Immunopathological mechanism of TNBS-induced inflammatory bowel disease in mice / 中华微生物学和免疫学杂志

Objective To study the possible pathogenesis of TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced inflammatory bowel disease (IBD) in a mouse model by analyzing histological changes in colon and the expression of cytokines and transcription factor RORγt related to T cell subsets in mesenteric lymph nodes.Methods Female BALB/c mice aged 6-8 weeks were randomly grouped into two groups: IBD model and normal control groups.The mouse model of IBD was established by treating mice with 200 μl of 5％ TNBS/50％ ethanol solution (1∶1) through intestinal instillation, while the mice in the normal control group were instilled with PBS.Pathological changes in colon samples of mice were observed.Real-time PCR was performed to detect the dynamic expression of Th1 cytokines (IL-2, IFN-γ and IL-12p40), Th2 cytokine (IL-4), Treg-related cytokine (IL-10), Th17 cell-related cytokines (IL-17, IL-21 and IL-23) and transcription factor RORγt in mesenteric lymph nodes.Results The mice in the model group begun to show abnormal vital signs such as diarrhea, loss of weight and reduced activity, and mild hyperemia of intestinal mucosa and edema from the third day after modeling.Slight lesions were observed in histological slices of colon tissues stained with hematoxylin and eosin (HE).The expression of IL-21, IL-23 and IL-17 at mRNA level were significantly increased, while the expression of other cytokines showed no significant change.On the sixth day after modeling, many pathological symptoms and intestinal mucosal lesions were aggravated, and marked infiltration of inflammatory cells was observed in histological slices of colon tissues, which indicated that the IBD model was successfully induced by TNBS.Compared with the control group, the IBD model group showed significantly enhanced expression of IL-2, IL-12p40 and IL-10 in mesenteric lymph nodes at mRNA level on the sixth day after modeling.Although the expression of IL-21, IL-23, IL-17 and RORγt at mRNA level on the sixth day were down-regulated to different extent as compared with those on the third day, they were still significantly higher than those of the control group.Conclusion Th17 cell-related cytokines play an important role in the early stage of TNBS-induced IBD.With the progression of the disease, both Th1 and Th17 cells are involved in the immunopathological injury of colon tissues.

Analysis of the co-expression of miRNA and mRNA in rats with TNBS/ethanol induced ulcerative colitis / 中华微生物学和免疫学杂志

Objective To investigate the correlations between miRNA and mRNA ( the regulatory effects of miRNA) in a rat model of trinitro-benzene-sulfonic acid (TNBS)/ethanol induced ulcerative colitis ( UC) .Methods TNBS and ethanol were used to induce the development of UC in rats .After the modeling procedure and oral administration of normal saline ( NS) for 14 days, rats from the control and model groups were dissected to collect the samples of colonic mucosa .General and histological evaluations were performed to validate the modeling of UC .The expression of miRNA was profiled using miRNA microarray .The target miRNAs that were closely related to the pathogenesis of UC were selected out according to the results of mi -croarray and related literatures .RT-PCR was performed to verify the differentially expressed miRNAs .The mirWalk database was used to predict the target genes of miRNAs .In order to verify whether the predicted results were in accordance with the actual results , the microarray technology was used for mRNA expression profiling .The genes that showed interactions with those miRNAs were screened out .The David database was used for gene annotation .An interaction net between miRNA and mRNA was formed .Results General and histological manifestation of colon tissue samples from the model group were in accordance with the features of UC.Sixty-eight miRNAs were identified to be differentially expressed in rats from the model group and the control group (fold change>2, P7).Six candidate miRNAs were selected as hav-ing close relations to the pathogenesis of UC referring to reported literatures , the expression of which was checked and verified by real-time polymerase chain reaction (PCR).Compared with the control group, 4 miRNAs (miR-146a-5p, miR-146b-5p, miR-126a-3p and miR-21-5p) were up-regulated (P<0.01, P<0.05) and 2 miRNAs (miR-200b-3p and miR-145-5p) were down-regulated (P<0.01) in rats with TNBS/ethanol induced UC.Four mRNAs (IL-6, Ccl5, Mapk3 and Smad7) that interacted with the 6 miRNAs were identified based on the results of target gene prediction of the above 6 miRNAs and gene expression pro-filing.The David database was used to annotate the interactions for elucidating their significance in the path -ogenesis of UC .Conclusion A miRNA can regulate many signaling pathways and a signaling pathway can also be regulated by many miRNAs .Therefore , simply inhibiting certain pathways may not radically stop the process of inflammation .Studying the functions of miRNAs and elucidating the correlations between miRNA and mRNA might fundamentally inhibit the development of UC .

