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Cardioprotective and hepatoprotective effects of ellagitannins from European oak bark (Quercus petraea L.) extract in rats

An Erratum to this article was published on 06 March 2012



Red wine contains many potentially bioactive polyphenols including resveratrol, catechins, anthocyanins and flavonoids as well as tannins derived from oak during maturation. This study examined the effects of a mixture of ellagitannins from oak bark (Quercus petraea L.) on cardiovascular, metabolic and liver changes in high-carbohydrate, high-fat diet–fed rats and in Spontaneously Hypertensive Rats (SHR).


First, 8-week-old male Wistar rats were divided into four groups and given either cornstarch diet, cornstarch diet + oak bark extract (0.5 mL/kg food), high-carbohydrate, high-fat diet or high-carbohydrate, high-fat diet + oak bark extract (0.5 mL/kg food) for 16 weeks. Oak bark extract was added to the diets for last 8 weeks of the feeding period. Secondly, SHR aged 42 weeks fed on standard chow diet were divided into two groups with and without oak bark extract treatment for 12 weeks (0.5 mL/kg food).


The high-carbohydrate, high-fat diet induced signs of metabolic syndrome along with cardiovascular remodelling and non-alcoholic steatohepatitis. Oak bark extract attenuated the signs of metabolic syndrome in high-carbohydrate, high-fat diet–fed rats and improved the structure and function of the heart and the liver. SHR after oak bark extract treatment for 12 weeks showed lower systolic blood pressure, lower cardiac fibrosis and cardiac stiffness and improved vascular reactivity.


Oak bark extract containing ellagitannins improved cardiovascular, metabolic and liver parameters in these rat models of human disease, suggesting that part of the benefits attributed to red wine may be produced by these ellagitannins.

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  1. 1.

    Pure castalagin, vescalagin, grandinin and roburin E for use as standards were kindly provided by Professor Stéphane Quideau, European Institute of Chemistry and Biology, University of Bordeaux I, France.


  1. 1.

    Saucier C, Jourdes M, Glories Y, Quideau S (2006) Extraction, detection, and quantification of flavano-ellagitannins and ethylvescalagin in a Bordeaux red wine aged in oak barrels. J Agric Food Chem 54:7349–7354

    Article  CAS  Google Scholar 

  2. 2.

    Garcia-Estevez I, Escribano-Bailon MT, Rivas-Gonzalo JC, Alcalde-Eon C (2010) Development of a fractionation method for the detection and identification of oak ellagitannins in red wines. Anal Chim Acta 660:171–176

    Article  CAS  Google Scholar 

  3. 3.

    Karonen M, Parker J, Agrawal A, Salminen JP (2010) First evidence of hexameric and heptameric ellagitannins in plants detected by liquid chromatography/electrospray ionisation mass spectrometry. Rapid Commun Mass Spectrom 24:3151–3156

    Article  CAS  Google Scholar 

  4. 4.

    Yoshida T, Amakura Y, Yoshimura M (2010) Structural features and biological properties of ellagitannins in some plant families of the order Myrtales. Int J Mol Sci 11:79–106

    Article  CAS  Google Scholar 

  5. 5.

    Cerda B, Tomas-Barberan FA, Espin JC (2005) Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts, and oak-aged wine in humans: identification of biomarkers and individual variability. J Agric Food Chem 53:227–235

    Article  CAS  Google Scholar 

  6. 6.

    Bakkalbasi E, Mentes Ãz, Artik N (2009) Food ellagitannins-occurrence, effects of processing and storage. Crit Rev Food Sci Nutr 49:283–298

    Article  CAS  Google Scholar 

  7. 7.

    Puech JL, Mertz C, Michon V, Le Guerneve C, Doco T, Herve Du Penhoat C (1999) Evolution of castalagin and vescalagin in ethanol solutions. Identification of new derivatives. J Agric Food Chem 47:2060–2066

    Article  CAS  Google Scholar 

  8. 8.

    Kroon PA, Iyer A, Chunduri P, Chan V, Brown L (2010) The cardiovascular nutrapharmacology of resveratrol: pharmacokinetics, molecular mechanisms and therapeutic potential. Curr Med Chem 17:2442–2455

    Article  CAS  Google Scholar 

  9. 9.

