The Journal of Nutritional Biochemistry
Volume 21, Issue 8 , Pages 717-725 , August 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

  • Mar Larrosa

      Affiliations

    • Department of Preclinical and Clinical Pharmacology, University of Florence, I-50139 Florence, Italy
  • ,
  • Antonio González-Sarrías

      Affiliations

    • Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain
  • ,
  • María J. Yáñez-Gascón

      Affiliations

    • Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain
  • ,
  • María V. Selma

      Affiliations

    • Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain
  • ,
  • María Azorín-Ortuño

      Affiliations

    • Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain
  • ,
  • Simona Toti

      Affiliations

    • Department of Preclinical and Clinical Pharmacology, University of Florence, I-50139 Florence, Italy
  • ,
  • Francisco Tomás-Barberán

      Affiliations

    • Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain
  • ,
  • Piero Dolara

      Affiliations

    • Department of Preclinical and Clinical Pharmacology, University of Florence, I-50139 Florence, Italy
  • ,
  • Juan Carlos Espín

      Affiliations

    • Department of Preclinical and Clinical Pharmacology, University of Florence, I-50139 Florence, Italy
    • Corresponding Author InformationCorresponding author. Department of Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain. Tel.: +34 968 396344; fax: +34 968 396213.

Received 24 February 2009 ,Revised 18 April 2009 ,Accepted 23 April 2009.