A Review on Chemical-Induced Inflammatory Bowel Disease Models in Rodents

Ulcerative colitis and Crohn's disease are a set of chronic, idiopathic, immunological and relapsing inflammatory disorders of the gastrointestinal tract referred to as inflammatory bowel disorder (IBD). Although the etiological factors involved in the perpetuation of IBD remain uncertain, development of various animal models provides new insights to unveil the onset and the progression of IBD. Various chemical-induced colitis models are widely used on laboratory scale. Furthermore, these models closely mimic morphological, histopathological and symptomatical features of human IBD. Among the chemical-induced colitis models, trinitrobenzene sulfonic acid (TNBS)-induced colitis, oxazolone induced-colitis and dextran sulphate sodium (DSS)-induced colitis models are most widely used. TNBS elicits Th-1 driven immune response, whereas oxazolone predominantly exhibits immune response of Th-2 phenotype. DSS-induced colitis model also induces changes in Th-1/Th-2 cytokine profile. The present review discusses the methodology and rationale of using various chemical-induced colitis models for evaluating the pathogenesis of IBD.

Changes of colonic endocrine cells in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis / 대한수의학회지

In this study, immunohistochemistry was used to examine the changes in the density of colonic endocrine cells - argyrophil and argentaffin cells, chromogranin A (CGA), serotonin, somatostatin and glucagon-containing cells in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Ulcerative colitis was induced by the instillation of 10 mg of TNBS into the colonic lumen through the anus. To confirm the inducement of ulcerative colitis, the macroscopic and microscopic scores as well as the colonic myeloperoxidase (MPO) activities were monitored for 8 days after TNBS instillation in the colonic lumens. In addition, the number of argyrophil and argentaffin cells, CGA, serotonin, somatostatin and glucagon-immunoreactive cells were counted in the colonic mucosa, respectively. After TNBS instillation into the lumen of the colon from the anus in rats, increases in macroscopic and microscopic scores in the colon tissues were observed along with increases in the colonic MPO activities. Therefore, ulcerative colitis was relatively well induced by the TNBS instillations. Marked decreases in the number of colonic endocrine cells were detected in the TNBS-treated animal compared to the sham control. These results suggest that colonic endocrine cells were also disrupted by TNBS-induced ulcerative colitis.

Probiotic therapy using live combined bifidobacterium, lactobacillus and enterococcus for experimental colitis in rats model / 中华内科杂志

Objective To evaluate the effect of live combined bifidobacterium, lactobacillus and enterococcus capsules for colitis in rats induced by trinitrobenzenesulfonic acid (TNBS), so as to explore a new therapy for inflammatory bowel diseases (IBD). Methods 50 female adult Sprague-Dawley rats were randomly divided into 5 groups i. e. normal control group(G1) ,untreated TNBS-induced colitis(G2) ,TNBS-induced colitis treated with live combined bifidobacterium, lactobacillus and enterococcus (G3), TNBS-induced colitis treated with olsalazine (G4) and TNBS-induced colitis treated with both live combined bifidobacterium, lactobacillus and enterococcus and olsalazine at the same dose and duration (G5). Each group received its respective treatment. Serum levels of C-reactive protein (CRP), TNFα and IL-10 were measured with ELISA, colonic myeloperoxidase (MPO) activity was determined with spectrophotometric method, histopathologic picture of the colon of each rat was studied with microscope and colonic mucosa damage index(CMDI) was recorded. Results Serum CRP,TNFα,IL-10,CMDI and colonic MPO in G1 were significantly lower than those in G2 (P < 0. 001) with normal colonic architecture. G2 exhibited the most severe colonic inflammation and the highest levels of CRP,TNFα, IL-10, CMDI and colonic MPO with stastical significance. Treatment groups G3, G4 and G5 showed more obvious colonic inflammatory remission and lower levels of serum CRP,TNFα , IL-10 and colonic MPO, G5 being most notable when compared to G2 with stastical significance. In G2, serum levels of CRP, TNFα, IL-10 and colonic MPO activity each correlated positively with CMDI (P < 0. 001). Conclusions Live combined bifidobacterium, lactobacillus and enterococcus can effectively ameliorate colitis in rats induced by TNBS; the underlying mechanism may possibly be associated with the serum levels of cytokines.

