An up-date of olive oil phenols in inflammation and cancer: Molecular mechanisms and clinical implications

Current Medicinal Chemistry

Volumn 20, Issue 37, 2013, Pages 4758-4776

  Cardeno A ^a   Sanchez Hidalgo M ^a   Alarcon De La Lastra C ^a  

^a UNIVERSITY OF SEVILLE   (Spain)

Author keywords

Cancer; Inflammation; Olive oil; Oxidative stress; Phenols

Indexed keywords

AMYLOID BETA PROTEIN; CAFFEIC ACID; CINNAMIC ACID DERIVATIVE; FLAVONOID; HYDROXYTYROSOL; HYDROXYTYROSOL 20; HYDROXYTYROSYL ACETATE; KAEMPFEROL; LIGNAN; OLEOCANTHAL; OLEUROPEIN; OLEUROPEIN AGLYCON; OLIVE OIL; PINORESINOL; POLYPHENOL; SECOIRIDOIDS; TYROSOL; TYROSOL 4 HYDROPHENYL ETHANOL; UNCLASSIFIED DRUG;

AGING; ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; ATHEROGENESIS; CELL DEATH; CHEMOPROPHYLAXIS; DRUG BIOAVAILABILITY; DRUG EFFECT; DRUG MECHANISM; DRUG STRUCTURE; HUMAN; INFLAMMATION; MALIGNANT NEOPLASTIC DISEASE; MOLECULAR BIOLOGY; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE;

ANIMALS; ANTI-INFECTIVE AGENTS; ANTINEOPLASTIC AGENTS; ANTIOXIDANTS; APOPTOSIS; HUMANS; INFLAMMATION; NEOPLASMS; NEUROPROTECTIVE AGENTS; PLANT OILS; POLYPHENOLS;

EID: 84889244212     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/09298673113209990159     Document Type: Article

References (146)

1. Alarcón de la Lastra, C.; Barranco, M.D.; Motilva, V.; Herrerías J.M. Mediterranean diet and health: biological importance of olive oil. Curr. Pharm. Des., 2001, 7(10), 933-950. (Pubitemid 32624438)
2. Angerosa, F.; Mostallino, R.; Basti, C.; Vito, R. Influence of malaxation temperature and time on the quality of virgin olive oils. Food Chemistry, 2001, 72, 19-28.
3. Cicerale, S.; Conlan X.A.; Sinclair, A.J.; Keast, R.S. Chemistry and health of olive oil phenolics. Crit. Rev. Food Sci. Nutr., 2009, 49(3), 218-236.
4. Gomez-Rico, A.; Salvador, M.D.; La Greca, M.; Fregapane, G. Phenolic and volatile compounds of EVOO (Olea europaea L. Cv. Cornicabra) with regard to fruit ripening and irrigation management. J. Agric. Food Chem., 2006, 54(19), 7130-7136. (Pubitemid 44554931)
5. Escrich, E.; Solanas, M.; Moral, R.; Escrich, R. Modulatory effects and molecular mechanisms of olive oil and other dietary lipids in breast cancer. Curr. Pharm. Des., 2011, 17(8), 813-830.
6. Gillingham, L.G.; Harris-Janz, S.; Jones, P.J. Dietary monounsaturated fatty acids are protective against metabolic syndrome and cardiovasculardisease risk factors. Lipids., 2011, 46(3), 209-228.
7. Escrich, E.; Moral, R.; Grau, L.; Costa, I.; Solanas, M. Molecular mechanisms of the effects of olive oil and other dietary lipids on cancer. Mol. Nutr. Food Res., 2007, 51(10), 1279-1292. (Pubitemid 350013175)
8. Medina-Remón, A.; Estruch, R.; Tresserra-Rimbau, A.; Vallverdú-Queralt, A.; Lamuela-Raventos, R.M. The Effect of Polyphenol Consumption on Blood Pressur. Mini Rev. Med. Chem., 2012. [Epub ahead of print].
9. Moreno-Luna, R.; Muñoz-Hernandez, R.; Miranda, M.L.; Costa, A.F.; Jimenez-Jimenez, L.; Vallejo-Vaz, A.J.; Muriana, F.J.; Villar, J.; Stiefel, P. Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Am. J. Hypertens., 2012, 25(12), 1299-1304.
10. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on the substantiation of a health claim related to polyphenols in olive and maintenance of normal blood HDLcholesterol concentrations (ID 1639, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/20061. EFSA Journal, 2012, 10, 2848.
11. Visioli, F.; Bernardini, E. Extra virgin olive oil's polyphenols: biological activities. Curr. Pharm. Des., 2011, 17(8), 786-804.
12. Giovannini, C.; Masella, R. Role of polyphenols in cell death control. Nutr. Neurosci., 2012, 15(3), 134-149.
13. López-Miranda, J.; Pérez-Jiménez, F.; Ros, E.; De Caterina, R.; Badimón, L et al. Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba 2008. Nutr. Metab. Cardiovasc. Dis., 2010, 20, 284-294.
14. Granados-Principal, S.; Quiles, J.L.; Ramirez-Tortosa, C.L.; Sanchez-Rovira, P.; Ramirez-Tortosa, M.C. Hydroxytyrosol: from laboratory investigations to future clinical trials. Nutr. Rev., 2010, 68(4), 191-206.
