Polyphenolic Antioxidants and Health

  • Lorenzo Loffredo
  • Francesco Violi


Oxidative stress is believed to play a pivotal role in several physiologic (aerobic metabolism, immunologic responses, cellular signaling, regulation of gene expression, cell differentiation) [1] and pathologic (atherosclerosis, tumorigenesis, neurodegenerative diseases, etc.) processes. Antioxidants react with oxygen free radicals protecting the cells from oxidative stress damage. Polyphenols are the most widely known antioxidant nutrients. Polyphenols are a class of natural, synthetic, and semisynthetic substances characterized by the presence of large multiples of phenol units. The term polyphenols was proposed in 1962 by the phytochemists White, Bate-Smith, Swain and Haslam [2]. They defined polyphenols as “water-soluble phenolic compounds having molecular weights between 500 and 3000 (Da). Besides giving the usual phenolic reactions, they have special properties such as the ability to precipitate alkaloids, gelatin and other proteins from solution” [2]. Polyphenols, in the form of flavonoids, are broadly classified into anthocyanidins (e.g., cyanidin, delphinidin, malvidin), flavanols (e.g., catechin, epicatechin), flavonols (e.g., quercetin, fisetin), and flavones (e.g., luteolin) [3]. Natural polyphenols are prevalent in cocoa, fruits, vegetables, wine and tea. Flavonoids account for two thirds of the total polypenolic daily intake (approximately 1 g) [4]. After oral ingestion, flavonols undergo a biotransformation from the gut microflora generating a large variety of metabolites [4, 5]; the maximum plasma concentration of flavonols rarely exceeds 1 μM [4, 5].


Amyotrophic Lateral Sclerosis NADPH Oxidase Chronic Granulomatous Disease Dark Chocolate NADPH Oxidase Inhibition 
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.


