Biological Effects of Hydroxytyrosol, a Polyphenol from Olive Oil Endowed with Antioxidant Activity

  • Caterina Manna
  • Fulvio Della Ragione
  • Valeria Cucciolla
  • Adriana Borriello
  • Stefania D’Angelo
  • Patrizia Galletti
  • Vincenzo Zappia
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 472)


A number of epidemiological studies indicate that dietary factors may influence the development of some types of cancer and degenerative pathologies, including cardiovascular diseases and cataract. In this respect, it is well documented that daily consumption of fruits and vegetables is associated with a lowered risk of these diseases.1 Polyphenols are bioactive substances that are widely distributed in the vegetable kingdom2,3 and therefore are present in high concentrations in typical components of the Mediterranean diet, such as fruit, vegetables, red wine, and olive oil. The aim of this article is to overview the most recent data on the nutritional value of the phenolic fraction of virgin olive oil in the ongoing studies on its beneficial effects on human health.


Mediterranean Diet Paracellular Transport Oleuropein Aglycone Elenolic Acid Nitroblue Tetrazolium Reduction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Ferro-Luzzi, A. and Ghiselli, A. (1993) Protective aspects of the Mediterranean Diet. In Advances in Nutrition and Cancer ( Zappia, V.; Salvatore, M. and Della Ragione, F., eds.) pp. 137–144. Plenum Publishing Corporation, New York.CrossRefGoogle Scholar
  2. 2.
    Decker, E.A. (1995) The role of phenolics, conjugated linoleic acid, carnosine, and pyrroloquinoline quinone as nonessential dietary antioxidants. Nutr. Rev., 53, 49–58.PubMedCrossRefGoogle Scholar
  3. 3.
    Bravo, L. (1998) Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr. Rev., 56, 317–333.PubMedCrossRefGoogle Scholar
  4. 4.
    Boskou, D. (ed.) (1996) Olive Oil. Chemistry and Technology, AOCS Press, Champain, Illinois.Google Scholar
  5. 5.
    Montedoro, G. and Servili, M. (1992) Olive oil quality parameters in relationship to agronomic and technological aspects. La rivista italiana delle sostanze grasse. LXIX, 563–573.Google Scholar
  6. 6.
    Montedoro, G., Servili, M., Baldioli, M., and Miniati, E. (1992) Simple and hydrolyzable phenolic compounds in virgin olive oil. 1. Their extraction, separation, and quantitative and semiquantitative evaluation by HPLC. J. Agric. Food Chem., 40, 1571–1576.CrossRefGoogle Scholar
  7. 7.
    Montedoro, G., Servili, M., Baldioli, M., and Miniati, E. (1992) Simple and hydrolyzable phenolic compounds in virgin olive oil. 2. Initial characterization of the hydrolyzable fraction. J. Agric. Food Chem., 40, 1577–1580.CrossRefGoogle Scholar
  8. 8.
    Capasso, R., Evidente, A., Visca, C., Gianfreda, L., Maremonti, M., and Greco, G. Jr. (1996) Production of glucose and bioactive aglycone by chemical and enzymatic hydrolysis of purified oleuropein from Olea europea. Appl. Biochem. Biotech., 60, 365–377.Google Scholar
  9. 9.
    Aeschbach, R., Loliger, J., Scott, B.C., Murcia, A., Butler, J., Halliwell, B., and Aruoma, O.I. (1994) Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone, and hydroxytyrosol. Food Chem. Toxic., 32, 31–36.CrossRefGoogle Scholar
  10. 10.
    Visioli, E. Bellomo and Galli, C. (1998) Free radical-scavenging properties of olive oil polyphenols. Biochem. Biophys Res. Commun., 247, 60–64.PubMedCrossRefGoogle Scholar
  11. 11.
    Tsimidou, M., Papadopoulos, G., and Boskou, D. (1992) Phenolic compounds and stability of virgin olive oil. Food Chem., 45, 141–144.CrossRefGoogle Scholar
  12. 12.
    Papadopoulos, G. and Boskou, D. (1991) Antioxidant effect of natural phenols on olive oil. J. Am. Oil Chem. Soc., 68, 669–671.CrossRefGoogle Scholar
  13. 13.
