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Published in: Nutrition Journal 1/2011

Open Access 01-12-2011 | Research

Evaluation of antiaggregatory activity of flavonoid aglycone series

Authors: Mirza Bojić, Željko Debeljak, Maja Tomičić, Marica Medić-Šarić, Siniša Tomić

Published in: Nutrition Journal | Issue 1/2011

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Abstract

Background

Among natural compounds, present in every day diet, flavonoids have shown beneficial effect in prevention of cardiovascular diseases that can be attributed, at least partially to the described antiaggregatory activity i.e. antiplatelet effects of flavonoids. Due to the ever increasing pharmacological interest in antiplatelet agents a systematic experimental evaluation of large flavonoid series is needed.

Methods

A set of thirty flavonoid aglycones has been selected for the evaluation. All measurements of aggregation were done under standardized and firmly controlled in vitro conditions. The whole blood samples, multiple platelet functional analyzer and adenosine diphosphate (ADP) as a weak agonist of aggregation were selected for this purpose.

Results

The results were expressed as minimal concentration of flavonoid that can significantly lower the platelet aggregation compared to the corresponding untreated sample (minimal antiaggregatory concentration - MINaAC). All analyzed flavonoids exhibited antiaggregatory activity MINaAC ranging from 0.119 μM to 122 μM, while the most potent representatives were 3,6-dihydroxyflavone (0.119 μM) and syringetin (0.119 μM).