References 

  1. Rubio CA, Befrits R. Colorectal cancer in Crohn's disease — review of a 56-year experience in Karolinska Institute University Hospital. J Environ Pathol Toxicol Oncol. 2008;27:257–266
  2. Itzkowitz SH, Yio X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol. 2004;287:G7–G17
  3. Stecher B, Hardt WD. The role of microbiota in infectious disease. Trends Microbiol. 2008;16:107–114
  4. Toklu HZ, Dumlu MU, Sehirli O, Ercan F, Gedik N, Gökmen V, et al. Pomegranate peel extract prevents liver fibrosis in biliary-obstructed rats. J Pharm Pharmacol. 2007;59:1287–1295
  5. Faria A, Monteiro R, Mateus N, Azevedo I, Calhau C. Effect of pomegranate (Punica granatum) juice intake on hepatic oxidative stress. Eur J Nutr. 2007;46:271–278
  6. Shukla M, Gupta K, Rasheed Z, Khan KA, Haqqi TM. Consumption of hydrolyzable tannins-rich pomegranate extract suppresses inflammation and joint damage in rheumatoid arthritis. Nutrition. 2008;24:733–743
  7. Cerdá B, Cerón JJ, Tomás-Barberán FA, Espín JC. Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic. J Agric Food Chem. 2003;51:3493–3501
  8. Cerdá B, Espín JC, Parra S, Martínez P, Tomás-Barberán FA. The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humans. Eur J Nutr. 2004;43:205–220
  9. Cerdá B, Periago P, Espín JC, Tomás-Barberán FA. Identification of urolithin a as a metabolite produced by human colon microflora from ellagic acid and related compounds. J Agric Food Chem. 2005;53:5571–5576
  10. Espín JC, González-Barrio B, Cerdá B, López-Bote C, Rey AI, Tomás-Barberán FA. The Iberian pig as a model to clarify obscure points in the bioavailability and metabolism of ellagitannins in humans. J Agric Food Chem. 2007;55:10476–10485
  11. Larrosa M, González-Sarrías A, García-Conesa MT, Tomás-Barberán FA, Espín JC. Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities. J Agric Food Chem. 2006;54:1611–1620
  12. González-Sarrías A, Espín JC, Tomás-Barberán FA, García-Conesa MT. Gene expression, cell cycle arrest and MAPK signalling regulation in Caco-2 cells exposed to acid ellagic and its metabolites, urolithins. Mol Nutr Food Res. 2009;53:686–698
  13. Seeram NP, Aronson WJ, Zhang Y, Henning SM, Moro A, Lee RP, et al. Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland. J Agric Food Chem. 2007;55:7732–7737
  14. Sartippour MR, Seeram NP, Rao JY, Moro A, Harris DM, Henning SM, et al. Ellagitannin-rich pomegranate extract inhibits angiogenesis in prostate cancer in vitro and in vivo. Int J Oncol. 2008;32:475–480
  15. Cerdá B, Tomás-Barberán F, Espín JC. Metabolism of chemopreventive and antioxidant ellagitannins from strawberries, raspberries, walnuts and oak-aged wines in humans: identification of biomarkers and individual variability. J Agric Food Chem. 2005;53:227–235
  16. Russell WR, Labat A, Scobbie L, Duncan SH. Availability of blueberry phenolics for microbial metabolism in the colon and the potential inflammatory implications. Mol Nutr Food Res. 2007;51:726–731
  17. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22:659–661
  18. Araki Y, Andoh A, Fujiyama Y, Bamba T. Development of dextran sulfate sodium-induced experimental colitis is suppressed in genetically mast cell-deficient Ws/Ws rats. Clin Exp Immunol. 2000;119:264–269
  19. Tsune I, Ikejima K, Hirose M, Yoshikawa M, Enomoto N, Takei Y, et al. Dietary glycine prevents chemical-induced experimental colitis in the rat. Gastroenterology. 2003;125:775–785
  20. Jozwik M, Wolczynski S, Jozwik M, Szamatowicz M. Oxidative stress markers in preovulatory follicular fluid in humans. Hum Reprod. 1999;5:409–413
  21. Luceri C, Giovannelli L, Pitozzi V, Toti S, Castagnini C, Routaboul JM, et al. Liver and colon DNA oxidative damage and gene expression profiles of rats fed Arabidopsis thaliana mutant seeds containing contrasted flavonoids. Food Chem Toxicol. 2008;46:1213–1220
  22. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc. 1995;57:289–300
  23. Doniger SW, Salomonis N, Dahlquist KD, Vranizan K, Lawlor SC, Conklin BR. MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data. Genome Biol. 2003;4:R7
  24. Roessner A, Kuester D, Malfertheiner P, Schneider-Stock R. Oxidative stress in ulcerative colitis-associated carcinogenesis. Pathol Res Pract. 2008;204:511–524
  25. Ogawa Y, Kanatsu K, Iino T, Kato S, Jeong YI, Shibata N, et al. Protection against dextran sulfate sodium-induced colitis by microspheres of ellagic acid in rats. Life Sci. 2002;71:827–839
  26. Krieglstein CF, Anthoni C, Cerwinka WH, Stokes KY, Russell J, Grisham MB, et al. Role of blood- and tissue-associated inducible nitric-oxide synthase in colonic inflammation. Am J Pathol. 2007;170:490–496
  27. Tugcu V, Kemahli E, Ozbek E, Arinci YV, Uhri M, Erturkuner P, et al. Protective effect of a potent antioxidant, pomegranate juice, in the kidney of rats with nephrolithiasis induced by ethylene glycol. J Endourol. 2008;22:2723–2731
  28. Shukla M, Gupta K, Rasheed Z, Khan KA, Haqqi TM. Bioavailable constituents/metabolites of pomegranate (Punica granatum L) preferentially inhibit COX2 activity ex vivo and IL-1β-induced PGE2 production in human chondrocytes in vitro. J Inflamm. 2008;13:5–9
  29. Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D. Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signalling in colon cancer cells. J Agric Food Chem. 2006;54:980–985
  30. Collier-Hyams LS, Neish AS. Innate immune relationship between commensal flora and the mammalian intestinal epithelium. Cell Mol Life Sci. 2005;62:1339–1348
  31. Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, et al. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009;
  32. Fooks LJ, Gibson GR. Probiotics as modulators of the gut flora. Br J Nutr. 2002;88:S39–S49
  33. Faure M, Mettraux C, Moennoz D, Godin JP, Vuichoud J, Rochat F, et al. Specific amino acids increase mucin synthesis and microbiota in dextran sulfate sodium-treated rats. J Nutr. 2006;136(6):1558–1564
  34. Barcenilla A, Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol. 2000;66:1654–1661
  35. Okamoto T, Sasaki M, Tsujikawa T, Fujiyama Y, Bamba T, Kusunoki M. Preventive efficacy of butyrate enemas and oral administration of Clostridium butyricum M588 in dextran sodium sulfate-induced colitis in rats. J Gastroenterol. 2000;35:341–346
  36. Candela M, Perna F, Carnevali P, Vitali B, Ciati R, Gionchetti P, et al. Interaction of probiotic Lactobacillus and Bifidobacterium strains with human intestinal epithelial cells: adhesion properties, competition against enteropathogens and modulation of IL-8 production. Int J Food Microbiol. 2008;125:286–292
  37. Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, et al. 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. 2005;16:360–367
  38. Larrosa M, Tomás-Barberán FA, Espín JC. The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway. J Nutr Biochem. 2006;17:611–625

 This work has been supported by the Projects CICYT-BFU2007-60576 and Consolider Ingenio 2010, CSD2007-00063 (Fun-C-Food). M.L. is holder of a postdoctoral grant from MCINN (Spain), M.V.S. is the holder of a I3P-postdoctoral grant from CSIC (Spain), A.G.S. is holder of a FPI predoctoral grant from MICINN and M.A.O. is the holder of a JAE-predoctoral grant from CSIC.

PII: S0955-2863(09)00099-0

doi: 10.1016/j.jnutbio.2009.04.012

The Journal of Nutritional Biochemistry
Volume 21, Issue 8 , Pages 717-725 , August 2010