Skip to main content
SpringerLink
Log in

Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Background

Fruits and nuts may prevent or reverse common human health conditions such as obesity, diabetes and hypertension; together, these conditions are referred to as metabolic syndrome, an increasing problem. This study has investigated the responses to ellagic acid, present in many fruits and nuts, in a diet-induced rat model of metabolic syndrome.

Methods

Eight- to nine-week-old male Wistar rats were divided into four groups for 16-week feeding with cornstarch diet (C), cornstarch diet supplemented with ellagic acid (CE), high-carbohydrate, high-fat diet (H) and high-carbohydrate, high-fat diet supplemented with ellagic acid (HE). CE and HE rats were given 0.8 g/kg ellagic acid in food from week 8 to 16 only. At the end of 16 weeks, cardiovascular, hepatic and metabolic parameters along with protein levels of Nrf2, NF-κB and CPT1 in the heart and the liver were characterised.

Results

High-carbohydrate, high-fat diet-fed rats developed cardiovascular remodelling, impaired ventricular function, impaired glucose tolerance, non-alcoholic fatty liver disease with increased protein levels of NF-κB and decreased protein levels of Nrf2 and CPT1 in the heart and the liver. Ellagic acid attenuated these diet-induced symptoms of metabolic syndrome with normalisation of protein levels of Nrf2, NF-κB and CPT1.

Conclusions

Ellagic acid derived from nuts and fruits such as raspberries and pomegranates may provide a useful dietary supplement to decrease the characteristic changes in metabolism and in cardiac and hepatic structure and function induced by a high-carbohydrate, high-fat diet by suppressing oxidative stress and inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kotronen A, Yki-Järvinen H (2008) Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol 28:27–38

    Article  CAS  Google Scholar 

  2. Almeda-Valdés P, Cuevas-Ramos D, Aguilar-Salinas CA (2009) Metabolic syndrome and non-alcoholic fatty liver disease. Ann Hepatol 8(Suppl 1):S18–S24

    Google Scholar 

  3. Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, Omatsu T, Nakajima T, Sarui H et al (2005) The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 143:722–728

    CAS  Google Scholar 

  4. Qiao Q, Gao W, Zhang L, Nyamdorj R, Tuomilehto J (2007) Metabolic syndrome and cardiovascular disease. Ann Clin Biochem 44:232–263

    Article  Google Scholar 

  5. Powell EE, Jonsson JR, Clouston AD (2005) Steatosis: co-factor in other liver diseases. Hepatology 42:5–13

    Article  CAS  Google Scholar 

  6. Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S (2005) Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 42:44–52

    Article  Google Scholar 

  7. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT (2002) The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 288:2709–2716

    Article  Google Scholar 

  8. Fabbrini E, Sullivan S, Klein S (2010) Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology 51:679–689

    Article  CAS  Google Scholar 

  9. Adiels M, Taskinen MR, Borén J (2008) Fatty liver, insulin resistance, and dyslipidemia. Curr Diab Rep 8:60–64

    Article  CAS  Google Scholar 

  10. Lee JM, Johnson JA (2004) An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol 37:139–143

    Article  CAS  Google Scholar 

  11. Li Q, Verma IM (2002) NF-kappaB regulation in the immune system. Nat Rev Immunol 2:725–734

    Article  CAS  Google Scholar 

  12. Sanyal AJ (2001) Insulin resistance and nonalcoholic steatohepatitis: fat or fiction? Am J Gastroenterol 96:274–276

    Article  CAS  Google Scholar 

  13. Pessayre D, Fromenty B (2005) NASH: a mitochondrial disease. J Hepatol 42:928–940

    Article  CAS  Google Scholar 

  14. Narasimhan S, Gokulakrishnan K, Sampathkumar R, Farooq S, Ravikumar R, Mohan V, Balasubramanyam M (2010) Oxidative stress is independently associated with non-alcoholic fatty liver disease (NAFLD) in subjects with and without type 2 diabetes. Clin Biochem 43:815–821

    Article  CAS  Google Scholar 

  15. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, Fadl YY, Fortmann SP, Hong Y et al (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107:499–511

    Article  Google Scholar 

  16. Libby P (2006) Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr 83:456S–460S

    CAS  Google Scholar 

  17. Dhalla NS, Temsah RM, Netticadan T (2000) Role of oxidative stress in cardiovascular diseases. J Hypertens 18:655–673

    Article  CAS  Google Scholar 

  18. Mari Kannan M, Darlin Quine S (2012) Mechanistic clues in the protective effect of ellagic acid against apoptosis and decreased mitochondrial respiratory enzyme activities in myocardial infarcted rats. Cardiovasc Toxicol 12:56–63

    Article  CAS  Google Scholar 

  19. Talcott ST, Lee JH (2002) Ellagic acid and flavonoid antioxidant content of muscadine wine and juice. J Agric Food Chem 50:3186–3192

    Article  CAS  Google Scholar 

  20. Ateşşahín A, Ceríbaşi AO, Yüce A, Bulmus Ö, Cikim G (2007) Role of ellagic acid against cisplatin-induced nephrotoxicity and oxidative stress in rats. Basic Clin Pharmacol Toxicol 100:121–126

