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Grape Seed Extract Reduces the Severity of Selected Disease Markers in the Proximal Colon of Dextran Sulphate Sodium-Induced Colitis in Rats

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Abstract

Background

Grape seed extract (GSE) constitutes a rich source of procyanidins. GSE has been demonstrated to exert encouraging anti-inflammatory and anti-ulcer properties in experimental settings, although its effects on inflammation of the colon remain undefined.

Aim

To determine the effects of GSE in a rat model of dextran sulphate sodium (DSS) for ulcerative colitis.

Methods

Male Sprague–Dawley rats were gavaged daily (days 0–10) with GSE (400 mg/kg). Ulcerative colitis was induced by substituting DSS (2 % w/v) for drinking water from days 5–10. A sucrose breath test was performed on day 11 to determine small bowel function and intestinal tissues were collected for histological analyses. Statistical analysis was by one-way or repeated-measures ANOVA and p < 0.05 was considered significant.

Results

Compared to DSS-treated controls, GSE significantly decreased ileal villus height (14 %; p < 0.01) and mucosal thickness (13 %; p < 0.01) towards the values of normal controls. GSE reduced qualitative histological severity score (p < 0.05) in the proximal colon, although no significant effect was evident in the distal colon. However, GSE failed to prevent DSS-induced damage to the crypts of both colonic regions. Administration of GSE did not negatively impact metabolic parameters, nor did it induce any deleterious gastrointestinal side effects in healthy animals.

Conclusions

GSE decreased the severity of selected markers of DSS-induced colitis in the distal ileum and proximal colon, suggesting the potential as an adjuvant therapy for the treatment of ulcerative colitis. Future studies of GSE should investigate alternative delivery methods and treatment regimens, further seeking to identify the individual bioactive factors.

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References

  1. Geier MS, Butler RN, Giffard PM, Howarth GS. Prebiotic and synbiotic fructooligosaccharide administration fails to reduce the severity of experimental colitis in rats. Dis Colon Rectum. 2007;50:1061–1069.

    Article  PubMed  Google Scholar 

  2. Danese S, Angelucci E, Malesci A, Caprilli R. Biological agents for ulcerative colitis: hypes and hopes. Med Res Rev. 2008;28:201–218.

    Article  PubMed  CAS  Google Scholar 

  3. Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2004;53:V1–V16.

    Article  PubMed  Google Scholar 

  4. Hendrickson BA, Gokhale R, Cho JH. Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev. 2002;15:79–94.

    Article  PubMed  Google Scholar 

  5. Podolsky DK. Inflammatory bowel disease (1). N Engl J Med. 1991;325:928–937.

    Article  PubMed  CAS  Google Scholar 

  6. Langan RC, Gotsch PB, Krafczyk MA, Skillinge DD. Ulcerative colitis: diagnosis and treatment. Am Fam Physician. 2007;76:1323–1330.

    PubMed  Google Scholar 

  7. Targan SR, Karp LC. Defects in mucosal immunity leading to ulcerative colitis. Immunol Rev. 2005;206:296–305.

    Article  PubMed  CAS  Google Scholar 

  8. Boismenu R, Chen Y. Insights from mouse models of colitis. J Leukoc Biol. 2000;67:267–278.

    PubMed  CAS  Google Scholar 

  9. Podolsky DK. Inflammatory bowel disease (2). N Engl J Med. 1991;325:1008–1016.

    Article  PubMed  CAS  Google Scholar 

  10. Murthy S, Flanigan A, Clearfield H. Colorectal cancer in inflammatory bowel disease: molecular and clinical features. Gastroenterol Clin North Am. 2002;31:551–564.

    Article  PubMed  Google Scholar 

  11. Tenikoff D, Murphy KJ, Le M, Howe PR, Howarth GS. Lyprinol (stabilised lipid extract of New Zealand green-lipped mussel): a potential preventative treatment modality for inflammatory bowel disease. J Gastroenterol. 2005;40:361–365.

    Article  PubMed  CAS  Google Scholar 

  12. Geier MS, Butler RN, Giffard PM, Howarth GS. Lactobacillus fermentum br11, a potential new probiotic, alleviates symptoms of colitis induced by dextran sulfate sodium (dss) in rats. Int J Food Microbiol. 2007;114:267–274.

    Article  PubMed  Google Scholar 

  13. Yazbeck R, Howarth GS, Geier MS, Demuth HU, Abbott CA. Inhibiting dipeptidyl peptidase activity partially ameliorates colitis in mice. Front Biosci. 2008;13:6850–6858.

    Article  PubMed  CAS  Google Scholar 

  14. Wright TH, Yazbeck R, Lymn KA, et al. The herbal extract, iberogast, improves jejunal integrity in rats with 5-fluorouracil (5-FU)-induced mucositis. Cancer Biol Ther. 2009;8:923–929.

    Article  PubMed  Google Scholar 

  15. Cheah KY, Howarth GS, Yazbeck R, et al. Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally induced mucositis. Cancer Biol Ther. 2009;8:382–390.

    Article  PubMed  CAS  Google Scholar 

  16. Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol. 1983;32:1141–1148.

    Article  PubMed  CAS  Google Scholar 

  17. Fine AM. Oligomeric proanthocyanidin complexes: history, structure, and phytopharmaceutical applications. Altern Med Rev. 2000;5:144–151.

    PubMed  CAS  Google Scholar 

  18. Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001;74:418–425.

    PubMed  CAS  Google Scholar 

  19. Tran CD, Ball JM, Sundar S, Coyle P, Howarth GS. The role of zinc and metallothionein in the dextran sulfate sodium-induced colitis mouse model. Dig Dis Sci. 2007;52:2113–2121.

