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Planta Med 2013; 79(15): 1392-1400
DOI: 10.1055/s-0033-1350710
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Protective Effect of Apocynin in a Mouse Model of Chemically-Induced Colitis

Marta Marín
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, València, Spain
,
Rosa María Giner
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, València, Spain
,
José-Luis Ríos
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, València, Spain
,
María del Carmen Recio
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, València, Spain
› Author Affiliations
Further Information

Publication History

received 08 March 2013
revised 10 July 2013

accepted 15 July 2013

Publication Date:
22 August 2013 (online)

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Protective Effect of Apocynin in a Mouse Model of Chemically-Induced ColitisPlanta Med 2013; 79(15): E4-E4
DOI: 10.1055/s-0033-1350889

Abstract

Apocynin, a constituent of Picrorhiza kurroa, successfully inhibits NADPH oxidase and shows promise as an anti-inflammatory drug. Now, we report anti-inflammatory effects of apocynin in an experimental colitis model induced by dextran sulfate sodium as well as the effects on the mediators involved in this process. Apocynin reduced the colitis induced in mice by administration of 5 % dextran sulfate sodium during 7 days. Mice were fed a control diet or a diet supplemented with 2 % of apocynin or 2 % of rutin. Sulfasalazine (50 mg/kg, p. o.) was used as a positive control. Treatment with apocynin and rutin ameliorated the course of colonic inflammation with results similar to those of the reference drug, as could be seen by reductions in the disease activity index scores and colon length. NO and PGE2 production as well as the iNOS and COX-2 expression were reduced by apocynin and rutin. Moreover, the activation of NF-κB p65 as well as STAT3 in dextran sulfate sodium-treated colon tissues was significantly reduced by apocynin. These results are promising for further experimental studies on treating gastrointestinal diseases and on the potential protective effects of apocynin.

Key words

apocynin - dextran sulfate sodium - inflammatory bowel disease - ulcerative colitis - inflammatory cytokines - Picrorhiza kurroa - Scrophulariaceae
 