    Ferro-Luzzi, A. and Sette, S. (1989) The Mediterranean diet: an attempt to define its present and past composition. Eur. J. Clin. Nutr., 43, 13–29.PubMedGoogle Scholar
  14. 14.
    Keys, A. and Keys, M. (1975) “How to Eat Well and Stay Well, The Mediterranean Way”, Doubleday and Co. Inc., New York.Google Scholar
  15. 15.
    Mattson, F.H. and Grundy, S.M. (1985) Comparison of dietary saturated, monounsaturated, and polyunsaturated fatty acids on plasma lipids and lipoproteins in man, J. Lipid Res., 26: 194–202.PubMedGoogle Scholar
  16. 16.
    Riccardi, G. and Rivellese, A. (1993) An update on monounsaturated fatty acids. Current Opinion in Lipidology, 4: 13–16.CrossRefGoogle Scholar
  17. 17.
    Witztum, J.L. (1994) The oxidation hypothesis of atherosclerosis. Lancet, 344, 793–795.PubMedCrossRefGoogle Scholar
  18. 18.
    Parthasarathy, S., Khoo, J.C., Miller, E., Witztum, J.L., and Steinberg, D. (1990) Low density lipoprotein rich in oleic acid is protected against oxidative modification: implication for dietary prevention of atherosclerosis. Proc. Natl. Acad. Sci. USA, 87, 3894–3898.PubMedCrossRefGoogle Scholar
  19. 19.
    Martin-Moreno, J.M., Willett, W.C., Gorgojo, L., Banegas, J.R., Rodriguez-Artalejo, E, Fernandez-Rodriguez, J.C., Maisonneuve, R, and Boyle, R (1994) Dietary fat, olive oil intake, and breast cancer risk. Int. J. Canc., 58, 774–780.CrossRefGoogle Scholar
  20. 20.
    Trichopoulou, A., Katsouyanni, K., Stuver, S., Tzala, L, Gnardellis, C., Rimm, E., and Trichopoulos, D. (1995) Consumption of olive oil and specific food groups in relation to breast cancer risk in Greece. J. Natl. Canc. Inst., 87, 110–116.CrossRefGoogle Scholar
  21. 21.
    Willett, W.C. (1997) Specific fatty acids and risks of breast and prostate cancer: dietary intake. Am. J. Clin. Invest., 66, 1557S - 1576S.Google Scholar
  22. 22.
    Braga, C., La Vecchia, C., Franceschi, S., Negri, E., Parpinel, M., Decarli, A., Giacosa, A., and Trichopoulos, D. (1998) Olive oil, other seasoning fats, and the risk of colorectal carcinoma. Cancer, 82, 448 453.Google Scholar
  23. 23.
    Sies, H. (ed.) (1991) Oxidative stress, oxidants, and antioxidants. London and New York: Academic Press.Google Scholar
  24. 24.
    Scott. Gerald (ed.) (1997) Antioxidants in science, technology, medicine, and nutrition, Albion Publishing Chichester.Google Scholar
  25. 25.
    Ames, B.N., Shigenaga, M.K., and Hagen, T.M. (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci. USA, 90, 7915–7922.PubMedCrossRefGoogle Scholar
  26. 26.
    Frei, B. (ed.) (1994) Natural antioxidant in human health and disease, Academic Press.Google Scholar
  27. 27.
    Halliwell, B., Murcia, M.A., Chirico, S., and Aruoma, O.I. (1995) Free radicals and antioxidants in food and in vivo: what they do and how they work, Critical Rev in Food Sci and Nutr., 35, 7–20.CrossRefGoogle Scholar
  28. 28.
    Montero, H.P. and Stren, A. (1996) Redox modulation of tyrosine phosphorylation-dependent signal transduction pathways. Free Rad. Biol. Med., 3, 323–333.Google Scholar
  29. 29.
    Palmer, H.J. and Pauling, K.P. (1997) Reactive oxygen species and antioxidants in signal transduction and gene expression. Nutr. Rev., 55, 353–361.PubMedCrossRefGoogle Scholar
  30. 30.
