Flavonoides and inflammatory bowel disease;Flavonoides y enfermedad inflamatoria intestinal

Ars Pharmaceutica

Volumn 47, Issue 1, 2006, Pages 5-21

  Ballester, I ^a   Camuesco, D ^a   Galvez J ^a   Sanchez De Medina F ^a   Zarzuelo, A ^a  

^a Facultad de Farmacia   (Spain)

Author keywords

Antioxidant; Cytocine; Flavonoids; Intestinal inflammatory disease; Leukotriene B4; NF B; Nitric acid

Indexed keywords

ANTIOXIDANT; APIGENIN; CYTOKINE; DA 6034; DIOSMIN; FLAVONOID; HESPERIDIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; LEUKOTRIENE B4; LUTEOLIN; MORIN; NITRIC ACID; NITRIC OXIDE; QUERCITRIN; RUTOSIDE; SILYMARIN; UNCLASSIFIED DRUG;

ACUTE DIARRHEA; ANTIINFLAMMATORY ACTIVITY; CHRONIC DIARRHEA; COLITIS; CROHN DISEASE; CYTOKINE PRODUCTION; DIET THERAPY; DRUG ACTIVITY; ENTERITIS; EXPERIMENTAL MODEL; FOOD INTAKE; INFLAMMATION; INTESTINE MOTILITY; INTESTINE SECRETION; NONHUMAN; NUTRITION; OXIDATIVE STRESS; REVIEW; ULCERATIVE COLITIS; VEGETABLE;

EID: 33750437752     PISSN: 00042927     EISSN: 00042927     Source Type: Journal    
DOI: None     Document Type: Review

References (113)

