Anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium-induced colitis of rats

AIM： To investigate the anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium （DSS）-induced colitis of rats. METHODS： Acute colitis was induced by giving 2% DSS orally in drinking water for 8 d. Twenty-six male rats were randomized into oxymatrine-treated group （group A, 10 rats）, DSS control （group B, 10 rats） and normal control （group C, 6 rats）. The rats in group A were injected muscularly with oxymatrine at the dosage of 63 mg/（kg·d） from d 1 to 11 and drank 2% DSS solution from d 4 to 11. The rats in group B were treated with 0.9% saline in an equal volume as group A and drank 2% DSS solution from d 4 to 11. The rats in group C were treated with 0.9% saline as group B from d 1 to 11 and drank water normally. Diarrhea and bloody stool as well as colonic histology were observed. The levels of serum tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were determined by ELISA, and nuclear factor-κB （NF-κB） activity and the expression of inter-cellular adhesion molecule-1 （ICAM-1） in colonic mucosa were detected by immunohistochemistry method. RESULTS： Compared with DSS control group, the inflammatory symptoms and histological damages of colonic mucosa in oxymatrine-treated group were significantly improved, the serum levels of TNF-α, IL-6, and the expression of NF-κB, ICAM-1 in colonic mucosa were significantly reduced. CONCLUSION： The fact that oxymatrine can reduce the serum levels of TNF-α, IL-6, and the expression of NF-κB and ICAM-1 in colonic mucosa in DSS-induced colitis of rats indicates that oxymatrine may ameliorate the colonic inflammation and thus alleviate diarrhea and bloody stool.

Evaluation of the effect of pyrrolidine dithiocarbamate in suppressing inflammation in mice with dextran sodium sulfate-induced colitis

AIM: To evaluate the effect of pyrrolidine dithio- carbamate (PDTC; an NF-κB inhibitor) administered at low (50 mg/kg) and high (100 mg/kg) doses in suppressing colitis in mice with dextran sodium sulfate (DSS)-induced colitis. METHODS: Mice were divided into a DSS-untreated group (normal group), DSS-treated control group, DSS+PDTC-treated groupⅠ(low-dose group), and DSS+PDTC-treated groupⅡ (high-dose group). In each group, the disease activity index score (DAI score), intestinal length, histological score, and the levels of activated NF-κB and inflammatory cytokines (IL-1β and TNF-α) in tissue were measured. RESULTS: The DSS+PDTC-treated groupⅡ exhibited suppression of shortening of intestinal length and reduction of DAI score. Activated NF-κB level and IL-1β and TNF-α levels were significantly lower in DSS+PDTC- treated groupⅡ. CONCLUSION: These findings suggest that PDTC is useful for the treatment of ulcerative colitis.

Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease

Inflammatory bowel disease(IBD),the most important being Crohn's disease and ulcerative colitis,results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract.Although the pathogenesis of IBD remains unclear,it is widely accepted that genetic,environmental,and immunological factors are involved.Recent studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative stresses.To investigate the etiology of IBD,animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for IBD.Several models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been described.In this manuscript,we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis(e.g.dextran sodium sulfate-,2,4,6-trinitrobenzene sulfonic acid-,oxazolone-,acetic acid-,and indomethacin-induced models).We also summarize some regulatory and pathogenic factors demonstrated by these models that can,hopefully,be exploited to develop future therapeutic strategies against IBD.

Calcitriol analog ZK191784 ameliorates acute and chronic dextran sodium sulfate-induced colitis by modulation of intestinal dendritic cell numbers and phenotype

AIM: To investigate the effects of ZK1916784, a low calcemic analog of calcitriol on intestinal inflammation. METHODS: Acute and chronic colitis was induced by dextran sodium sulfate (DSS) according to standard procedures. Mice were treated intraperitoneally with ZK1916784 or placebo and colonic inflammation was evaluated. Cytokine production by mesenterial lymph node (MLN) cells was measured by ELISA. Immunohistochemistry was performed to detect intestinal dendritic cells (DCs) within the colonic tissue, and the effect of the calcitriol analog on DCs was investigated. RESULTS: Treatment with ZK191784 resulted in significant amelioration of disease with a reduced histological score in acute and chronic intestinal inflammation. In animals with acute DSS colitis, down- regulation of colonic inflammation was associated with a dramatic reduction in the secretion of the proinflammatory cytokine interferon (IFN)-γ and a significant increase in intereleukin (IL)-10 by MLN cells. Similarly, in chronic colitis, IL-10 expression in colonic tissue increased 1.4-fold when mice were treated with ZK191784, whereas expression of the Th1-specific transcription factor T-beta decreased by 81.6%. Lower numbers of infiltrating activated CD11c+ DCs were found in the colon in ZK191784-treated mice with acute DSScolitis, and secretion of proinflammatory cytokines by primary mucosal DCs was inhibited in the presence of the calcitriol analog. CONCLUSION: The calcitriol analog ZK191784 demonstrated significant anti-inflammatory properties in experimental colitis that were at least partially mediated by the immunosuppressive effects of the derivate on mucosal DCs.