    Seeram NP, Henning SM, Zhang Y, Suchard M, Li Z, Heber D (2006) Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. J Nutr 136:2481–2485

    CAS  Google Scholar 

  10. 10.

    Coates EM, Popa G, Gill CI, McCann MJ, McDougall GJ, Stewart D, Rowland I (2006) Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer. J Carcinog 6:4

    Article  Google Scholar 

  11. 11.

    Basu A, Penugonda K (2009) Pomegranate juice: a heart-healthy fruit juice. Nutr Rev 67:49–56

    Article  Google Scholar 

  12. 12.

    Jadeja R, Thounaojam M, Patel D, Devkar R, Ramachandran A (2010) Pomegranate (Punica granatum L.) juice supplementation attenuates isoproterenol-induced cardiac necrosis in rats. Cardiovasc Toxicol 10:174–180

    Article  CAS  Google Scholar 

  13. 13.

    Mohan M, Waghulde H, Kasture S (2010) Effect of pomegranate juice on angiotensin II-induced hypertension in diabetic Wistar rats. Phytother Res 24:S196–S203

    Article  Google Scholar 

  14. 14.

    de Nigris F, Balestrieri ML, Williams-Ignarro S, D’Armiento FP, Fiorito C, Ignarro LJ, Napoli C (2007) The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats. Nitric Oxide 17:50–54

    Article  Google Scholar 

  15. 15.

    Seeram NP, Lee R, Heber D (2004) Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice. Clinica Chimica Acta 348:63–68

    Article  CAS  Google Scholar 

  16. 16.

    Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJL (2006) Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367:1747–1757

    Article  Google Scholar 

  17. 17.

    Alberti KG, Zimmet P, Shaw J (2005) The metabolic syndrome-a new worldwide definition. Lancet 366:1059–1062

    Article  Google Scholar 

  18. 18.

    Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, Cristanini G, Tiribelli C (2000) Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 132:112–117

    CAS  Google Scholar 

  19. 19.

    Doggrell SA, Brown L (1998) Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res 39:89–105

    Article  CAS  Google Scholar 

  20. 20.

    Panchal SK, Poudyal H, Iyer A, Nazer R, Alam MA, Diwan V, Kauter K, Sernia C, Campbell F et al (2011) High-carbohydrate high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol 57:611–624

    Article  Google Scholar 

  21. 21.

    Panchal SK, Brown L (2011) Rodent models for metabolic syndrome research. J Biomed Biotechnol 2011:351982

    Article  Google Scholar 

  22. 22.

    Chan V, Fenning A, Levick SP, Loch D, Chunduri P, Iyer A, Teo YL, Hoey A, Wilson K et al (2011) Cardiovascular changes during maturation and ageing in male and female Spontaneously Hypertensive Rats. J Cardiovasc Pharmacol 57:469–478

    Article  CAS  Google Scholar 

  23. 23.

    Poudyal H, Campbell F, Brown L (2010) Olive leaf extract attenuates cardiac, hepatic, and metabolic changes in high carbohydrate-, high fat-fed rats. J Nutr 140:946–953

    Article  CAS  Google Scholar 

  24. 24.

    Sim AS, Salonikas C, Naidoo D, Wilcken DE (2003) Improved method for plasma malondialdehyde measurement by high-performance liquid chromatography using methyl malondialdehyde as an internal standard. J Chromatogr B Anal Technol Biomed Life Sci 785:337–344

    Article  CAS  Google Scholar 

  25. 25.

    Lexis LA, Fenning A, Brown L, Fassett RG, Coombes JS (2006) Antioxidant supplementation enhances erythrocyte antioxidant status and attenuates cyclosporine-induced vascular dysfunction. Am J Transpl 6:41–49

    Article  CAS  Google Scholar 

  26. 26.

    Bertelli AA, Das DK (2009) Grapes, wines, resveratrol, and heart health. J Cardiovasc Pharmacol 54:468–476

    Article  CAS  Google Scholar 

  27. 27.

    Waterhouse AL (2002) Wine phenolics. Ann N Y Acad Sci 957:21–36

    Article  CAS  Google Scholar 

  28. 28.