1. Kuhnau J. The flavonoids. A class of semi-essential food components: their role in human nutrition. World Rev Nutr Diet 1976; 24: 117-91.
2. Hertog MGL, Hollman PCH, Katan MB, Krombout D. Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutr Cancer 1993; 20: 21-29.
3. Hertog MGL, Krombout D, Aravanis C, Blackburn H, Buzina R, Fidanza F et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 1995; 155: 381-86.
4. Justesen U, Knuthsen P, Leth T. Determination of plant polyphenols in Danish foodstuffs by HPLC-UV and LC-MS detection. Cancer Lett 1997; 117: 165-67.
5. Böhm H, Boeing H, Hempel J, Raab B, Kroke AZ. Flavonols, flavone and anthocyanins as natural antioxidants of food and their possible role in the prevention of chronic diseases. Z Ernährungswiss 1998; 37: 147-63.
6. Noroozi M, Burns J, Crozier A, Kelly LE, Lean ME. Prediction of dietary flavonol consumption from fasting plasma concentration or urinary excretion. Eur J Clin Nutr 2000; 54: 143-49.
7. Wollenweber E. Plant Flavonoids in Biology and Medicine II: Biochemical, Cellular, and Medicinal Properties. Cody V, Middleton E, Harborne JB, Beretz A (Eds.). A.R. Liss, New York. 1988: 45-55.
8. Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 1983; 32: 1141-48.
9. Amoros M, Simoes CM, Girre L, Sauvager F, Cormier M. Synergistic effect of flavones and flavonols against herpes simplex virus type 1 in cell culture. Comparison with the antiviral activity of propolis. J Nat Prod 1992; 55: 1732-40.
10. Ohnishi E, Bannai H. Quercetin potentiates TNF-induced antiviral activity. Antiviral Res 1993; 22: 327-31.
11. Moroney MA, Alcaraz MJ, Forder RA, Carey F, Holt RS. Selectivity of neutrophil 5-lipoxygenase and cyclooxygenase inhibition by an anti-inflammatory flavonoid glycoside and related aglycone flavonoids. J Pharm Pharmacol 1988; 40: 787-92.
12. Emim JA, Oliveira AB, Lapa AJ. Pharmacological evaluation of the anti-inflammatory activity of a citrus bioflavonoid, hesperidin, and the isoflavonoids, duartin and claussequinone, in rats and mice. J Pharm Pharmacol 1994; 46: 118-22.
13. Capasso A, Pinto A, Sorrentino R, Capasso F. Inhibitory effects of quercetin and other flavonoids on electrically-induced contractions of guinea pig isolated ileum. J Ethnopharmacol 1991a; 34: 279-81.
14. Capasso A, Pinto A, Mascolo N, Autore G, Capasso F. Reduction of agonist-induced contractions of guinea-pig isolated ileum by flavonoids. Phytother Res 1991b; 5: 85-87.
15. Batista LM, de Almeida AB, de Pietro Magri L, Toma W, Calvo TR, Vilegas W et al. Gastric antiulcer activity of Syngonanthus arthrotrichus SILVEIRA. Biol Pharm Bull 2004; 27(3): 328-32
16. Duarte J, Perez Vizcaino F, Utrilla P, Jimenez J, Tamargo J, Zarzuelo A. Vasodilatory effects of flavonoids in rat aortic smooth muscle. Structure-activity relationships. Gen Pharmacol 1993a; 24: 857-82.
17. Duarte J, Perez Vizcaino F, Zarzuelo A, Jimenez J, Tamargo J. Vasodilator effects of quercetin in isolated rat vascular smooth muscle. Eur J Pharmacol 1993b; 239: 1-7.
18. Landolfi R, Mower RL, Steiner M. Modification of platelet function and arachidonic acid metabolism by bioflavonoids. Structure-activity relations. Biochem Pharmacol 1984; 33: 1525-30.
19. Gryglewski RJ, Korbut R, Robak J, Swies J. On the mechanism of antithrombotic action of flavonoids. Biochem Pharmacol 1987; 36: 317-22.
20. Edwards JM, Raffauf RF, Le Quesne PW. Antineoplastic activity and cytotoxicity of flavones, isoflavones, and flavanones. J Nat Prod 1979; 42: 85-91.
21. Cushman M, Nagarathnam D. Cytotoxicities of some flavonoid analogues. J Nat Prod 1991; 54: 1656-60.
22. Virgili F, Acconcia F, Ambra R, Rinna A, Totta P, Marino M. Nutritional flavonoids modulate estrogen receptor alpha signalling. IUBMB Life 2004; 56(3): 145-51.
23. Hong T, Nakagawa T, Pan W, Kim MY, Kraus WL, Ikehara T, et al. Isoflavones stimulate estrogen receptor-mediated core histone acetylation. Biochem Biophys Res Commun. 2004; 317(1): 259-64.
