The Gastrointestinal Tract as a Key Target Organ for the Health-Promoting Effects of Dietary Proanthocyanidins

Frontiers in Nutrition

Volumn 3, Issue , 2017, Pages

  Cires, María José ^a   Wong, Ximena ^a   Carrasco Pozo, Catalina ^a   Gotteland, Martin ^a,b  

^a UNIVERSITY OF CHILE   (Chile)

^b UNIVERSITY OF CHILE   (Chile)

Author keywords

digestive enzymes; gastrointestinal tract; Helicobacter pylori; intestinal microbiota; proanthocyanidins

Indexed keywords

EID: 85013861501     PISSN: None     EISSN: 2296861X     Source Type: Journal    
DOI: 10.3389/fnut.2016.00057     Document Type: Review

References (226)

1. Rodrigo R, Libuy M, Feliu F, Hasson D. Polyphenols in disease: from diet to supplements. Curr Pharm Biotechnol (2014) 15(4):304–17.10.2174/138920101504140825113815
2. Quideau S, Deffieux D, Douat-Casassus C, Pouysegu L. Plant polyphenols: chemical properties, biological activities, and synthesis. Angew Chem Int Ed Engl (2011) 50(3):586–621.10.1002/anie.20100004421226137
3. Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A. Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal (2013) 18(14):1818–92.10.1089/ars.2012.458122794138
4. Shoji T. Chemical properties, bioavailability, and metabolomics of fruit proanthocyanidins. In: Watson RR, Preedy VR, Zibadi S, editors. Polyphenols in Human Health and Disease. San Diego: Academic Press (2014). p. 339–51.
5. Santos-Buelga C, Scalbert A. Proanthocyanidins and tannin-like compounds – nature, occurrence, dietary intake and effects on nutrition and health. J Sci Food Agric (2000) 80(7):1094–117.10.1002/(SICI)1097-0010(20000515)80:7<1094::AID-JSFA569>3.0.CO;2-1
6. Clifford MN, Crozier A. Phytochemicals in Teas and Tisanes and Their Bioavailability. Teas, Cocoa and Coffee. Oxford: Wiley-Blackwell (2011). p. 45–98.
7. Monagas M, Urpi-Sarda M, Sanchez-Patan F, Llorach R, Garrido I, Gomez-Cordoves C, et al. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food Funct (2010) 1(3):233–53.10.1039/c0fo00132e21776473
8. Wang W, Bostic TR, Gu L. Antioxidant capacities, procyanidins and pigments in avocados of different strains and cultivars. Food Chem (2010) 122(4):1193–8.10.1016/j.foodchem.2010.03.114
9. Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M. A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Phytochemistry (2005) 66(18):2281–91.10.1016/j.phytochem.2005.05.022
10. Foo LY, Lu YR, Howell AB, Vorsa N. A-type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli. J Nat Prod (2000) 63(9):1225–8.10.1021/np000128u11000024
11. Nandakumar V, Singh T, Katiyar SK. Multi-targeted prevention and therapy of cancer by proanthocyanidins. Cancer Lett (2008) 269(2):378–87.10.1016/j.canlet.2008.03.04918457915
12. de la Iglesia R, Milagro FI, Campión J, Boqué N, Martínez JA. Healthy properties of proanthocyanidins. Biofactors (2010) 36(3):159–68.10.1002/biof.79
13. Bladé C, Arola L, Salvadó M-J. Hypolipidemic effects of proanthocyanidins and their underlying biochemical and molecular mechanisms. Mol Nutr Food Res (2010) 54(1):37–59.10.1002/mnfr.20090047619960459
14. Rasmussen SE, Frederiksen H, Struntze Krogholm K, Poulsen L. Dietary proanthocyanidins: occurrence, dietary intake, bioavailability, and protection against cardiovascular disease. Mol Nutr Food Res (2005) 49(2):159–74.10.1002/mnfr.20040008215635686
15. Hanhineva K, Torronen R, Bondia-Pons I, Pekkinen J, Kolehmainen M, Mykkanan H, et al. Impact of dietary polyphenols on carbohydrate metabolism. Int J Mol Sci (2010) 11(4):1365–402.10.3390/ijms1104136520480025
16. Gonzalez-Abuin N, Pinent M, Casanova-Marti A, Arola L, Blay M, Ardevol A. Procyanidins and their healthy protective effects against type 2 diabetes. Curr Med Chem (2015) 22(1):39–50.10.2174/092986732166614091611551925245512
17. Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr (2005) 81(1 Suppl):230S–42S.15640486
18. Deprez S, Brezillon C, Rabot S, Philippe C, Mila I, Lapierre C, et al. Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids. J Nutr (2000) 130(11):2733–8.11053514
19. Jenner AM, Rafter J, Halliwell B. Human fecal water content of phenolics: the extent of colonic exposure to aromatic compounds. Free Radic Biol Med (2005) 38(6):763–72.10.1016/j.freeradbiomed.2004.11.02015721987
20. Rinaldi A, Jourdes M, Teissedre PL, Moio L. A preliminary characterization of Aglianico (Vitis vinifera L. cv.) grape proanthocyanidins and evaluation of their reactivity towards salivary proteins. Food Chem (2014) 164:142–9.10.1016/j.foodchem.2014.05.05024996317
21. Tsuchiya H, Sato M, Kato H, Okubo T, Juneja LR, Kim M. Simultaneous determination of catechins in human saliva by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl (1997) 703(1–2):253–8.10.1016/S0378-4347(97)00412-X9448083
22. Weiss E, Lev-Dor R, Sharon N, Ofek I. Inhibitory effect of a high-molecular-weight constituent of cranberry on adhesion of oral bacteria. Crit Rev Food Sci Nutr (2002) 42(3):285–92.10.1080/1040839020935191712058987
23. Kim D, Hwang G, Liu Y, Wang Y, Singh A, Vorsa N, et al. Cranberry flavonoids modulate cariogenic properties of mixed-species biofilm through exopolysaccharides-matrix disruption. PLoS One (2015) 10(12):e0145844.10.1371/journal.pone.014584426713438
24. Phansalkar R, Nam J, Chen S, McAlpine J, Napolitano J, Leme A, et al. A galloylated dimeric proanthocyanidin from grape seed exhibits dentin biomodification potential. Fitoterapia (2015) 101:169–78.10.1016/j.fitote.2014.12.00625542682
25. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med (2001) 345(11):784–9.10.1056/NEJMoa00199911556297
26. Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev (2006) 19(3):449–90.10.1128/CMR.00054-0516847081
27. Kalali B, Mejias-Luque R, Javaheri A, Gerhard M. H. pylori virulence factors: influence on immune system and pathology. Mediators Inflamm (2014) 426309(10):21.10.1155/2014/426309
28. Bauerfeind P, Garner R, Dunn BE, Mobley HL. Synthesis and activity of Helicobacter pylori urease and catalase at low pH. Gut (1997) 40(1):25–30.10.1136/gut.40.1.259155571
29. Stein M, Rappuoli R, Covacci A. The cag pathogenicity island. In: Mobley HLT, Mendz GL, Hazell SL, editors. Helicobacter pylori: Physiology and Genetics. Washington, DC: ASM Press (2001). p. 345–54.
