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새로운 플라보노이드 유도체인 DA-6034의 TNBS 유발성 염증성대장염 모델에서의 치료효과
손미원(Mi Won Son),고준일(Jun Il Ko),김희기(Hee Kee kim),장동경(Dong Kyung Jang),유무희(Moo Hi You),김원배(Won Bae Kim),이강춘(Kang Chun Lee),송인성(In Sung Song) 대한약학회 1998 약학회지 Vol.42 No.2
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 B4 (LTB4) 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 LTB4 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 LTB4 synthesis and MPO inhibition.
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