Conclusions

Measurable antiplatelet activity established at submicromolar flavonoid concentrations suggests that even a dietary consumption of some flavonoids can make an impact on in vivo aggregation of platelets. These findings also point out a therapeutical potential of some flavonoids.
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Literature
1.
go back to reference Sweetman S: Martindale: The Complete Drug Reference. 2011, London: Pharmaceutical Press Sweetman S: Martindale: The Complete Drug Reference. 2011, London: Pharmaceutical Press
2.
go back to reference de Lange DW, Verhoef S, Gorter G, Kraaijenhagen RJ, van de Wiel A, Akkerman JW: Polyphenolic grape extract inhibits platelet activation through PECAM-1: an explanation for the French paradox. Alcohol Clin Exp Res. 2007, 31: 1308-1314. 10.1111/j.1530-0277.2007.00439.x.CrossRefPubMed de Lange DW, Verhoef S, Gorter G, Kraaijenhagen RJ, van de Wiel A, Akkerman JW: Polyphenolic grape extract inhibits platelet activation through PECAM-1: an explanation for the French paradox. Alcohol Clin Exp Res. 2007, 31: 1308-1314. 10.1111/j.1530-0277.2007.00439.x.CrossRefPubMed
3.
go back to reference Leifert WR, Abeywardena MY: Cardioprotective actions of grape polyphenols. Nutr Res. 2008, 28: 729-737. 10.1016/j.nutres.2008.08.007.CrossRefPubMed Leifert WR, Abeywardena MY: Cardioprotective actions of grape polyphenols. Nutr Res. 2008, 28: 729-737. 10.1016/j.nutres.2008.08.007.CrossRefPubMed
4.
go back to reference Sumpio BE, Cordova AC, Berke-Schlessel DW, Qin F, Chen QH: Green tea, the "Asian paradox," and cardiovascular disease. J Am Coll Surg. 2006, 202: 813-825. 10.1016/j.jamcollsurg.2006.01.018.CrossRefPubMed Sumpio BE, Cordova AC, Berke-Schlessel DW, Qin F, Chen QH: Green tea, the "Asian paradox," and cardiovascular disease. J Am Coll Surg. 2006, 202: 813-825. 10.1016/j.jamcollsurg.2006.01.018.CrossRefPubMed
5.
go back to reference Medić-Šarić M, Rastija V, Bojić M, Maleš Ž: From functional food to medicinal product: systematic approach in analysis of polyphenolics from propolis and wine. Nutr J. 2009, 8: 33-10.1186/1475-2891-8-33.CrossRefPubMedPubMedCentral Medić-Šarić M, Rastija V, Bojić M, Maleš Ž: From functional food to medicinal product: systematic approach in analysis of polyphenolics from propolis and wine. Nutr J. 2009, 8: 33-10.1186/1475-2891-8-33.CrossRefPubMedPubMedCentral
6.
go back to reference Akhlaghi M, Bandy B: Mechanisms of flavonoid protection against myocardial ischemia-reperfusion injury. J Mol Cell Cardiol. 2009, 46: 309-317. 10.1016/j.yjmcc.2008.12.003.CrossRefPubMed Akhlaghi M, Bandy B: Mechanisms of flavonoid protection against myocardial ischemia-reperfusion injury. J Mol Cell Cardiol. 2009, 46: 309-317. 10.1016/j.yjmcc.2008.12.003.CrossRefPubMed
7.
go back to reference Lill G, Voit S, Schrör K, Weber AA: Complex effects of different green tea catechins on human platelets. FEBS Lett. 2003, 546: 265-270. 10.1016/S0014-5793(03)00599-4.CrossRefPubMed Lill G, Voit S, Schrör K, Weber AA: Complex effects of different green tea catechins on human platelets. FEBS Lett. 2003, 546: 265-270. 10.1016/S0014-5793(03)00599-4.CrossRefPubMed
8.
go back to reference 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. 2006, 20: 1082-1089. 10.1096/fj.05-5269com.CrossRefPubMed 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. 2006, 20: 1082-1089. 10.1096/fj.05-5269com.CrossRefPubMed
9.
go back to reference Dell'Agli M, Maschi O, Galli GV, Fagnani R, Dal Cero E, Caruso D, Bosisio E: Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase. Br J Nutr. 2008, 99: 945-951.CrossRefPubMed Dell'Agli M, Maschi O, Galli GV, Fagnani R, Dal Cero E, Caruso D, Bosisio E: Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase. Br J Nutr. 2008, 99: 945-951.CrossRefPubMed
10.
go back to reference Freedman JE, Parker C, Li L, Perlman JA, Frei B, Ivanov V, Deak LR, Iafrati MD, Folts JD: Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001, 103: 2792-2798.CrossRefPubMed Freedman JE, Parker C, Li L, Perlman JA, Frei B, Ivanov V, Deak LR, Iafrati MD, Folts JD: Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001, 103: 2792-2798.CrossRefPubMed
11.
