Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease

Abstract

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.

Salicylate-Based Anti-Inflammatory Drugs Inhibit the Early Lesion of Diabetic Retinopathy

“…Age-matched nondiabetic rats were set up each time as normal controls. The doses of aspirin and sodium salicylate were chosen according to the dose of aspirin previously reported by us, which has beneficial effects on diabetic retinopathy (5), while the dose of sulfasalazine was selected based on the dose used in studies of inflammation (32,33). Isolation of retinal vasculature.…”

Effects of Nanocrystalline Silver (NPI 32101) in a Rat Model of Ulcerative Colitis

“…The colon was excised between the ileocecal junction and the rectum, and opened longitudinally. After scoring of the consistency of the stool the colon was rinsed in normal saline and examined, and the thickness of the colonic wall and number and size of ulcers were scored [17][18][19]. Stool consistency was graded on a scale of 0-3: 0 = normal stool, well-formed pellets, rigid as normal; 1 = loose stool, formed pellet with moisture, soft stool staying in stool shape; 2 = loose stool, stools of abnormal form with much moisture, softer, shapeless stool; 3 = watery or bloody diarrhea.…”

“…Colitis was produced according to published methods [15][16][17]. Animals were anesthetized by intraperitoneal injection of 75 mg/kg ketamine plus 5 mg/kg xylazine.…”

A potent and selective inhibitor of group IIa secretory phospholipase A2 protects rats from TNBS-induced colitis

“…Sulfasalazine is widely used in the clinic for the treatment of mild or moderately active ulcerative colitis and Crohn's disease, and has been previously shown to be highly effective in the rat TNBS-induced colitis model [27][28][29][30]. The precise mechanism of action for sulfasalazine in IBD is not entirely understood, however it likely involves the inhibition of various pathways including eicosanoid, PAF, and interleukin-1 production by macrophages, immunoglobulin production by plasma cells, and formation of reactive oxygen species [31].…”