30. Zhang L, Ma J, Pan K, Go VL, Chen J, You WC. Efficacy of cranberry juice on Helicobacter pylori infection: a double-blind, randomized placebo-controlled trial. Helicobacter (2005) 10(2):139–45.10.1111/j.1523-5378.2005.00301.x15810945
31. Cote J, Caillet S, Doyon G, Sylvain JF, Lacroix M. Bioactive compounds in cranberries and their biological properties. Crit Rev Food Sci Nutr (2010) 50(7):666–79.10.1080/1040839090304410720694928
32. Gotteland M, Andrews M, Toledo M, Munoz L, Caceres P, Anziani A, et al. Modulation of Helicobacter pylori colonization with cranberry juice and Lactobacillus johnsonii La1 in children. Nutrition (2008) 24(5):421–6.10.1016/j.nut.2008.01.00718343637
33. Shmuely H, Burger O, Neeman I, Yahav J, Samra Z, Niv Y, et al. Susceptibility of Helicobacter pylori isolates to the antiadhesion activity of a high-molecular-weight constituent of cranberry. Diagn Microbiol Infect Dis (2004) 50(4):231–5.10.1016/j.diagmicrobio.2004.08.01115582295
34. Burger O, Ofek I, Tabak M, Weiss EI, Sharon N, Neeman I. A high molecular mass constituent of cranberry juice inhibits helicobacter pylori adhesion to human gastric mucus. FEMS Immunol Med Microbiol (2000) 29(4):295–301.10.1111/j.1574-695X.2000.tb01537.x
35. Burger O, Weiss E, Sharon N, Tabak M, Neeman I, Ofek I. Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice. Crit Rev Food Sci Nutr (2002) 42(3 Suppl):279–84.10.1080/1040839020935191612058986
36. Federico F, Francisco AT-B. Flavonoids. Handbook of Analysis of Active Compounds in Functional Foods. Boca Raton, FL: CRC Press (2012). p. 289–316.
37. ®, French Maritime Pine Bark Extract. Encyclopedia of Dietary Supplements. New York: Taylor & Francis (2005). p. 545–53.
38. Rohdewald P, Beil W. In vitro inhibition of Helicobacter pylori growth and adherence to gastric mucosal cells by Pycnogenol. Phytother Res (2008) 22(5):685–8.10.1002/ptr.240918350522
39. Kayser O, Kolodziej H. Antibacterial activity of extracts and constituents of Pelargonium sidoides and Pelargonium reniforme. Planta Med (1997) 63(6):508–10.10.1055/s-2006-9577529434601
40. Wittschier N, Lengsfeld C, Vorthems S, Stratmann U, Ernst JF, Verspohl EJ, et al. Large molecules as anti-adhesive compounds against pathogens. J Pharm Pharmacol (2007) 59(6):777–86.10.1211/jpp.59.6.000417637170
41. Beil W, Kilian P. EPs 7630, an extract from Pelargonium sidoides roots inhibits adherence of Helicobacter pylori to gastric epithelial cells. Phytomedicine (2007) 6:5–8.10.1016/j.phymed.2006.11.02417188478
42. Wittschier N, Faller G, Hensel A. An extract of Pelargonium sidoides (EPs 7630) inhibits in situ adhesion of Helicobacter pylori to human stomach. Phytomedicine (2007) 14(4):285–8.10.1016/j.phymed.2006.12.00817350240
43. Adeniyi BA, Onwubuche BC, Anyiam FM, Ekundayo O, Mahady GB. Anti-Helicobacter pylori activities of Eucalyptus grandis: effects on susceptibility, urease activity and cell surface hydrophobicity. Pharm Biol (2009) 47(1):13–7.10.1080/13880200802397988
44. Pastene E, Troncoso M, Figueroa G, Alarcon J, Speisky H. Association between polymerization degree of apple peel polyphenols and inhibition of Helicobacter pylori urease. J Agric Food Chem (2009) 57(2):416–24.10.1021/jf802569819128009
45. Pastene E, Parada V, Avello M, Ruiz A, Garcia A. Catechin-based procyanidins from Peumus boldus Mol. aqueous extract inhibit Helicobacter pylori urease and adherence to adenocarcinoma gastric cells. Phytother Res (2014) 28(11):1637–45.10.1002/ptr.517624853276
46. Yahiro K, Shirasaka D, Tagashira M, Wada A, Morinaga N, Kuroda F, et al. Inhibitory effects of polyphenols on gastric injury by Helicobacter pylori VacA toxin. Helicobacter (2005) 10(3):231–9.10.1111/j.1523-5378.2005.00315.x15904481
47. Ruggiero P, Rossi G, Tombola F, Pancotto L, Lauretti L, Del Giudice G, et al. Red wine and green tea reduce H. pylori- or VacA-induced gastritis in a mouse model. World J Gastroenterol (2007) 13(3):349–54.10.3748/wjg.v13.i3.34917230601
48. Hribova P, Khazneh E, Zemlicka M, Svajdlenka E, Ghoneim MM, Elokely KM, et al. Antiurease activity of plants growing in the Czech Republic. Nat Prod Res (2014) 28(12):868–73.10.1080/14786419.2014.88855324579848
49. Saito M, Hosoyama H, Ariga T, Kataoka S, Yamaji N. Antiulcer activity of grape seed extract and procyanidins. J Agric Food Chem (1998) 46(4):1460–4.10.1021/jf9709156
50. Tadic VM, Dobric S, Markovic GM, Dordevic SM, Arsic IA, Menkovic NR, et al. Anti-inflammatory, gastroprotective, free-radical-scavenging, and antimicrobial activities of hawthorn berries ethanol extract. J Agric Food Chem (2008) 56(17):7700–9.10.1021/jf801668c18698794
51. Chai WM, Chen CM, Gao YS, Feng HL, Ding YM, Shi Y, et al. Structural analysis of proanthocyanidins isolated from fruit stone of Chinese hawthorn with potent antityrosinase and antioxidant activity. J Agric Food Chem (2014) 62(1):123–9.10.1021/jf405385j24313351
52. Scarpignato C, Hunt RH. Nonsteroidal antiinflammatory drug-related injury to the gastrointestinal tract: clinical picture, pathogenesis, and prevention. Gastroenterol Clin North Am (2010) 39(3):433–64.10.1016/j.gtc.2010.08.01020951911
53. Marlicz W, Loniewski I, Grimes DS, Quigley EM. Nonsteroidal anti-inflammatory drugs, proton pump inhibitors, and gastrointestinal injury: contrasting interactions in the stomach and small intestine. Mayo Clin Proc (2014) 89(12):1699–709.10.1016/j.mayocp.2014.07.01525440891
54. Berenguer B, Trabadela C, Sanchez-Fidalgo S, Quilez A, Mino P, De la Puerta R, et al. The aerial parts of Guazuma ulmifolia Lam. protect against NSAID-induced gastric lesions. J Ethnopharmacol (2007) 114(2):153–60.10.1016/j.jep.2007.07.01917884315
55. Kim TH, Jeon EJ, Cheung DY, Kim CW, Kim SS, Park SH, et al. Gastroprotective effects of grape seed proanthocyanidin extracts against nonsteroid anti-inflammatory drug-induced gastric injury in rats. Gut Liver (2013) 7(3):282–9.10.5009/gnl.2013.7.3.28223710308
56. Gonzalez-Gomez JC, Ayala-Burgos A, Gutierrez-Vazquez E. Total phenols and condensed tannins in tree species with potential as forage sources in the tropics. Livest Res Rural Dev (2006) 18(11):1–5.
