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Original Articles

Metabolic Fate of Ellagitannins: Implications for Health, and Research Perspectives for Innovative Functional Foods

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REFERENCES

  • Acosta-Montoya , O. , Vaillant , F. , Cozzano , S. , Mertz , C. , Perez , A. M. and Castro , M. V. 2010 . Phenolic content and antioxidant capacity of tropical highland blackberry (Rubus adenotrichus Schltdl.) during three edible maturity stages . Food Chem. , 119 : 1497 – 1501 .
  • Adams , L. S. , Zhang , Y. , Seeram , N. P. , Heber , D. and Chen , , S. 2010 . Pomegranate ellagitannin-derived compounds exhibit antiproliferative and antiaromatase activity in breast cancer cells in vitro . Cancer Prev. Res. , 1 : 108 – 113 .
  • Adams , L. S. , Seeram , N. P. , Aggarwal , B. B. , Takada , Y. , Sand , D. and Heber , D. 2006 . Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells . J. Agric. Food. Chem. , 54 : 980 – 985 .
  • Aguilera-Carbo , A. , Augur , C. , Prado-Barragan , L. A. , Favela-Torres , E. and N. Aguilar , C. 2007 . Microbial production of ellagic acid and biodegradation of ellagitannins . Appl. Microbiol. Biotechnol. , 78 : 189 – 199 .
  • Aura , A. 2008 . Microbial metabolism of dietary phenolic compounds in the colon . Phytochem Rev. , 7 : 22
  • Aura , A. M. 2005 . In vitro digestion models for dietary phenolic compounds . VTT Technical Research Center of Finland, VTT publication No. 575
  • Aviram , M. and Dornfeld , L. 2001 . Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure . Atherosclerosis , 158 : 195 – 198 .
  • Aviram , M. , Rosenblat , M. , Gaitini , D. , Nitecki , S. , Hoffman , A. , Dornfeld , L. , Volkova , N. , Presser , D. , Attias , J. , Liker , H. and Hayek , T. 2004 . Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation . Clin Nutr. , 23 : 423 – 433 .
  • Aviram , M. , Volkova , N. , Coleman , R. , Dreher , M. , Reddy , M. K. , Ferreira , D. and Rosenblat , M. 2008 . Pomegranate phenolics from the peels, arils, and flowers are antiatherogenic: Studies in vivo in atherosclerotic apolipoprotein E-deficient (E0) mice and in vitro in cultured macrophages and lipoproteins . J. Agric. Food. Chem. , 56 : 1148 – 1157 .
  • Azorin-Ortuno , M. , Urban , C. , Ceron , J. J. , Tecles , F. , Gil-Izquierdo , A. , Pallares , F. J. , Tomas-Barberan , F. A. and Espin , J. C. 2008 . Safety evaluation of an oak-flavored milk powder containing ellagitannins upon oral administration in the rat . J. Agric. Food. Chem. , 56 : 2857 – 2865 .
  • Bakkalbai , E. , Mente , Ö. and Artik , N. 2009 . Food ellagitannins-occurrence, effects of processing and storage . Crit. Rev. Food Sci. Nutr. , 49 : 6
  • Bialonska , D. , Kasimsetty , S. G. , Khan , S. I. and Ferreira , D. 2009a . Urolithins, intestinal microbial metabolites of pomegranate ellagitannins, exhibit potent antioxidant activity in a cell-based assay . J. Agric. Food. Chem. , 57 : 10181 – 10186 .
  • Bialonska , D. , Kasimsetty , S. G. , Schader , K. and Daneel , F. 2009b . The effect of pomegranate (Punica granatum L.) byproducts and ellagitannins on the growth of human gut bacteria . J. Agric. Food. Chem. , 57 : 5
  • Bialonska , D. , Ramnani , P. , Kasimsetty , S. G. , Muntha , K. R. , Gibson , G. R. and Ferreira , D. 2010 . The influence of pomegranate by-product and punicalagins on selected groups of human intestinal microbiota . Int. J. Food Microbiol. , 140 : 175 – 182 .