15. Cortesi, N.; Fedeli, E. Polar components of virgin olive oil. Riv. Ital. Sostanze Grasse, 1983, 60, 341-351.
16. Carrasco-Pancorbo, A.; Cerretani, L.; Bendini, A.; Segura-Carretero, A.; Gallina-Toschi, T.; Fernandez-Gutierrez, A. Analytical determination of polyphenols in olive oils. J. Sep. Sci., 2005, 28, 837-858. (Pubitemid 40909090)
17. Lavelli, V.; Bondesan, L. Secoiridoids, tocopherols, and antioxidant activity of monovarietal extra virgin olive oils extracted from destoned fruits. J. Agric. Food Chem., 2005, 53(4), 1102-1107. (Pubitemid 40270403)
18. Gallina-Toschi, T.; Cerretani, L.; Bendini, A.; Bonoli-Carbognin, M.; Lercker, G. Oxidative stability and phenolic content of virgin olive oil: an analytical approach by traditional and high resolution techniques. J. Sep. Sci., 2005, 28, 859-870. (Pubitemid 40909091)
19. Owen, R.W.; Giacosa, A.; Hull, W.E.; Haubner, R.; Würtele, G.; Spiegelhalder, B.; Bartsch, H. Olive-oil consumption and health: the possible role of antioxidants. Lancet Oncol., 2000, 1, 107-112.
20. Montedoro, G.F.; Servili, M.; Baldioli, M.; Miniati, E. Simple and hydrolyzable compounds in virgin olive oil. J. Agric. Food Chem., 1992, 40, 1571.
21. De La Torre-Carbot, K.; Jauregui, O.; Gimeno, E.; Castellote, A.I.; Lamuela-Raventós, R.M.; López-Sabater, M.C. Characterization and quantification of phenolic compounds in olive oils by solidphase extraction, HPLC-DAD, and HPLC-MS/MS. J. Agric. Food Chem., 2005, 53(11), 4331-4340. (Pubitemid 40855453)
22. de la Torre, R. Bioavailability of olive oil phenolic compounds in humans. Inflammopharmacology, 2008, 16(5), 245-247.
23. Karakaya, S. Biovailability of phenolic compounds. Crit. Rev. Food Sci. Nutr., 2004, 44(6), 453-464.
24. Visioli, F.; Galli, C.; Bornet, F.; Mattei, A.; Patelli, R.; Galli, G.; Caruso, D. Olive oil phenolics are dose-dependently absorbed in humans. FEBS Lett., 2000, 468(2-3), 159-160. (Pubitemid 30110787)
25. Miro-Casas, E.; Covas, M.I.; Farre, M.; Fito, M.; Ortuño, J.; Weinbrenner, T.; Roset, P.; de la Torre, R. Hydroxytyrosol disposition in humans. Clin. Chem., 2003, 49(6), 945-952. (Pubitemid 36623475)
26. Caruso, D.; Visioli, F.; Patelli, R.; Galli, C.; Galli, G. Urinary excretion of olive oil phenols and their metabolites in humans. Metabolism., 2001, 50(12), 1426-8. (Pubitemid 34007411)
27. Garcia-Villalba, R.; Carrasco-Pancorbo, A.; Nevedomskaya, E.; Mayboroda, O.A.; Deelder, A.M.; Segura-Carretero, A.; Fernández-Gutiérrez, A. Exploratory analysis of human urine by LC-ESITOFMS after high intake of olive oil: understanding the metabolism of polyphenols. Anal. Bioanal. Chem., 2010, 398(1), 463-475.
28. García-Villalba, R.; Carrasco-Pancorbo, A.; Oliveras-Ferraros C.; Menéndez, J.A.; Segura-Carretero, A.; Fernández-Gutiérrez, A. Uptake and metabolism of olive oil polyphenols in human breast cancer cells using nano-liquid chromatography coupled to electrospray ionization-time of flight-mass spectrometry. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci., 2012, 898, 69-77.
29. Manna, C.; Migliardi, V.; Sannino, F.; De Martino, A.; Capasso, R. Protective effects of synthetic hydroxytyrosol acetyl derivatives against oxidative stress in human cells. J. Agric. Food Chem., 2005, 53(24), 9602-9607. (Pubitemid 41784171)
30. Vissers, M.N.; Zock, P.L.; Katan, M.B. Bioavailability and antioxidant effects of olive oil phenols in humans: a review. Eur. J. Clin. Nutr., 2004, 58(6), 955-965. (Pubitemid 38923195)
31. Cicerale, S.; Lucas, L.; Keast, R. Biological activities of phenolic compounds present in virgin olive oil. Int. J. Mol. Sci., 2010, 11(2), 458-479.
32. Priora, R.; Summ, a D.; Frosali, S.; Margaritis, A.; Di Giuseppe, D.; Lapucci, C.; Ieri, F.; Pulcinelli, F.M.; Romani, A.; Franconi, F; Di Simplicio, P. Administration of minor polar compound-enriched extra virgin olive oil decreases platelet aggregation and the plasma concentration of reduced homocysteine in rats. J. Nutr., 2008, 138(1), 36-41.
33. Alarcon de la Lastra, C.; Villegas, I.; Ramon Martin, A. In: Reveratrol in health disease, Resveratrol as an antioxidant; B.B. Aggarwal, S. Shishodia, Ed.; Taylor & Francis: Boca Raton, pp. 200633-200655.
34. Förstermann, U. Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies. Nat. Clin. Pract. Cardiovasc. Med., 2008, 5(6), 338-349. (Pubitemid 351761708)
35. Cotelle, N. Role of flavonoids in oxidative stress. Curr. Topics Med. Chem., 2011, 1(6), 569-590.
36. de la Lastra, C.A.; Villegas, I. Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem. Soc. Trans., 2007, 35(15), 1156-1160. (Pubitemid 350206449)
37. Raederstorff, D. Antioxidant activity of olive polyphenols in humans: a review. Int. J. Vitam. Nutr. Res., 2009, 79(3), 152-165.