57. Moraes Tde M, Rodrigues CM, Kushima H, Bauab TM, Villegas W, Pellizzon CH, et al. Hancornia speciosa: indications of gastroprotective, healing and anti-Helicobacter pylori actions. J Ethnopharmacol (2008) 120(2):161–8.10.1016/j.jep.2008.08.00118761076
58. Hiruma-Lima CA, Rodrigues CM, Kushima H, Moraes TM, Lolis Sde F, Feitosa SB, et al. The anti-ulcerogenic effects of Curatella americana L. J Ethnopharmacol (2009) 121(3):425–32.10.1016/j.jep.2008.10.01719022369
59. Tanae MM, Lima-Landman MT, De Lima TC, Souccar C, Lapa AJ. Chemical standardization of the aqueous extract of Cecropia glaziovii Sneth endowed with antihypertensive, bronchodilator, antiacid secretion and antidepressant-like activities. Phytomedicine (2007) 14(5):309–13.10.1016/j.phymed.2007.03.00217434301
60. Souccar C, Cysneiros RM, Tanae MM, Torres LM, Lima-Landman MT, Lapa AJ. Inhibition of gastric acid secretion by a standardized aqueous extract of Cecropia glaziovii Sneth and underlying mechanism. Phytomedicine (2008) 15(6–7):462–9.10.1016/j.phymed.2008.02.00618462931
61. Santos RC, Kushima H, Rodrigues CM, Sannomiya M, Rocha LR, Bauab TM, et al. Byrsonima intermedia A. Juss.: gastric and duodenal anti-ulcer, antimicrobial and antidiarrheal effects in experimental rodent models. J Ethnopharmacol (2012) 140(2):203–12.10.1016/j.jep.2011.12.00822265748
62. Pierre JF, Heneghan AF, Feliciano RP, Shanmuganayagam D, Roenneburg DA, Krueger CG, et al. Cranberry proanthocyanidins improve the gut mucous layer morphology and function in mice receiving elemental enteral nutrition. JPEN J Parenter Enteral Nutr (2013) 37(3):401–9.10.1177/014860711246307623064255
63. Xu X, Xie B, Pan S, Liu L, Wang Y, Chen C. Effects of sea buckthorn procyanidins on healing of acetic acid-induced lesions in the rat stomach. Asia Pac J Clin Nutr (2007) 16(Suppl 1):234–8.17392110
64. Iwasaki Y, Matsui T, Arakawa Y. The protective and hormonal effects of proanthocyanidin against gastric mucosal injury in Wistar rats. J Gastroenterol (2004) 39(9):831–7.10.1007/s00535-004-1399-515565401
65. Zayachkivska OS, Gzhegotsky MR, Terletska OI, Lutsyk DA, Yaschenko AM, Dzhura OR. Influence of Viburnum opulus proanthocyanidins on stress-induced gastrointestinal mucosal damage. J Physiol Pharmacol (2006) 57(Suppl 5):155–67.17218766
66. González-Abuín N, Martínez-Micaelo N, Blay M, Ardévol A, Pinent M. Grape-seed procyanidins prevent the cafeteria-diet-induced decrease of glucagon-like peptide-1 production. J Agric Food Chem (2014) 62(5):1066–72.10.1021/jf405239p24410268
67. Serrano J, Casanova-Marti A, Gil-Cardoso K, Blay MT, Terra X, Pinent M, et al. Acutely administered grape-seed proanthocyanidin extract acts as a satiating agent. Food Funct (2016) 7(1):483–90.10.1039/c5fo00892a26514231
68. Ko JL, Tsai CH, Liu TC, Lin MY, Lin HL, Ou CC. Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity. Hum Exp Toxicol (2016) 35(8):808–17.10.1177/096032711560707926429932
69. Miller MJ, Reuter BK, Wallace JL, Sharkey KA. A unique therapeutic approach to emesis and itch with a proanthocyanidin-rich genonutrient. J Transl Med (2008) 6:3.10.1186/1479-5876-6-3
70. Li QZ, Cho HS, Jeun SH, Kim KJ, Choi SJ, Sung KW. Effects of grape seed proanthocyanidin on 5-hydroxytryptamine3 receptors in NCB-20 neuroblastoma cells. Biol Pharm Bull (2011) 34(7):1109–15.10.1248/bpb.34.1109
71. Spencer JP, Chaudry F, Pannala AS, Srai SK, Debnam E, Rice-Evans C. Decomposition of cocoa procyanidins in the gastric milieu. Biochem Biophys Res Commun (2000) 272(1):236–41.10.1006/bbrc.2000.274910872833
72. Rios LY, Bennett RN, Lazarus SA, Remesy C, Scalbert A, Williamson G. Cocoa procyanidins are stable during gastric transit in humans. Am J Clin Nutr (2002) 76(5):1106–10.12399286
73. Deprez S, Mila I, Huneau JF, Tome D, Scalbert A. Transport of proanthocyanidin dimer, trimer, and polymer across monolayers of human intestinal epithelial Caco-2 cells. Antioxid Redox Signal (2001) 3(6):957–67.10.1089/15230860131720350311813991
74. Gonthier MP, Donovan JL, Texier O, Felgines C, Remesy C, Scalbert A. Metabolism of dietary procyanidins in rats. Free Radic Biol Med (2003) 35(8):837–44.10.1016/S0891-5849(03)00394-014556848
75. Baba S, Osakabe N, Natsume M, Muto Y, Takizawa T, Terao J. In vivo comparison of the bioavailability of (+)-catechin, (-)-epicatechin and their mixture in orally administered rats. J Nutr (2001) 131(11):2885–91.11694613
76. Donovan JL, Crespy V, Manach C, Morand C, Besson C, Scalbert A, et al. Catechin is metabolized by both the small intestine and liver of rats. J Nutr (2001) 131(6):1753–7.11385063
77. Kivits GAA, van der Sman FJP, Tijburg LBM. Analysis of catechins from green and black tea in humans: a specific and sensitive colorimetric assay of total catechins in biological fluids. Int J Food Sci Nutr (1997) 48(6):387–92.10.3109/09637489709028587
78. Auger C, Mullen W, Hara Y, Crozier A. Bioavailability of polyphenon E flavan-3-ols in humans with an ileostomy. J Nutr (2008) 138(8):1535S–42S.18641203
79. Donovan JL, Manach C, Rios L, Morand C, Scalbert A, Remesy C. Procyanidins are not bioavailable in rats fed a single meal containing a grapeseed extract or the procyanidin dimer B3. Br J Nutr (2002) 87(4):299–306.10.1079/BJN200151712064339
80. Tsang C, Auger C, Mullen W, Bornet A, Rouanet JM, Crozier A, et al. The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats. Br J Nutr (2005) 94(2):170–81.10.1079/BJN2005148016115350
81. Shoji T, Masumoto S, Moriichi N, Akiyama H, Kanda T, Ohtake Y, et al. Apple procyanidin oligomers absorption in rats after oral administration: analysis of procyanidins in plasma using the porter method and high-performance liquid chromatography/tandem mass spectrometry. J Agric Food Chem (2006) 54(3):884–92.10.1021/jf052260b16448199
82. Choy YY, Jaggers GK, Oteiza PI, Waterhouse AL. Bioavailability of intact proanthocyanidins in the rat colon after ingestion of grape seed extract. J Agric Food Chem (2013) 61:121–7.10.1021/jf301939e23244439
83. Jimenez-Ramsey LM, Rogler JC, Housley TL, Butler LG, Elkin RG. Absorption and distribution of 14C-labeled condensed tannins and related sorghum phenolics in chickens. J Agric Food Chem (1994) 42(4):963–7.10.1021/jf00040a024
84. Terrill TH, Waghorn GC, Woolley DJ, McNabb WC, Barry TN. Assay and digestion of 14C-labelled condensed tannins in the gastrointestinal tract of sheep. Br J Nutr (1994) 72(3):467–77.10.1079/BJN199400487947660
85. Choy YY, Quifer-Rada P, Holstege DM, Frese SA, Calvert CC, Mills DA, et al. Phenolic metabolites and substantial microbiome changes in pig feces by ingesting grape seed proanthocyanidins. Food Funct (2014) 5(9):2298–308.10.1039/c4fo00325j25066634
86. Kahle K, Huemmer W, Kempf M, Scheppach W, Erk T, Richling E. Polyphenols are intensively metabolized in the human gastrointestinal tract after apple juice consumption. J Agric Food Chem (2007) 55(26):10605–14.10.1021/jf071942r18047284
87. Van Amelsvoort JM, Van Hof KH, Mathot JN, Mulder TP, Wiersma A, Tijburg LB. Plasma concentrations of individual tea catechins after a single oral dose in humans. Xenobiotica (2001) 31(12):891–901.10.1080/0049825011007914911780763
88. Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols. J Nutr (2000) 130(8):2073S–85S.