  • References

  • 1 Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol 2010; 28: 573-621
    CrossrefPubMedGoogle Scholar
  • 2 Krieglstein CF, Cerwinka WH, Laroux FS, Salter JW, Russell JM, Schuermann G, Grisham MB, Ross CR, Granger DN. Regulation of murine intestinal inflammation by reactive metabolites of oxygen and nitrogen, divergent roles of superoxide and nitric oxide. J Exp Med 2001; 194: 1207-1218
    CrossrefPubMedGoogle Scholar
  • 3 Rogler G, Brand K, Vogl D, Page S, Hofmeister R, Andus T, Knuechel R, Baeuerle PA, Scholmerich J, Gross V. Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology 1998; 115: 357-369
    CrossrefPubMedGoogle Scholar
  • 4 Pallone F, Monteleone G. Mechanisms of tissue damage in inflammatory bowel disease. Curr Opin Gastroenterol 2001; 17: 307-312
    CrossrefPubMedGoogle Scholar
  • 5 Perše M, Cerar A. Dextran sodium sulphate colitis mouse model, traps and tricks. J Biomed Biotechnol advance online publication 4 May 2012 DOI: 10.1155/2012/718617.
    PubMedGoogle Scholar
  • 6 Sánchez-Fidalgo S, Cárdeno A, Villegas I, Talero E, de la Lastra CA. Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice. Eur J Pharmacol 2010; 633: 78-84
    CrossrefPubMedGoogle Scholar
  • 7 Deguchi Y, Andoh A, Inatomi O, Yagi Y, Bamba S, Araki Y, Hata K, Tsujikawa T, Fujiyama Y. Curcumin prevents the development of dextran sulfate sodium (DSS)-induced experimental colitis. Dig Dis Sci 2007; 52: 2993-2998
    CrossrefPubMedGoogle Scholar
  • 8 Ye Z, Liu Z, Henderson A, Lee K, Hostetter J, Wannemuehler M, Hendrich S. Increased CYP4B1 mRNA is associated with the inhibition of dextran sulfate sodium-induced colitis by caffeic acid in mice. Exp Biol Med (Maywood) 2009; 234: 605-616
    CrossrefPubMedGoogle Scholar
  • 9 Kwon KH, Murakami A, Tanaka T, Ohigashi H. Dietary rutin, but not its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental colitis in mice, attenuation of pro-inflammatory gene expression. Biochem Pharmacol 2005; 69: 395-406
    CrossrefPubMedGoogle Scholar
  • 10 Andújar I, Recio MC, Giner RM, Cienfuegos-Jovellanos E, Laghi S, Muguerza B, Ríos JL. Inhibition of ulcerative colitis in mice after oral administration of a polyphenol-enriched cocoa extract is mediated by inhibition of STAT1 and STAT3 phosphorylation in colon cells. J Agric Food Chem 2011; 59: 6474-6483
    CrossrefPubMedGoogle Scholar
  • 11 Giner E, Andújar I, Recio MC, Ríos JL, Cerdá-Nicolás JM, Giner RM. Oleuropein ameliorates acute colitis in mice. J Agric Food Chem 2011; 59: 12882-12892
    CrossrefPubMedGoogle Scholar
  • 12 Andújar I, Ríos JL, Giner RM, Cerdá MJ, Recio MC. Beneficial effect of shikonin on experimental colitis induced by dextran sulfate sodium in BALB/c mice. Evid Based Complement Alternat Med 2012; 2012: 271606
    PubMedGoogle Scholar
  • 13 Kim SJ, Kim MC, Um JY, Hong SH. The beneficial effect of vanillic acid on ulcerative colitis. Molecules 2010; 15: 7208-7217
    CrossrefPubMedGoogle Scholar
  • 14 Peters EA, Hiltermann JT, Stolk J. Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics. Free Radic Biol Med 2001; 31: 1442-1447
    CrossrefPubMedGoogle Scholar
  • 15 Pandey A, Kour K, Bani S, Suri KA, Satti NK, Sharma P, Qazi GN. Amelioration of adjuvant induced arthritis by apocynin. Phytother Res 2009; 23: 1462-1468
    CrossrefPubMedGoogle Scholar
  • 16 Impellizzeri D, Esposito E, Mazzon E, Paterniti I, Di Paola R, Bramanti P, Cuzzocrea S. Effect of apocynin, a NADPH oxidase inhibitor, on acute lung inflammation. Biochem Pharmacol 2011; 81: 636-648
    CrossrefPubMedGoogle Scholar
  • 17 Kim SY, Moon KA, Jo HY, Jeong S, Seon SH, Jung E, Cho YS, Chun E, Lee KY. Anti-inflammatory effects of apocynin, an inhibitor of NADPH oxidase, in airway inflammation. Immunol Cell Biol 2012; 90: 441-448
    CrossrefPubMedGoogle Scholar
  • 18 Palmen MJHJ, Beukelman CJ, Mooij RGM, Meuwissen SGM, van Rees EP. Beneficial effect of apocynin, a plant-derived NADPH oxidase antagonist, in TNBS-induced experimental colitis. Immunol Microbiol Inflamm Disord 1995; A889
    PubMedGoogle Scholar
  • 19 Rachmilewitz D, Okon E, Karmeli F. Sulphydryl blocker induced small intestinal inflammation in rats: a new model mimicking Crohnʼs disease. Gut 1997; 41: 358-365
    CrossrefPubMedGoogle Scholar
  • 20 Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008; 22: 659-661
    CrossrefPubMedGoogle Scholar
  • 21 Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 1993; 69: 238-249
    PubMedGoogle Scholar
  • 22 Sann H, Erichsen JV, Hessmann M, Pahl A, Hoffmeyer A. Efficacy of drugs used in the treatment of IBD and combinations thereof in acute DSS-induced colitis in mice. Life Sci 2013; 92: 708-718
    CrossrefPubMedGoogle Scholar
  • 23 Axelsson LG, Landström E, Bylund-Fellenius AC. Experimental colitis induced by dextran sulphate sodium in mice: beneficial effects of sulphasalazine and olsalazine. Aliment Pharmacol Ther 1998; 12: 925-934
