A novel insight on an ancient aromatic plant: the rosemary (Rosmarinus officinalis L.). Trends Food Sci. Technol. 45 (2015), 355–368.
104. Rink, T.J., Sage, S.O., Calcium signaling in human platelets. Annu. Rev. Physiol. 52 (1990), 431–449.
105. Ross, J.A., Kasum, C.M., Dietary flavonoids: bioavailability, metabolic effects, and safety. Ann. Rev. Nutr. 22 (2002), 19–34.
106. Rull, G., Mohd-Zain, Z.N., Shiel, J., Lundberg, M.H., Collier, D.J., Johnston, A., Warner, T.D., Corder, R., Effects of high flavanol dark chocolate on cardiovascular function and platelet aggregation. Vasc. Pharmacol. 71 (2015), 70–78.
107. Schmidt, E.M., Schmid, E., Münzer, P., Hermann, A., Eyrich, A.K., Russo, A., Walker, B., Gu, S., vom Hagen, J.M., Faggio, C., Chorein sensitivity of cytoskeletal organization and degranulation of platelets. FASEB J. 27 (2013), 2799–2806.
108. Schumacher, E., Vigh, E., Molnár, V., Kenyeres, P., Fehér, G., Késmárky, G., Tóth, K., Garai, J., Thrombosis preventive potential of chicory coffee consumption: a clinical study. Phytother. Res. 25:5 (2011), 744–748.
109. Scull, C.M., Hays, W.D., Fischer, T.H., Macrophage pro-inflammatory cytokine secretion is enhanced following interaction with autologous platelets. J. Inflamm., 7, 2010, 53.
110. Senchenkova, E., Seifert, H., Granger, D.N., Hypercoagulability and platelet abnormalities in inflammatory bowel disease. Semin. Thromb. Hemost. 41:6 (2015), 582–589.
111. Shattil, S., Brass, L., Induction of the fibrinogen receptor on human platelets by intracellular mediators. J. Biol. Chem. 262 (1987), 992–1000.
112. Sheu, J.R., Hsiao, G., Chou, P.H., Shen, M.Y., Chou, D.S., Mechanisms involved in the antiplatelet activity of rutin, a glycoside of the flavonol quercetin, in human platelets. J. Agric. Food Chem. 52:14 (2004), 4414–4418.
113. Simons, A.L., Renouf, M., Hendrich, S., Murphy, P.A., Metabolism of glycitein (7,4′-dihydroxy-6-methoxy-isoflavone) by human gut microflora. J. Agric. Food Chem. 53:22 (2005), 8519–8525.
114. Stephen, J., Emerson, B., Fox, K.A., Dransfield, I., The uncoupling of monocyte–platelet interactions from the induction of proinflammatory signaling in monocytes. J. Immunol. 191 (2013), 5677–5683.
115. Thon, J.N., Peters, C.G., Machlus, K.R., Aslam, R., Rowley, J., Macleod, H., Devine, M.T., Fuchs, T.A., Weyrich, A.S., Semple, J.W., T granules in human platelets function in TLR9 organization and signaling. J. Cell Biol. 198 (2012), 561–574.
116. Tian, X., Chang, L., Ma, G., Wang, T., Lv, M., Wang, Z., Chen, L., Wang, Y., Gao, X., Zhu, Y., Delineation of platelet activation pathway of scutellarein revealed its intracellular target as protein kinase C. Biol. Pharm. Bull. 39:2 (2016), 181–191.
117. Tran, H., Anand, S.S., Oral antiplatelet therapy in cerebrovascular disease, coronary artery disease, and peripheral arterial disease. JAMA 292 (2004), 1867–1874.
118. Trischitta, F., Faggio, C., Effect of the flavonol quercetin on ion transport in the isolated intestine of the eel, Anguilla anguilla. Comp. Biochem. Physiol. C: Toxicol. Pharmacol. 143 (2006), 17–22.
119. Tzeng, S.H., Ko, W.C., Ko, F.N., Teng, C.M., Inhibition of platelet aggregation by some flavonoids. Thromb. Res. 64 (1991), 91–100.
120. Vieira-de-Abreu, A., Campbell, R.A., Weyrich, A.S., Zimmerman, G.A., Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum. Semin. Immunopathol. 34 (2012), 5–30.