89. Nemeth K, Plumb GW, Berrin JG, Juge N, Jacob R, Naim HY, et al. Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr (2003) 42(1):29–42.10.1007/s00394-003-0397-312594539
90. Henry-Vitrac C, Desmouliere A, Girard D, Merillon JM, Krisa S. Transport, deglycosylation, and metabolism of trans-piceid by small intestinal epithelial cells. Eur J Nutr (2006) 45(7):376–82.10.1007/s00394-006-0609-817009167
91. Aherne SA, O’Brien NM. Dietary flavonols: chemistry, food content, and metabolism. Nutrition (2002) 18(1):75–81.10.1016/S0899-9007(01)00695-511827770
92. Ahmed Nasef N, Mehta S, Ferguson LR. Dietary interactions with the bacterial sensing machinery in the intestine: the plant polyphenol case. Front Genet (2014) 5:64.10.3389/fgene.2014.0006424772116
93. Cardona F, Andrés-Lacueva C, Tulipania S, Tinahones FJ, Queipo-Ortuño MI. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem (2013) 24(8):1415–22.10.1016/j.jnutbio.2013.05.00123849454
94. Stalmach A, Mullen W, Steiling H, Williamson G, Lean ME, Crozier A. Absorption, metabolism, and excretion of green tea flavan-3-ols in humans with an ileostomy. Mol Nutr Food Res (2010) 54(3):323–34.10.1002/mnfr.200900194
95. Hollman PCH, Arts ICW. Flavonols, flavones and flavanols – nature, occurrence and dietary burden. J Sci Food Agric (2000) 80(7):1081–93.10.1002/(SICI)1097-0010(20000515)80:7<1081::AID-JSFA566>3.0.CO;2-G
96. García-Ramírez B, Fernández-Larrea J, Salvadó MJ, Ardèvol A, Arola L, Bladé C. Tetramethylated dimeric procyanidins are detected in rat plasma and liver early after oral administration of synthetic oligomeric procyanidins. J Agric Food Chem (2006) 54(7):2543–51.10.1021/jf052775316569041
97. Lee MJ, Wang ZY, Li H, Chen L, Sun Y, Gobbo S, et al. Analysis of plasma and urinary tea polyphenols in human subjects. Cancer Epidemiol Biomarkers Prev (1995) 4(4):393–9.7655336
98. Clifford MN. Diet-derived phenols in plasma and tissues and their implications for health. Planta Med (2004) 70(12):1103–14.10.1055/s-2004-83583515643541
99. Aura AM. Colon-derived microbial metabolites of dietary phenolic compounds. In: Crozier A, editor. Flavonoids and Related Compounds: Bioavailability and Function. CRC Press (2012).10.1201/b11872-11
100. Scalbert A, Deprez S, Mila I, Albrecht AM, Huneau JF, Rabot S. Proanthocyanidins and human health: systemic effects and local effects in the gut. Biofactors (2000) 13(1–4):115–20.10.1002/biof.552013011911237169
101. Hagerman AE, Butler LG. The specificity of proanthocyanidin-protein interactions. J Biol Chem (1981) 256(9):4494–7.7217094
102. Williamson G. Possible effects of dietary polyphenols on sugar absorption and digestion. Mol Nutr Food Res (2013) 57(1):48–57.10.1002/mnfr.20120051123180627
103. Barrett A, Ndou T, Hughey CA, Straut C, Howell A, Dai Z, et al. Inhibition of alpha-amylase and glucoamylase by tannins extracted from cocoa, pomegranates, cranberries, and grapes. J Agric Food Chem (2013) 61(7):1477–86.10.1021/jf304876g
104. Guzmán-Maldonado H, Paredes-López O, Biliaderis CG. Amylolytic enzymes and products derived from starch: a review. Crit Rev Food Sci Nutr (1995) 35(5):373–403.10.1080/104083995095277068573280
105. Lee YA, Cho EJ, Tanaka T, Yokozawa T. Inhibitory activities of proanthocyanidins from persimmon against oxidative stress and digestive enzymes related to diabetes. J Nutr Sci Vitaminol (2007) 53(3):287–92.10.3177/jnsv.53.28717874835
106. Hassan HMM. Inhibitory effects of red grape seed extracts on pancreatic α-amylase and lipase. Glob J Biotechnol Biochem (2014) 9(4):130–6.