  • Borges , G. , Degenve , A. , Mullen , W. and Crozier , A. 2010 . Identification of flavonoid and phenolic antioxidants in black currants, blueberries, raspberries, red currants, and cranberries . J. Agric. Food. Chem. , 58 : 8
  • Cerda , B. , Espin , J. C. , Parra , S. , Martínez , P. and Tomás-Barberán , F. 2004 . 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. , 43 : 205 – 220 .
  • Cerda , B. , Llorach , R. , Cerón , J. , Espín , J. C. and Tomás-Barberán , F. A. 2003 . Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice . Eur. J. Nutr. , 42 : 18 – 28 .
  • Cerda , B. , Periago , P. , Espin , J. C. and Tomas-Barberan , F. A. 2005a . Identification of urolithin A as a metabolite produced by human colon microflora from ellagic acid and related compounds . J. Agric. Food. Chem , 53 : 5571 – 5576 .
  • Cerda , B. , Soto , C. , Albaladejo , M. D. , Martinez , P. , Sanchez-Gascon , F. , Tomas-Barberan , F. and Espin , J. C. 2006 . Pomegranate juice supplementation in chronic obstructive pulmonary disease: A 5-week randomized, double-blind, placebo-controlled trial . Eur. J. Clin. Nutr. , 60 : 245 – 253 .
  • Cerda , B. , Tomas-Barberan , F. A. and Espin , J. C. 2005b . 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 .
  • Cerda , B. , Cerón , J. , Tomás Barberán , F. and Espín , C. 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 : 8
  • Chang , R. L. , Tuan Huang , M. , Wood , A. W. , Wong , C.-Q. , Newmark , H. L. , Yagi , H. , Sayer , J. M. , Jerina , D. M. and Conney , A. H. 1985 . Effect of ellagic acid and hydroxylated flavonoids on the tumorigenidty of benzo[a]pyrene and (±)-7β3,8α;-dihydroxy-9α,10α−epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene on mouse skin and in the newborn mouse . Carcinogenesis , 6 : 6
  • Chris , G. I. R. , Mcdougall , G. J. , Glidewell , S. , Stewart , D. , Shen , Q. , Tuohy , K. , Dobbin , A. B. , AINE , Brown , E. , Haldar , S. and Rowland , I. R. 2010 . Profiling of phenols in human fecal water after raspberry supplementation . J. Agric. Food. Chem , 58 : 6
  • Clifford , M. and Scalbert , A. 2000 . Review ellagitannins—Nature, occurrence and dietary burden . J. Food Sci. Agric , 80 : 7
  • Corbett , S. , Daniel , J. , Drayton , R. , Field , M. , Steinhardt , R. and Garrett , N. 2010 . Evaluation of the anti-inflammatory effects of ellagic acid . J. Peri Anesth. Nurs , 25 : 6
  • D’Archivio , M. , Filesi , C. , Varì , R. , Scazzocchio , B. and Roberta , M. 2010 . Review: Bioavailability of the polyphenols: Status and controversies . Int. J. Mol. Sci , 11 : 21
  • Davis , C. D. and Milner , J. A. 2009 . Gastrointestinal microflora, food components and colon cancer prevention . J. Nutr. Biochem , 20 : 743 – 752 .
  • Espín , J. C. , González-Barrio , R. , Cerdá , B. , López-Bote , C. , Rey , A. I. and Tomás-Barberán , F. A. 2007 . Iberian pig as a model to clarify obscure points in the bioavailability and metabolism of ellagitannins in humans . J. Agric. Food. Chem. , 55 : 10476 – 10485 .
  • FAO/WHO . 2004 . “ Fruit and vegetables for health ” . In Report of a Joint FAO/WHO Workshop , Kobe , , Japan : FAO .