38. O'Dowd, Y.; Driss, F.; Dang, PM.; Elbim, C.; Gougerot-Pocidalo, M.A.; Pasquier, C.; El-Benna, J. Antioxidant effect of hydroxytyrosol, a polyphenol from olive oil: scavenging of hydrogen peroxide but not superoxide anion produced by human neutrophils. J. Biochem. Pharmacol., 2004, 68(10), 2003-2008. (Pubitemid 39346190)
39. Rietjens, S.J.; Bast, A.; de Vente, J.; Haenen, G.R. The olive oil antioxidant hydroxytyrosol efficiently protects against the oxidative stress-induced impairment of the NO bullet response of isolated rat aorta. Am. J. Physiol. Heart. Circ. Physiol., 2007, 292(4), 1931-1936.
40. Martín, M.A.; Ramos, S.; Granado-Serrano, A.B.; Rodríguez-Ramiro, I.; Trujillo, M.; Bravo, L.; Goya, L. Hydroxytyrosol induces antioxidant/detoxificant enzymes and Nrf2 translocation via extracellular regulated kinases and phosphatidylinositol-3-kinase/protein kinase B pathways in HepG2 cells. Mol. Nutr. Food Res., 2010, 54(7), 956-66.
41. Goya, L.; Mateos, R.; Bravo, L. Effect of the olive oil phenol hydroxytyrosol on human hepatoma HepG2 cells. Protection against oxidative stress induced by tert-butylhydroperoxide. Eur. J. Nutr., 2007, 46, 70-78. (Pubitemid 46295311)
42. Katsiki, M.; Chondrogianni, N.; Chinou I.; Rivett, A.J.; Gonos, E.S. The olive constituent oleuropein exhibits proteasome stimulatory properties in vitro and confers life span extension of human embryonic fibroblasts. Rejuvenation. Res., 2007, 10(2), 157-172. (Pubitemid 46944984)
43. Loru, D.; Incani, A.; Deiana, M.; Corona, G.; Atzeri, A.; Melis, M.P.; Rosa, A.; Dessì, M.A. Protective effect of hydroxytyrosol and tyrosol against oxidative stress in kidney cells. Toxicol. Ind. Health, 2009, 25(4-5), 301-310.
44. 2-induced cell injury and protection by hydroxytyrosol and its metabolite homovanillic alcohol. Mol. Nutr. Food Res., 2010, 54(6), 788-796.
45. Deiana, M.; Incani A.; Rosa A.; Corona, G.; Atzeri, A.; Loru, D.; Melis, P.; Dessì, M.A. Protective effect of hydroxytyrosol and its metabolite homovanillic alcohol on (2)O(2) induced lipid peroxidation in renal tubular epithelial cells. Food Chem. Toxicol., 2008, 4(9), 2984-2990.
46. Visioli F.; Galli C.; Plasmati E.; Viappiani, S.; Hernandez, A.; Colombo, C.; Sala A. Olive phenol hydroxytyrosol prevents passive smoking-induced oxidative stress. Circulation, 2000, 102(18), 2169-2171.
47. Robertson, R.P.; Harmon, J.; Tran, P.O.; Tanaka, Y.; Takahashi, H. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes, 2003, 52(3), 581-587. (Pubitemid 36323562)
48. Lenzen, S.; Drinkgern, J.; Tiedge, M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic. Biol. Med., 1996, 20(3), 463-466. (Pubitemid 26077870)
49. Oliveras-López, M.J.; Berná, G.; Carneiro, E.M.; López-García de la Serrana, H.; Martín, F.; López, M.C. An extra-virgin olive oil rich in polyphenolic compounds has antioxidant effects in OF1 mice. J. Nutr., 2008, 138(6), 1074-1078. (Pubitemid 351769131)
50. Bogani, P.; Galli, C.; Villa, M.; Visioli, F. Postprandial antiinflammatory and antioxidant effects of extra virgin olive oil. Atherosclerosis, 2007, 190(1), 181-186. (Pubitemid 44908313)
51. Simonyi A.; Wang Q.; Miller RL.; Yusof, M.; Shelat, P.B.; Sun, A.Y.; Sun, G.Y. Polyphenols in cerebral ischemia: novel targets for neuroprotection. Mol. Neurobiol., 2005, 31(1-3), 135-147. (Pubitemid 41271199)
52. González-Correa, J.A.; Navas, M.D.; Lopez-Villodres, J.A.; Trujillo, M.; Espartero, J.L.; De La Cruz, J.P. Neuroprotective effect of hydroxytyrosol and hydroxytyrosol acetate in rat brain slices subjected to hypoxia-reoxygenation. Neurosci. Lett., 2008, 446(2-3), 143-146.
53. Schaffer, S.; Podstawa, M.; Visioli, F.; Bogani, P.; Müller, W.E.; Eckert, G.P. Hydroxytyrosol-rich olive mill wastewater extract protects brain cells in vitro and ex vivo. J. Agric. Food. Chem., 2007, 55(13), 5043-5049. (Pubitemid 47056055)
54. Bu, Y.; Rho, S.; Kim J.; Kim, M.Y.; Lee, D.H.; Kim, S.Y.; Choi, H.; Kim, H. Neuroprotective effect of tyrosol on transient focal cerebral ischemia in rats. Neurosci. Lett., 2007, 414(3), 218-221.