    Irani, K., Xia, Y., Zweier, J.L., Sollot, S.J., Der, C.J., Fearo, E.R., Sundaresan, M., Finkel, T., and Goldschmidt-Clemont, P.J. (1997) Mitogenic signaling mediated by oxidants in ras-transformed fibroblasts. Science, 275, 296–299.CrossRefGoogle Scholar
  31. 31.
    Cimmino, F., Esposito, E, Ammendola, R., and Russo, T. (1997) Gene regulation by reactive oxygen species, Current topics in cellular regulation, 35, 123–147.CrossRefGoogle Scholar
  32. 32.
    Scaccini, C., Nardini, M., D’Aquino, M., Gentili, V., Di Felice, M., and Tomassi, G. (1992) Effect of dietary oils on lipid peroxidation and on antioxidant parameters of rat plasma and lipoprotein fractions. J. Lipid Res., 33, 627–633.PubMedGoogle Scholar
  33. 33.
    Wiseman, S.A., Mathot, J.N., de Fouw, N.J., and Tijburg, L.B. (1996) Dietary non-tocopherol antioxidants present in extra virgin olive oil increase the resistance of low density lipoproteins to oxidation in rabbits. Atherosclerosis., 120, 15–23.PubMedCrossRefGoogle Scholar
  34. 34.
    Salami, M., Galli, C., De Angelis, L., and Visioli, F. (1995) Formation of F2-isoprostanes in oxidized low density lipoprotein: inhibitory effect of hydroxytyrosol. Pharmacol. Res., 31, 275–279.PubMedCrossRefGoogle Scholar
  35. 35.
    Visioli, E, Bellomo, G., Montedoro, G.E, and Galli, C. (1995) Low density lipoprotein oxidation is inhibited in vitro by olive oil constituents. Atherosclerosis., 117, 25–32.PubMedCrossRefGoogle Scholar
  36. 36.
    Visioli, E and Galli, C. (1998) The effect of minor constituents of olive oil on cardiovascular disease: new findings. Nutr. Rev., 56, 142–147.PubMedCrossRefGoogle Scholar
  37. 37.
    Manna, C., Galletti, E, Cucciolla, V., Moltedo, O., Leone, A., and Zappia, V. (1997) The protective effect of the olive oil polyphenol (3,4-dihydroxyphenyl)ethanol counteracts reactive oxygen metabolite-induced cytotoxicity in Caco-2 cells. J. Nutr., 127, 286–292.PubMedGoogle Scholar
  38. 38.
    Manna, C., Galletti, E, Cucciolla, V., Montedoro G., and Zappia, V. (1999) Olive oil hydroxytyrosol protects human erythrocytes against oxidative damages. J. Nutr. Biochem., 10, 159–165.PubMedCrossRefGoogle Scholar
  39. 39.
    Hidalgo, I.J., Raub, T.J., and Borchardt, R.T. (1989) Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology, 96, 736–749.PubMedGoogle Scholar
  40. 40.
    Granger D.N., McCord, J.M., Parks, D.A., and Hollwarth, M.E. (1986) Xanthine oxidase inhibitors attenuate ischemia-induced vascular permeability changes in the cat intestine. Gastroenterology, 90, 80–84.PubMedGoogle Scholar
  41. 41.
    Nakayama, T. (1994) Suppression of hydroperoxide-induced cytotoxicity by polyphenols. Cancer Res., 54, 1991s - 1993s.PubMedGoogle Scholar
  42. 42.
    Khan, S.G., Katiyar, S.K., Agarwal, R., and Mukhtar, H. (1992) Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention. Cancer Res., 52, 4050–4052.PubMedGoogle Scholar
  43. 43.
    Misra, H.P. and Fridovich, I. (1972) The generation of superoxide radical during the autoxidation of hemoglobin. J. Biol. Chem., 247, 6960–6962.PubMedGoogle Scholar
  44. 44.
    Van Dyke, B.R. and Saltman, P. (1996) Hemoglobin: a mechanism for the generation of hydroxyl radicals. Free Rad. Biot Med., 20, 985–989.CrossRefGoogle Scholar
  45. 45.
