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Erschienen in: European Journal of Nutrition 2/2013

01.03.2013 | Original Contribution

Antiplatelet effect of new lipophilic hydroxytyrosol alkyl ether derivatives in human blood

verfasst von: J. J. Reyes, J. P. De La Cruz, J. Muñoz-Marin, A. Guerrero, J. A. Lopez-Villodres, A. Madrona, J. L. Espartero, J. A. Gonzalez-Correa

Erschienen in: European Journal of Nutrition | Ausgabe 2/2013

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Abstract

Purpose

To investigate the in vitro antiplatelet and anti-inflammatory effects of five alkyl hydroxytyrosol (HT) ether derivatives in human whole blood and compare these effects with those of HT.

Methods

Blood samples from healthy volunteers were incubated with HT and HT alkyl ether derivatives (ethyl, butyl, hexyl, octyl and dodecyl). Maximum intensity of platelet aggregation was induced with collagen, arachidonic acid or ADP. Calcium-induced thromboxane B2 and nitric oxide production, LPS-induced prostaglandin E2 and nitric oxide production and LPS-induced interleukin 1β production were measured.

Results

All compounds inhibited platelet aggregation, thromboxane B2 and inflammatory mediators in a concentration-dependent manner. The concentrations of each compound that inhibited the corresponding variable by 50 % compared to control samples (IC50) were in the range of 10−7–10−6 M for HT hexyl ether; for the other compounds, these values were in the range of 10−5 M. The IC50 for thromboxane B2 production was in the range of 10−4 M. The effects of HT alkyl ether derivatives were greater than those of HT. These compounds increased nitric oxide production. There was no direct relationship between the effects of these compounds and alkyl chain length. Maximum effects were observed in the C4–C6 range.