55. Pezzella, A.; d'Ischia, M.; Napolitano, A.; Misuraca, G.; Prota, G. Iron-mediated generation of the neurotoxin 6-hydroxydopamine quinone by reaction of fatty acid hydroperoxides with dopamine: a possible contributory mechanism for neuronal degeneration in Parkinson's disease. J. Med. Chem., 1997, 40(14), 2211-2216. (Pubitemid 27284359)
56. Vauzour, D.; Corona, G.; Spencer, J.P. Caffeic acid, tyrosol and pcoumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity. Arch. Biochem. Biophys., 2010, 501(1), 106-111.
57. Vassallo, N.; Scerri, C. Mediterranean Diet and Dementia of the Alzheimer Type. Curr. Aging Sci., 2012, [Epub ahead of print].
58. Campdelacreu, J. Parkinson disease and Alzheimer disease: environmental risk factors. Neurologia, 2012, [Epub ahead of print].
59. St-Laurent-Thibault, C.; Arseneault, M.; Longpré F.; Ramassamy, C. Tyrosol and hydroxytyrosol, two main components of olive oil, protect N2a cells against amyloid-β-induced toxicity. Involvement of the NF-kB signalling. Curr. Alzheimer. Res., 2011, 8(5), 543-551.
60. Spillantini, M.G.; Murrell, J.R.; Goedert, M.; Farlow, M.; Klug, A.; Ghetti, B. Mutations in the tau gene (MAPT) in FTDP-17: the family with multiple system tauopathy with presenile dementia (MSTD). J. Alzheimer Dis., 2006, 9, 373-380. (Pubitemid 44253331)
61. Li, W.; Sperry, J.B.; Crowe, A.; Trojanowski, J.Q.; Smith, A.B. 3rd.; Lee, V.M. Inhibition of tau fibrillization by oleocanthal via reaction with amino groups of tau. J. Neurochem., 2009, 110, 1339-1351.
62. Terry, R.D.; Masliah, E.; Salmon, D.P.; Butters, N.; DeTeresa, R.; Hill, R.; Hansen, L.A.; Katzman, R. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol., 1991, 30(4), 572-580.
63. Lacor, P.N.; Buniel, M.C.; Furlow, P.W.; Clemente, A.S.; Velasco, P.T.; Wood, M.; Viola, K.L.; Klein, W.L. Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J. Neurosci., 2007, 27(4), 796-807. (Pubitemid 46174498)
64. Hu, W.; Ralay-Ranaivo, H.; Roy, S.M.; Behanna, H.A.; Wing, L.K.; Munoz, L.; Guo, L.; Van Eldik, L.J.; Watterson, D.M. Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits. Bioorg. Med. Chem. Lett., 2007, 17, 414-418. (Pubitemid 46084908)
65. Pitt, J.; Roth, W.; Lacor, P.; Smith, A.B. 3rd.; Blankenship, M.; Velasco, P.; De Felice, F.; Breslin, P.; Klein, W.L. Alzheimer'sassociated A-beta oligomers show altered structure immunoreactivity and synaptotoxicity with low doses of Oleocanthal. Toxicol. Appl. Pharmacol., 2009, 240(2), 189-197.
66. Khalatbary, A.R.; Ahmadvand, H. Effect of oleuropein on tissue myeloperoxidase activity in experimental spinal cord trauma. Iran Biomed. J., 2011, 15(4), 164-167.
67. Khalatbary, A.R.; Zarrinjoei, G.R. Anti-inflammatory effect of oleuropein in experimental rat spinal cord trauma. Iran Red. Crescent. Med. J., 2012, 14(4), 229-234.
68. Braam, B.; Langelaar-Makkinje, M.; Verkleij, A.; Bluyssen, H.; Verrips, T.; Koomans, HA.; Joles, JA.; Post, JA. Anti-oxidant sensitivity of donor age-related gene expression in cultured fibroblasts. Eur. J. Pharmacol., 2006, 542(1-3), 154-161. (Pubitemid 44066365)
69. Fabiani, R.; Rosignoli, P.; De Bartolomeo, A.; Fuccelli, R.; Servili, M.; Montedoro, G.F.; Morozzi, G. Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells. J. Nutr., 2008, 138, 1411-1416.
70. Grasso, S.; Siracusa, L.; Spatafora, C.; Renis M.; Tringali, C. Hydroxytyrosol lipophilic analogues: enzymatic synthesis, radical scavenging activity and DNA oxidative damage protection. Bioorg. Chem., 2007, 35, 137-152. (Pubitemid 46365829)
71. Paiva-Martins, F.; Fernandes, J.; Rocha, S.; Nascimento, H.; Vitorino, R.; Amado, F.; Borges, F.; Belo, L.; Santos-Silva, A. Effects of olive oil polyphenols on erythrocyte oxidative damage. Mol. Nutr. Food Res., 2009, 53(5), 609-616.
72. Zhu, L.; Liu Z.; Feng, Z.; Hao, J.; Shen, W.; Li, X.; Sun, L.; Sharman, E.; Wang Y.; Wertz, K.; Weber, P.; Shi, X.; Liu, J. Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells. J. Nutr. Biochem., 2010, 21(11), 1089-1098.
73. Cañuelo, A.; Gilbert-López, B.; Pacheco-Liñán, P.; Martínez-Lara, E.; Siles, E.; Miranda-Vizuete, A. Tyrosol, a main phenol present in extra virgin olive oil, increases lifespan and stress resistance in Caenorhabditis elegans. Mech. Ageing. Dev., 2012, 133(8), 563-574.
74. Moore.; M. M.; Chua, W.; Charles.; K. A.; Clarke.; S. J. Inflammation and cancer: causes and consequences Clin. Pharmacol. Ther., 2010, 87, 504-508.