24. Gassul M A, Cabré E. Management of inflammatory Bowel disease. Gassull MA, Obrador A, Chantar C (Eds.). Prous Science, Barcelona 1994: 7-12.
25. Obrador A, Riera J. Definitions. Management of Inflammatory Bowel Disease. Gassull MA, Obrador A, Chantar C (Eds.). Prous Science, Barcelona 1994: 1-6.
26. Shanahan F, Targan SR. Inflammatory bowel disease: from bench to bedside. En: Targan SR y Shanahan F, eds. Inflammatory Bowel Disease: From Bench to BedSide. Baltimore (Maryland): Williams & Wilkins, 1994: 2-4.
27. Fiocchi C. Inflammatory bowel disease: aetiology and pathogenesis. Gastroenterology 1998; 115: 182-205.
28. MacDermott RP. Alterations of the mucosal immune system in inflammatory bowel disease. J Gastroenterol 1996; 31: 907-16.
29. McKay DM. Intestinal inflammation and the gut microflora. Can J Gastroenterol 1999; 13(6): 509-16.
30. Andus T, Gross V. Etiology and pathophysiology of inflammatory bowel disease-environmental factors. HepatoGastroenterology 2000; 47: 29-43.
31. Kappeler A, Mueller C. The role of activated cytotoxic T cells in inflammatory bowel disease. Histol Histopathol 2000; 15: 167-172.
32. Mahida YR. The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis 2000; 6: 12-16.
33. Katz JA, Itoh J, Fiocchi C. Pathogenesis of inflammatory bowel disease. Curr Opin Gastroenterol 1999; 15: 291-97.
34. Middleton E, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000; 52: 673-51.
35. Middleton E. Effect of plant flavonoids on immune and inflammatory cell function. Adv Exp Med Biol 1998; 439: 175-82.
36. Mora A, Paya M, Rios JL, Alcaraz MJ. Structure-activity relationships of polymethoxyflavones and other flavonoids as inhibitors of non-enzymic lipid peroxidation. Biochem Pharmacol 1990; 36: 317-22.
37. Valenzuela A, Aspigalla M, Vial S, Guerra R. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med 1989; 55: 420-22.
38. Galvez J, de la Cruz JP, Zarzuelo A, Sanchez de Medina F, Sanchez de la Cuesta F. Oral administration of quercitrin modifies intestinal oxidative status in rats. Gen Pharmacol 1994; 25: 1237-43.
39. Galsanov SB, Turova AD, Klimenko ED. Effect of quercitrin on structural changes in the large and small intestines during experimental enterocolitis. Byull Eksp Biol Med 1976; 81: 623-25.
40. Elson CO, Sartor B, Tennyson GS, Riddell RH. Experimental models of inflammatory bowel disease. Gastroenterology 1995; 109: 1344-57.
41. Sanchez de Medina F, Galvez J, Romero JA, Zarzuelo A. Effects of quercitrin on acute and chronic experimental colitis in the rat. J Pharm Exp Ther 1996; 278: 771-79.
42. Camuesco D, Comalada M, Rodriguez-Cabezas ME, Nieto A, Lorente MD, Concha A, et al. The intestinal anti-inflammatory effect of quercitrin is associated with an inhibition in iNOS expression. Br J Pharmacol 2004; 143(7): 908-18.
43. Galvez J, Cruz T, Crespo ME, Ocete MA, Lorente MD, Sanchez de Medina F et al. Rutoside as mucosal protective in acetic-acid induced rat colitis. Planta Med 1997; 63: 409-14.
44. Cruz T, Galvez J, Ocete MA, Crespo ME, Sanchez de Medina F, Zarzuelo A. Oral administration of rutoside can ameliorate inflammatory bowel disease in rats. Life Sci 1998; 62: 687-95.
45. Crespo ME, Galvez J, Cruz T, Ocete MA, Zarzuelo A. Anti-inflammatory activity of diosmin and hesperidin in rat colitis induced by TNBS. Planta Med 1999; 65: 651-53.
46. Ocete MA, Galvez J, Crespo ME, Cruz T, Gonzalez M, Torres MI et al. Effects of morin on an experimental model of acute colitis in rats. Planta Med 1998; 63: 261-70.
47. Galvez J, Coelho G, Crespo ME, Cruz T, Rodríguez-Cabezas ME, Concha A, et al. Intestinal anti-inflammatory activity of morin on chronic experimental colitis in the rat. Aliment Pharmacol Ther 2001; 15: 2027-39.
48. Cruz T, Galvez J, Crespo ME, Ocete MA, Zarzuelo A. Effects of sylimarin on the acute stage of the trinitrobenzenesulphonic acid model of rat colitis. Planta Med 2001; 67: 94-96