107. Adisakwattana S, Lerdsuwankij O, Poputtachai U, Minipun A, Suparpprom C. Inhibitory activity of cinnamon bark species and their combination effect with acarbose against intestinal alpha-glucosidase and pancreatic alpha-amylase. Plant Food Hum Nutr (2011) 66(2):143–8.10.1007/s11130-011-0226-4
108. ®) effectively inhibit α-glucosidase. Diabetes Res Clin Pract (2007) 77(1):41–6.10.1016/j.diabres.2006.10.011
109. ®), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther (2002) 40(4):158–68.10.5414/CPP40158
110. Zhang HW, Yerigui YY, Ma CM. Structures and antioxidant and intestinal disaccharidase inhibitory activities of A-type proanthocyanidins from peanut skin. J Agric Food Chem (2013) 61(37):8814–20.10.1021/jf402518k23971511
111. Tsujita T, Shintani T, Sato H. Preparation and characterisation of peanut seed skin polyphenols. Food Chem (2014) 151:15–20.10.1016/j.foodchem.2013.11.07224423496
112. Tsujita T, Shintani T, Sato H. alpha-Amylase inhibitory activity from nut seed skin polyphenols. 1. Purification and characterization of almond seed skin polyphenols. J Agric Food Chem (2013) 61(19):4570–6.10.1021/jf400691q
113. Naz S, Siddiqi R, Dew TP, Williamson G. Epigallocatechin-3-gallate inhibits lactase but is alleviated by salivary proline-rich proteins. J Agric Food Chem (2011) 59(6):2734–8.10.1021/jf103072z21348516
114. Tomaru M, Takano H, Osakabe N, Yasuda A, Inoue K, Yanagisawa R, et al. Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice. Nutrition (2007) 23(4):351–5.10.1016/j.nut.2007.01.00717350804
115. Kawakami K, Aketa S, Nakanami M, Iizuka S, Hirayama M. Major water-soluble polyphenols, proanthocyanidins, in leaves of persimmon (Diospyros kaki) and their alpha-amylase inhibitory activity. Biosci Biotechnol Biochem (2010) 74(7):1380–5.10.1271/bbb.10005620622463
116. Wood IS, Trayhurn P. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr (2003) 89(1):3–9.10.1079/BJN200276312568659
117. Thorens B. Facilitated glucose transporters in epithelial cells. Annu Rev Physiol (1993) 55:591–608.10.1146/annurev.ph.55.030193.0031118466187
118. Leturque A, Brot-Laroche E, Le Gall M. GLUT2 mutations, translocation, and receptor function in diet sugar managing. Am J Physiol Endocrinol Metab (2009) 296(5):E985–92.10.1152/ajpendo.00004.200919223655
119. Kellett GL, Helliwell PA. The diffusive component of intestinal glucose absorption is mediated by the glucose-induced recruitment of GLUT2 to the brush-border membrane. Biochem J (2000) 350(Pt 1):155–62.10.1042/bj350015510926839
120. Helliwell PA, Richardson M, Affleck J, Kellett GL. Stimulation of fructose transport across the intestinal brush-border membrane by PMA is mediated by GLUT2 and dynamically regulated by protein kinase C. Biochem J (2000) 350(Pt 1):149–54.10.1042/bj350014910926838
121. Farrell TL, Ellam SL, Forrelli T, Williamson G. Attenuation of glucose transport across Caco-2 cell monolayers by a polyphenol-rich herbal extract: interactions with SGLT1 and GLUT2 transporters. Biofactors (2013) 39(4):448–56.10.1002/biof.109023361943
122. Alzaid F, Cheung HM, Preedy VR, Sharp PA. Regulation of glucose transporter expression in human intestinal caco-2 cells following exposure to an anthocyanin-rich berry extract. PLoS One (2013) 8(11):e78932.10.1371/journal.pone.007893224236070
123. Oliveira DM, Freitas HS, Souza MF, Arcari DP, Ribeiro ML, Carvalho PO, et al. Yerba mate (Ilex paraguariensis) aqueous extract decreases intestinal SGLT1 gene expression but does not affect other biochemical parameters in alloxan-diabetic Wistar rats. J Agric Food Chem (2008) 56(22):10527–32.10.1021/jf8021404
124. Schulze C, Bangert A, Kottra G, Geillinger KE, Schwanck B, Vollert H, et al. Inhibition of the intestinal sodium-coupled glucose transporter 1 (SGLT1) by extracts and polyphenols from apple reduces postprandial blood glucose levels in mice and humans. Mol Nutr Food Res (2014) 58(9):1795–808.10.1002/mnfr.20140001625074384
125. de la Garza AL, Etxeberria U, Lostao MP, San Roman B, Barrenetxe J, Martinez JA, et al. Helichrysum and grapefruit extracts inhibit carbohydrate digestion and absorption, improving postprandial glucose levels and hyperinsulinemia in rats. J Agric Food Chem (2013) 61(49):12012–9.10.1021/jf402156924261475
126. Cermak R, Landgraf S, Wolffram S. Quercetin glucosides inhibit glucose uptake into brush-border-membrane vesicles of porcine jejunum. Br J Nutr (2004) 91(6):849–55.10.1079/BJN2004112815182388
127. Manzano S, Williamson G. Polyphenols and phenolic acids from strawberry and apple decrease glucose uptake and transport by human intestinal Caco-2 cells. Mol Nutr Food Res (2010) 54:1773–80.10.1002/mnfr.20100001920564476
128. Kobayashi Y, Suzuki M, Satsu H, Arai S, Hara Y, Suzuki K, et al. Green tea polyphenols inhibit the sodium-dependent glucose transporter of intestinal epithelial cells by a competitive mechanism. J Agric Food Chem (2000) 48(11):5618–23.10.1021/jf000683211087528
129. Johnston K, Sharp P, Clifford M, Morgan L. Dietary polyphenols decrease glucose uptake by human intestinal Caco-2 cells. FEBS Lett (2005) 579(7):1653–7.10.1016/j.febslet.2004.12.09915757656
130. Constanzo LS. Gastrointestinal physiology. 4 ed. In: Constanzo LS, editor. Physiology. Philadelphia: Saunders Elsevier (2010). p. 327–78.
131. Masson CJ, Plat J, Mensink RP, Namiot A, Kisielewski W, Namiot Z, et al. Fatty acid- and cholesterol transporter protein expression along the human intestinal tract. PLoS One (2010) 5(4):e10380.10.1371/journal.pone.0010380
132. Iqbal J, Hussain MM. Intestinal lipid absorption. Am J Physiol Endocrinol Metab (2009) 296(6):E1183–94.10.1152/ajpendo.90899.200819158321
133. Redinger RN. Nuclear receptors in cholesterol catabolism: molecular biology of the enterohepatic circulation of bile salts and its role in cholesterol homeostasis. J Lab Clin Med (2003) 142(1):7–20.10.1016/S0022-2143(03)00088-X12878981
134. Sugiyama H, Akazome Y, Shoji T, Yamaguchi A, Yasue M, Kanda T, et al. Oligomeric procyanidins in apple polyphenol are main active components for inhibition of pancreatic lipase and triglyceride absorption. J Agric Food Chem (2007) 55(11):4604–9.10.1021/jf078004b17458979
135. Sugiyama H, Akazome Y, Shoji T, Yamaguchi A, Yasue M, Kanda T, et al. Oligomeric procyanidins in apple polyphenol are main active components for inhibition of pancreatic lipase and tri-glyceride absorption. J Agric Food Chem (2007) 55(14):5906.10.1021/jf078004b
136. Gu Y, Hurst WJ, Stuart DA, Lambert JD. Inhibition of key digestive enzymes by cocoa extracts and procyanidins. J Agric Food Chem (2011) 59(10):5305–11.10.1021/jf200180n21495725
137. Wong X, Madrid AM, Tralma K, Castillo R, Carrasco-Pozo C, Navarrete P, et al. Polyphenol extracts interfere with bacterial lipopolysaccharide in vitro and decrease postprandial endotoxemia in human volunteers. J Funct Foods (2016) 26:406–17.10.1016/j.jff.2016.08.011
138. Matsumoto K, Kadowaki A, Ozaki N, Takenaka M, Ono H, Yokoyama S, et al. Bile acid-binding ability of kaki-tannin from young fruits of persimmon (Diospyros kaki) in vitro and in vivo. Phytother Res (2011) 25(4):624–8.10.1002/ptr.330620922818
139. Adisakwattana S, Moonrat J, Srichairat S, Chanasit C, Tirapongporn H, Chanathong B, et al. Lipid-Lowering mechanisms of grape seed extract (Vitis vinifera L) and its antihyperlidemic activity. J Med Plants Res (2010) 4(20):2113–20.