75. Sánchez-Fidalgo, S.; Villegas, I.; Sánchez-Hidalgo, M.; de la Lastra, C.A. Sirtuin modulators: mechanisms and potential clinical implications. Curr. Med. Chem., 2012, 19(15), 2414-2441.
76. Medzhitov.; R. Origin and physiological roles of inflammation. Nature, 2008, 454 (7203), 428-435.
77. Libby, P. Inflammation in atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 2012 32(9), 2045-2051.
78. Romeo, G.R.; Lee, J.; Shoelson, S.E. Metabolic syndrome, insulin resistance, and roles of inflammation-mechanisms and therapeutic targets. Arterioscler. Thromb. Vasc. Biol., 2012, 32(8), 1771-1776.
79. Hursting, S.D.; Hursting, M.J. Growth signals, inflammation, and vascular perturbations: mechanistic links between obesity, metabolic syndrome, and cancer. Arterioscler. Thromb. Vasc. Biol., 2012, 32(8), 1766-1770.
80. Lima, I.V.; Bastos, L.F.; Limborço-Filho, M.; Fiebich, B.L.; de Oliveira, A.C. Role of prostaglandins in neuroinflammatory and neurodegenerative diseases. Mediators Inflamm., 2012.
81. Dinarello, C.A.; Simon, A.; van der Meer, J.W. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat. Rev. Drug Discov., 2012, 11(8), 633-52.
82. Richard, N.; Arnold, S.; Hoeller, U.; Kilpert, C.; Wertz, K.; Schwager, J. Hydroxytyrosol is the major anti-inflammatory compound in aqueous olive extracts and impairs cytokine and chemokine production in macrophages. Planta Med., 2011, 77(17), 90-97.
83. Miles, E.A.; Zoubouli, P.; Calder, P.C Differential antiinflammatory effects of phenolic compounds from extra virgin olive oil identified in human whole blood cultures. Nutrition., 2005, 21(3), 389-94. (Pubitemid 40387940)
84. Zhang, X.; Cao, J.; Zhong, L: Hydroxytyrosol inhibits proinflammatory cytokines, iNOS, and COX-2 expression in human monocytic cells. Naunyn-Schmiedeberg's Arch Pharmacol., 2009, 379, 581-586.
85. Zhang, X.; Cao, J.; Jiang L.; Zhong, L. Suppressive effects of hydroxytyrosol on oxidative stress and nuclear Factor-kappaB activation in THP-1 cells. Biol. Pharm. Bull., 2009, 32(4), 578-582.
86. Maiuri, M.C.; De Stefano, D.; Di Meglio, P.; Irace, C.; Savarese, M.; Sacchi, R.; Cinelli, M.P.; Carnuccio, R. Hydroxytyrosol, a phenolic compound from virgin olive oil, prevents macrophage activation. Naunyn Schmiedebergs Arch. Pharmacol., 2005, 371(6), 457-465. (Pubitemid 41218965)
87. Brunelleschi, S; Bardelli, C.; Amoruso, A.; Gunella, G.; Ieri, F.; Romani, A; Malorni, W; Franconi, F. Minor polar compounds extra-virgin olive oil extract (MPC-OOE) inhibits NF-kappa B translocation in human monocyte/macrophages. Pharmacol. Res., 2007, 56(6), 542-549. (Pubitemid 350137776)
88. Dell'Agli, M; Fagnani R.; Galli, GV.; Maschi, O.; Gilardi, F.; Bellosta, S.; Crestani, M.; Bosisio, E.; De Fabiani, E.; Caruso, D. Olive oil phenols modulate the expression of metalloproteinase 9 in THP-1 cells by acting on nuclear factor-kB signalling. J. Agric. Food Chem., 2010, 58, 2246-2252.
89. Jung, H.W.; Mahesh, R.; Lee, J.G.; Lee, S.H.; Kim, Y.S.; Park, Y.K. Pinoresinol from the fruits of Forsythia koreana inhibits inflammatory responses in LPS-activated microglia. Neurosci. Lett., 2010, 480(3), 215-220.
90. During, A.; Debouche, C.; Raas, T.; Larondelle, Y. Among plant lignans, pinoresinol has the strongest antiinflammatory properties in human intestinal caco-2 cells. J. Nutr., 2012, 142(10), 1798-1805.
91. Montedoro, G.; Servili, M. Simple and hydrolyzable compounds in virgin olive oil. Spectroscopic characterizations of the secoiridoid derivatives. J. Agric. Food Chem. 1993, 41, 2228-2234.
92. Andrewes, P.; Busch, J.L.; de Joode, T.; Groenewegen, A.; Alexandre, H. Sensory properties of virgin olive oil polyphenols: identification of deacetoxy-ligstroside aglycon as a key contributor to pungency. J. Agric. Food Chem., 2003, 51(5), 1415-1420.
93. Beauchamp, G.K.; Keast, R.S.; Morel, D.; Lin, J.; Pika, J.; Han, Q.; Lee, C.H.; Smith, A.B.; Breslin, P.A. Phytochemistry: ibuprofenlike activity in extra-virgin olive oil. Nature, 2005, 437(7055), 45-46. (Pubitemid 41613421)
94. Iacono, A.; Gómez, R.; Sperry, J.; Conde, J.; Bianco, G.; Meli, R.; Gómez-Reino, J.J.; Smith, A.B. 3rd.; Gualillo, O. Effect of oleocanthal and its derivatives on inflammatory response induced by lipopolysaccharide in a murine chondrocyte cell line. Arthritis Rheum., 2010, 62(6), 1675-1682.