  • Gancel , A.-L. , Feneuila , A. , Acosta , O. , Pérez , A. M. and Vaillant , F. 2010 . Impact of industrial processing and storage on major polyphenols and the antioxidant capacity of tropical highland blackberry (Rubus adenotrichus) . Food Res. Int , 44 : 2243 – 2251 .
  • Gasperotti , M. , Masuero , D. , Urska , V. , Guella , G. and Mattivi , F. 2010 . Profiling and accurate quantification of Rubus ellagitannins and ellagic acid conjugates using direct UPLC-Q-TOF HDMS and HPLC-DAD analysis . J. Agric. Food. Chem , 58 : 14
  • Gonzalez-Barrio , R. , Christine , E. and Crozier , A. 2011 . Colonic Catabolism of Ellagitannins, Ellagic acid and Raspberry Anthocyanins: In Vivo and In Vitro Studies . Drug Metab. Dispos , 39 : 1680 – 1688 .
  • González-Barrio , R. , Gina , B. , William , M. and Alan , C. 2010 . Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy . J. Agric. Food. Chem , 58 : 3933 – 3939 .
  • González-Barrio , R. o. , Truchado , P. , Ito , H. , Espín , J. C. and Tomás-Barberán , F. A. 2011 . UV and MS identification of urolithins and nasutins, the bioavailable metabolites of ellagitannins and ellagic acid in different mammals . J. Agric. Food. Chem. , 59 : 1152 – 1162 .
  • Gonzalez-Sarrias , A. , Azorin-Ortuno , M. , Yanez-Gascon , M. J. , Tomas-Barberan , F. A. , Garcia-Conesa , M. T. and Espin , J. C. 2009a . Dissimilar in vitro and in vivo effects of ellagic acid and its microbiota-derived metabolites, urolithins, on the cytochrome P450 1A1 . J. Agric. Food. Chem , 57 : 5623 – 5632 .
  • Gonzalez-Sarrias , A. , Espin , J. C. , Tomas-Barberan , F. A. and Garcia-Conesa , M. T. 2009b . Gene expression, cell cycle arrest and MAPK signalling regulation in Caco-2 cells exposed to ellagic acid and its metabolites, urolithins . Mol. Nutr. Food Res , 53 : 686 – 698 .
  • Gonzalez-Sarrias , A. , Gimenez-Bastida , J. A. , Garcia-Conesa , M. T. , Gomez-Sanchez , M. B. , Garcia-Talavera , N. V. , Gil-Izquierdo , A. , Sanchez-Alvarez , C. , Fontana-Compiano , L. O. , Morga-Egea , J. P. , Pastor-Quirante , F. A. , Martinez-Diaz , F. , Tomas-Barberan , F. A. and Espin , J. C. 2010 . Occurrence of urolithins, gut microbiota ellagic acid metabolites and proliferation markers expression response in the human prostate gland upon consumption of walnuts and pomegranate juice . Mol. Nutr. Food Res , 54 : 311 – 322 .
  • González , E. , Vaillant , F. , Rojas , G. and Pérez , A. 2010 . Novel semiautomated method for assessing in vitro cellular antioxidant activity using the light-scattering properties of human erythrocytes . J. Agric. Food. Chem , 58 : 1455 – 1461 .
  • Hager , T. , Howard , L. , Liyanage , R. , Jackson , L. and Ronald , P. 2008 . Ellagitannin composition of blackberry as determined by HPLC-ESI-MS and MALDI-TOF-MS . J. Agric. Food. Chem , 56 : 8
  • Hamad , A. , Al-Momani , W. , Janakat , S. and Oran , S. 2009 . Bioavailavility of Ellagic acid after single doses administration by HPLC . Pak. J. Nutr , 8 : 3
  • Hassimotto , N. M. A. and Lajolo , F. M. 2011 . Antioxidant status in rats after long-term intake of anthocyanins and ellagitannins from blackberries . J. Sci. Food Agriculture , 91 : 523 – 531 .