    Google Scholar 

  21. Türk G, Ateşşahín A, Sönmez M, Ceribaşi AO, Yüce A (2008) Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant system, and the histologic structure of the rat testis by ellagic acid. Fertil Steril 89:1474–1481

    Article  Google Scholar 

  22. Yüce A, Ateşşahín A, Ceribaşi AO, Aksakal M (2007) Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats. Basic Clin Pharmacol Toxicol 101:345–349

    Article  Google Scholar 

  23. Mari Kannan M, Darlin Quine S (2011) Pharmacodynamics of ellagic acid on cardiac troponin-T, lyosomal enzymes and membrane bound ATPases: mechanistic clues from biochemical, cytokine and in vitro studies. Chem Biol Interact 193:154–161

    Article  CAS  Google Scholar 

  24. Mari Kannan M, Darlin Quine S (2011) Ellagic acid ameliorates isoproterenol induced oxidative stress: evidence from electrocardiological, biochemical and histological study. Eur J Pharmacol 659:45–52

    Article  Google Scholar 

  25. Losso JN, Bansode RR, Trappey A 2nd, Bawadi HA, Truax R (2004) In vitro anti-proliferative activities of ellagic acid. J Nutr Biochem 15:672–678

    Article  CAS  Google Scholar 

  26. Rosillo MA, Sanchez-Hidalgo M, Cardeno A, de la Lastra CA (2011) Protective effect of ellagic acid, a natural polyphenolic compound, in a murine model of Crohn’s disease. Biochem Pharmacol 82:737–745

    Article  CAS  Google Scholar 

  27. Gümüş M, Yüksel H, Evliyaoğlu O, Kapan M, Böyük A, Önder A, Aldemir M (2011) Effects of ellagic acid on copper, zinc, and biochemical values in serum and liver of experimental cholestatic rats. Biol Trace Elem Res 143:386–393

    Article  Google Scholar 

  28. Hwang JM, Cho JS, Kim TH, Lee YI (2010) Ellagic acid protects hepatocytes from damage by inhibiting mitochondrial production of reactive oxygen species. Biomed Pharmacother 64:264–270

    Article  CAS  Google Scholar 

  29. Girish C, Koner BC, Jayanthi S, Ramachandra Rao K, Rajesh B, Pradhan SC (2009) Hepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in mice. Fundam Clin Pharmacol 23:735–745

    Article  CAS  Google Scholar 

  30. Panchal SK, Brown L (2011) Cardioprotective and hepatoprotective effects of ellagitannins from European oak bark (Quercus petraea L.) extract in rats. Eur J Nutr. doi:101007/s00394-011-0277-1

  31. 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 

  32. 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 

  33. Poudyal H, Panchal SK, Waanders J, Ward L, Brown L (2012) Lipid redistribution by alpha-linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats. J Nutr Biochem 23:153–162

    Article  CAS  Google Scholar 

  34. Ward LC, Battersby KJ (2009) Assessment of body composition of rats by bioimpedance spectroscopy validation against dual-energy X-ray absorptiometry. Scand J Lab Anim Sci 36:253–261

    CAS  Google Scholar 

  35. 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 

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

    Article  CAS  Google Scholar 

  37. Diwan V, Poudyal H, Brown L (2011) Piperine attenuates cardiovascular, liver and metabolic changes in high carbohydrate, high fat-fed rats. Cell Biochem Biophys. doi:101007/s12013-011-9306-1

  38. Tak PP, Firestein GS (2001) NF-κB: a key role in inflammatory diseases. J Clin Invest 107:7–11

    Article  CAS  Google Scholar 

  39. Bachmann K, Pardoe D, White D (1996) Scaling basic toxicokinetic parameters from rat to man. Environ Health Perspect 104:400–407

    Article  CAS  Google Scholar 

  40. Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22:659–661

    Article  CAS  Google Scholar 

  41. Scalbert A, Williamson G (2000) Dietary intake and bioavailability of polyphenols. J Nutr 130:2073S–2085S

    CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Dr Red Nutraceuticals, Mt Nebo, QLD, Australia. This project was also partially funded by grants from The Prince Charles Hospital Foundation, Brisbane, QLD, Australia. We thank Mr. Paul Addison, School of Biomedical Sciences, and Mr. Brian Bynon, School of Veterinary Science, both at The University of Queensland, for their help with histopathological studies and plasma biochemical analyses, respectively. We also thank Dr. Thiruma V. Arumugam, School of Biomedical Sciences, The University of Queensland, for his assistance with Western blot analysis and Dr. Fiona Campbell, School of Veterinary Science, The University of Queensland, for her assistance with echocardiography.

Conflict of interest

No conflict of interest.

Author information

Authors and Affiliations

  1. Department of Biological and Physical Sciences, University of Southern Queensland, Toowoomba, QLD, 4350, Australia

    Sunil K. Panchal & Lindsay Brown

  2. School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia

    Sunil K. Panchal

  3. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia

    Leigh Ward

Authors
  1. Sunil K. Panchal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leigh Ward
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lindsay Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lindsay Brown.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Panchal, S.K., Ward, L. & Brown, L. Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats. Eur J Nutr 52, 559–568 (2013). https://doi.org/10.1007/s00394-012-0358-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-012-0358-9

Keywords

Search

Navigation