95. Scotece, M.; Gómez, R.; Conde, J.; Lopez, V.; Gómez-Reino, J.J.; Lago, F.; Smith, A.B. 3rd.; Gualillo, O. Further evidence for the anti-inflammatory activity of oleocanthal: Inhibition of MIP-1α and IL-6 in J774 macrophages and in ATDC5 chondrocytes. Life Sci., 2012, [Epub ahead of print].
96. Impellizzeri, D.; Esposito, E.; Mazzon, E.; Paterniti, I.; Di Paola, R.; Morittu, V.M.; Procopio, A.; Britti, D.; Cuzzocrea, S. Oleuropein aglycone, an olive oil compound, ameliorates development of arthritis caused by injection of collagen type II in mice. J. Pharmacol. Exp. Ther. 2011, 339(3), 859-869.
97. Impellizzeri,; D.; Esposito, E.; Mazzon, E.; Paterniti, I.; Di Paola, R.; Bramanti, P.; Morittu, V.M.; Procopio, A.; Perri, E.; Britti, D.; Cuzzocrea, S. The effects of a polyphenol present in olive oil, oleuropein aglycone, in an experimental model of spinal cord injury in mice. Biochem. Pharmacol., 2012, 83(10), 1413-1426.
98. Gong, D.; Geng, C.; Jiang, L.; Cao, J.; Yoshimura, H.; Zhong, L. Effects of hydroxytyrosol-20 on carrageenan-induced acute inflammation and hyperalgesia in rats. Phytother. Res., 2009, 23(5), 646-650.
99. Martínez-Domínguez, E.; de la Puerta, R.; Ruiz-Gutiérrez, V. Protective effects upon experimental inflammation models of a polyphenol-supplemented virgin olive oil diet. Inflamm. Res., 2001, 50(2), 102-106. (Pubitemid 32210151)
100. Feng, Z.; Bai, L.; Yan, J.; Li, Y.; Shen, W.; Wang, Y.; Wertz, K.; Weber, P.; Zhang, Y.; Chen, Y.; Liu, J. Mitochondrial dynamic remodeling in strenuous exercise-induced muscle and mitochondrial dysfunction: regulatory effects of hydroxytyrosol. Free Radic. Biol. Med., 2011, 50(10), 1437-1446.
101. Kim, H.Y.; Kim, J.K.; Choi, J.H.; Jung, J.Y.; Oh, W.Y.; Kim, D.C.; Lee, H.S.; Kim, Y.S.; Kang, S.S.; Lee, S.H.; Lee, S.M. Hepatoprotective effect of pinoresinol on carbon tetrachloride-induced hepatic damage in mice. J. Pharmacol. Sci., 2010, 112(1), 105-112.
102. Frontela, C.; Canali, R.; Virgili, F. Use of dietary phenols to modulate inflammatory bowel response. Gastroenterol. Hepatol., 2010, 33(4), 307-312.
103. Rosillo, M.A.; Sánchez-Hidalgo, M.; Cárdeno, A.; Aparicio-Soto, M.; Sánchez-Fidalgo, S.; Villegas, I.; de la Lastra, C.A. Dietary supplementation of an ellagic acid-enriched pomegranate extract attenuates chronic colonic inflammation in rats. Pharmacol. Res., 2012, 66(3), 235-242.
104. Sánchez-Fidalgo, S.; Sánchez de Ibargüen, L.; Cárdeno, A.; Alarcón de la Lastra, C. Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a chronic DSS colitis model. Eur. J. Nutr., 2012, 51(4), 497-506.
105. Alirezaei, M.; Dezfoulian, O.; Neamati, S.; Rashidipour, M.; Tanideh, N.; Kheradmand A. Oleuropein prevents ethanol-induced gastric ulcers via elevation of antioxidant enzyme activities in rats. J. Physiol. Biochem., 2012. [Epub ahead of print]
106. Giner, E.; Andújar, I.; Recio, M.C.; Ríos, J.L.; Cerdá-Nicolás, J.M.; Giner, R.M. Oleuropein ameliorates acute colitis in mice. J. Agric. Food Chem., 2011, 59(24), 12882-12892.
107. Solinas, G.; Germano, G; Mantovani A.; Allavena, P. Tumorassociated macrophages (TAM) as major players of the cancer-related inflammation. J. Leukocyte. Bio., 2009, 86(5), 1065.
108. McGeer, PL.; McGeer, E.G.; Schwab, C. Inflammatory processes exacerbate degenerative neurological disorders. Curr. Hypoth. Res. Mile. Alzheim. Dis., 2009, 1-9.
