YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Effect of DA-6034, a New Flavonoid Derivative, on TNBS-Induced Colitis in the Rats

새로운 플라보노이드 유도체인 DA-6034의 TNBS 유발성 염증성대장염 모델에서의 치료효과

  • Son, Mi-Won (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Ko, Jun-Il (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Kim, Hee-Kee (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Jang, Dong-Kyung (Department of Internal Medicine, Lever Research, College of Medicine, Seoul National University) ;
  • Yoo, Moo-Hi (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Kim, Won-Bae (Research Laboratories, Dong-A Pharm. Co. Ltd.) ;
  • Lee, Kang-Chun (College of Pharmacy, Sung Kyun Kwan University) ;
  • Song, In-Sung (Department of Internal Medicine, Lever Research, College of Medicine, Seoul National University)
  • Published : 1998.04.01
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Abstract

The efficacy of DA-6034, a new flavonoid derivative, was investigated in comparison with sulfasalazine in a trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Under light anaesthesia with ether, rats were subjected to intracolonic administration of 30mg TNBS in 50% ethanol (0.5ml) and were then sacrificed at 7 or 21 days after colitis induction. The TNBS control group (the saline treated colitic rat) exhibited ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections. Moreover, an increase in colonic myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and an elevated colonic leukotriene $B_4$ ($LTB_4$) level were observed. The colitic rats received DA6034 (0.3-30mg/kg) or sulfasalazine (50-100mg/kg), prednisolone (0.3-3mg/kg) after the induction of colitis until they were sacrificed. Oral treatment with DA-6034 resulted in significant reductions of macroscopic colonic damage, colonic inflammation. DA6034 had a more potent effect than sulfasalazine and prednisolone on macroscopic colonic damage, while it has similar effect with prednisolone on the reduction of colonic $LTB_4$ synthesis and MPO activity. This study show, therefore, that DA-6034 is effective m attenuating the colonic lesion in an TNBS-induced colitis model. Furthermore, the results suggest that the effect of DA-6034 is partially related to its action on $LTB_4$ synthesis and MPO inhibition.