Conclusions

Alkyl ether derivatives of HT exert antiplatelet and anti-inflammatory effects that are greater than those of HT.
Literatur
1.
Zurück zum Zitat Trichopoulou A, Costacou T, Bamia C, Trichopoulos D (2003) Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 348:2599–2608CrossRef Trichopoulou A, Costacou T, Bamia C, Trichopoulos D (2003) Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 348:2599–2608CrossRef
2.
Zurück zum Zitat Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, van Staveren WA (2004) Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA 292:1433–1439CrossRef Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, van Staveren WA (2004) Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA 292:1433–1439CrossRef
3.
Zurück zum Zitat Piscopo S (2009) The Mediterranean diet as a nutrition education, health promotion and disease prevention tool. Public Health Nutr 12:1648–1655CrossRef Piscopo S (2009) The Mediterranean diet as a nutrition education, health promotion and disease prevention tool. Public Health Nutr 12:1648–1655CrossRef
4.
Zurück zum Zitat Covas MI (2008) Bioactive effects of olive oil phenolic compounds in humans: reduction of heart disease factors and oxidative damage. Inflammopharmacology 16:216–218CrossRef Covas MI (2008) Bioactive effects of olive oil phenolic compounds in humans: reduction of heart disease factors and oxidative damage. Inflammopharmacology 16:216–218CrossRef
5.
Zurück zum Zitat Visioli F, Bernardini E (2011) Extra virgin olive oil’s polyphenols: biological activities. Curr Pharm Des 17:786–804CrossRef Visioli F, Bernardini E (2011) Extra virgin olive oil’s polyphenols: biological activities. Curr Pharm Des 17:786–804CrossRef
6.
Zurück zum Zitat Tripoli E, Giammanco M, Tabacchi G, Di Majo D, Giammanco S, La Guardia M (2005) The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health. Nutr Res Rev 18:98–112CrossRef Tripoli E, Giammanco M, Tabacchi G, Di Majo D, Giammanco S, La Guardia M (2005) The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health. Nutr Res Rev 18:98–112CrossRef
7.
Zurück zum Zitat Montedoro G, Servili M, Baldioli M, Selvaggini R, Miniati E, Macchioni A (1993) Simple and hydrolyzable compounds in virgen olive oil. Spectroscopic characterizations of the secoiridoid derivatives. J Agric Food Chem 41:2228–2234CrossRef Montedoro G, Servili M, Baldioli M, Selvaggini R, Miniati E, Macchioni A (1993) Simple and hydrolyzable compounds in virgen olive oil. Spectroscopic characterizations of the secoiridoid derivatives. J Agric Food Chem 41:2228–2234CrossRef
8.
Zurück zum Zitat Brenes M, Garcia A, Garcia P, Rios JJ, Garrido A (1999) Phenolic compounds in Spanish olive oils. J Agric Food Chem 47:3535–3540CrossRef Brenes M, Garcia A, Garcia P, Rios JJ, Garrido A (1999) Phenolic compounds in Spanish olive oils. J Agric Food Chem 47:3535–3540CrossRef
9.
Zurück zum Zitat Gimeno E, de la Torre-Carbot K, Lamuela-Raventós RM, Castellote AI, Fitó M, de la Torre R, Covas MI, López-Sabater MC (2007) Changes in the phenolic content of low density lipoprotein after olive oil consumption in men. A randomized crossover controlled trial. Br J Nutr 98:1243–1250CrossRef Gimeno E, de la Torre-Carbot K, Lamuela-Raventós RM, Castellote AI, Fitó M, de la Torre R, Covas MI, López-Sabater MC (2007) Changes in the phenolic content of low density lipoprotein after olive oil consumption in men. A randomized crossover controlled trial. Br J Nutr 98:1243–1250CrossRef
10.
Zurück zum Zitat González-Correa JA, Navas MD, Muñoz-Marín J, Trujillo M, Fernández-Bolaños J, De La Cruz JP (2008) Effects of hydroxytyrosol and hydroxytyrosol acetate administration to rats on platelet function compared to acetylsalicylic acid. J Agric Food Chem 56:7872–7876CrossRef González-Correa JA, Navas MD, Muñoz-Marín J, Trujillo M, Fernández-Bolaños J, De La Cruz JP (2008) Effects of hydroxytyrosol and hydroxytyrosol acetate administration to rats on platelet function compared to acetylsalicylic acid. J Agric Food Chem 56:7872–7876CrossRef
11.
Zurück zum Zitat González-Correa JA, López-Villodres JA, Asensi R, Espartero JL, Rodríguez-Gutiérez G, De La Cruz JP (2009) Virgin olive oil polyphenol hydroxytyrosol acetate inhibits in vitro platelet aggregation in human whole blood: comparison with hydroxytyrosol and acetylsalicylic acid. Br J Nutr 101:1157–1164CrossRef González-Correa JA, López-Villodres JA, Asensi R, Espartero JL, Rodríguez-Gutiérez G, De La Cruz JP (2009) Virgin olive oil polyphenol hydroxytyrosol acetate inhibits in vitro platelet aggregation in human whole blood: comparison with hydroxytyrosol and acetylsalicylic acid. Br J Nutr 101:1157–1164CrossRef
12.
