Kim Y S, Son M, Ko J I, Cho H, Yoo M, Kim W B, Song I S, Kim C Y
Department of Internal Medicine, Seoul National University, College of Medicine, Korea.
Arch Pharm Res. 1999 Aug;22(4):354-60. doi: 10.1007/BF02979057.
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.
炎症性肠病（IBD）是一种病因和发病机制不明的多因素疾病。DA - 6034，即7 - 羧甲基氧基 - 3'，4'，5 - 三甲氧基黄酮，是一种已知具有抗炎活性的合成类黄酮。本研究旨在评估DA - 6034在三种IBD实验动物模型中的口服治疗效果：两种大鼠化学诱导性IBD模型以及已知无需使用外源性药物即可发生自发性结肠炎的人类白细胞抗原（HLA）- B27转基因大鼠模型。通过向结肠内注入1.2 ml 4%的乙酸溶液诱导急性化学性结肠炎。在这些大鼠中，泼尼松龙（1 mg/kg）、柳氮磺胺吡啶（100 mg/kg）和DA - 6034（0.3至约3 mg/kg）每天口服给药两次，持续6天。此外，通过向结肠内给予50%乙醇中30 mg的三硝基苯磺酸（TNBS）诱导慢性化学性结肠炎，并将药物口服给药6天或20天。在化学诱导性IBD模型中，所有这些药物均降低了结肠炎的严重程度，特别是DA - 6034（3 mg/kg）在宏观病变评分方面显示出比其他药物更强的效果。在HLA - B27转基因大鼠中，DA - 6034（3 mg/kg）和泼尼松龙（0.5 mg/kg）每天口服给药两次，持续6周。与化学诱导性结肠炎模型相比，HLA - B27转基因大鼠仅表现出轻度结肠炎。DA - 6034改善了稀便并减少了微观损伤，这是该模型的重要指标。总之，DA - 6034的口服治疗减轻了所有三种IBD实验模型中结肠的宏观和组织学损伤，这表明DA - 6034可能是治疗IBD的一种有前景的药物。