go back to reference Guerrero JA, Lozano ML, Castillo J, Benavente-García O, Vicente V, Rivera J: Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor. J Thromb Haemost. 2005, 3: 369-376. 10.1111/j.1538-7836.2004.01099.x.CrossRefPubMed Guerrero JA, Lozano ML, Castillo J, Benavente-García O, Vicente V, Rivera J: Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor. J Thromb Haemost. 2005, 3: 369-376. 10.1111/j.1538-7836.2004.01099.x.CrossRefPubMed
12.
go back to reference Nakahata N: Thromboxane A2: physiology/pathophysiology, cellular signal transduction and pharmacology. Pharmacol Ther. 2008, 118: 18-35. 10.1016/j.pharmthera.2008.01.001.CrossRefPubMed Nakahata N: Thromboxane A2: physiology/pathophysiology, cellular signal transduction and pharmacology. Pharmacol Ther. 2008, 118: 18-35. 10.1016/j.pharmthera.2008.01.001.CrossRefPubMed
13.
go back to reference Janssen K, Mensink RP, Cox FJ, Harryvan JL, Hovenier R, Hollman PC, Katan MB: Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. Am J Clin Nutr. 1998, 67: 255-262.PubMed Janssen K, Mensink RP, Cox FJ, Harryvan JL, Hovenier R, Hollman PC, Katan MB: Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. Am J Clin Nutr. 1998, 67: 255-262.PubMed
14.
go back to reference Weng JR, Chan SC, Lu YH, Lin HC, Ko HH, Lin CN: Antiplatelet prenylflavonoids from Artocarpus communis. Phytochemistry. 2006, 67: 824-829. 10.1016/j.phytochem.2006.01.030.CrossRefPubMed Weng JR, Chan SC, Lu YH, Lin HC, Ko HH, Lin CN: Antiplatelet prenylflavonoids from Artocarpus communis. Phytochemistry. 2006, 67: 824-829. 10.1016/j.phytochem.2006.01.030.CrossRefPubMed
15.
go back to reference Heptinstall S, May J, Fox S, Kwik-Uribe C, Zhao L: Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc Pharmacol. 2006, 47 (Suppl 2): S197-205.CrossRefPubMed Heptinstall S, May J, Fox S, Kwik-Uribe C, Zhao L: Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc Pharmacol. 2006, 47 (Suppl 2): S197-205.CrossRefPubMed
16.
go back to reference Hubbard GP, Wolffram S, Lovegrove JA, Gibbins JM: Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemost. 2004, 2: 2138-2145. 10.1111/j.1538-7836.2004.01067.x.CrossRefPubMed Hubbard GP, Wolffram S, Lovegrove JA, Gibbins JM: Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemost. 2004, 2: 2138-2145. 10.1111/j.1538-7836.2004.01067.x.CrossRefPubMed
17.
go back to reference Jin YR, Han XH, Zhang YH, Lee JJ, Lim Y, Chung JH, Yun YP: Antiplatelet activity of hesperetin, a bioflavonoid, is mainly mediated by inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1 activity. Atherosclerosis. 2007, 194: 144-152. 10.1016/j.atherosclerosis.2006.10.011.CrossRefPubMed Jin YR, Han XH, Zhang YH, Lee JJ, Lim Y, Chung JH, Yun YP: Antiplatelet activity of hesperetin, a bioflavonoid, is mainly mediated by inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1 activity. Atherosclerosis. 2007, 194: 144-152. 10.1016/j.atherosclerosis.2006.10.011.CrossRefPubMed
18.
go back to reference Pignatelli P, Pulcinelli FM, Celestini A, Lenti L, Ghiselli A, Gazzaniga PP, Violi F: The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide. Am J Clin Nutr. 2000, 72: 1150-1155.PubMed Pignatelli P, Pulcinelli FM, Celestini A, Lenti L, Ghiselli A, Gazzaniga PP, Violi F: The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide. Am J Clin Nutr. 2000, 72: 1150-1155.PubMed
19.
go back to reference Furusawa M, Tsuchiya H, Nagayama M, Tanaka T, Nakaya K, Iinuma M: Anti-platelet and membrane-rigidifying flavonoids in brownish scale of onion. J Health Sci. 2003, 49: 475-480. 10.1248/jhs.49.475.CrossRef Furusawa M, Tsuchiya H, Nagayama M, Tanaka T, Nakaya K, Iinuma M: Anti-platelet and membrane-rigidifying flavonoids in brownish scale of onion. J Health Sci. 2003, 49: 475-480. 10.1248/jhs.49.475.CrossRef
20.
go back to reference Hendrich AB: Flavonoid-membrane interactions: possible consequences for biological effects of some polyphenolic compounds. Acta Pharmacol Sin. 2006, 27: 27-40. 10.1111/j.1745-7254.2006.00238.x.CrossRefPubMed Hendrich AB: Flavonoid-membrane interactions: possible consequences for biological effects of some polyphenolic compounds. Acta Pharmacol Sin. 2006, 27: 27-40. 10.1111/j.1745-7254.2006.00238.x.CrossRefPubMed
21.