49. Villegas I, Alarcon de la Lastra C, Orjales A, La Casa C. A new flavonoid derivative, dosmalfate, attenuates the development of dextran sulphate sodium-induced colitis in mice. Int Immunopharmacol 2003; 3(13-14): 1731-41.
50. Villegas I, La Casa C, Orjales A, Alarcón de la Lastra C. Effects of Dosmalfate, a new cytoprotective agent, on acute and chronic trinitrobencensulfonic-induced colitis in rats. Eur J Pharmacol 2003; 460: 209-18.
51. Kim YS, Son M, Ko JI, Cho H, Yoo M, Kim WB et al. Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease. Arch Pharm Res 1999; 22(4): 354-60.
52. Loguercio C, D'Argenio G, Dell Cave M, Cosenza V, Della Valle N, Mazzacca G et al. Direct evidence of oxidative damage in acute and chronic phases of experimental colitis in rats. Dig Dis Sci 1996; 41: 1204-11.
53. Galvez J, Garrido M, Merlos M, Torres MI, Zarzuelo A. Intestinal anti-inflammatory activity of UR-12746, a novel 5-ASA conjugate, on acute and chronic experimental colitis in the rat. Br J Pharmacol 2000; 130: 1949-59.
54. Yamada T, Grisham MB. Pathogenesis of tissue injury: role of reactive metabolites of oxygen and nitrogen. Inflammatory Bowel Disease: From Bench to Bedside. Targan SR, Shanahan F (Eds.). Willians and Wilkins, Baltimore, Maryland 1994: 133-50.
55. Grisham MB, Jourd'heuil D, Wink DA. Nitric oxide I. Physiological chemistry of nitric oxide and its metabolites: implications in inflammation. Am J Physiol 1999; 276: G315-G320.
56. Lefer AM, Lefer DJ. Nitric oxide protects in intestinal inflammation. Am J Physiol 1999; 276: G572-G575.
57. Lefer AM, Lefer DJ. Nitric oxide II. Nitric oxide protects in intestinal inflammation. Am J Physiol 1999; 276: G572-G575.
58. Miller MJS, Sandoval M. Nitric oxide III. A molecular to intestinal prelude inflammatory. Am J Physiol 1999; 276: G795-G799.
59. Sichel G, Corsaro C, Scalia M, Di Bilio AJ, Bonomo RP. In vitro scavenger activity of some flavonoids and melanins against O2-(.). Free Rad Biol Med 1991; 11: 1-8.
60. Chan MM, Fong D, Ho CT, Huang HI. Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate, a natural product from green tea. Biochem Pharmacol 1997; 54: 1281-86.
61. Haenen GR, Paquay JB, Korthouwer EM, Bast A. Peroxynitrite scavenging by flavonoids. Biochem Biophys Res Commun 1997; 236: 591-93.
62. Bertran X, Mañe J, Fernandez-Bañares E, Castella R, Bartoli I, Ojanguren M et al. Intracolonic administration of zileuton, a selective 5-lipoxygenase inhibitor, accelerates healing in a rat model of chronic colitis. Gut 1996; 38: 899-904.
63. Fretland DJ, Widomski D, Tsai D-S, Zemaitis JM, Levin S, Djuric SW, Shone RL et al. Effect of the leukotriene B4 receptor antagonist SC-41930 on colonic inflammation in rat, guinea pig and rabbit. J Pharmacol Exp Ther 1990; 255: 572-76.
64. Veljaca M, Lesch CA, Pllana R, Sanchez B, Chan K, Guglietta A. BPC-15 reduces trinitrobenzene sulphonic acid-induced colonic damage in rats. J Pharmacol Exp Ther 1995; 272: 417-22.
65. Rask-Madsen J, Bukhave K, Laursen LS, Lauritsen K. 5-Lipoxygenase inhibitors for the treatment of inflammatory bowel disease. Agents Actions 1992; Spec No: C37-46.
66. Manthey JA, Grohmann K, Guthrie N. Biological properties of citrus flavonoids pertaining to cancer and inflammation. Curr Med Chem 2001; 8(2): 135-53.
67. Xagorari A, Papapetropoulos A, Mauromatis A, Economou M, Fotsis T, Roussos C. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J Pharm Exp Ther 2001; 296: 181-87.
68. Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, et al. Molecular mechanisms underlying chemopreventive activities of antiinflammatory phytochemicals: downregulation of COX-2 and iNOS though supression of NF?B activation. Mutat Res 2001; 480-481: 243-68.
69. Comalada M, Camuesco D, Sierra S, Ballester I, Xaus J, Gálvez J, Zarzuelo A. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through the downregulation of NF- B pathway. Eur J Immunol 2005; 35: 584-92.