Zurück zum Zitat Bitler CM, Viale TM, Damaj B, Crea R (2005) Hydrolyzed olive vegetation water in mice has anti-inflammatory activity. J Nutr 135:1475–1479 Bitler CM, Viale TM, Damaj B, Crea R (2005) Hydrolyzed olive vegetation water in mice has anti-inflammatory activity. J Nutr 135:1475–1479
13.
Zurück zum Zitat Paiva-Martins F, Fernandes J, Santos V, Silva L, Borges F, Rocha S, Belo L, Santos-Silva A (2010) Powerful protective role of 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde against erythrocyte oxidative-induced hemolysis. J Agric Food Chem 58:135–140CrossRef Paiva-Martins F, Fernandes J, Santos V, Silva L, Borges F, Rocha S, Belo L, Santos-Silva A (2010) Powerful protective role of 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde against erythrocyte oxidative-induced hemolysis. J Agric Food Chem 58:135–140CrossRef
14.
Zurück zum Zitat Buch MH, Prendergast BD, Storey RF (2010) Antiplatelet therapy and vascular disease: an update. Ther Adv Cardiovasc Dis 4:249–275CrossRef Buch MH, Prendergast BD, Storey RF (2010) Antiplatelet therapy and vascular disease: an update. Ther Adv Cardiovasc Dis 4:249–275CrossRef
15.
Zurück zum Zitat Dell’Agli M, Maschi O, Galli GV, Fagnani R, Dal Cero E, Caruso D, Bosisio E (2008) Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase. Br J Nutr 99:945–951 Dell’Agli M, Maschi O, Galli GV, Fagnani R, Dal Cero E, Caruso D, Bosisio E (2008) Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase. Br J Nutr 99:945–951
16.
Zurück zum Zitat Zbidi H, Salido S, Altarejos J, Perez-Bonilla M, Bartegi A, Rosado JA, Salido GM (2009) Olive tree wood phenolic compounds with human platelet antiaggregant properties. Blood Cells Mol Dis 42:279–285CrossRef Zbidi H, Salido S, Altarejos J, Perez-Bonilla M, Bartegi A, Rosado JA, Salido GM (2009) Olive tree wood phenolic compounds with human platelet antiaggregant properties. Blood Cells Mol Dis 42:279–285CrossRef
17.
Zurück zum Zitat Madrona A, Pereira-Caro G, Mateos R, Rodríguez G, Trujillo M, Fernández-Bolaños J, Espartero JL (2009) Synthesis of hydroxytyrosyl alkyl ethers from olive oil waste waters. Molecules 14:1762–1772CrossRef Madrona A, Pereira-Caro G, Mateos R, Rodríguez G, Trujillo M, Fernández-Bolaños J, Espartero JL (2009) Synthesis of hydroxytyrosyl alkyl ethers from olive oil waste waters. Molecules 14:1762–1772CrossRef
18.
Zurück zum Zitat Pereira-Caro G, Mateos R, Saha S, Madrona A, Espartero JL, Bravo L, Kroon PA (2010) Transepithelial transport and metabolism of new lipophilic ether derivatives of hydroxytyrosol by enterocyte-like Caco-2/TC7 cells. J Agric Food Chem 58:11501–11509CrossRef Pereira-Caro G, Mateos R, Saha S, Madrona A, Espartero JL, Bravo L, Kroon PA (2010) Transepithelial transport and metabolism of new lipophilic ether derivatives of hydroxytyrosol by enterocyte-like Caco-2/TC7 cells. J Agric Food Chem 58:11501–11509CrossRef
19.
Zurück zum Zitat Pereira-Caro G, Bravo L, Madrona A, Espartero JL, Mateos R (2010) Uptake and metabolism of new synthetic lipophilic derivatives, hydroxytyrosyl ethers, by human hepatoma HepG2 cells. J Agric Food Chem 58:798–806CrossRef Pereira-Caro G, Bravo L, Madrona A, Espartero JL, Mateos R (2010) Uptake and metabolism of new synthetic lipophilic derivatives, hydroxytyrosyl ethers, by human hepatoma HepG2 cells. J Agric Food Chem 58:798–806CrossRef
20.
Zurück zum Zitat Brideau C, Kargman S, Liu S, Dallob AL, Ehrich EW, Rodger IW, Chan CC (1996) A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors. Inflamm Res 45:68–74CrossRef Brideau C, Kargman S, Liu S, Dallob AL, Ehrich EW, Rodger IW, Chan CC (1996) A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors. Inflamm Res 45:68–74CrossRef
21.
Zurück zum Zitat Patrignani P, Panara MR, Greco A, Fusco O, Natoli C, Iacobelli S, Cipollone F, Ganci A, Creminon C, Maclouf J et al (1994) Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J Pharmacol Exp Ther 271:1705–1712 Patrignani P, Panara MR, Greco A, Fusco O, Natoli C, Iacobelli S, Cipollone F, Ganci A, Creminon C, Maclouf J et al (1994) Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J Pharmacol Exp Ther 271:1705–1712
22.
Zurück zum Zitat de Roos B, Zhang X, Rodriguez Gutierrez G, Wood S, Rucklidge GJ, Reid MD, Duncan GJ, Cantlay LL, Duthie GG, O’Kennedy N (2011) Anti-platelet effects of olive oil extract: in vitro functional and proteomic studies. Eur J Nutr 50:553–562CrossRef de Roos B, Zhang X, Rodriguez Gutierrez G, Wood S, Rucklidge GJ, Reid MD, Duncan GJ, Cantlay LL, Duthie GG, O’Kennedy N (2011) Anti-platelet effects of olive oil extract: in vitro functional and proteomic studies. Eur J Nutr 50:553–562CrossRef
23.
Zurück zum Zitat Petroni A, Blasevich M, Salami M, Papini N, Montedoro GF, Galli C (1995) Inhibition of platelet aggregation and eicosanoid production by phenolic components of olive oil. Thromb Res 78:151–160CrossRef Petroni A, Blasevich M, Salami M, Papini N, Montedoro GF, Galli C (1995) Inhibition of platelet aggregation and eicosanoid production by phenolic components of olive oil. Thromb Res 78:151–160CrossRef