go back to reference O'Malley BA: Primary Hemostasis. Clinical Laboratory Hematology. Edited by: McKenzie SB, Williams JL. 2010, New York: Pearson, 612-638. 2 O'Malley BA: Primary Hemostasis. Clinical Laboratory Hematology. Edited by: McKenzie SB, Williams JL. 2010, New York: Pearson, 612-638. 2
22.
go back to reference Božina N, Bradamante V, Lovrić M: Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol. 2009, 60: 217-242.PubMed Božina N, Bradamante V, Lovrić M: Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol. 2009, 60: 217-242.PubMed
23.
go back to reference Navarro-Núñez L, Castillo J, Lozano ML, Martínez C, Benavente-García O, Vicente V, Rivera J: Thromboxane A2 receptor antagonism by flavonoids: structure-activity relationships. J Agric Food Chem. 2009, 57: 1589-1594. 10.1021/jf803041k.CrossRefPubMed Navarro-Núñez L, Castillo J, Lozano ML, Martínez C, Benavente-García O, Vicente V, Rivera J: Thromboxane A2 receptor antagonism by flavonoids: structure-activity relationships. J Agric Food Chem. 2009, 57: 1589-1594. 10.1021/jf803041k.CrossRefPubMed
24.
go back to reference Hertog MG, Hollman PC, Katan MB, Kromhout D: Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutr Cancer. 1993, 20: 21-29. 10.1080/01635589309514267.CrossRefPubMed Hertog MG, Hollman PC, Katan MB, Kromhout D: Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutr Cancer. 1993, 20: 21-29. 10.1080/01635589309514267.CrossRefPubMed
25.
go back to reference Hollman PC, de Vries JH, van Leeuwen SD, Mengelers MJ, Katan MB: Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr. 1995, 62: 1276-1282.PubMed Hollman PC, de Vries JH, van Leeuwen SD, Mengelers MJ, Katan MB: Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am J Clin Nutr. 1995, 62: 1276-1282.PubMed
26.
go back to reference Stalmach A, Mullen W, Steiling H, Williamson G, Lean ME, Crozier A: Absorption, metabolism, and excretion of green tea flavan-3-ols in humans with an ileostomy. Mol Nutr Food Res. 2010, 54: 323-334. 10.1002/mnfr.200900194.CrossRefPubMed Stalmach A, Mullen W, Steiling H, Williamson G, Lean ME, Crozier A: Absorption, metabolism, and excretion of green tea flavan-3-ols in humans with an ileostomy. Mol Nutr Food Res. 2010, 54: 323-334. 10.1002/mnfr.200900194.CrossRefPubMed
27.
go back to reference Gardana C, Guarnieri S, Riso P, Simonetti P, Porrini M: Flavanone plasma pharmacokinetics from blood orange juice in human subjects. Br J Nutr. 2007, 98: 165-172. 10.1017/S0007114507699358.CrossRefPubMed Gardana C, Guarnieri S, Riso P, Simonetti P, Porrini M: Flavanone plasma pharmacokinetics from blood orange juice in human subjects. Br J Nutr. 2007, 98: 165-172. 10.1017/S0007114507699358.CrossRefPubMed
28.
go back to reference Bredsdorff L, Nielsen IL, Rasmussen SE, Cornett C, Barron D, Bouisset F, Offord E, Williamson G: Absorption, conjugation and excretion of the flavanones, naringenin and hesperetin from alpha-rhamnosidase-treated orange juice in human subjects. Br J Nutr. 2010, 103: 1602-1609. 10.1017/S0007114509993679.CrossRefPubMed Bredsdorff L, Nielsen IL, Rasmussen SE, Cornett C, Barron D, Bouisset F, Offord E, Williamson G: Absorption, conjugation and excretion of the flavanones, naringenin and hesperetin from alpha-rhamnosidase-treated orange juice in human subjects. Br J Nutr. 2010, 103: 1602-1609. 10.1017/S0007114509993679.CrossRefPubMed
29.
go back to reference Mullen W, Archeveque MA, Edwards CA, Matsumoto H, Crozier A: Bioavailability and metabolism of orange juice flavanones in humans: impact of a full-fat yogurt. J Agric Food Chem. 2008, 56: 11157-11164. 10.1021/jf801974v.CrossRefPubMed Mullen W, Archeveque MA, Edwards CA, Matsumoto H, Crozier A: Bioavailability and metabolism of orange juice flavanones in humans: impact of a full-fat yogurt. J Agric Food Chem. 2008, 56: 11157-11164. 10.1021/jf801974v.CrossRefPubMed
Metadata
Title
Evaluation of antiaggregatory activity of flavonoid aglycone series
Authors
Mirza Bojić
Željko Debeljak
Maja Tomičić
Marica Medić-Šarić
Siniša Tomić
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Nutrition Journal / Issue 1/2011
Electronic ISSN: 1475-2891
DOI
https://doi.org/10.1186/1475-2891-10-73

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