    Snyder, L.M., Fortier, N.L., Trainor, J., Jacobs, J., Leb, L., Lubin, B., Chiu, D., Shohet, S., and Mohan-das, N. (1985) Effect of hydrogen peroxide exposure on normal human erythrocyte deformability, morphology, surface characteristics, and spectrin-hemoglobin cross-linking. J. Clin. Invest., 76, 1971–1977.PubMedCrossRefGoogle Scholar
  46. 46.
    Johnson, G.J., Allen, D.W., Cadman, S., Fairbanks, V.F., White, J. G., Lampkin, B.C., and Kaplan, M.E. (1979) Red-cell-membrane polypeptide aggregates in glucose-6-phosphate dehydrogenase mutants with chronic hemolytic disease. N. Engl. J. Med., 301, 522–527.PubMedCrossRefGoogle Scholar
  47. 47.
    Shinar, E and Rachmilewitz, E.A. (1990) Oxidative denaturation of red blood cells in thalassemia. Semin. Hematol., 27, 70–82.PubMedGoogle Scholar
  48. 48.
    Hebbel, R.P., Eaton, J.W., Balasingam, M., and Steinberg, M.H. (1982) Spontaneous oxygen radical generation by sickle erythrocytes. J. Clin. Invest., 70, 1253–1259.PubMedCrossRefGoogle Scholar
  49. 49.
    Rohn, T.T., Hinds, T.R., and Vincenzi, F.F. (1993) Ion transport ATPases as targets for free radical damage. Protection by an aminosteroid of the Capump ATPase and Na’/K+ pump ATPase of human red blood cell membranes. Biochem. Pharmacol., 46, 525–534.PubMedCrossRefGoogle Scholar
  50. 50.
    Boyle, P., Zaridze, D.G., and Smans, M. (1985) Descriptive epidemiology of colorectal cancer. Int. J. Cancer, 36, 9–18.PubMedCrossRefGoogle Scholar
  51. 51.
    Greenwald, E, Kelloff, G.J., Burch-Whitman, C., and Kramer, B.S. (1995) Chemoprevention. CA Cancer J. Clin., 45, 31–49.PubMedCrossRefGoogle Scholar
  52. 52.
    Wolf, D. and Rotter, V. (1985) Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells. Proc. Natl. Acad. Sci. USA, 82, 790–794.PubMedCrossRefGoogle Scholar
  53. 53.
    Petroni, A., Blasevich, M., Salami, M., Papini, N., Montedoro, G.F., and Galli, C. (1995) Inhibition of platelet aggregation and eicosanoid production by phenolic components of olive oil. Thromb. Res., 78, 151–160.PubMedCrossRefGoogle Scholar
  54. 54.
    Kohyama, N., Nagata, T., Fujimoto S., and Sekiya, K. (1997) Inhibition of arachidonate lipoxygenase activities by 2-(3,4-dihydro xyphenyl)ethanol, a phenolic compound from olives. Biosci. Biotech. Biochem., 61, 347–350.CrossRefGoogle Scholar
  55. 55.
    de la Puerta, R., Ruiz Gutierrez, V., and Hoult, JR. (1999) Inhibition of leukocyte 5-lipoxygenase by phenolics from virgin olive oil. Biochem Pharmacol., 57, 445–449.PubMedCrossRefGoogle Scholar
  56. 56.
    Visioli, E, Bellosta, S., and Galli, C. (1998) Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages. Life Sci., 62, 541–546.PubMedCrossRefGoogle Scholar
  57. 57.
    Deiana, M., Arouma, O.I., Bianchi, M. de L.P., Spencer, J.P.E., Kaur, H., Halliwell, B., Aeschbach, R., Banni, S., Dessi, M.A., and Corongiu, F.P. (1999) Inhibition of peroxynitrite dependent DNA base modification and tyrosine nitration by the extra virgin olive oil-derived antioxidant hydroxytyrosol. Free Rad. Biol. Med., 26, 762–769.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Caterina Manna
    • 1
  • Fulvio Della Ragione
    • 1
  • Valeria Cucciolla
    • 1
  • Adriana Borriello
    • 1
  • Stefania D’Angelo
    • 1
  • Patrizia Galletti
    • 1
  • Vincenzo Zappia
    • 1
  1. 1.Institute of Biochemistry of Macromolecules Medical SchoolSecond University of NaplesNaplesItaly

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