  • Heber , D. 2008 . Multitargeted therapy of cancer by ellagitannins . Cancer Lett , 269 : 262 – 268 .
  • Heber , D. , Seeram , N. P. , Wyatt , H. , Henning , S. M. , Zhang , Y. J. , Ogden , L. G. , Dreher , M. and Hill , J. O. 2007 . Safety and antioxidant activity of a pomegranate ellagitannin-enriched polyphenol dietary supplement in overweight individuals with increased waist size . J. Agric. Food. Chem. , 55 : 10050 – 10054 .
  • Henning , S. M. , Seeram , N. P. , Zhang , Y. J. , Li , L. Y. , Gao , K. , Lee , R. P. , Wang , D. C. , Zerlin , A. , Karp , H. , Thames , G. , Kotlerman , J. , Li , Z. P. and Heber , D. 2010 . Strawberry consumption is associated with increased antioxidant capacity in serum . J. Med. Food , 13 : 116 – 122 .
  • Hideyuki , I. 2011 . Metabolites of the ellagitannins geraniin and their antioxidant activities . Planta Med. , 2011 Jul;77(11):1110. 77: 1110
  • Hong , M. Y. , Seeram , N. P. and Heber , D. 2008 . Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor . J. Nutr. Biochem , 19 : 848 – 855 .
  • Hourdes , M. , Lefeuvre , D. and Quideau , S. 2009 . “ C-Glycosidic ellagitannins and their influence on wine chemistry ” . In Chemistry and Biology of Ellagitannins: An Underestimated Class of Bioactive Plant Polyphenols , Edited by: Quideau , S. 320 – 365 . Bordeaux , , France : World Scientific Publishing Co .
  • Huang , W. , Niu , H. , Li , Z. , Lin , W. , Gong , G. and Wang , W. 2007 . Effect of ellagitannin acyl hydrolase, xylanase and cellulase on ellagic acid production from cups extract of valonia acorns . Process Biochem , 42 : 1291 – 1295 .
  • Ishimoto , H. , Shibata , M. , Myojin , Y. , Ito , H. , Sugimoto , Y. , Tai , A. and Hatano , T. 2011 . In vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite urolithin A . Bioorg. Med. Chem. Lett , 21 : 5901 – 5904 .
  • Ito , H. 2011 . Metabolites of the ellagitannin geraniin and their antioxidant activities . Planta Medica , 77 : 1110 – 1115 .
  • Kasimsetty , S. G. , Bialonska , D. , Reddy , M. K. , Ma , G. Y. , Khan , S. I. and Ferreira , D. 2010 . Colon cancer chemopreventive activities of pomegranate ellagitannins and urolithins . J. Agric. Food. Chem. , 58 : 2180 – 2187 .
  • Kasimsetty , S. G. , Bialonska , D. , Reddy , M. K. , Thornton , C. , Willett , K. L. and Ferreira , D. 2009 . Effects of pomegranate chemical constituents/intestinal microbial metabolites on CYP1B1 in 22Rv1 prostate cancer cells . J. Agric. Food. Chem. , 57 : 10636 – 10644 .
  • Kresty , L. , Morse , M. , Morgan , C. S. , C. P. , Lu , J. , Gupta , A. , Blackwood , M. and Stoner , G. D. 2001 . Chemoprevention of esophageal tumorigenesis by dietary administration of lyophilized black raspberries . Cancer Res. , 61 : 7
  • Landete , J. M. 2011 . Ellagitannins, ellagic acid and their derived metabolites: A review about source, metabolism, functions and health . Food Res. Int , 44 : 1150 – 1160 .
  • Lansky , E. P. and Newman , R. A. 2007 . Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer . J. Ethnopharmacol , 109 : 177 – 206 .
  • Larrosa , M. , González-Sarrías , A. , García-Conesa , M. T. , Tomás-Barberán , F. A. and Espín , J. C . 2006a . Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities . J. Agric. Food. Chem , 54 : 1611 – 1620 .