121. Walle, T., Absorption and metabolism of flavonoids. Free Radic. Biol. Med. 36 (2004), 829–837.
122. Wang, S.B., Jang, J.Y., Chae, Y.H., Min, J.H., Baek, J.Y., Kim, M., Park, Y., Hwang, G.S., Ryu, J.S., Chang, T.S., Kaempferol suppresses collagen-induced platelet activation by inhibiting NADPH oxidase and protecting SHP-2 from oxidative inactivation. Free Radic. Biol. Med. 83 (2015), 41–53.
123. Wang, W., Heideman, L., Chung, C.S., Pelling, J.C., Koehler, K.J., Birt, D.F., Cell‐cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines. Mol. Carcinog. 28 (2000), 102–110.
124. Watson, S., Auger, J., McCarty, O., Pearce, A., GPVI and integrin αIIbβ3 signaling in platelets. J. Thromb. Haemost. 3 (2005), 1752–1762.
125. Wei, Y., Wu, B., Jiang, W., Yin, T., Jia, X., Basu, S., Yang, G., Hu, M., Revolving door action of breast cancer resistance protein (BCRP) facilitates or controls the efflux of flavone glucuronides from UGT1A9-overexpressing HeLa cells. Mol. Pharm. 10:5 (2013), 1736–1750.
126. Weseler, A.R., Ruijters, E.J., Drittij-Reijnders, M.J., Reesink, K.D., Haenen, G.R., Bast, A., Pleiotropic benefit of monomeric and oligomeric flavanols on vascular health-a randomized controlled clinical pilot study. PLoS One, 6(12), 2011, e28460.
127. White, J.G., Clawson, C., The surface-connected canalicular system of blood platelets-a fenestrated membrane system. Am. J. Pathol. 101 (1980), 353–364.
128. White, J.G., Krumwiede, M.D., Escolar, G., Glycoprotein Ib is homogeneously distributed on external and internal membranes of resting platelets. Am. J. Pathol. 155 (1999), 2127–2134.
129. Williamson, J., Cooper, R., Joseph, S., Thomas, A., Inositol trisphosphate and diacylglycerol as intracellular second messengers in liver. Am. J. Physiol. Cell Physiol. 248 (1985), C203–C216.
130. Wright, B., Gibson, T., Spencer, J., Lovegrove, J.A., Gibbins, J.M., Platelet-mediated metabolism of the common dietary flavonoid, quercetin. PLoS One, 5(3), 2010, e9673.
131. Wright, B., Moraes, L.A., Kemp, C.F., Mullen, W., Crozier, A., Lovegrove, J.A., Gibbins, J.M., A structural basis for the inhibition of collagen‐stimulated platelet function by quercetin and structurally related flavonoids. Br. J. Pharmacol. 159 (2010), 1312–1325.
132. Wright, B., Spencer, J.P., Lovegrove, J.A., Gibbins, J.M., Insights into dietary flavonoids as molecular templates for the design of anti-platelet drugs. Cardiovasc. Res. 97 (2013), 13–22.
133. Wu, B., Kulkarni, K., Basu, S., Zhang, S., Hu, M., First-pass metabolism via UDP-glucuronosyltransferase: a barrier to oral bioavailability of phenolics. J. Pharm. Sci. 100:9 (2011), 3655–3681.
134. Yang, Z., Zhu, W., Gao, S., Yin, T., Jiang, W., Hu, M., Breast cancer resistance protein (ABCG2) determines distribution of genistein phase II metabolites: reevaluation of the roles of ABCG2 in the disposition of genistein. Drug Metab. Dispos. 40:10 (2012), 1883–1893.
135. Yeaman, M.R., Platelets in defense against bacterial pathogens. Cell. Mol. Life Sci. 67 (2010), 525–544.
136. Zern, T.L., Wood, R.J., Greene, C., West, K.L., Liu, Y., Aggarwal, D., Shachter, N.S., Fernandez, M.L., Grape polyphenols exert a cardioprotective effect in pre-and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J. Nutr. 135 (2005), 1911–1917.
137. Zubair, M.H., Zubair, M.H., Zubair, M.N., Zubair, M.M., Aftab, T., Asad, F., Augmentation of anti-platelet effects of aspirin. J. Pak. Med. Assoc. 61:3 (2011), 304–307.
138. Zufferey, A., Schvartz, D., Nolli, S., Reny, J.L., Sanchez, J.C., Fontana, P., Characterization of the platelet granule proteome: evidence of the presence of MHC1 in alpha-granules. J. Proteom. 101 (2014), 130–140.