    Article  PubMed  CAS  Google Scholar 

  20. Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98:694–702.

    PubMed  CAS  Google Scholar 

  21. Geier MS, Tenikoff D, Yazbeck R, McCaughan GW, Abbott CA, Howarth GS. Development and resolution of experimental colitis in mice with targeted deletion of dipeptidyl peptidase iv. J Cell Physiol. 2005;204:687–692.

    Article  PubMed  CAS  Google Scholar 

  22. Tomas FM, Knowles SE, Owens PC, et al. Increased weight gain, nitrogen retention and muscle protein synthesis following treatment of diabetic rats with insulin-like growth factor (IGF)-I and des(1–3)IGF-I. Biochem J. 1991;276:547–554.

    PubMed  CAS  Google Scholar 

  23. Howarth GS, Xian CJ, Read LC. Insulin-like growth factor-I partially attenuates colonic damage in rats with experimental colitis induced by oral dextran sulphate sodium. Scand J Gastroenterol. 1998;33:180–190.

    Article  PubMed  CAS  Google Scholar 

  24. Tooley KL, Saxon BR, Webster J, et al. A novel non-invasive biomarker for assessment of small intestinal mucositis in children with cancer undergoing chemotherapy. Cancer Biol Ther. 2006;5:1275–1281.

    PubMed  CAS  Google Scholar 

  25. Sehirli O, Ozel Y, Dulundu E, Topaloglu U, Ercan F, Sener G. Grape seed extract treatment reduces hepatic ischemia-reperfusion injury in rats. Phytother Res. 2008;22:43–48.

    Article  PubMed  Google Scholar 

  26. Sato M, Bagchi D, Tosaki A, Das DK. Grape seed proanthocyanidin reduces cardiomyocyte apoptosis by inhibiting ischemia/reperfusion-induced activation of jnk-1 and c-jun. Free Radic Biol Med. 2001;31:729–737.

    Article  PubMed  CAS  Google Scholar 

  27. Saito M, Hosoyama H, Ariga T, Kataoka S, Yamaji N. Antiulcer activity of grape seed extract and procyanidins. J Agric Food Chem. 1998;46:1460–1464.

    Article  CAS  Google Scholar 

  28. Ohtsuka Y, Sanderson IR. Dextran sulfate sodium-induced inflammation is enhanced by intestinal epithelial cell chemokine expression in mice. Pediatr Res. 2003;53:143–147.

    PubMed  CAS  Google Scholar 

  29. Tanaka M, Kazuma K. Ulcerative colitis: factors affecting difficulties of life and psychological well being of patients in remission. J Clin Nurs. 2005;14:65–73.

    Article  PubMed  Google Scholar 

  30. Geier MS, Smith CL, Butler RN, Howarth GS. Small-intestinal manifestations of dextran sulfate sodium consumption in rats and assessment of the effects of lactobacillus fermentum BR11. Dig Dis Sci. 2009;54:1222–1228.

    Article  PubMed  CAS  Google Scholar 

  31. Haxhija EQ, Yang H, Spencer AU, Sun X, Teitelbaum DH. Intestinal epithelial cell proliferation is dependent on the site of massive small bowel resection. Pediatr Surg Int. 2007;23:379–390.

    Article  PubMed  Google Scholar 

  32. Fukushima K, Haneda S, Funayama Y, et al. An approach to analyze mechanisms of intestinal adaptation following total proctocolectomy. J Gastrointest Surg. 2006;10:662–671.

    Article  PubMed  Google Scholar 

  33. Houde V, Grenier D, Chandad F. Protective effects of grape seed procyanidins against oxidative stress induced by lipopolysaccharides of periodontopathogens. J Periodontol. 2006;77:1371–1379.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge Ruth Lindsay, Roger Yazbeck, Mark Geier, Lynn Scarman, and Jo Cool for their assistance with the animal experiments, data collection, and data analysis. Professor Gordon Howarth is supported by the Sally Birch Cancer Council Australia Research Fellowship in Cancer Control.

Conflict of interest

None.

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Authors and Affiliations

  1. Wine Science and Business Group School of Agriculture, Food and Wine, Waite Campus, The University of Adelaide, PMB 1, Glen Osmond, SA, 5064, Australia

    Ker Y. Cheah & Susan E. P. Bastian

  2. School of Animal and Veterinary Sciences, Roseworthy Campus, The University of Adelaide, Adelaide, SA, 5371, Australia

    Thomas M. V. Acott, Kerry A. Lymn & Gordon S. Howarth

  3. Centre for Paediatric and Adolescent Gastroenterology, Children, Youth and Women’s Health Service, 72 King William Road, North Adelaide, SA, 5006, Australia

    Suzanne M. Abimosleh, Kerry A. Lymn & Gordon S. Howarth

  4. Discipline of Physiology, School of Medical Sciences, The University of Adelaide, Adelaide, SA, 5001, Australia

    Suzanne M. Abimosleh

Authors
  1. Ker Y. Cheah
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  2. Susan E. P. Bastian
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  3. Thomas M. V. Acott
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  4. Suzanne M. Abimosleh
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  6. Gordon S. Howarth
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Correspondence to Gordon S. Howarth.

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Cheah, K.Y., Bastian, S.E.P., Acott, T.M.V. et al. Grape Seed Extract Reduces the Severity of Selected Disease Markers in the Proximal Colon of Dextran Sulphate Sodium-Induced Colitis in Rats. Dig Dis Sci 58, 970–977 (2013). https://doi.org/10.1007/s10620-012-2464-1

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  • DOI: https://doi.org/10.1007/s10620-012-2464-1

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