    CrossrefPubMedGoogle Scholar
  • 24 Kwon KH, Murakami A, Tanaka T, Ohigashi H. Dietary rutin, but not its aglycone quercetin, ameliorates dextran sulfate sodium-induced experimental colitis in mice: attenuation of pro-inflammatory gene expression. Biochem Pharmacol 2005; 69: 395-406
    CrossrefPubMedGoogle Scholar
  • 25 Hur SJ, Kang SH, Jung HS, Kim SC, Jeon HS, Kim IH, Lee JD. Review of natural products actions on cytokines in inflammatory bowel disease. Nutr Res 2012; 32: 801-816
    CrossrefPubMedGoogle Scholar
  • 26 Soriano A, Salas A, Salas A, Sans M, Gironella M, Elena M, Anderson DC, Piqué JM, Panés J. VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice. Lab Invest 2000; 80: 1541-1551
    CrossrefPubMedGoogle Scholar
  • 27 Sans M, Panés J, Ardite E, Elizalde JI, Arce Y, Elena M, Palacín A, Fernández-Checa JC, Anderson DC, Lobb R, Piqué JM. VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis. Gastroenterology 1999; 116: 874-883
    CrossrefPubMedGoogle Scholar
  • 28 Rumi G, Tsubouchi R, Nishio H, Kato S, Mózsik G, Takeuchi K. Dual role of endogenous nitric oxide in development of dextran sodium sulfate-induced colitis in rats. J Physiol Pharmacol 2004; 55: 823-836
    PubMedGoogle Scholar
  • 29 Arafa HM, Hemeida RA, El-Bahrawy AI, Hamada FM. Prophylactic role of curcumin in dextran sulfate sodium (DSS)-induced ulcerative colitis murine model. Food Chem Toxicol 2009; 47: 1311-1317
    PubMedGoogle Scholar
  • 30 Mäkelä SM, Strengell M, Pietilä TE, Osterlund P, Julkunen I. Multiple signaling pathways contribute to synergistic TLR ligand-dependent cytokine gene expression in human monocyte-derived macrophages and dendritic cells. J Leukoc Biol 2009; 85: 664-672
    CrossrefPubMedGoogle Scholar
  • 31 Domènech E. Inflammatory bowel disease, current therapeutic options. Digestion 2006; 73: 67-76
    CrossrefPubMedGoogle Scholar
  • 32 Jiang R, Wang H, Deng L, Hou J, Shi R, Yao M, Gao Y, Yao A, Wang X, Yu L, Sun B. IL-22 is related to development of human colon cancer by activation of STAT3. BMC Cancer 2013; 13: 59
    CrossrefPubMedGoogle Scholar
  • 33 Li Y, de Haar C, Chen M, Deuring J, Gerrits MM, Smits R, Xia B, Kuipers EJ, van der Woude CJ. Disease-related expression of the IL6/STAT3/SOCS3 signaling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis. Gut 2010; 59: 227-235
    CrossrefPubMedGoogle Scholar
  • 34 Lee MJ, Lee JK, Choi JW, Lee CS, Sim JH, Cho CH, Lee KH, Cho IH, Chung MH, Kim HR, Ye SK. Interleukin-6 induces S100A9 expression in colonic epithelial cells through STAT3 activation in experimental ulcerative colitis. PLoS One 2012; 7: e38801
    CrossrefPubMedGoogle Scholar
  • 35 Itoh A, Isoda K, Kondoh M, Kawase M, Kobasashi M, Tamesada M, Yagi K. Hepatoprotective effect of syringic acid and vanillic acid on concanavalin a-induced liver injury. Biol Pharm Bull 2009; 32: 1215-1219
    CrossrefPubMedGoogle Scholar
  • 36 Simons JM, Hart BA, Ip Vai Ching TR, Van Dijk H, Labadie RP. Metabolic activation of natural phenols into selective oxidative burst agonists by activated human neutrophils. Free Radic Biol Med 1990; 8: 251-258
    CrossrefPubMedGoogle Scholar
  • 37 Wong AP, Clark AL, Garnett EA, Acree M, Cohen SA, Ferry GD, Heyman MB. Use of complementary medicine in pediatric patients with inflammatory bowel disease: results from a multicenter survey. J Pediatr Gastroenterol Nutr 2009; 48: 55-60
    CrossrefPubMedGoogle Scholar
  • 38 Suskind DL, Wahbeh G, Burpee T, Cohen M, Christie D, Weber W. Tolerability of curcumin in pediatric inflammatory bowel disease: a forced-dose titration study. J Pediatr Gastroenterol Nutr 2013; 56: 277-279
    CrossrefPubMedGoogle Scholar
  • 39 Peters EA, Hiltermann JT, Stolk J. Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics. Free Radic Biol Med 2001; 31: 1442-1447
    CrossrefPubMedGoogle Scholar
  • 40 Sugimoto K, Hanai H, Tozawa K, Aoshi T, Uchijima M, Nagata T, Koide Y. Curcumin prevents and ameliorates trinitrobenzene sulfonic acid-induced colitis in mice. Gastroenterology 2002; 123: 1912-1922
    CrossrefPubMedGoogle Scholar
  • 41 Deguchi Y, Andoh A, Inatomi O, Yagi Y, Bamba S, Araki Y, Hata K, Tsujikawa T, Fujiyama Y. Curcumin prevents the development of dextran sulfate Sodium (DSS)-induced experimental colitis. Dig Dis Sci 2007; 52: 2993-2998
    CrossrefPubMedGoogle Scholar
  • 42 Billerey-Larmonier C, Uno JK, Larmonier N, Midura AJ, Timmermann B, Ghishan FK, Kiela PR. Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent. Inflamm Bowel Dis 2008; 14: 780-793
    CrossrefPubMedGoogle Scholar
  • 43 Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T. Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Anal Biochem 1983; 132: 345-352
    CrossrefPubMedGoogle Scholar
  • 44 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254
    CrossrefPubMedGoogle Scholar