70. Omoya T, Shimizu I, Zhou Y, Okamura Y, Inoue H, Lu G, et al. Effects of idoxifene and estradiol on NF-kappaB activation in cultured rat hepatocytes undergoing oxidative stress. Liver, 2001; 21(3): 183-91.
71. McKenzie SJ, Baker MS, Buffinton GD, Doe WF. Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease. Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease. J Clin Invest 1996; 98(1): 136-41.
72. Wendland BE, Aghdassi E, Tam C, Carrrier J, Steinhart AH, Wolman SL, Baron D, Allard JP. Lipid peroxidation and plasma antioxidant micronutrients in Crohn disease. Am J Clin Nutr 2001; 74(2): 259-64.
73. Nieto N, Torres MI, Fernandez MI, Giron MD, Rios A, Suarez MD, et al. Experimental ulcerative colitis impairs antioxidant defense system in rat intestine. Dig Dis Sci 2000; 45(9): 1820-7.
74. Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev 2004; 18(18): 2195-224.
75. 2)-induced NF?B, degradation of I?B DNA binding activity and DNA damage in HepG2 cells. Carcinogenesis 1998; 19: 1583-89.
76. Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF?B, activator protein-1, and apoptosis: potencial role of reactive oxygen intermediates and lipid peroxidation. J Inmunol 2000; 164: 6509-19.
77. Ginn-Pease, ME, Whisler, RL. Redox signals and NF?B activation in T cells. Free Rad Biol Med 1998; 25: 346-61.
78. Schoonbroodt S, Piette J. Oxidative stress interference with the nuclear factor-kappa B activation pathways. Biochem Pharmacol 2000; 60(8): 1075-83.
79. Bowie A, O'Neill LAJ. Vitamin C inhibits NF?B activation by TNF via the activation of p38 mitogen-activated protein kinase. J Inmunol 2000; 165: 7180-88.
80. Bowie A, O'Neill LAJ. Oxidative stress and nuclear factor-?B activation. A reassessment of the evidence of the light of recent discoveries. Biochem Pharmacol 2000; 59: 13-23.
81. Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev 1995; 9(22): 2723-35.
82. Peet GW, Li J. I?B kinases ? and ? show a random sequential kinetic mechanism and are inhibited by stausporine and quercetin. J Biol Chem 1999; 274: 32655-61.
83. Park Y C, Rimbach G, Saliou C, Valacchi G, Packer L. Activity of monomeric, dimeric and trimeric flavonoids on NO production, TNF? secretion, and NF?B-dependent gene expresión in RAW 264.7 macrophages. FEBS Lett 2000; 465: 93-97.
84. Natarajan K, Manna S K, Chaturvedi M M, Aggarwal B B. Protein tyrosine kinase inhibitors block tumor necrosis factor-induced activation of NF?B, degradation of I-?B?, nuclear traslocation of p65, and subsequent gene expresión. Arch Biochem Biophys 1998; 352: 59-70.
85. Panes J, Gerritsen ME, Anderson DC, Miyasaka M, Granger DN. Apigenin inhibits tumor necrosis factor-induced intercellular adhesion molecule-1 upregulation in vivo. Microcirculation 1996; 3: 279-86.
86. Habtemariam S. Flavonoids as inhibitors or enhancers of the cytotoxicity of tumor necrosis factor-? in L-929 tumor cells. J Nat Prod 1997; 60: 775-78.
87. Ishikawa Y, Sugiyama H, Stylianou E, Kitamura M. Bioflavonoid quercetin inhibits interleukin-1-induced transcriptional expression of monocyte chemoattractant protein-1 in glomerular cells via suppression of nuclear factor-?B. J Am Soc Nephrol 1999; 10: 2290-96.
88. Ligumsky M, Simon PL, Karmeli F, Rachmilewitz D. Role of interleukin-1 in inflammatory bowel disease-enhanced production during active disease. Gut 1990; 31: 686-89.
89. Rachmilewitz D, Simon PL, Schawartz LW, Griswold DE, Fondacaro JD, Wasserman MA. Inflammatory mediators of experimental colitis in the rats. Gastroenterology 1989; 97: 326-37.
90. Van Dijk APM, Keuskamp ZJ, Wilson JHP, Zijilstra FJ. Sequential release of cytokines, lipid mediators and nitric oxide in experimental colitis. Mediators of Inflammation 1995; 4: 186-90.
91. Sánchez de Medina F, Perez R, Martínez-Augustin O, Gonzalez R, Lorente MD, Galvez J, et al. Disturbances of colonic ion secretion in inflammation: role of enteric nervous system and cAMP. Pflug Arch Eur J Physiol 2002; 444: 378-88.
