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Resveratrol requires red wine polyphenols for optimum antioxidant activity



There is substantial evidence that a diet rich in fruit and vegetables may reduce the risk of aging and stress oxidative associated diseases. It has been suggested that benefits associated with fruit and red wine consumption could be due to pooled antioxidant microcomponents in diet. The aim of this study was to investigate the antioxidant activities of pure resveratrol (a well known phytoalexin, RSV) and red wine polyphenols (RWP), using UV-B radiated isolated rat hepatocytes as a model of oxidative stress.


Rat hepatocytes were isolated by the collagenase method. The cells were loaded with resveratrol and/or polyphenols at different concentrations. The production of thiobarbituric acid reactive substances (TBARS) released by UV-B radiated cells and the levels of lipid-soluble antioxidants (Dolichol, Vitamin E, Coenzyme Q9 and Q10) were measured.


Resveratrol had pro-oxidant or antioxidant effects depending on (lower or higher) dosage. RWP protection from photolipoperoxidation was dose-dependent and increased with dosage. Combination of the two compounds exhibited synergistic antioxidant effect, and made resveratrol effective both at lower and higher dosages.


These results suggest that resveratrol requires red wine polyphenols for optimum antioxidant activity.

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  1. 1.

    Kesse-Guyot E, Andreeva VA, Touvier M, Jeandel C, Ferry M, Hercberg S, Galan P, SU.VI.MAX 2 Research Group. Overall and abdominal adiposity in midlife and subsequent cognitive function. J Nutr Health Aging 2015;19:183–189

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Maxwell SR. Prospects for the use of antioxidant therapies. Drugs 49:345–361

  3. 3.

    Willett WC. Balancing life-style and genomics research for disease prevention. Science 2002;296:695–698

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Kelewala NS, Ananthanarayan L. Antioxidant acitivity of selected food-stuffs. Int J Food Sci Nutr 2004;55:511–516

    Article  Google Scholar 

  5. 5.

    Berger RG, Lunkenbein S, Strohle A, Hahn A. Antioxidants in food: Mere myth or magic medicine? Crit Rev Food Sci Nutr 2012;52:162–171

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Potenza L, Calcabrini C, De Bellis R, Mancini U, Cucchiarini L, Dachà M. Effect of quercetin on oxidative nuclear and mitochondrial DNA damage BioFactors 2008;33: 33–48

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Rice-Evans CA, Miller NJ, Bolwell PG, Bramley PM, Pridham JB. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic Res 1995;22:375–383.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Morton LW, Abu-Amsha Caccetta R, Puddey IB, Croft KD. Chemistry and biological effects of dietary phenolic compounds: relevance to cardiovascular disease. Clin Exp Pharmacol Physiol 2000;27:152–159.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Elattar TM, Virji AS. The effect of red wine and its components on growth and proliferation of human oral squamous carcinoma cells. Anticancer Res 1999;19:5407–5414

    CAS  PubMed  Google Scholar 

  10. 10.

    Stagos D, Kazantzoglou G, Theofanidou D, Kakalopoulou G, Magiatis P, Mitaku S, Kouretas D. Activity of grape extracts from Greek varieties of Vitis vinifera against mutagenicity induced by bleomycin and hydrogen peroxide in Salmonella typhimurium strain TA102. Mutat Res 2006;609:165–175

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Liu Y, He XQ, Huang X, Ding L, Xu L, Shen YT, Zhang F, Zhu MB, Xu BH, Qi ZQ, Wang HL. Resveratrol protects mouse oocytes from methylglyoxal-induced oxidative damage. PLoS One 2013;8:e77960

    Article  Google Scholar 

  12. 12.

    Bai Y, Mao QQ, Qin J, Zheng XY, Wang YB, Yang K, Shen HF, Xie LP. Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo. Cancer Sci 2010;101:488–493

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Baek SJ, Wilson LC, Eling TE. Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-1) by increasing the expression of p53. Carcinogenesis 2002;23:425–434

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Su HC, Hung LM, Chen JK. Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab 2006;290:e1339–1346

    Article  Google Scholar 

  15. 15.

    Gűlçin İ. Antioxidant properties of resveratrol: a structure-activity insight. Innov Food Sci Emerg Tech 2010;11:210–218

    Article  Google Scholar 

  16. 16.

    De Salvia R, Festa F, Ricordy R, Perticone P, Cozzi R. Resveratrol affects in a different way primary versus fixed DNA damage induced by H(2)O(2) in mammalian cells in vitro. Toxicol Lett 2002;135:1–9

    Article  PubMed  Google Scholar 

  17. 17.