Saccharomyces boulardii Reduced Intestinal Inflammation in Mice Model of 2,4,6-trinitrobencene Sulfonic Acid Induced Colitis: Based on Microarray / 대한소화기학회지

BACKGROUND/AIMS: Saccharomyces boulardii has been reported to be beneficial in the treatment of inflammatory bowel disease. The aim of this work was to evaluate the effect of S. boulardii in a mice model of 2,4,6-trinitrobencene sulfonic acid (TNBS) induced colitis and analyze the expression of genes in S. boulardii treated mice by microarray. METHODS: BALB/c mice received TNBS or TNBS and S. boulardii treatment for 4 days. Microarray was performed on total mRNA form colon, and histologic evaluation was also performed. RESULTS: In mice treated with S. boulardii, the histological appearance and mortality rate were significantly restored compared with rats receiving only TNBS. Among 330 genes which were altered by both S. boulardii and TNBS (>2 folds), 193 genes were down-regulated by S. boulardii in microarray. Most of genes which were down-regulated by S. bouardii were functionally classified as inflammatory and immune response related genes. CONCLUSIONS: S. boulardii may reduce colonic inflammation along with regulation of inflammatory and immune responsive genes in TNBS-induced colitis.

Therapeutic Effect of Allogenic Bone Marrow Transplantation in Acute TNBS-induced Colitis / 대한소화기학회지

BACKGROUND/AIMS: Bone marrow-derived cells (BMDC) contribute to tissue maintenance under many kinds of pathologic conditions. We carried out a study to see how BMDC play a role in the treatment of experimental murine colitis. METHODS: We divided the animals into 3 groups and treated them with 50% ethanol (control group), 2,4,6-trinitrobenzene sulfinic acid colitis (TNBS group), and TNBS+bone marrow transplant (BMT group). To induce colitis, TNBS (5.0 mg/mouse) dissolved in 50% ethanol was injected into anus weekly for two weeks. Bone marrow transplantations were performed using bone marrow of male transgenic mouse (donor) with green fluoresence protein (GFP) into female wild type mouse (recipient) three weeks before TNBS instillation. All animals were sacrificed, and colons were extracted one week after the last TNBS instillation. We measured microscopic scores of mucosal injury and investigated the GFP expression for bone marrow engraftment. The immunostaining of vimentin and alpha-smooth muscle actin (alpha-SMA) for myofibroblasts was performed. RESULTS: The score of mucosal injury in the TNBS group was much more severe than those in control, and reduced significantly by BMT (p<0.05). GFP-positive cells were almost deposited in pericryptal niche of BMT group but not at all in both control and TNBS group. Most of myofibroblasts stained with both vimentin and SMA also infiltrated into pericryptal niche. But, the number of myofibroblasts stained with vimentin and SMA in both control and TNBS group was smaller than that in BMT group. CONCLUSIONS: BMDC deposited on pericryptal niche might have a significant role in repairing acute experimental murine colitis.

Granulocyte Colony Stimulating Factor (G-CSF) Attenuates 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)-induced Colitis in Mice

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is known as a cytokine central to the hematopoiesis of blood cells and to modulate their cellular functions. Besides granulocytes and their precursors, monocytes/macrophages and endothelial cells are direct target cells of G-CSF action. G-CSF influences immune cells in an anti-inflammatory way. METHODS: To evaluate whether G-CSF has a potential for preventing or ameliorating diseases characterized by mucosal inflammation, we used a mouse model with trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. To the mice model G-CSF was administrated daily by intraperitoneal injection. Macroscopic evaluation and immunohistochemical analysis of colonic tissues were performed. RESULTS: Recombinant human G-CSF significantly inhibited LPS-induced TNF-alpha mRNA expression in THP-1 cells. As for in vivo relevance, G-CSF dramatically reduced the weight loss of mice, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, G-CSF suppressed the expression of tumor necrosis factor-alpha, interleukin-1beta, and intercellular adhesion molecule-1 in TNBS colitis. CONCLUSION: Current results demonstrate that G-CSF may be an effective agent for the treatment of diseases characterized by mucosal inflammation.