92. Brandzaeg P, Haraldsen L, Baekkevold ES, Jahnsen FL, Nilsen EM. Intestinal Mucosa and its Diseases. Pathophysiolgy and Clinics. Domschke W, Stoll R, Brasitus TA, Kagnoff MF (Eds.). Kluwer Academic Publishers BV, Dordrecht 1999: 383-400.
93. Asfaha S, Macnaughton WK, Appleyard CB, Chadee K, Wallace JL. Persistent epithelial dysfunction and bacterial translocation after resolution of intestinal inflammation. Am J Physiol 2001; 281: G635-G644.
94. Rao VS, Santos FA, Sobreira TT, Souza MF, Melo CL, Silveira ER. Investigations on the gastroprotective and antidiarrhoeal properties of ternatin, a tetramethoxyflavone from Egletes viscosa. Planta Med 1997; 63: 146-49.
95. Di Carlo G, Autore G, Izzo AA, Maiolino P, Mascolo N, Viola P et al. Inhibition of intestinal motility and secretion by flavonoids in mice and rats: structure-activity relationships. J Pharm Pharmacol 1993; 45: 1054-59.
96. Meli R, Autore G, Di Carlo G, Capasso F. Inhibitory action of quercetin on itestinal transit time. Phytother Res 1990; 4: 201-02.
97. Galvez J, Duarte J, Sanchez de Medina F, Jiménez J, Zarzuelo A. Inhibitory effects of quercetin on guinea-pig ileum contractions. Phytother Res 1996; 10: 66-69.
98. Abdalla S, Zarga MA, Afifi F, Al-Khalil S, Mahasneh A, Sabri S. Effects of 3,3′-di-O-methylquercetin on guinea-pig isolated smooth muscle. J Pharm Pharmacol 1989; 41: 138-41.
99. Morales MA, Tortoriello J, Meckes M, Paz D, Lozoya X. Calcium-antagonist effect of quercetin and its relation with the spasmolytic properties of Psidium guajava L. Arch Med Res 1994; 25: 17-21.
100. Beretz A, Anton R, Cazenave JP. Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological, and Structure-Activity Relationships. Cody V, Middleton E, Harborne JB, Beretz A (Eds.). AR Liss, New York 1996: 281-96.
101. Kuppusamy UR, Das NP. Effects of flavonoids on cyclic AMP phosphodiesterase and lipid mobilization in rat adipocytes. Biochem Pharmacol 1992; 44: 1307-15.
102. Nikaido T, Ohmoto T, Sankawa U, Hamanka T, Totsuka K. Inhibition of cyclic AMP phosphodiesterase by flavonoids. Planta Med 1982; 46: 162-66.
103. Ferriola PC, Cody V, Middleton E. Protein kinase C inhibition by plant flavonoids. Kinetic mechanisms and structure-activity relationships. Biochem Pharmacol 1989; 38: 1617-24.
104. Dharmsathaphorn K, Madara JL. Established intestinal cell lines as model systems for electrolyte transport studies. Methods Enzymol 1990; 192: 354-89.
105. Cermak R, Föllmer U, Wolffram S. Dietary flavonol quercetin induces chloride secretion in rat colon. Am J Physiol 1998; 274: G1166-G1172.
106. Nguyen TD, Canada AT, Heintz GG, Gettys TW, Cohn JA. Stimulation of secretion by the T84 colonic epithelial cell line with dietary flavonols. Biochem Pharmacol 1991; 21: 1879-86.
107. Sanchez de Medina F, Galvez J, Gonzalez M, Zarzuelo A, Barrett K. Effects of quercetin on epithelial chloride secretion. Life Sci 1997; 61: 2049-55.
108. Diener M, Hug F. Modulation of Cl- secretion in rat distal colon by genistein, a protein tyrosine kinase inhibitor. Eur J Pharmacol 1996; 299: 161-70.
109. - secretion in T84 cell monolayers. Am J Physiol 1995; 269: G874-G882.
110. Illek B, Fischer H, Machen TE. Alternate stimulation of apical CFTR by genistein in epithelia. Am J Physiol 1996; 270: C265-C275.
111. Wang F, Zeltwanger S, Yang IC, Nairn AC, Hwang TC. Actions of genistein on cystic fibrosis transmembrane conductance regulator channel gating. Evidence for two binding sites with opposite effects. J Gen Physiol 1998; 111: 477-90.
112. Randak C, Auerswald EA, Assfalg-Machleidt I, Reenstra WW, Machleidt W. Inhibition of ATPase, GTPase and adenylate kinase activities of the second nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator by genistein. Biochem J 1999; 340: 227-35.
113. Nguyen TD, Canada AT. Citrus flavonoids stimulate secretion by human colonic T84 cells. J Nutr 1993; 123: 259-68.