    Sareen D, Darjatmoko SR, Albert DM, Polans AS. Mitochondria, calcium, and calpain are key mediators of resveratrol-induced apoptosis in breast cancer. Mol Pharmacol 2007;72:1466–1475

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Pirola L, Frojdo S. Resveratrol: one molecule, many targets. IUBMB Life 2008;60:323–332

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003;425:191–196

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 2004;430:686–689

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006;444:337–342

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Collins JJ, Evason K, Kornfeld K. Pharmacology of delayed aging and extended lifespan of Caenorhabditis elegans. Exp Gerontol 2006;41:1032–1039

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet1992; 339:1523–1526

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Scott E, Steward WP, Gescher AJ, Brown K. Resveratrol in human cancer chemoprevention-choosing the ‘right’ dose. Mol Nutr Food Res 2012;56:7–13

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Dixon RA. Natural products and plant disease resistance. Nature 2001;411:843–847

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Parentini I, Bergamini E, Cecchi L, Cavallini G, Donati A, Maccheroni M, Tamburini I, Gori Z. The effect of carbon tetrachloride and ultraviolet radiation on dolichol levels in liver cells isolated from 3- and 24-month old male Sprague-Dawley rats. Biogerontology 2003;4:365–370

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Bergamini E, Bizzarri R, Cavallini G, Cerbai B, Chiellini E, Donati A, Gori Z, Manfrini A, Parentini I, Signori F, Tamburini I. Ageing and oxidative stress: a role for dolichol in the antioxidant machinery of cell membranes? J Alzheimers Dis 2004;6:129–135

    CAS  PubMed  Google Scholar 

  28. 28.

    Afri M, Ehrenberg B, Talmon Y, Schmidt J, Cohen Y, Frimer AA. Active oxygen chemistry within the liposomal bilayer. Part III: Locating Vitamin E, ubiquinol and ubiquinone and their derivatives in the lipid bilayer. Chem Phys Lipids 2004;13:107–121

    Article  Google Scholar 

  29. 29.

    Seglen PO. Preparation of isolated rat liver cells. Methods Cell Biol 1976;13:29–83

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Cavallini G, Dachà M, Potenza L, Ranieri A, Scattino C, Castagna A, Bergamini E. Use of red blood cell membranes to evaluate the antioxidant potential of plant extracts. Plant Foods Hum Nutr 2014;69:108–114

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Grotto D, Santa Maria LD, Boeira S, Valentini J, Charão MF, Moro AM, Nascimento PC, Pomblum VJ, Garcia SC. Rapid quantification of malondialdehyde in plasma by high performance liquid chromatography-visible detection. J Pharm Biomed Anal 2007;43:619–624

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Lang JK, Gohil K, Packer L. Simultaneous determination of tocopherols, ubiquinols, and ubiquinones in blood, plasma, tissue homogenates, and subcellular fractions. Anal Biochem 1986;157:106–116

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Maltese WA, Erdman RA. Characterization of isoprenoid involved in the posttraslational modification of mammalian cell proteins. J Biol Chem 1989;264:18168–18172

    CAS  PubMed  Google Scholar 

  34. 34.

    Ruperez FJ, Barbas C, Castro M, Martinez S, Herrera E. Simplified method for Vitamin E determination in rat adipose tissue and mammary glands by highperformance liquid chromatography. J Chromatogr A 1998;823:483–487

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Gullett NP, Ruhul Amin AR, Bayraktar S, Pezzuto JM, Shin DM, Khuri FR, Aggarwal BB, Surh YJ, Kucuk O. Cancer prevention with natural compounds. Semin Oncol 2010;37:258–281

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9:515–540

  37. 37.

    Sun AY, Simonyi A, Sun GY. The “French Paradox” and beyond: the neuroprotective effects of polyphenols. Free Radic Biol Med 2002;32:314–318

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Rice-Evans CA, Miller NJ, Paganga G. Antioxidant properties of phenolic compounds. Trends Plant Sci Rev 1997;2:152–159

    Article  Google Scholar 

  39. 39.

    Suwalsky M, F Villena, Gallardo MJ. In vitro protective effects of resveratrol against oxidative damage in human erythrocytes. Biochim Biophys Acta 2015;1848:76–82

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Guarini M, Stabile A, Cavallini G, Donati A, Bergamini E. Effects of oxidative stress on the Dolichol content of isolated rat liver cells. Free Radic Res 2007;41:1283–1288

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005;81: 230S–242S

    CAS  PubMed  Google Scholar 

  42. 42.

    Pacheco-Palencia LA, Noratto G, Hingorani L, Talcott ST, Mertens-Talcott SU. Protective effects of standardized pomegranate (Punica granatum L.) polyphenolic extract in ultraviolet-irradiated human skin fibroblasts. J Agric Food Chem 2008;56:8434–8441

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Pandey KB, Rizvi SI. Protective effect of resveratrol on formation of membrane protein carbonyls and lipid peroxidation in erythrocytes subjected to oxidative stress. Appl Physiol Nutr Metab 2009;34:1093–1097

    Article  PubMed  Google Scholar 

  44. 44.

    Mikstacka R, Rimando AM, Ignatowicz E. Antioxidant effect of trans-resveratrol, pterostilbene, quercetin and their combinations in human erythrocytes in vitro. Plant Foods Hum Nutr 2010;65:57–63

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Luo H, Yang A, Schulte BA, Wargovich MJ, Wang GY. Resveratrol induces premature senescence in lung cancer cells via ROS-mediated DNA damage. PLoS One 2013;8:e60065

    Article  Google Scholar 

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Corresponding author

Correspondence to Sara Straniero.

Additional information

Gabriella Cavallini and Sara Straniero contributed equally to this manuscript

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Cavallini, G., Straniero, S., Donati, A. et al. Resveratrol requires red wine polyphenols for optimum antioxidant activity. J Nutr Health Aging 20, 540–545 (2016).

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Key words

  • Resveratrol
  • red wine polyphenols
  • oxidative stress
  • lipid-soluble antioxidants