  • Larrosa , M. , Gonzalez-Sarrias , A. , Yanez-Gascon , M. J. , Selma , M. V. , Azorin-Ortuno , M. , Toti , S. , Tomas-Barberan , F. , Dolara , P. and Espin , J. C. 2009 . 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 : 715 – 725 .
  • Larrosa , M. , Tomás-Barberán , F. A. and Espín , J. C. 2006b . 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 , 17 : 611 – 625 .
  • Lee , J.-H. , Johnson , J. and Talcott , S. 2005 . Identification of ellagic acid conjugates and other polyphenolics in muscadine grapes by HPLC-ESI-MS . J. Agric. Food. Chem , 53 : 7
  • Leser , T. D. and Mølbak , L. 2009 . Better living through microbial action: the benefits of the mammalian gastrointestinal microbiota on the host . Environ. Microbiol , 11 : 12
  • Losso , J. , Bansodea , R. R. , Trappey , A. and Bawadi , H. A. 2004 . In vitro anti-proliferative activities of ellagic acid . J. Nutr. Biochem , 15 : 6
  • Machado , T. d. B. , Leala , I. C. R. , Amaral , A. C. , Dos-Santos , K. R. N. , Da-Silva , M. G. and Kuster , R. M. 2002 . Antimicrobial ellagitannin of Punica granatum fruits . J. Braz. Chem. Soc. , 13 : 606 – 610 .
  • Mari Kannan , M. and Darlin Quine , S. 2012 . Ellagic acid protects mitochondria from β-adrenergic agonist induced myocardial damage in rats: Evidence from in vivo, in vitro and ultra structural study . Food Res. Int , 45 : 1 – 8 .
  • Mattiello , T. , Elisabetta , Trifirò , Saccani Jotti , G. and Pulcinelli , F. M. 2009 . Effects of pomegranate juice and extract polyphenols on platelet function . J. Med. Food , 12 : 7
  • Mertens-Talcott , S. U. , Jilma-Stohlawetz , P. , Rios , J. , Hingorani , L. and Derendorf , H. 2006 . Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum L.) polyphenols after ingestion of a standardized extract in healthy human volunteers . J. Agric. Food. Chem. , 54 : 8956 – 8961 .
  • Mingshu , L. , Kai , Y. , Qiang , H. and Dongying , J. 2006 . Biodegradation of gallotannins and ellagitannins . J. Basic Microbiol , 46 : 68 – 84 .
  • Mullen , W. , Steward , A. , Lean , M. , Gardner , P. , Duthie , G. and Crozier , A. 2002 . Effect of freezing and storage on the phenolics, ellagitannins, flavonoids, and antioxidant capacity of red raspberries . J. Agric. Food. Chem , 50 : 5
  • Mullen , W. , Takao , Y. , Leanc , M. E. J. and Croziera , A. 2003 . Analysis of ellagitannins and conjugates of ellagic acid and quercetin in raspberry fruits by LC–MSn . Phyrochemistry , 64 : 7
  • Nanberg , E. and Fjaeraa , C. 2009 . Effect of ellagic acid on proliferation, cell adhesion and apoptosis in SH-SY5Y human neuroblastoma cells . Biomed. Pharmacother , 63 : 254 – 261 .
  • Narayanan , B. A. and Re , G. G. 2001 . IGF-II down regulation associated cell cycle arrest in colon cancer cells exposed to phenolic antioxidant ellagic acid . Anticancer Res , 21 : 359 – 364 .
  • Narayanana , B. A. , Geoffroya , O. , Willinghama , M. C. , Reb , G. G. and Nixon , D. W. 1998 . p53/p21(WAF1/CIP1) expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells . Cancer Lett. , 136 : 5
  • Niemetz , R. and Gross , G. G. 2005 . Enzymology of gallotannin and ellagitannin biosynthesis . Chem. Inform , 66 : 2001 – 2011 .