HO-1 Reduces the Severity of Trinitrobenzene Sulfonic Acid-induced Colitis through Suppression of NF-kappaB Activation / 대한해부학회지

Heme oxygenage-1 (HO-1), rate-limiting enzyme in heme catabolism, has been known to show strong immune-suppressive properties although its mechanisms are not completely understood. In this study, the authors investigated the mechanism whereby HO-1 has anti-inflammatory properties in trinitrobenzene sulfonic acid (TNBS)-induced colitis. Body weight was evaluated and tumor necrosis factor (TNF-alpha), interleukin (IL)-1beta and intercellular adhesion molecule-1 (ICAM-1) were detected by immunohistochemical staining. Heme oxygenase-1 (HO-1) expression was analyzed by Western blot and immunohistochemical staining. In a mouse model, HO-1 inducer, cobalt-protoporphyrin IX (CoPPIX) administration significantly improved the clinical symptoms and histopathologic changes of trinitrobenzene sulfonic acid (TNBS) colitis as well as significantly suppressed the expression of several inflammatory mediators such as TNF-alpha, IL-1beta and ICAM-1 induced by TNBS. Furthermore CoPPIX suppressed NF-kappaB activation that is an important transcription factor for expression of proinflammatory mediators in TNBS colitis while HO-1 activity inhibitor, zinc protoporphyrin IX (ZnPPIX) reversed the protective effects of CoPPIX in TNBS colitis. Collectively, these results suggest that HO-1 exerts anti-inflammatory effects by down-regulation of NF-kappaB activity via induction of HO-1 during pathogenesis of TNBS-induced colitis.

Rebamipide Protects TNBS Induced Colonic Damage Through Down-regulation of NF-kappaB Activation and Induction of Heme Oxygenase -1 Expression / 대한해부학회지

Crohn 's disease is characterized by a chronic relapsing inflammation of the bowel in which pro-inflammatory cytokines play an important role. Rebamipide is an anti-gastric ulcer drug with anti-inflammatory properties in vivo and in vitro. The effects of rebamipide on Crohn 's disease have not been carefully evaluated. This study investigated the potential of rebamipide to protect Crohn 's disease using a murine model of colitis induced by trinitrobenzene sulfonic acid (TNBS). Rebamipide dramatically improved histopathological symptom involving myeloperoxidase (MPO)activation and increase of microscopic damage score in TNBS induced colitis. Rebamipide suppressed IL-8 secretion, ICAM-1 induction and nuclear factor-kappaB (NF-kappaB) activation by TNF-alpha and induced heme oxygenase-1(HO-1)in HT-29 cells. HO-1 inducer cobalt protoporphyrin IX (CoPPIX)suppressed NF-kappaB activation by TNF-alpha in HT-29 cells like rebamipide, and mimicked the protective effects of rebamipide on TNBS induced colitis. This suggests that rebamipide exerts anti-inflammatory effects by down-regulating NF-kappaB activity via inducting HO-1 expression. In conclusion, this study suggests that rebamipide represents a potential therapeutic agent and HO-1 is an important therapeutic target for the treatment of Crohn's disease.

Rebamipide Protects Colonic Damage Induced by Trinitrobenzene Sulfonic Acid (TNBS) via Down-Regulation of TNF-alpha IL-1beta and ICAM-1 / 대한해부학회지

During inflammation of the colon, cells of the gut mucosa produce or express numerous inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), and intercellular adhesion molecule 1 (ICAM-1). These mediators have been implicated as contributory factors to the inflammatory process, which results in colitis during inflammatory bowel disease (IBD). Rebamipide is an anti-gastric ulcer drug with anti-inflammatory properties in vivo and in vitro. The effects of Rebamipide on IBD have not been largely evaluated. Therefore, this study investigated the potential of Rebamipide to regulate the production of inflammatory mediators such as TNF-alpha, IL-1beta, and ICAM-1. Mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis (IBD animal model), were treated intrarectally with 2 mM Rebamipide. Body weight, macro- and micro-histological scores, and activity were evaluated. As an index of tissue edema, the thickness of the colonic wall was measured between the serosal surface and the luminal surface of the mucosa. TNF-alpha, IL-1 beta, and ICAM-1 were detected by immunohistochemical staining. Rebamipide treatment of mice exhibiting TNBS-induced colitis dramatically improved the clinical and histopathological findings of inflammation. In addition, Rebamipide suppressed TNF-alpha, IL-1 beta, and ICAM-1 expression in TNBS-treated animals. Taken together, these findings suggest that Rebamipide is a potential therapeutic agent for treating patients with IBD.