Keywords

References

  1. Med. J. Aus. v.160 Inflammatory bowel disease-its history, current status and outlook Andrews, J.;Goulston, K.
  2. Am. J. Med. v.100 The basis of current and future therapy for inflammatory bowel disease Elson, C.O.
  3. Semin. Gastrointest. Dis. v.5 Inflammatory bowel disease:diagnosis and treatment Israel, E.J.;Kleinman, R.E.
  4. 대한내과학회 추계학술대회지 한국인의 염증성 장질환 최규완
  5. World Rev. Nutri. Diet. v.24 The flavonoids. A class of semi-essential food components: Their role in human nutrition Kuhnau, J.
  6. The flavonoids: Advances in research The impact of plant flavonoids on mammalian biology:implecations for immunity, inflammation and cancer Middleton, E.;Kandaswami, C.;Harbone, J.B.(Ed.)
  7. Plant flavonoids in biology and medicine Ⅱ: Biochemical, Cellular and medicinal properties Flavonoids in the environment: Structure-activity relationship Harborne, J.B.;Cody, V.(ed.);Middleton, E.(ed.);Harbone, J.B.(ed.);Beretz, A.(ed.)
  8. Prog. Clin. Biol. Res. v.280 Role pf flavonoids in the oxygen-free radical modulation of the immune response Pignal, B.;Etienne, A.;Brastes de Paulet, A.;Deby, C.;Mencia-Huerta, J.M.;Braquet, P.
  9. Plant flavonoids in biology and medicine Ⅱ:Biochemical, cellular and medicinal properties Flavonoids and arachidonic acid metabolism Welton, A.F.;Hurley, J.;Will, P.;Cody, V.(ed.);Middleton, E.(ed.);Harbone, J.B.(ed.);Beretz, A.(ed.)
  10. In Plant flavonoids in biology and medicine Ⅱ: Biochemical, cellular and medicinal properties Effect of lfavonoid compounds on the immune response Berg, P.A.;Daniel, P.T.;Cody, V.(ed.);Middleton, E.(ed.);Harone, J.B.(Ed.);Beretz, A.(ed.)
  11. Arzneim. Forch. v.37(Ⅱ) Effect of chronic treatment with a purified flavonoids fraction on inflammatory graniloma in the rat Damon, B.M.;Flandre, O.;Michel, F.;Perdrix, L.;Labrid, C.;Crastes dePaulet A.
  12. Biochem. Pharmacol. v.43 no.6 Effects of flavonoids on immune and inflammatory cell functions Elliott, M.J.;Chithan, K.
  13. J. pharmacol. Exp. Ther. v.278 Effect of quercitrin on acute and chronic experimential colitis in the rat Fermin, L.H.;Julio, G.;Jose, A.R.;Antonio, Z.
  14. Am. J. Pathol. v.147 no.2 Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression Gerritsen, M.E.;Carley, W.W.;Ranges, G.E.;Shen, C.P.;Phan, S.A.;Ligon, G.F.;Pery, C.A.
  15. J. Immunopharmac v.13 In vitro immunopharmacological profile of the plant Flavonoids baohuoside-1 Li, S.Y.;The, B.S.;Seow, W.K.;Liu, Y.L.;Thong, Y.H.
  16. Gastroenterology v.109 Experimental models of inflammatory bowel disease Elson, C.O.;Sartor, R.B.;Tennyson, G.S.;Roddell, R.H.
  17. Gastrenterolgy v.96 Hapten-induced model of chromic inflammation and ulceration in the rat colon Morris, G.P.;Beck, P.L.;Herridge, W.;Szewczuk. M.R.;Wallace, J.L.
  18. Dig, Endosc. v.5 Endoscopic scoring system for experimental colitis with trinitrobenzene-sulfonic acid in rats Shibata, Y.;Ashida, TR.;Ayabe, T.;Tarushi, M.;Yokota;Okuyama, S.;Saitoh, Y.;Okamura, K.;Namiki, M.
  19. 대한내과학회지 v.47 흰쥐에서 TNBS로 유발된 염증성대장염의 병태생리에 관한 연구 김나영;김재준;송인성;김정룡;김우호
  20. Can. J. Physiol. Pharmacol. v.66 Release of platelet-activating factor (PAF) and accelerated healing induced by a PAF antagonist in an animal model of chronic colitis Wallace, J.L.
  21. J. Invest. Dermatol. v.78 Measurement of cutaneous inflammation:estimation of neutrophil content with an enzyme marker Bradley, P.P.;Priebat, D.A.;Christensen, R.D.;Rothstein, G.
  22. Gastroenterology v.87 Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity Krawisz, J.E.;Sharonl, P.;Stenson, W.F.
  23. Br. J. Pharmacol. v.94 The effect of anti-inflammatory drugs on eicosanoid formation in a chronic model of inflammatory bowel disease in the rat Boughton-Smith, N.K.;Wallace, J.L.;Morris, G.P.;Whittle, B.J.R.