  1. 1.
    Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313PubMedCrossRefGoogle Scholar
  2. 2.
    Quideau S, Deffieux D, Douat-Casassus C et al (2011) Plant polyphenols: chemical properties, biological activities, and synthesis. Angew Chem Int Ed Engl 50:586–621PubMedCrossRefGoogle Scholar
  3. 3.
    Obrenovich ME, Nair NG, Beyaz A et al (2010) The role of polyphenolic antioxidants in health, disease, and aging. Rejuvenation Res 13:631–643PubMedCrossRefGoogle Scholar
  4. 4.
    Scalbert A, Williamson G (2000) Dietary intake and bioavailability of polyphenols. J Nutr 130:2073S–2085SPubMedGoogle Scholar
  5. 5.
    Schroeter H, Heiss C, Balzer J et al (2006) (−)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci U S A 103:1024–1029PubMedCrossRefGoogle Scholar
  6. 6.
    Lopez AD, Mathers CD, Ezzati M et al (2006) Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367:1747–1757PubMedCrossRefGoogle Scholar
  7. 7.
    Bayard V, Chamorro F, Motta J et al (2007) Does flavanol intake influence mortality from nitric oxide-dependent processes? Ischemic heart disease, stroke, diabetes mellitus, and cancer in Panama. Int J Med Sci 4:53–58PubMedCrossRefGoogle Scholar
  8. 8.
    Arts IC, Hollman PC, Feskens EJ et al (2001) Catechin intake might explain the inverse relation between tea consumption and ischemic heart disease: the Zutphen Elderly Study. Am J Clin Nutr 74:227–232PubMedGoogle Scholar
  9. 9.
    Buijsse B, Feskens EJ, Kok FJ et al (2006) Cocoa intake, blood pressure, and cardiovascular mortality: the Zutphen Elderly Study. Arch Intern Med 166:411–417PubMedGoogle Scholar
  10. 10.
    Buijsse B, Weikert C, Drogan D et al (2010) Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur Heart J 31:1616–1623PubMedCrossRefGoogle Scholar
  11. 11.
    Arts IC, Jacobs DR Jr, Harnack LJ et al (2001) Dietary catechins in relation to coronary heart disease death among postmenopausal women. Epidemiology 12:668–675PubMedCrossRefGoogle Scholar
  12. 12.
    Hertog MG, Feskens EJ, Hollman PC et al (1993) Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 342:1007–1011PubMedCrossRefGoogle Scholar
  13. 13.
    Renaud S, de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339:1523–1526PubMedCrossRefGoogle Scholar
  14. 14.
    Artaud-Wild SM, Connor SL, Sexton G et al (1993) Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox. Circulation 88:2771–2779CrossRefGoogle Scholar
  15. 15.
    Gronbaek M, Becker U, Johansen D et al (2000) Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer. Ann Intern Med 133:411–419PubMedGoogle Scholar
  16. 16.
    Janszky I, Mukamal KJ, Ljung R et al (2009) Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program. J Intern Med 266:248–257PubMedCrossRefGoogle Scholar
  17. 17.
    Corti R, Flammer AJ, Hollenberg NK et al (2009) Cocoa and cardiovascular health. Circulation 119:1433–1441PubMedCrossRefGoogle Scholar
  18. 18.
    Taubert D, Roesen R, Lehmann C et al (2007) Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA 298:49–60PubMedCrossRefGoogle Scholar
  19. 19.
    Erlund I, Koli R, Alfthan G et al (2008) Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol. Am J Clin Nutr 87:323–331PubMedGoogle Scholar
  20. 20.
    Gilchrist M, Shore AC, Benjamin N (2011) Inorganic nitrate and nitrite and control of blood pressure. Cardiovasc Res 89:492–498PubMedCrossRefGoogle Scholar
  21. 21.
    Taubert D, Roesen R, Schomig E (2007) Effect of cocoa and tea intake on blood pressure: a meta-analysis. Arch Intern Med 167:626–634PubMedCrossRefGoogle Scholar
  22. 22.
    Burton-Freeman B, Linares A, Hyson D et al (2010) Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women. J Am Coll Nutr 29:46–54PubMedGoogle Scholar
  23. 23.
    Baba S, Osakabe N, Kato Y et al (2007) Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. Am J Clin Nutr 85:709–717PubMedGoogle Scholar
  24. 24.
    Kondo K, Hirano R, Matsumoto A et al (1996) Inhibition of LDL oxidation by cocoa. Lancet 348:1514PubMedCrossRefGoogle Scholar
  25. 25.
    Brasnyo P, Molnar GA, Mohas M et al (2011) Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr 106:383–389PubMedCrossRefGoogle Scholar
  26. 26.
    Grassi D, Desideri G, Necozione S et al (2008) Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming highpolyphenol dark chocolate. J Nutr 138:1671–1676PubMedGoogle Scholar
  27. 27.
    Steinberg D, Witztum JL (2002) Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation 105:2107–2111PubMedCrossRefGoogle Scholar
  28. 28.
    Violi F, Marino R, Milite MT et al (1999) Nitric oxide and its role in lipid peroxidation. Diabetes Metab Res Rev 15:283–288PubMedCrossRefGoogle Scholar
  29. 29.
    Cave AC, Brewer AC, Narayanapanicker A et al (2006) NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal 8:691–728PubMedCrossRefGoogle Scholar
  30. 30.
    Pignatelli P, Di Santo S, Buchetti B et al (2006) Polyphenols enhance platelet nitric oxide by inhibiting protein kinase C-dependent NADPH oxidase activation: effect on platelet recruitment. FASEB J 20:1082–1089PubMedCrossRefGoogle Scholar
  31. 31.
    Heiss C, Keen CL, Kelm M (2010) Flavanols and cardiovascular disease prevention. Eur Heart J 31:2583–2592PubMedCrossRefGoogle Scholar
  32. 32.
    Heitzer T, Schlinzig T, Krohn K et al (2001) Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 104(22):2673–2678PubMedCrossRefGoogle Scholar
  33. 33.
    Forstermann U (2008) Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies. Nat Clin Pract Cardiovasc Med 5:338–349PubMedCrossRefGoogle Scholar
  34. 34.
    Bendall JK, Rinze R, Adlam D et al (2007) Endothelial Nox2 overexpression potentiates vascular oxidative stress and hemodynamic response to angiotensin II: studies in endothelialtargeted Nox2 transgenic mice. Circ Res 100:1016–1025PubMedCrossRefGoogle Scholar
  35. 35.
    Oelze M, Warnholtz A, Faulhaber J et al (2006) NADPH oxidase accounts for enhanced superoxide production and impaired endothelium-dependent smooth muscle relaxation in BKbeta1-/-mice. Arterioscler Thromb Vasc Biol 26:1753–1759PubMedCrossRefGoogle Scholar
  36. 36.
    Jung O, Schreiber JG, Geiger H et al (2004) gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension. Circulation 109:1795–1801PubMedCrossRefGoogle Scholar
  37. 37.
    Violi F, Sanguigni V, Carnevale R et al (2009) Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter study. Circulation 120:1616–1622PubMedCrossRefGoogle Scholar
  38. 38.
    Heiss C, Kleinbongard P, Dejam A et al (2005) Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J Am Coll Cardiol 46:1276–1283PubMedCrossRefGoogle Scholar
  39. 39.
    Jennings LK (2009) Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost 102:248–257PubMedGoogle Scholar
  40. 40.
    Violi F, Pignatelli P, Basili S (2010) Nutrition, supplements, and vitamins in platelet function and bleeding. Circulation 121:1033–1044PubMedCrossRefGoogle Scholar
  41. 41.
    Ferlay J, Shin HR, Bray F et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917PubMedCrossRefGoogle Scholar
  42. 42.
    Queen BL, Tollefsbol TO (2010) Polyphenols and aging. Curr Aging Sci 3:34–42PubMedGoogle Scholar
  43. 43.
    Yang CS, Wang X, Lu G et al (2009) Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer 9:429–439PubMedCrossRefGoogle Scholar
  44. 44.
    Sun GY, Horrocks LA, Farooqui AA (2007) The roles of NADPH oxidase and phospholipases A2 in oxidative and inflammatory responses in neurodegenerative diseases. J Neurochem 103:1–16PubMedCrossRefGoogle Scholar
  45. 45.
    Zhang F, Shi JS, Zhou H et al (2010) Resveratrol protects dopamine neurons against lipopolysaccharide-induced neurotoxicity through its anti-inflammatory actions. Mol Pharmacol 78:466–477PubMedCrossRefGoogle Scholar
  46. 46.
    Mandel SA, Amit T, Weinreb O et al (2008) Simultaneous manipulation of multiple brain targets by green tea catechins: a potential neuroprotective strategy for Alzheimer and Parkinson diseases. CNS Neurosci Ther 14:352–365PubMedCrossRefGoogle Scholar
  47. 47.
    Koh SH, Lee SM, Kim HY et al (2006) The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice. Neurosci Lett 395:103–107PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Lorenzo Loffredo
    • 1
  • Francesco Violi
  1. 1.Department of Internal Medicine and Medical Specialties “Sapienza”University of RomeRomeItaly

Personalised recommendations