Gliotoxin Protects Against TNBS-induced Colitis Via Down-regulation of NF B Activation / 대한해부학회지

During inflammation of the colon, cells of the gut mucosa express numerous inflammatory mediators including interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta(IL-1beta). These cytokines have been implicated as contributing factors in the inflammatory process, which may result in colitis during inflammatory bowel disease (IBD). Gliotoxin is a fungal metabolite of an epipolythiodioxopiperazine analogue with immunosup-pressive properties in vivo and in vitro, but the effects of gliotoxin on IBD have not been largely evaluated. Therefore, this study evaluated the potential of gliotoxin to protect against TNBS-induced colitis. One microgram of gliotoxin in 100microliter of vehicle was intra-rectally administered into mice exhibiting trinitrobenzene sulfonic acid (TNBS)-induced colitis. IL-8 secretion was measured using an enzyme-linked immu-nosorbent assay (ELISA), myeloperoxidase (MPO) activity was evaluated spectrophotometically, and IkappaB degradation was analyzed on Western blots. Gliotoxin treatment of mice bearing TNBS-induced colitis improved macro-and micro-pathological findings and dramatically decreased MPO activity, a marker of leukocyte infiltration. Furthermore, gliotoxin decreased IkappaB degradation and IL-8 induction caused by TNF-alpha or IL-1beta in HT-29 cells. These findings suggest that gliotoxin partially protects against TNBS-induced colitis through the sup-pression of IL-8 induction and IkappaB degradation by inflammatory mediators such as TNF-alpha or IL-1beta.

Effects of rheum tanguticum polysaccharides on ulcerative colitis induced by TNBS in mice / 中国临床药理学与治疗学

AIM: To explore the effects of rheum tanguticum polysaccharides(RTP) on TNBS-induced colitis in mice and its probable mechanisms.METHODS: Mice colitis model was induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS).The mice were randomly divided into 5 groups,normal group,model group,RTP-100,200 and 400 group.The macroscopical and histological changes of the colon were evaluated and the cytokines IL-8,IL-10,TNF-?and IL-4 produced by splenocyts were analyzed with ELISA.RESULTS: Compared with the model group,both symptoms and the lesions of colonic mucosa of RTP-200 and 400 group were slighter on ulcerative colitis induced by TNBS in mice. Furthermore,the expressions of TNF-?and IL-8 in colon tissue of mice with TNBS-induced colitis were higher and the IL-10 and IL-4 were lower than that of normal control(P

Effect of 5-aminosalicylic acid on antioxidant mechanism and attenuation of proinflammatory cytokines in trinitrobenzene sulfonic acid-induced colitis in rats / 中国临床药理学与治疗学

AIM: To investigate the effect and mechanism of 5-aminosalicylic acid (5-ASA) in topical treatment on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. METHODS: Colitis was induced by intracolonic administration of TNBS and was treated with 5-ASA at the dose of 100 mg?kg -1 for 2 weeks. Normal control group was administrated with normal saline and TNBS control group was treated with TNBS, not with 5-ASA. Macroscopic damage, histological changes and myeloperoxidase (MPO) activity were evaluated. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in colonic mucosa were detected by kits. The expression of interleukin-1? (IL-1?) and tumor necrosis factor-? (TNF-?) mRNAs in colonic mucosa was determined by a reverse transcription and polymerase chain reaction method. RESULTS: Compared with TNBS control group, the macroscopic and histological changes and MPO activity in 5-ASA treated groups were improved. SOD activity was increased and the level of MDA in colonic mucosa was reduced significantly. The expression of IL-1? and TNF-? mRNAs in colonic mucosa was also decreased significantly. CONCLUSION: 5-ASA enema can significantly ameliorate TNBS-induced colitis in rats via antioxidant mechanism and attenuation of proinflammatory cytokine expression.