140. Qin BL, Dawson HD, Schoene NW, Polansky MM, Anderson RA. Cinnamon polyphenols regulate multiple metabolic pathways involved in insulin signaling and intestinal lipoprotein metabolism of small intestinal enterocytes. Nutrition (2012) 28(11–12):1172–9.10.1016/j.nut.2012.03.02022858201
141. Quesada H, Diaz S, Pajuelo D, Fernandez-Iglesias A, Garcia-Vallve S, Pujadas G, et al. The lipid-lowering effect of dietary proanthocyanidins in rats involves both chylomicron-rich and VLDL-rich fractions. Br J Nutr (2012) 108(2):208–17.10.1017/S000711451100547222011563
142. Delehanty JB, Johnson BJ, Hickey TE, Pons T, Ligler FS. Binding and neutralization of lipopolysaccharides by plant proanthocyanidins. J Nat Prod (2007) 70(11):1718–24.10.1021/np070360117949054
143. Ghoshal S, Witta J, Zhong J, de Villiers W, Eckhardt E. Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res (2009) 50(1):90–7.10.1194/jlr.M800156-JLR20018815435
144. Cani PD, Bibiloni R, Knauf C, Neyrinck AM, Neyrinck AM, Delzenne NM, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes (2008) 57(6):1470–81.10.2337/db07-140318305141
145. Taylor A. Aminopeptidases – structure and function. FASEB J (1993) 7(2):290–8.
146. Broer S. Amino acid transport across mammalian intestinal and renal epithelia. Physiol Rev (2008) 88(1):249–86.10.1152/physrev.00018.200618195088
147. Adibi SA. The oligopeptide transporter (Pept-1) in human intestine: biology and function. Gastroenterology (1997) 113(1):332–40.10.1016/S0016-5085(97)70112-49207295
148. Goncalves R, Soares S, Mateus N, de Freitas V. Inhibition of trypsin by condensed tannins and wine. J Agric Food Chem (2007) 55(18):7596–601.10.1021/jf071490i17696448
149. Gonçalves R, Mateus N, Pianet I, Laguerre M, de Freitas V. Mechanisms of tannin-induced trypsin inhibition: a molecular approach. Langmuir (2011) 27(21):13122–9.10.1021/la202280c21877746
150. Horigome T, Kumar R, Okamoto K. Effects of condensed tannins prepared from leaves of fodder plants on digestive enzymes in vitro and in the intestine of rats. Br J Nutr (1988) 60(2):275–85.10.1079/BJN198800992461730
151. Brás NF, Goncalves R, Mateus N, Fernandes PA, Ramos MJ, de Freitas V. Inhibition of pancreatic elastase by polyphenolic compounds. J Agric Food Chem (2010) 58(19):10668–76.10.1021/jf101793420839876
152. Brás NF, Goncalves R, Fernandes PA, Mateus N, Ramos MJ, de Freitas V. Understanding the binding of procyanidins to pancreatic elastase by experimental and computational methods. Biochemistry (2010) 49(25):5097–108.10.1021/bi100410q20481639
153. Uchida S, Ikari N, Ohta H, Niwa M, Nonaka G, Nishioka I, et al. Inhibitory effects of condensed tannins on angiotensin converting enzyme. Jpn J Pharmacol (1987) 43(2):242–6.10.1254/jjp.43.2423033368
154. Davila AM, Blachier F, Gotteland M, Andriamihaja M, Benetti PH, Sanz Y, et al. Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host. Pharmacol Res (2013) 69(1):95–107.10.1016/j.phrs.2013.01.003
155. Patra AK, Saxena J. Exploitation of dietary tannins to improve rumen metabolism and ruminant nutrition. J Sci Food Agric (2011) 91(1):24–37.10.1002/jsfa.415220815041
156. Cássia Santos R, Kushima H, Martins Rodrigues C, Sannomiya M, Machado Rocha LR, Bauab TM, et al. Byrsonima intermedia A. Juss.: gastric and duodenal anti-ulcer, antimicrobial and antidiarrheal effects in experimental rodent models. J Ethnopharmacol (2012) 140:203–12.10.1016/j.jep.2011.12.00822265748
157. Velazquez C, Calzada F, Esquivel B, Barbosa E, Calzada S. Antisecretory activity from the flowers of Chiranthodendron pentadactylon and its flavonoids on intestinal fluid accumulation induced by Vibrio cholerae toxin in rats. J Ethnopharmacol (2009) 126(3):455–8.10.1016/j.jep.2009.09.01619781621
158. Valcheva-Kuzmanova S, Kuzmanov K. Inhibitory effect of Aronia melanocarpa fruit juice on intestinal transit rate in rats. Acta Aliment (2011) 40(3):396–9.10.1556/AAlim.2010.0009
159. Rozhon EJ, Khandwala AS, Sabouni A, Balwani GP, Chan JW-H, Sesin DF. Method of Treating Secretory Diarrhea with Enteric Formulations of Proanthocyanidin Polymer. US Patent No 7341744 B1 (2008).
160. Etxeberria U, Fernandez-Quintela A, Milagro FI, Aguirre L, Martinez JA, Portillo MP. Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition. J Agric Food Chem (2013) 61(40):9517–33.10.1021/jf402506c24033291
161. Laparra JM, Sanz Y. Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol Res (2010) 61(3):219–25.10.1016/j.phrs.2009.11.00119914380
162. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr (1995) 125(6):1401–12.7782892
163. Hamer HM, De Preter V, Windey K, Verbeke K. Functional analysis of colonic bacterial metabolism: relevant to health? Am J Physiol Gastrointest Liver Physiol (2012) 302(1):G1–9.10.1152/ajpgi.00048.201122016433
164. Duda-Chodak A, Tarko T, Satora P, Sroka P. Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review. Eur J Nutr (2015) 54(3):325–41.10.1007/s00394-015-0852-y25672526
165. Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold G, et al. The gut microbiota and host health: a new clinical frontier. Gut (2016) 65(2):330–9.10.1136/gutjnl-2015-309990
166. Blaut M, Clavel T. Metabolic diversity of the intestinal microbiota: implications for health and disease. J Nutr (2007) 137(3 Suppl 2):751S–5S.17311972
167. Appeldoorn MM, Vincken JP, Aura AM, Hollman PC, Gruppen H. Procyanidin dimers are metabolized by human microbiota with 2-(3,4-dihydroxyphenyl)acetic acid and 5-(3,4-dihydroxyphenyl)-gamma-valerolactone as the major metabolites. J Agric Food Chem (2009) 57(3):1084–92.10.1021/jf803059z19191673
168. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther (2008) 27(2):104–19.10.1111/j.1365-2036.2007.03562.x17973645
169. Blachier F, Mariotti F, Huneau JF, Tome D. Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences. Amino Acids (2007) 33(4):547–62.10.1007/s00726-006-0477-917146590
170. Brunser O, Gotteland M. Probiotics and prebiotics in human health: an overview. In: Watson R, Preedy V, editors. Bioactive Foods in Promoting Health: Probiotics and Prebiotics. Kidlington: Academic Press (2010). p. 73–93.