24.
Zurück zum Zitat Togna GI, Togna AR, Franconi M, Marra C, Guiso M (2003) Olive oil isochromans inhibit human platelet reactivity. J Nutr 133:2532–2536 Togna GI, Togna AR, Franconi M, Marra C, Guiso M (2003) Olive oil isochromans inhibit human platelet reactivity. J Nutr 133:2532–2536
25.
Zurück zum Zitat De La Cruz JP, Villalobos MA, Carmona JA, Martín-Romero M, Smith-Agreda JM, Sánchez de la Cuesta F (2000) Antithrombotic potential of olive oil administration in rabbits with elevated cholesterol. Thromb Res 100:305–315CrossRef De La Cruz JP, Villalobos MA, Carmona JA, Martín-Romero M, Smith-Agreda JM, Sánchez de la Cuesta F (2000) Antithrombotic potential of olive oil administration in rabbits with elevated cholesterol. Thromb Res 100:305–315CrossRef
26.
Zurück zum Zitat González-Correa JA, Muñoz-Marín J, Arrebola MM, Guerrero A, Narbona F, López-Villodres JA, De La Cruz JP (2007) Dietary virgin olive oil reduces oxidative stress and cellular damage in rat brain slices subjected to hypoxia-reoxygenation. Lipids 42:921–929CrossRef González-Correa JA, Muñoz-Marín J, Arrebola MM, Guerrero A, Narbona F, López-Villodres JA, De La Cruz JP (2007) Dietary virgin olive oil reduces oxidative stress and cellular damage in rat brain slices subjected to hypoxia-reoxygenation. Lipids 42:921–929CrossRef
27.
Zurück zum Zitat De La Cruz JP, Blanco E, Sánchez de la Cuesta F (2000) Effect of dipyridamole and aspirin on the platelet-neutrophil interaction via the nitric oxide pathway. Eur J Pharmacol 397:35–41CrossRef De La Cruz JP, Blanco E, Sánchez de la Cuesta F (2000) Effect of dipyridamole and aspirin on the platelet-neutrophil interaction via the nitric oxide pathway. Eur J Pharmacol 397:35–41CrossRef
28.
Zurück zum Zitat Freedman JE, Parker C 3rd, Li L, Perlman JA, Frei B, Ivanov V, Deak LR, Iafrati MD, Folts JD (2001) Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation 103:2792–2798CrossRef Freedman JE, Parker C 3rd, Li L, Perlman JA, Frei B, Ivanov V, Deak LR, Iafrati MD, Folts JD (2001) Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation 103:2792–2798CrossRef
29.
Zurück zum Zitat Stoll G, Bendszus M (2006) Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke 37:1923–1932CrossRef Stoll G, Bendszus M (2006) Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke 37:1923–1932CrossRef
30.
Zurück zum Zitat Mallika V, Goswami B, Rajappa M (2007) Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective. Angiology 58:513–522CrossRef Mallika V, Goswami B, Rajappa M (2007) Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective. Angiology 58:513–522CrossRef
31.
Zurück zum Zitat Zhang X, Cao J, Zhong L (2009) Hydroxytyrosol inhibits pro-inflammatory cytokines, iNOS, and COX-2 expression in human monocytic cells. Naunyn Schmiedebergs Arch Pharmacol 379:581–586CrossRef Zhang X, Cao J, Zhong L (2009) Hydroxytyrosol inhibits pro-inflammatory cytokines, iNOS, and COX-2 expression in human monocytic cells. Naunyn Schmiedebergs Arch Pharmacol 379:581–586CrossRef
32.
Zurück zum Zitat Laguerre M, López Giraldo LJ, Lecomte J, Figueroa-Espinoza MC, Baréa B, Weiss J, Decker EA, Villeneuve P (2010) Relationship between hydrophobicity and antioxidant ability of “phenolipids” in emulsion: a parabolic effect of the chain length of rosmarinate esters. J Agric Food Chem 58:2869–2876CrossRef Laguerre M, López Giraldo LJ, Lecomte J, Figueroa-Espinoza MC, Baréa B, Weiss J, Decker EA, Villeneuve P (2010) Relationship between hydrophobicity and antioxidant ability of “phenolipids” in emulsion: a parabolic effect of the chain length of rosmarinate esters. J Agric Food Chem 58:2869–2876CrossRef
33.
Zurück zum Zitat Tofani D, Balducci V, Gasperi T, Incerpi S, Gambacorta A (2010) Fatty acid hydroxytyrosyl esters: structure/antioxidant activity relationship by ABTS and in cell-culture DCF assays. J Agric Food Chem 58:5292–5299CrossRef Tofani D, Balducci V, Gasperi T, Incerpi S, Gambacorta A (2010) Fatty acid hydroxytyrosyl esters: structure/antioxidant activity relationship by ABTS and in cell-culture DCF assays. J Agric Food Chem 58:5292–5299CrossRef
Metadaten
Titel
Antiplatelet effect of new lipophilic hydroxytyrosol alkyl ether derivatives in human blood
verfasst von
J. J. Reyes
J. P. De La Cruz
J. Muñoz-Marin
A. Guerrero
J. A. Lopez-Villodres
A. Madrona
J. L. Espartero
J. A. Gonzalez-Correa
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
European Journal of Nutrition / Ausgabe 2/2013
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-012-0361-1

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