Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease.
Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034, 7-carboxymethyloxy-3', 4', 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD: two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3 to approximately 3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. 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, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.
Kim
Y S
YS
Department of Internal Medicine, Seoul National University, College of Medicine, Korea.
Son
M
M
Ko
J I
JI
Cho
H
H
Yoo
M
M
Kim
W B
WB
Song
I S
IS
Kim
C Y
CY
D019342:Acetic Acid; D000818:Animals; D030801:Animals, Genetically Modified; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy; D005419:Flavonoids / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D015796:HLA-B27 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011239:Prednisolone / Q000627:therapeutic use; D051381:Rats; D012460:Sulfasalazine / Q000627:therapeutic use; D014302:Trinitrobenzenesulfonic Acid; D015431:Weight Loss / Q000187:drug effects; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D005765:Gastrointestinal Agents; D015796:HLA-B27 Antigen; D001613:beta 2-Microglobulin; D012460:Sulfasalazine; D014302:Trinitrobenzenesulfonic Acid; D011239:Prednisolone; D019342:Acetic Acid; C121889:recoflavone