171. Cardona F, Andres-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuno MI. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem (2013) 24(8):1415–22.10.1016/j.jnutbio.2013.05.00123849454
172. Tzounis X, Vulevic J, Kuhnle GG, George T, Leonczak J, Gibson GR, et al. Flavanol monomer-induced changes to the human faecal microflora. Br J Nutr (2008) 99(4):782–92.10.1017/S000711450785338417977475
173. Cueva C, Sanchez-Patan F, Monagas M, Walton GE, Gibson GR, Martin-Alvarez PJ, et al. In vitro fermentation of grape seed flavan-3-ol fractions by human faecal microbiota: changes in microbial groups and phenolic metabolites. FEMS Microbiol Ecol (2013) 83(3):792–805.10.1111/1574-6941.1203723121387
174. Tzounis X, Rodriguez-Mateos A, Vulevic J, Gibson GR, Kwik-Uribe C, Spencer JP. Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. Am J Clin Nutr (2011) 93(1):62–72.10.3945/ajcn.110.00007521068351
175. Yamakoshi J, Tokutake S, Kikuchi M, Konishi H, Mitsuoka T. Effect of proanthocyanidin-rich extract from grape seeds on human fecal flora and fecal odor. Microb Ecol Health Dis (2001) 13:25–31.
176. Walle TW, Walgren RA, Walle K, Galijatovic A, Vaidyanathan J. Understanding the bioavailability of flavonoids through studies in caco-2 cells. In: Rice-Evans CA, Packer L, editors. Flavonoids in Health and Disease. New York, NY: Marcel Dekker, Inc (2003). p. 349–61.
177. Aura A-M. Microbial metabolism of dietary phenolic compounds in the colon. Phytochem Rev (2008) 7(3):407–29.10.1007/s11101-008-9095-3
178. Selma MV, Espín JC, Tomás-Barberán FA. Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem (2009) 57(15):6485–501.10.1021/jf902107d19580283
179. Roowi S, Stalmach A, Mullen W, Lean ME, Edwards CA, Crozier A. Green tea flavan-3-ols: colonic degradation and urinary excretion of catabolites by humans. J Agric Food Chem (2010) 58(2):1296–304.10.1021/jf903297520041649
180. Das NP. Studies on flavonoid metabolism. Absorption and metabolism of (+)-catechin in man. Biochem Pharmacol (1971) 20(12):3435–45.10.1016/0006-2952(71)90449-7
181. Li C, Lee MJ, Sheng S, Meng X, Prabhu S, Winnik B, et al. Structural identification of two metabolites of catechins and their kinetics in human urine and blood after tea ingestion. Chem Res Toxicol (2000) 13(3):177–84.10.1021/tx990183710725114
182. Ottaviani JI, Kwik-Uribe C, Keen CL, Schroeter H. Intake of dietary procyanidins does not contribute to the pool of circulating flavanols in humans. Am J Clin Nutr (2012) 95(4):851–8.10.3945/ajcn.111.02834022378733
183. Aura A-M, Mattila I, Seppänen-Laakso T, Miettinen J, Oksman-Caldentey K-M, Orešič M. Microbial metabolism of catechin stereoisomers by human faecal microbiota: comparison of targeted analysis and a non-targeted metabolomics method. Phytochem Lett (2008) 1(1):18–22.10.1016/j.phytol.2007.12.001
184. Gonthier MP, Cheynier V, Donovan JL, Manach C, Morand C, Mila I, et al. Microbial aromatic acid metabolites formed in the gut account for a major fraction of the polyphenols excreted in urine of rats fed red wine polyphenols. J Nutr (2003) 133(2):461–7.12566484
185. van’t Slot G, Humpf HU. Degradation and metabolism of catechin, epigallocatechin-3-gallate (EGCG), and related compounds by the intestinal microbiota in the pig cecum model. J Agric Food Chem (2009) 57(17):8041–8.10.1021/jf900458e19670865
186. Engemann A, Hubner F, Rzeppa S, Humpf HU. Intestinal metabolism of two A-type procyanidins using the pig cecum model: detailed structure elucidation of unknown catabolites with Fourier transform mass spectrometry (FTMS). J Agric Food Chem (2012) 60(3):749–57.10.1021/jf203927g22175758
187. Meselhy MR, Nakamura N, Hattori M. Biotransformation of (-)-epicatechin 3-O-gallate by human intestinal bacteria. Chem Pharm Bull (Tokyo) (1997) 45(5):888–93.10.1248/cpb.45.8889178524
188. Rios LY, Gonthier MP, Remesy C, Mila I, Lapierre C, Lazarus SA, et al. Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects. Am J Clin Nutr (2003) 77(4):912–8.12663291
189. Urpi-Sarda M, Monagas M, Khan N, Lamuela-Raventos RM, Santos-Buelga C, Sacanella E, et al. Epicatechin, procyanidins, and phenolic microbial metabolites after cocoa intake in humans and rats. Anal Bioanal Chem (2009) 394(6):1545–56.10.1007/s00216-009-2676-119333587
190. Ward NC, Croft KD, Puddey IB, Hodgson JM. Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic Acid, an important metabolite of proanthocyanidins in humans. J Agric Food Chem (2004) 52(17):5545–9.10.1021/jf049404r15315398
191. van Dorsten FA, Peters S, Gross G, Gomez-Roldan V, Klinkenberg M, de Vos RC, et al. Gut microbial metabolism of polyphenols from black tea and red wine/grape juice is source-specific and colon-region dependent. J Agric Food Chem (2012) 60(45):11331–42.10.1021/jf303165w23072624
192. Bazzocco S, Mattila I, Guyot S, Renard CM, Aura AM. Factors affecting the conversion of apple polyphenols to phenolic acids and fruit matrix to short-chain fatty acids by human faecal microbiota in vitro. Eur J Nutr (2008) 47(8):442–52.10.1007/s00394-008-0747-218931964
193. Ou K, Sarnoski P, Schneider KR, Song K, Khoo C, Gu L. Microbial catabolism of procyanidins by human gut microbiota. Mol Nutr Food Res (2014) 58(11):2196–205.10.1002/mnfr.20140024325045165
194. Carrasco-Pozo C, Gotteland M, Castillo RL, Chen C. 3,4-Dihydroxyphenylacetic acid, a microbiota-derived metabolite of quercetin, protects against pancreatic beta-cells dysfunction induced by high cholesterol. Exp Cell Res (2015) 334(2):270–82.10.1016/j.yexcr.2015.03.021
195. Amiot A, Peyrin-Biroulet L. Current, new and future biological agents on the horizon for the treatment of inflammatory bowel diseases. Therap Adv Gastroenterol (2015) 8(2):66–82.10.1177/1756283X1455819325729432
196. Yoshioka Y, Akiyama H, Nakano M, Shoji T, Kanda T, Ohtake Y, et al. Orally administered apple procyanidins protect against experimental inflammatory bowel disease in mice. Int Immunopharmacol (2008) 8(13–14):1802–7.10.1016/j.intimp.2008.08.02118824249
197. Cheah KY, Bastian SE, Acott TM, Abimosleh SM, Lymn KA, Howarth GS. 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 (2013) 58(4):970–7.10.1007/s10620-012-2464-123143736
198. Shoji T, Mutsuga M, Nakamura T, Kanda T, Akiyama H, Goda Y. Isolation and structural elucidation of some procyanidins from apple by low-temperature nuclear magnetic resonance. J Agric Food Chem (2003) 51(13):3806–13.10.1021/jf030018412797747