CoPPIX Protects against TNBS Induced Colitis Through HO-1 Induction / 대한해부학회지

Crohn`s disease is a severe chronic inflammation that is treated mainly by immunosuppression, which often has serious side effects. There is a need to develop new drugs for treating this disease that have few side effects. Heme oxygenase-1 (HO-1) has immunosuppressive properties, but the mechanism of its anti-inflammatory actions is unclear. We investigated the protective effects of HO-1 on trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. An HO-1 inducer, cobalt protoporphyrin IX (CoPPIX), dramatically improved the clinical and histopathological symptoms in TNBS-induced colitis. CoPPIX suppressed tumor necrosis factor-alpha and interleukin-1beta expression and down-regulated the nuclear transcription factor kappa B activity caused by TNBS. The vehicle copper protoporphyrin IX (CuPPIX) failed to duplicate the protective effects seen with CoPPIX. Moreover, an inhibitor of HO-1 activity-zinc protoporphyrin IX-reversed the protective effects of CoPPIX on TNBS-induced colitis. In conclusion CoPPIX protects against TNBS-induced colonic damage by inducing HO-1, which might be an important target in the treatment of Crohn`s disease.

The Change of CD_4~+CD_(25)~+ and CD_8~+CD_(28)~- T Regulatory Cells in Rats with the Experimental Colitis Induced by TNBS / 中国医师杂志

Objective To explore the change and function of CD 4 +CD 25 + and CD 8 +CD 28 -T regulatory cells in peripherel blood monocyte cell (PBMC), spleen and colon in rat experimental colitis induced by trinitrobenzenesulfonic acid (TNBS) . Methods The rat model of experimental colitis was established by enema with TNBS/ethanol. The proportion of CD 4 +CD 25 + and CD 8 +CD 28 - T regulatory cells in PBMC, spleen and colon was determined by flow cytometry at the first and third weeks after establishing model, respectively. Results The model of experimental colitis in rats was successfully established(n=15). Compared with control group, the proportion of CD 8 +CD 28 -T regulatory cells significantly increased in colon at the first week after establishing model [(12.7?5.4)% versus(3.87?3.7)%,P

The Effect of DA-6034, Eupatilin Derivatives of Flavonoids, on the Rats with Trinitrobenzene Sulfonic Acid (TNBS) - Induced Colitis / 대한내과학회지

OBJECTIVE: In traditional medicine, Artemisia capillaris has been used for treatment of chronic diarrhea. Previously we found Artemisia capillaris had an effect on rats with TNBS-induced colitis. Eupatilin, a kind of flavonoids, may be a probable effective component. To evaluate the effect of a eupatilin derivative compound DA-6034 on the rat with TNBS-induced colitis, we perfomed this study. METHODS: Colitis was induced with 1ml of 50 mg/ml TNBS mixed with 60 % ethanol (vol/vol) in Sprague- Dawley rats. From the next day, 1ml methylcellulose, 1 mg/kg prednisolone, 0.3 or 3 mg/kg of DA-6017 and DA-6034 were administered through rectum once daily for 2 weeks. At 2days, 1week, and 2weeks later, we evaluated the effect by gross damage score (0-10) and measured myeloperoxidase, PGE2, and LTB4 from the damaged mucosa. RESULTS: The mean gross damage scores of prednisolone and 3 mg/kg of DA-6034 groups were significantly lower than that of a placebo group at 2weeks (0.8, 0.9 vs. 4.0, p<0.05). Myeloperoxidase activities also seemed to be lower in those effective groups but were not statistically significant. LTB4 levels were lower in prednisolone and, 0.3 and 3 mg/kg of DA-6034 groups than in a placebo group at 2weeks (7.91, 7.23, and 7.13 vs. 13.90 ng/mg protein, p<0.05). PGE2 levels were decreased in prednisolone and 0.3 mg/kg of DA-6034 groups at 2days. DA-6017 showed no effects. CONCLUSIONS: Eupatilin derivative compound, DA- 6034 was effective in rats with TNBS-induced colitis. In that LTB4 level is lowered with some decrease of PGE2 level, this agent probably has an inhibitory effect on arachidonic acid metabolism.