  • Osawa , R. , Kuroiso , K. , Goto , S. and Shimizu , A. 2000 . Isolation of tannin-degrading lactobacilli from humans and fermented foods . Appl. Environ. Microbiol. , 66 : 3093 – 3097 .
  • Ovaskainen , M. L. , Torronen , R. , Koponen , J. M. , Sinkko , H. , Hellstrom , J. , Reinivuo , H. and Mattila , P. 2008 . Dietary intake and major food sources of polyphenols in Finnish adults . J. Nutr. , 138 : 562 – 566 .
  • Pantuck , A. J. , Leppert , J. T. , Zomorodian , N. , Aronson , W. , Hong , J. , Barnard , R. J. , Seeram , N. , Liker , H. , Wang , H. J. , Elashoff , R. , Heber , D. , Aviram , M. , Ignarro , L. and Belldegrun , A. 2006 . Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer . Clin. Cancer Res , 12 : 4018 – 4026 .
  • Perez-Jimenez , J. , Serrano , J. , Tabernero , M. , Arranz , S. , Diaz-Rubio , M. E. , Garcia-Diz , L. , Goni , I. and Saura-Calixto , F. 2009 . Bioavailability of phenolic antioxidants associated with dietary fiber: Plasma antioxidant capacity after acute and long-term intake in humans . Plant Foods Hum. Nutr. , 64 : 102 – 107 .
  • Qin , J. , Li , R. , Raes , J. , Arumugam , M. , Burgdorf , K. S. , Manichanh , C. , Nielsen , T. , Pons , N. , Levenez , F. , Yamada , T. , Mende , D. R. , Li , J. , Xu , J. , Li , S. , Li , D. , Cao , J. , Wang , B. , Liang , H. , Zheng , H. , Xie , Y. , Tap , J. , Lepage , P. , Bertalan , M. , Batto , J.-M. , Hansen , T. , Le Paslier , D. , Linneberg , A. , Nielsen , H. B. , Pelletier , E. , Renault , P. , Sicheritz-Ponten , T. , Turner , K. , Zhu , H. , Yu , C. , Li , S. , Jian , M. , Zhou , Y. , Li , Y. , Zhang , X. , Li , S. , Qin , N. , Yang , H. , Wang , J. , Brunak , S. , Dore , J. , Guarner , F. , Kristiansen , K. , Pedersen , O. , Parkhill , J. , Weissenbach , J. , Bork , P. , Ehrlich , S. D. and Wang , J. 2010 . A human gut microbial gene catalogue established by metagenomic sequencing . Nature , 464 : 59 – 65 .
  • Reddy , M. K. , Gupta , S. K. , Jacob , M. R. , Khan , S. I. and Ferreira , D. 2007 . Antioxidant, antimalarial and antimicrobial activities of tannin-rich fractions, ellagitannins and phenolic acids from Punica granatum L . Planta Medica , 73 : 461 – 467 .
  • Rosenblat , M. , Hayek , T. and Aviram , M. 2006 . Anti-Oxidative Effects of Pomegranate Juice (PJ) Consumption by Diabetic Patients on Serum and on Macrophages , Vol. 187 , Amsterdam , , Netherland : Elsevier .
  • Ross , H. A. , McDougall , G. J. and Stewart , D. 2007 . Antiproliferative activity is predominantly associated with ellagitannins in raspberry extracts . Phytochemistry , 68 : 218 – 228 .
  • Rouanet , J. M. , Decorde , K. , Del Rio , D. , Auger , C. , Borges , G. , Cristol , J. P. , Lean , M. E. J. and Crozier , A. 2010 . Berry juices, teas, antioxidants and the prevention of atherosclerosis in hamsters . Food Chem. , 118 : 266 – 271 .