109. Mantovani, A.; Allavena, P.; Sica, A.; Balkwill, F. Cancer-related inflammation. Nature, 2008, 454(7203), 24.
110. Guerra, C.; Schuhmacher, A.J.; Cañamero, M.; Grippo, P.J.; Verdaguer, L.; Pérez-Gallego, L.; Dubus, P.; Sandgren, EP.; Barbacid, M. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell, 2007, 11(3), 291-302. (Pubitemid 46349841)
111. Sumimoto, H., Imabayashi, F., Iwata, T.; Kawakami, Y. The BRAF-MAPK signalling pathway is essential for cancer-immune evasion in human melanoma cells. J. Exp. Med., 2006, 203(7), 1651-1656. (Pubitemid 44036269)
112. Langowski, J.L.; Zhang, X.; Wu L.; Mattson, J.D.; Chen, T.; Smith, K.; Basham, B.; McClanahan, T.; Kastelein, R.A.; Oft, M. IL-23 promotes tumour incidence and growth. Nature, 2006, 442(7101), 461-465. (Pubitemid 44264796)
113. Grivennikov, S.; Karin, M. Autocrine IL-6 signalling: a key event in tumorigenesis? Cancer Cell, 2008, 13(11), 7-9. (Pubitemid 350309747)
114. Balkwill, F. Cancer and the chemokine network. Nature Rev. Cancer, 2004, 4(7), 540-550. (Pubitemid 38868623)
115. Evan, G.I.; Vousden, K.H. Proliferation, cell cycle and apoptosis in cancer. Nature, 2001, 411(6835), 342-348. (Pubitemid 32467043)
116. Di Fronzo, V.; Gente, R.; Pacioni, D.H.; Riccio, E.H.; Ferrara, L.A. Olive oil and health effects on blood pressure, diabetes, arteriosclerosis, cancer and inflammatory diseases Agro Food Ind. Hi Tech., 2007, 18(4), 4-5. (Pubitemid 47346066)
117. Owen, R.W.; Haubner, R.; Wurtele, G.; Hull, W.E.; Spiegelhalder, B.; Bartsch, H. Olives and olive oil in cancer prevention. Eur. J. Cancer Prev., 2004, 13(4), 319-326. (Pubitemid 39096085)
118. Fabiani, R.; De Bartolomeo, A.; Rosignoli, P.; Servili, M.; Selvaggini, R.; Montedoro, G.F.; Di Saverio, C.; Morozzi, G. Virgin olive oil phenols inhibit proliferation of human promyelocytic leukemia cells (HL60) by inducing apoptosis and differentiation. J. Nutr., 2006, 136(3), 614-619. (Pubitemid 43363744)
119. Hashim, Y.Z.; Rowland, I.R.; McGlynn, H.; Servili, M.; Selvaggini, R.; Taticchi, A.; Esposto, S.; Montedoro, G.; Kaisalo, K.; Wähälä, K.; Gill, C.I. Inhibitory effects of olive oil phenolics on invasion in human colon adenocarcinoma cells in vitro. Int. J. Cancer, 2008, 122(2), 495-500. (Pubitemid 350308939)
120. Manna, C.; Galletti P.; Cucciolla, V.; Moltedo, O.; Leone, A.; Zappia, V. The protective effect of the olive oil polyphenols (3, 4-dihydroxyphenyl)- ethanol counteracts reactive oxygen metabolite induced cytotoxicity in Caco-2 cells. J. Nutr., 1997, 127(2), 286-292. (Pubitemid 27079958)
121. Deiana, M.; Corona, G.; Incani, A.; Loru, D.; Rosa, A.; Atzeri, A.; Melis, M.P.; Dessi, M.A. Protective effect of simple phenols from extra virgin olive oil against lipid peroxidation in intestinal Caco-2 cells. Food Chem. Toxicol., 2010, 48(10), 3008-3016.
122. D'Angelo, S.; Ingrosso, D.; Migliardi, V.; Sorrentino, A.; Donnarumma, G.; Baroni, A.; Masella, L.; Trufano, M. A.; Zappia, M.; Galleti, P. Hydroxytyrosol, a natural antioxidant from olive oil, prevents protein damage induced by long-wave ultraviolet radiation in melanoma cells. Free Radical Biol. Med., 2005, 38(7), 908-919. (Pubitemid 40321083)
123. Fabiani, R.; De Bartolomeo, A.; Rosignoli, P.; Servili, M.; Montedoro, G.F.; Morozzi, G. Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. Eur. J. Cancer Prev., 2002, 11(4), 351-358. (Pubitemid 34948203)
124. Fabiani, R.; Rosignoli, P.; De Bartolomeo, A.; Fuccelli, R.; Morozzi, G. Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells. J. Nutr., 2008, 138(8), 1411-1416.
125. Han, J.; Talorete, T.P.; Yamada, P.; Isoda, H. Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells. Cytotechnology. 2009, 59(1), 45-53.
126. Sirianni, R.; Chimento, A.; De Luca, A.; Casaburi, I.; Rizza, P.; Onofrio, A.; Iacopetta, D.; Puoci, F.; Andò, S.; Maggiolini, M.; Pezzi, V. Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activation. Mol. Nutr. Food Res., 2010, 54(6), 833-840.
127. Obied, H.K.; Prenzler, P.D.; Konczak, I.; Rehman, A.U.; Robards, U. Chemistry and bioactivity of olive biophenols in some antioxidant and antiproliferative in vitro bioassays. Chem. Res. Toxicol., 2009, 22(1), 227-234.
128. Ragione, F.D.; Cucciolla, V.; Borriello, A.; Pietra, V.D.; Pontoni, G.; Racioppi, L.; Manna, C.; Galletti, P.; Zappia, V. Hydroxytyrosol, a natural molecule occurring in olive oil, induces cytochrome c-dependent apoptosis. Biochem Biophys. Res. Commun., 2000, 278(3), 733-739.
129. Goulas, V.; Exarchou, V.; Troganis, A.N.; Psomiadou, E.; Fotsis, T.; Briasoulis, E.; Gerothanassis, I.P. Phytochemicals in olive-leaf extracts and their antiproliferative activity against cancer and endothelial cells. Mol. Nutr. Food Res., 2009, 53(5), 600-608.
130. Fu, S.; Arráez-Roman, D.; Segura-Carretero, A.; Menéndez, J.A.; Menéndez-Gutiérrez, M.P.; Micol, V.; Fernández- Gutiérrez, A. Qualitative screening of phenolic compounds in olive leaf extracts by hyphenated liquid chromatography and preliminary evaluation of cytotoxic activity against human breast cancer cells. Anal. Bioanal. Chem., 2010, 397(2), 643-654.