  24. Inflammatory bowel disease from bench to bedside Eicosanoids Wallace, J.L.
  25. New Engl J Med v.325 Inflammatory bowel disease Podolsky, D.K.
  26. Gastroenterology v.102 A comparative study of two models of experimental colitis in rats Yamada, T.;Marshall, S.;Specian, R.D.;Grisham, M.B.
  27. Gastroenterology v.86 Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease Sharon, P.;Stenson, W.F.
  28. Gastroenterology v.96 Inhibition of leukotriene synthesis markedly accelerates healing in a rat model of inflammatory bowel disease Wallace, J.L.;MacNaughton, W.K.;Morris, G.P.;Beck, P.L.
  29. Eur Clin Pharmacol. v.26 Soybean lipoxugenase inhibition studies with sulphasalazine metabolites N-acetylamonisalicyclic acid, 5-aminosalicyclic acid and sulfapyridine Allgayer, H.;Eisenberg, J.;Paumgartnet, G.
  30. Agents Actions v.38 The properties of A-69412 A small hydrophilic 5-lipoxygenase inhibitor Bell, R.L.;Bouska, J.;Young, P.R.;Lanni, C.;Machinist, J.;Malo, P.E.;Summers, J.B.;Brooks, D.W.;Carter, G.W.
  31. Biochem. Pharmacol. v.34 A novel biologically actove seleno organic compound-Ⅴ: Inhibition by Ebselen(PZ51) of rat peritoneal neutrophil lipoxygenase Safayhi, H.;Tiegs, G.;Wendel, A.
  32. Agents Actions v.39 Effects of zukeuton, a new 5-lipoxygebase inhibitor in experimentally induces colitis in rats Zingarelli, B.;Squadrito, F.;Graziani, P.;Camerini, R.;Caputi, A.P.
  33. Blood v.58 Leukotriene B4 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence Plamblas, J.;Malmsten, C.;Uden, A.;Rdmak, O.;Engstrot, L.;Samuelsson, B.
  34. Inflammation v.7 Aggregation, chemotzxis and chemiluminescence of canine granulocytes Redl, H.;Flynn, P.;Lamche, H.;Schiesser, A.;Schlag, G.;Hammerschmidt, D.
  35. Nature Lond v.286 Leukotriene B4, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes Ford-Hutchison, A.W.;Brey, M.;Doig, M.;Shireley, M.;Smith, M.
  36. Proc. Natl. Acad Sci. U.S.A. Leukotiene $B_4$ action on endothelium mediates augmented neutrophil/endothelial adhesion Hoover, R.;Karnovsky, M.;Austin, K.F.;Corey, E.;Lewis, R.
  37. Dig Dis Sci v.32 Chemotactic activity in inflammatory bowel disease. Role of leukotriene $B_4$ Lobos, E.A.;Sharon, P.;Stenson, W.F.
  38. The leukotrienes. their biological significance Leukotriene $B_4$ Biological properties and regulation of biosynthsis Ford-Hutchison, A.W.;Evans, J.F.;Piper PJ(ed.)
  39. Inflammation v.6 Increase in vascular permeability induced by leukotriene $B_4$ and the role of polymorphonuclear leukocytes Bjork, J.;Hedqvist, P.;Arfors, K.E.
  40. Digestion v.14 Exsperimental colitis MacPherson, B.;Pfeiffer, C.J.
  41. Gastroenterology v.75 Role of prostaglandins in ulcerative solotos:Enhanced production during active disease and inhibition by sulfasalazine Sharon, P.;Ligumsky, M.;Rachmilewitz, D.;Zor, U.
  42. Gastroenterology v.91 Effects of topical 5-aminosalicyclic acid and prednisolone on prostaglandin $E_2$ and leukotriene $B_4$ levels determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis Lauristsen, K.;Laursen, L.S.;Bukhave, K.;Rask-Madsen, J.
  43. Br. J. Pharmacol. v.94 The effect of antiinflammatory drugs on eicosanoid formation in a chronic model of inflammatory bowel disease in the rat Boughton-Smith, N.K.;Wallace, J.L.;Morris, G.P.;Whittle, B.J.R.
  44. Gut v.24 Prostanoid synthesis by ciltures intestinal epithelial and mononuclear cells in inflammatory bowel disease Zifroni, A.;Treves, A.J.;Sachar, D.B.;Rachmilewitz, D.
  45. Gastroenterology v.80 Temporal relationship between cyclooxygenase inhibition measured as prostacyclin biosynthesis and gastointestinal damage induced by indomethacin in the rat Whittle, B.J.R.
  46. Gastroenterology v.98 Misoprostol provides a colonic mucosal effect during acetic acid-induced colitis in rats Fedorak, R.N.;Empey, L.R.;MacArthur, C.;Jewell, L.D.