Shin, C.Y.; Son, M.; Lee, I.K.; Jung, M.Y.; Kim, D.S.; Kim, S.H.; Yoo, M.; Song, I.S.; Kim, W.B.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA63
Academic Journal
DA-6034, 7-carboxymethyloxy-3', 4', 5-trimethoxy flavones, is a synthetic flavonoid known to possess anti-inflammatory activity. In this study, we evaluated the oral therapeutic effect of DA-6034 in four experimental animal models of inflammatory bowel disease (IBD). In acetic acid (4%) induced IBD rat models, prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (3 mg/kg) significantly reduced the severity of colitis. Especially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score, tn trinitrobenzene sulfonic acid (TNBS) induced IBD rat models, prednisolone (3.0mg/kg) or DA-6034 (3.0mg/kg) inhibited the colonic mucosal damage. DA-6034 (3.0mg/kg) significantly decreased the prostaglandin E[sub 2] levels, leukotriene B[sub 4] levels and myeloperoxidase activity at 7 day as compared with control. In Dextran sulfate sodium (DSS)-induced colitis mice, DA-6034 reduced the colitis index-diarrhea incidence, body weight, mortality, and intestinal gross lesion. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 mg/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, DA-6034 attenuated the macroscopic and histological damages of the colon in all four experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD and we will set out clinical Phase I study of DA-6034 in next year.


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