131. Bouallagui, Z.; Han, J.; Isoda, H.; Sayadi, S. Hydroxytyrosol rich extract from olive leaves modulates cell cycle progression in MCF-7 human breast cancer cells. Food Chem. Toxicol., 2011, 49(1), 179-184.
132. Menendez, J.A; Vazquez-Martin, A.; Oliveras-Ferraros, C.; Garcia-Villalba, R.; Carrasco-Pancorbo, A.; Fernandez-Gutierrez, A.; Segura-Carretero, A. Analyzing effects of extra-virgin olive oil polyphenols on breast cancer-associated fatty acid synthase protein expression using reverse-phase protein microarrays. Int J Mol Med., 2008, 22(4), 433-439.
133. Menendez, J.A.; Vazquez-Martin A.; Oliveras-Ferraros, C.; Garcia-Villalba, R.; Carrasco-Pancorbo, A.; Fernandez-Gutierrez, A.; Segura-Carretero, A. Extra-virgin olive oil polyphenols inhibit HER2 (erbB-2)-induced malignant transformation in human breast epithelial cells: relationship between the chemical structures of extravirgin olive oil secoiridoids and lignans and their inhibitory activities on the tyrosine kinase activity of HER2. Int. J. Oncol., 2009, 34(1), 43-51.
134. Warleta, F.; Quesada CS.; Campos M.; Allouche Y.; Beltrán G.; Gaforio JJ. Hydroxytyrosol protects against oxidative DNA damage in human breast cells. Nutrients., 2011, 3(10), 839-857.
135. Guichard, C.; Pedruzzi E.; Fay, M.; Marie, J.C.; Braut-Boucher, F.; Daniel, F.; Grodet, A.; Gougerot-Pocidalo, M.A.; Chastre, E.; Kotelevets, L.; Lizard, G.; Vandewalle, A.; Driss, F.; Ogier-Denis, E. Dihydroxyphenylethanol induces apoptosis by activating serine/ threonine protein phosphatase PP2A and promotes the endoplasmic reticulum stress response in human colon carcinoma cells. Carcinogenesis., 2006, 27(9), 1812-1827. (Pubitemid 44288663)
136. Corona, G.; Deiana, M.; Incani, A.; Vauzour, D.; Dessì, M.A.; Spencer, J.P. Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their antiproliferative effects. Biochem. Biophys. Res. Commun., 2007, 362(3), 606-611. (Pubitemid 47368135)
137. Notarnicola, M.; Pisanti, S.; Tutino, V.; Bocale, D.; Rotelli, M.T.; Gentile, A.; Memeo, V.; Bifulco, M.; Perri, E.; Caruso, M.G. Effects of olive oil polyphenols on fatty acid synthase gene expression and activity in human colorectal cancer cells. Genes Nutr., 2011, 6(1), 63-69.
138. Hamdi, H.K.; Castellon, R. Oleuropein, a nontoxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor. Biochem. Biophys. Res. Commun, 2005, 334(3), 769-778. (Pubitemid 41033188)
139. Menendez, J.A.; Vazquez-Martin, A.; Colomer, R.; Brunet, J.; Carrasco-Pancorbo, A.; Garcia-Villalba, R.; Fernandez-Gutierrez, A. Segura-Carretero, A. Olive oil's bitter principle reverses acquired autoresistance to trastuzumab (Herceptin) in HER2- overexpressing breast cancer cells. BMC Cancer, 2007, 9(7), 80.
140. Acquaviva, R.; Di Giacomo, C.; Sorrenti, V.; Galvano, F.; Santangelo, R.; Cardile, V.; Gangia, S.; D'Orazio, N.; Abraham, N.G.; Vanella, L. Antiproliferative effect of oleuropein in prostate cell lines. Int. J. Oncol., 2012, 41(1), 31-38.
141. Gill, C.I.; Boyd, A.; McDermott, E.; Servili, M.; Selvaggini, R.; Taticchi, A.; Esposto, S.; Montedoro, G.; McGlynn, H.; Rowland, I. Potential anti-cancer effects of virgin olive oil phenols on colorectal carcinogenesis models in vitro. Int. J. Cancer, 2005, 117(11), 1-7. (Pubitemid 41262753)
142. Elnagar, A.Y.; Sylvester, P.W.; El Sayed, K.A. (S)-Oleocanthal as a c- Met inhibitor for the control of metastatic breast and prostate cancers. Planta Med., 2011, 77(10), 1013-1019.
143. Khanal, P.; Oh, W.K.; Yun, H.J.; Namgoong, G.M.; Ahn, S.G.; Kwon, S.M.; Choi, H.K.; Choi, H.S. p-HPEA-EDA, a phenolic compound of virgin olive oil, activates AMP-activated protein kinase to inhibit carcinogenesis. Carcinogenesis, 2011, 32(4), 545-553.
144. Fini, L.; Hotchkiss, E.; Fogliano, V.; Graziani, G.; Romano, M.; De Vol, E.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. 2008, 29(1), 139-146. (Pubitemid 351201752)
145. Kimura, Y.; Sumiyoshi, M. Olive leaf extract and its main component oleuropein prevent chronic ultraviolet B radiation-induced skin damage and carcinogenesis in hairless mice. J. Nutr., 2009, 139(11), 2079-2086.
146. Grawish, M.E.; Zyada, M.M.; Zaher, A.R. Inhibition of 4-NQOinduced F433 rat tongue carcinogenesis by oleuropein-rich extract. Med. Oncol., 2011, 28(4), 1163-1168.