199. Yang T, Li X, Zhu W, Chen C, Sun Z, Tan Z, et al. Alteration of antioxidant enzymes and associated genes induced by grape seed extracts in the primary muscle cells of goats in vitro. PLoS One (2014) 9(9):e107670.10.1371/journal.pone.010767025238394
200. Chen Y, Chou K, Fuchs E, Havran WL, Boismenu R. Protection of the intestinal mucosa by intraepithelial gamma delta T cells. Proc Natl Acad Sci U S A (2002) 99(22):14338–43.10.1073/pnas.21229049912376619
201. Li XL, Cai YQ, Qin H, Wu YJ. Therapeutic effect and mechanism of proanthocyanidins from grape seeds in rats with TNBS-induced ulcerative colitis. Can J Physiol Pharmacol (2008) 86(12):841–9.10.1139/Y08-08919088805
202. Wang YH, Yang XL, Wang L, Cui MX, Cai YQ, Li XL, et al. Effects of proanthocyanidins from grape seed on treatment of recurrent ulcerative colitis in rats. Can J Physiol Pharmacol (2010) 88(9):888–98.10.1139/Y10-07120921975
203. Wang YH, Ge B, Yang XL, Zhai J, Yang LN, Wang XX, et al. Proanthocyanidins from grape seeds modulates the nuclear factor-kappa B signal transduction pathways in rats with TNBS-induced recurrent ulcerative colitis. Int Immunopharmacol (2011) 11(10):1620–7.10.1016/j.intimp.2011.05.02421642017
204. Li X, Yang X, Cai Y, Qin H, Wang L, Wang Y, et al. Proanthocyanidins from grape seeds modulate the NF-kappaB signal transduction pathways in rats with TNBS-induced ulcerative colitis. Molecules (2011) 16(8):6721–31.10.3390/molecules16086721
205. Gentile C, Perrone A, Attanzio A, Tesoriere L, Livrea MA. Sicilian pistachio (Pistacia vera L.) nut inhibits expression and release of inflammatory mediators and reverts the increase of paracellular permeability in IL-1beta-exposed human intestinal epithelial cells. Eur J Nutr (2015) 54(5):811–21.10.1007/s00394-014-0760-6
206. Jung M, Triebel S, Anke T, Richling E, Erkel G. Influence of apple polyphenols on inflammatory gene expression. Mol Nutr Food Res (2009) 53(10):1263–80.10.1002/mnfr.20080057519764067
207. Wong X, Carrasco-Pozo C, Escobar E, Navarrete P, Blachier F, Andriamihaja M, et al. Deleterious effect of p-cresol on human colonic epithelial cells prevented by proanthocyanidin-containing polyphenol extracts from fruits and proanthocyanidin bacterial metabolites. J Agric Food Chem (2016) 64(18):3574–83.10.1021/acs.jafc.6b0065627039931
208. WHO Organization. Key Facts About Cancer. (2016). Available from: http://www.who.int/cancer/about/facts/en/
209. Katiyar SK, Athar M. Grape seeds: ripe for cancer chemoprevention. Cancer Prev Res (Phila) (2013) 6(7):617–21.10.1158/1940-6207.CAPR-13-019323771521
210. Kaur M, Agarwal C, Agarwal R. Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products. J Nutr (2009) 139(9):1806S–12S.10.3945/jn.109.10686419640973
211. Pan MH, Lai CS, Wu JC, Ho CT. Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds. Mol Nutr Food Res (2011) 55(1):32–45.10.1002/mnfr.20100041221207511
212. Woo HD, Kim J. Dietary flavonoid intake and risk of stomach and colorectal cancer. World J Gastroenterol (2013) 19(7):1011–9.10.3748/wjg.v19.i7.101123467443
213. Hsu C, Lin Y, Chou C, Zhou S, Hsu Y, Liu C, et al. Mechanisms of grape seed procyanidin-induced apoptosis in colorectal carcinoma cells. Anticancer Res (2009) 29(1):283–9.19331163
214. Yi W, Fischer J, Krewer G, CC A. Phenolic compounds from blueberries can inhibit colon cancer cell proliferation and induce apoptosis. J Agric Food Chem (2005) 53:7320–9.10.1021/jf051333o16131149
215. Kaur M, Singh RP, Gu M, Agarwal R, Agarwal C. Grape seed extract inhibits in vitro and in vivo growth of human colorectal carcinoma cells. Clin Cancer Res (2006) 12(20 Pt 1):6194–202.10.1158/1078-0432.CCR-06-146517062697
216. Kim YJ, Park HJ, Yoon SH, Kim MJ, Leem KH, Chung JH, et al. Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4. World J Gastroenterol (2005) 11(30):4674–8.10.3748/wjg.v11.i30.4674
217. Minker C, Duban L, Karas D, Jarvinen P, Lobstein A, Muller CD. Impact of procyanidins from different berries on caspase 8 activation in colon cancer. Oxid Med Cell Longev (2015) 2015:154164.10.1155/2015/15416426180579
218. Huang S, Yang N, Liu Y, Gao J, Huang T, Hu L, et al. Grape seed proanthocyanidins inhibit colon cancer-induced angiogenesis through suppressing the expression of VEGF and Ang1. Int J Mol Med (2012) 30(6):1410–6.10.3892/ijmm.2012.114723026853
219. Singletary KW, Meline B. Effect of grape seed proanthocyanidins on colon aberrant crypts and breast tumors in a rat dual-organ tumor model. Nutr Cancer (2001) 39(2):252–8.10.1207/S15327914nc392_1511759289
220. Nomoto H, Iigo M, Hamada H, Kojima S, Tsuda H. Chemoprevention of colorectal cancer by grape seed proanthocyanidin is accompanied by a decrease in proliferation and increase in apoptosis. Nutr Cancer (2004) 49(1):81–8.10.1207/s15327914nc4901_1115456639
221. Rossi M, Negri E, Parpinel M, Lagiou P, Bosetti C, Talamini R, et al. Proanthocyanidins and the risk of colorectal cancer in Italy. Cancer Causes Control (2010) 21(2):243–50.10.1007/s10552-009-9455-320012183
222. Theodoratou E, Kyle J, Cetnarskyj R, Farrington SM, Tenesa A, Barnetson R, et al. Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev (2007) 16(4):684–93.10.1158/1055-9965.EPI-06-078517416758
223. Zamora-Ros R, Not C, Guinó E, Luján-Barroso L, García RM, Biondo S, et al. Association between habitual dietary flavonoid and lignan intake and colorectal cancer in a Spanish case–control study (the Bellvitge Colorectal Cancer Study). Cancer Causes Control (2013) 24:549–57.10.1007/s10552-012-9992-z
224. Kyle JA, Sharp L, Little J, Duthie GG, McNeill G. Dietary flavonoid intake and colorectal cancer: a case-control study. Br J Nutr (2010) 103(3):429–36.10.1017/S000711450999178419732470
225. Cutler GJ, Nettleton JA, Ross JA, Harnack LJ, Jacobs DR, Jr Scrafford CG, et al. Dietary flavonoid intake and risk of cancer in postmenopausal women: the Iowa Women’s Health Study. Int J Cancer (2008) 123(3):664–71.10.1002/ijc.23564
226. Bobe G, Murphy G, Albert PS, Sansbury LB, Lanza E, Schatzkin A, et al. Dietary lignan and proanthocyanidin consumption and colorectal adenoma recurrence in the Polyp Prevention Trial. Int J Cancer (2012) 130(7):1649–59.10.1002/ijc.2618421618513