  • Sartippour , M. R. , Seeram , N. P. , Rao , J. Y. , Moro , A. , Harris , D. M. , Henning , S. M. , Firouzi , A. , Rettig , M. B. , Aronson , W. J. , Pantuck , A. J. and Heber , D. 2008 . Ellagitannin-rich pomegranate extract inhibits angiogenesis in prostate cancer in vitro and in vivo . Int. J. Oncol , 32 : 475 – 480 .
  • Seeram , N. P. , Adams , L. S. , Henning , S. M. , Niu , Y. T. , Zhang , Y. J. , Nair , M. G. and 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 .
  • Seeram , N. P. , Adams , L. S. , Zhang , Y. J. , Lee , R. , Sand , D. , Scheuller , H. S. and Heber , D. 2006a . Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro . J. Agric. Food. Chem , 54 : 9329 – 9339 .
  • Seeram , N. P. , Aronson , W. J. , Zhang , Y. , Henning , S. M. , Moro , A. , Lee , R. P. , Sartippour , N. , Harris , D. M. , Rettig , M. , Suchard , M. A. , Pantuck , A. J. , Belldegrun , A. and Heber , D. 2007 . Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland . J. Agric. Food. Chem , 55 : 7732 – 7737 .
  • Seeram , N. P. , Henning , S. , Lee , R. P. , Niu , Y. T. , Zhang , Y. J. , Suchard , M. , Scheuller , H. S. , Li , Z. P. , Thames , G. and Heber , D. 2006b . Pharmacokinetics and ex-vivo bioactivties of pomegranate polyphenols in humans . Faseb J. , 20 : A1019 – A1019 .
  • Seeram , N. P. , Henning , S. M. , Zhang , Y. , Suchard , M. , Li , Z. and Heber , D. 2006c . Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours . J. Nutr , 136 : 5
  • Seeram , N. P. , Lee , R. and 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 .
  • Seeram , N. P. , Zhang , Y. , McKeever , R. , Henning , S. M. , Lee , R. P. , Suchard , M. A. , Li , Z. P. , Chen , S. , Thames , G. , Zerlin , A. , Nguyen , M. , Wang , D. , Dreher , M. and Heber , D. 2008 . Pomegranate juice and extracts provide similar levels of plasma and urinary ellagitannin metabolites in human subjects . J. Med. Food. , 11 : 390 – 394 .
  • Seguin , C. M. , Wang , L. S. and Stoner , G. D. 2011 . Chemopreventive Effects of Berries and Berry Components in the Rodent Esophagus , New York : Springer .
  • Selma , M. V. , Espin , J. C. and Tomas-Barberan , F. A. 2009 . Interaction between phenolics and gut microbiota: Role in human health . J. Agric. Food. Chem , 57 : 6485 – 6501 .
  • Sharma , M. , Li , L. Y. , Celver , J. , Killian , C. , Kovoor , A. and Seeram , N. P. 2010 . Effects of fruit ellagitannin extracts, ellagic acid, and their colonic metabolite, urolithin A, on wnt signaling . J. Agric. Food. Chem. , 58 : 3965 – 3969 .
  • Stoner , G. D. , Chen , T. , Kresty , L. A. , Aziz , R. M. , Reinemann , T. and Nines , R. 2006 . Protection against esophageal cancer in rodents with lyophilized berries: Potential mechanisms . Nutr. Cancer , 54 : 33 – 46 .
  • Stoner , G. D. , Wanga , L. S. , Zikri , N. , Chen , T. , Hechtd , S. S. , Huange , C. , Sardo , C. and Lechner , J. F. 2007 . Cancer prevention with freeze-dried berries and berry components . National Inst. Health , 17 : 7
  • Sudhandiran , G. and Umesalma , S. 2011 . Ellagic acid prevents rat colon carcinogenesis induced by 1, 2 dimethyl hydrazine through inhibition of AKT-phosphoinositide-3 kinase pathway . Eur. J. Pharmacol , 660 : 249 – 258 .