    Cerda B, Ceron JJ, Tomas-Barberan FA, Espin JC (2003) Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic. J Agric Food Chem 51:3493–3501

    Article  CAS  Google Scholar 

  29. 29.

    Seeram NP, Lee R, Heber D (2004) Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice. Clin Chim Acta 348:63–68

    Article  CAS  Google Scholar 

  30. 30.

    Cerda B, Llorach R, Ceron JJ, Espin JC, Tomas-Barberan FA (2003) Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice. Eur J Nutr 42:18–28

    Article  CAS  Google Scholar 

  31. 31.

    Panchal SK, Poudyal H, Arumugam TV, Brown L (2011) Rutin attenuates metabolic changes, non-alcoholic steatohepatitis, and cardiovascular remodeling in high carbohydrate-, high-fat diet-fed rats. J Nutr 141:1062–1069

    Article  CAS  Google Scholar 

  32. 32.

    Poudyal H, Panchal S, Brown L (2010) Comparison of purple carrot juice and beta-carotene in a high-carbohydrate, high-fat diet-fed rat model of the metabolic syndrome. Br J Nutr 104:1322–1332

    Article  CAS  Google Scholar 

  33. 33.

    Poudyal H, Panchal SK, Waanders J, Ward L, Brown L (2011) Lipid redistribution by α-linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats. J Nutr Biochem. doi:10.1016/j.jnutbio.2010.11.011

  34. 34.

    Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D (2005) In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem 16:360–367

    Article  CAS  Google Scholar 

  35. 35.

    Larrosa M, Gonzalez-Sarrias A, Yanez-Gascon MJ, Selma MV, Azorin-Ortuno M, Toti S, Tomas-Barberan F, Dolara P, Espin JC (2010) Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism. J Nutr Biochem 21:717–725

    Article  CAS  Google Scholar 

  36. 36.

    de Nigris F, Williams-Ignarro S, Sica V, Lerman LO, D’Armiento FP, Byrns RE, Casamassimi A, Carpentiero D, Schiano C et al (2007) Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis. Cardiovasc Res 73:414–423

    Article  Google Scholar 

  37. 37.

    Shukla M, Gupta K, Rasheed Z, Khan KA, Haqqi TM (2008) Consumption of hydrolyzable tannins-rich pomegranate extract suppresses inflammation and joint damage in rheumatoid arthritis. Nutrition 24:733–743

    Article  CAS  Google Scholar 

  38. 38.

    Lei F, Zhang XN, Wang W, Xing DM, Xie WD, Su H, Du LJ (2007) Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obes (Lond) 31:1023–1029

    Article  CAS  Google Scholar 

  39. 39.

    Iyer A, Brown L (2010) Lipid mediators and inflammation in glucose intolerance and insulin resistance. Drug Discov Today Dis Mech 7(3–4):e191–e197

    Article  CAS  Google Scholar 

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This study was supported by The Prince Charles Hospital Foundation, Brisbane, Australia. We thank Mr. Paul Addison, School of Biomedical Sciences, and Mr. Gary Wilson, School of Human Movement Studies, both at The University of Queensland, Australia, for their help with histopathological studies and plasma oxidant analyses, respectively. We also thank Dr. Fiona Campbell and Mr. Brian Bynon both at School of Veterinary Science, The University of Queensland, Australia, for their assistance with echocardiography and plasma analyses, respectively; Dr Thiruma Arumugam (The University of Queensland) for assistance with expression studies and Dr Kate Kauter (University of Southern Queensland) for assistance with C-reactive protein measurements. We also thank Prof. Stéphane Quideau, European Institute of Chemistry and Biology, University of Bordeaux I, France, and Dr. Daniel Jardine, Flinders University, Australia, for providing ellagitannin standards and ellagitannin analyses in the extract, respectively.

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Correspondence to Lindsay Brown.

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Panchal, S.K., Brown, L. Cardioprotective and hepatoprotective effects of ellagitannins from European oak bark (Quercus petraea L.) extract in rats. Eur J Nutr 52, 397–408 (2013).

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  • Obesity
  • Cardiovascular disease
  • Dyslipidaemia
  • Ellagitannins
  • Hypertension