  • Suh , J. R. , Romain , C. , González-Barrio , R. , Cristol , J. P. , Teissèdre , P. L. , Crozier , A. and Rouanet , J. M. 2011 . Raspberry juice consumption, oxidative stress and reduction of atherosclerosis risk factors in hypercholesterolemic golden Syrian hamsters . Food & Funct , 2 : 400 – 405 .
  • Sumner , M. D. , Elliott-Eller , M. , Weidner , G. , Daubenmier , J. J. , Chew , M. H. , Marlin , R. , Raisin , C. J. and Ornish , D. 2005 . Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease . Am. J. Cardiol. , 96 : 810 – 814 .
  • Tanaka , T. and Sugie , S. 2007 . Inhibition of colon carcinogenesis by dietary non-nutritive compounds . J. Toxicol. Pathol , 20 : 215 – 235 .
  • Torronen . 2009 . “ Sources and health effects of dietary ellagitannins. ” . In Chemistry and Biology of Ellagitannins: An Underestimated Class of Bioactive Plant Polyphenols , Edited by: Quideau , S. 298 – 319 . Bordeaux , , France : World Scientific Publishing Co .
  • Tulipani , S. , Llorach , R. , Jáuregui , O. , López-Uriarte , P. , Garcia-Aloy , M. , Bullo , M. , Salas-Salvadó , J. and Andrés-Lacueva , C. 2011 . Metabolomics unveils urinary changes in subjects with metabolic syndrome following 12-week nut consumption . J. Proteome. Res , 10 : 5047 – 5058 .
  • Vaquero , I. , Marcobal , Á. and Muñoz , R. 2004 . Tannase activity by lactic acid bacteria isolated from grape must and wine . Int. J. Food Microbiol , 96 : 199 – 204 .
  • Venkatesh , M. , Kakali , M. , Kuntal , M. and Pulok , M. , K. 2009 . Enhanced oral bioavailability and antioxidant profile of ellagic acid by phospholipids . J. Agric. Food. Chem , 57 : 6
  • Venketeshwer , R. and Snyder , D. 2010 . Raspberries and human health: A review . J. Agric. Food. Chem , 58 : 12
  • Ventura , M. , Turroni , F. , Canchaya , C. , Vaughan , E. E. , O’Toole , P. W. and van Sinderen , D. 2009 . Microbial diversity in the human intestine and novel insights from metagenomics . Front. Biosci , 14 : 3214 – U3863 .
  • Viuda-Martos , J. , Fernández-López and Pérez-Alvarez , J. A. 2010 . Pomegranate and its many functional components as related to human health: A review . Compr. Rev. Food Sci. Food Saf , 10 : 20
  • WHO . 2003 . Fruit and Vegetable Promotion Initiative—Report of the Meeting Geneva , , Switzerland
  • Yuan , J. P. , Wang , J. H. and Liu , X. 2007 . Metabolism of dietary soy isoflavones to equol by human intestinal microflora—Implications for health . Mol. Nutr. & Food Res , 51 : 765 – 781 .
  • Zafrilla , P. , Ferreres , F. and Tomas-Barberan , F. A. 2001 . Effect of processing and storage on the antioxidant ellagic acid derivatives and flavonoids of red raspberry (Rubus idaeus) jams . J. Agric. Food Chem. , 49 : 6
  • Zhang , J. , Xiong , Y. , Peng , B. , Gao , H. and Zhou , Z. 2011 . Density functional study on the bioactivity of ellagic acid, its derivatives and metabolite . Comput. Theor. Chem , 963 : 148 – 153 .
  • Zhang , Y. , Seeram , N. , Lee , R. , Feng , L. and Heber , D. 2008 . Isolation and identification of strawberry phenolics with antioxidant and human cancer cell antiproliferative properties . J. Agric. Food. Chem , 56 : 5
  • Zuninoa , S. J. , Stormsa , D. H. , Zhangb , Y. and Seeramb , N. P. 2009 . Growth arrest and induction of apoptosis in high-risk leukemia cells by strawberry components in vitro . J. Funct. Foods , I : 7

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