Effects In Experimental Colitis Research Articles

TNBS에 의해 유도된 마우스 대장염모델에서 유산균 발효 마의 항염효과

마(Dioscorea batatas)의 건강보조제로의 개발을 위해, 3가지 유산균, Lactobacillus acidophilus, Lactobacillus plantarum 그리고 Bifidobacterium longum 균주를 이용하여 발효를 하였다. 발효물은 10% 발효물 수용액으로 pH 측정결과 3.83, 총 유산균수는 <TEX>$8{\times}10^6$</TEX> CFU/mL로 표준화 하였다. TNBS-로 유도된 대장염 마우스 모델에 일반 마(400 mg/kg)와 발효된 마(200, 400mg/kg)를 섭취한 결과, 조직학 및 형태학적 손상정도 그리고 MPO 활성 등이 비발효 마처리군에 비하여 발효된 마를 처리한 군에서 현저하게 감소되는 것을 확인하였다. 농도별로는 발효된 마가 200 mg/kg으로 처리된 군보다 400 mg/kg으로 처리된 마에서 설변이나 조직의 붕괴 현상을 현저하게 억제시키는 것을 알 수 있었다. 유산균 발효 마를 투여한 대장염 마우스에서는 체중감소 및 염증세포의 침윤을 효과적으로 억제하였다. 이러한 결과를 통하여, 유산균 발효물이 대장염 모델에서 매우 효과적으로 항염효과를 보였으며, 대장염 치료 및 예방에 매우 유용한 자료로 활용될 것으로 사료된다. To develop a health-aid preparation of Dioscorea batatas (DB), lactic acid fermentation was attempted using a mixed starter comprising of Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium longum. The anaerobic fermentation of a 10% DB flour suspension gave a uniform suspension of pH 3.65, containing <TEX>$8{\times}10^6$</TEX> CFU/mL lactic acid bacteria. During the administration of the lactic acid fermented DB (FDB) and DB to trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse model, histological lesions, morphological damage, and myeloperoxidase acitivity were significantly reduced at a dosage of 200 and 400 mg/kg/day. Dose-response (200 and 400 mg/kg/day) studies revealed that FDB pre-treatment of mice significantly ameliorated the appearance of diarrhoea and the disruption of colonic architecture. In FDB-pretreated mice, there was a significant reduction in the degree of both neutrophil infiltration (measured as decrease in myeloperoxidase activity) and weight loss rates. Theses findings suggest that FDB exerts beneficial effects in experimental colitis and may be useful in the treatment of inflammatory bowel disease.

T cell-dependent protective effects of CpG motifs of bacterial DNA in experimental colitis are mediated by CD11c+ dendritic cells

BackgroundOligodeoxynucleotides (ODNs) containing unmethylated cytosine–guanosine (CpG) sequence motifs constitute the immunostimulatory components of bacterial DNA which potently activate innate immunity. Administration of CpG-ODNs before the onset of experimental colitis prevents...

Control of enteric neuromuscular functions by purinergic A3 receptors in normal rat distal colon and experimental bowel inflammation

Adenosine A(3) receptors mediate beneficial effects in experimental colitis, but their involvement in enteric neuromuscular functions during bowel inflammation is undetermined. This study investigated the regulatory role of A(3) receptors on colonic motility in the presence of experimental colitis. Colitis was induced in rats by 2,4-dinitrobenzenesulfonic acid. A(3) receptors and adenosine deaminase (ADA, adenosine catabolic enzyme) mRNA were examined by RT-PCR. Tissue distribution of A(3) receptors was detected by confocal immunofluorescence. The effects of 2,3-ethyl-4,5-dipropyl-6-phenylpyridine-3-thiocarboxylate-5-carboxylate (MRS1523) (MRS, A(3) receptor antagonist), 2-chloro-N(6) -(3-iodobenzyl)-adenosine-5'-N-methyluronamide (2Cl-IB-MECA) (CIB, A(3) receptor agonist), dipyridamole (DIP, adenosine transport inhibitor) and ADA were assayed on contractile responses evoked by electrical stimulation (ES) or carbachol in colonic longitudinal muscle preparations (LMP). RT-PCR showed A(3) receptors and ADA mRNA in normal colon and their increased level in inflamed tissues. Immunofluorescence showed a predominant distribution of A(3) receptors in normal myenteric ganglia and an increased density during colitis. MRS enhanced ES-induced cholinergic contractions in normal LMP, but was less effective in inflamed tissues. After pretreatment with dipyridamole plus ADA, to reduce extracellular adenosine, CIB decreased cholinergic motor responses of normal LMP to ES, with enhanced efficacy in inflamed LMP. A(3) receptor ligands did not affect carbachol-induced contractions in LMP from normal or inflamed colon. Normally, adenosine modulated colonic cholinergic motility via activation of A(3) receptors in the myenteric plexus. A(3) receptor-mediated tonic inhibitory control by adenosine was impaired in inflamed bowel, despite increased density of functioning and pharmacologically recruitable A(3) receptors.

Attenuation of experimental murine colitis by Acanthoic acid from Acanthopanax koreanum

Acanthoic acid (AA) is a pimaradiene diterpene isolated from Acanthopanax koreanum. We examined the effect of AA in dextran sulfate sodium (DSS)-induced colitis. AA (100 mg/kg or 300 mg/kg) was administered p.o. daily for 7 days. AA significantly inhibited Disease Activity Index, histological score, and myeloperoxidase activity. Furthermore, AA markedly suppressed the protein expression of TNF-alpha, COX-2, NF-kappaB and chymase as well as the mRNA expression of TNF-alpha and COX-2. These results suggest that AA exerts beneficial effects in experimental colitis, and therefore we propose that this compound may have therapeutic implications for ulcerative colitis.

Genomic analysis of sulfasalazine effect in experimental colitis is consistent primarily with the modulation of NF-κB but not PPAR-γ signaling

Sulfasalazine (SAZ) is a widely used drug in inflammatory bowel disease patients but its mechanism of action is incompletely understood. The objective of our study was to further characterize SAZ mechanism by studying its effect on the colonic transcriptome in a suitable preclinical model of inflammatory bowel disease. The trinitrobenzenesulfonic acid model of colitis in rats was used. The effect of SAZ on mRNA expression was assessed with Affymetrix Rat Expression 230 2.0 arrays used in triplicate (sextuplicate for controls), validated in separate samples with quantitative reverse-time PCR analysis. Some nongenomic experiments were also carried out. SAZ (500 mg/kg) had a marked anti-inflammatory effect as expected, which was correlated with a dramatic impact on colonic gene expression. In addition to immune/inflammatory genes, SAZ responsive genes were involved in distinct metabolic and signaling pathways. The effect of sulfasalazine was generally of normalization of colitis-modulated genes to control levels, with very few exceptions. Postgenomic validation showed an excellent correlation with microarray data and seemed to be slightly more sensitive. SAZ generally modulated the expression of nuclear factor-kappaB-driven genes. SAZ was also shown to inhibit IkappaB-alpha phosphorylation in rat primary splenocytes and in HT29 and IEC18 cells. In contrast, SAZ had only a modest effect on peroxisome proliferator-activated receptor (PPAR)-gamma-regulated genes and it was confirmed to induce PPAR-gamma in enterocytes but not splenocytes. Mechanistically, our data are consistent primarily with nuclear factor-kappaB inhibition, and there is little evidence of a prominent role of activation of PPAR-gamma receptors or antioxidative actions.

Crocetin reduces TNBS-induced experimental colitis in mice by downregulation of NFkB

Background/Aim:Ulcerative colitis (UC) is characterized by oxidative and nitrosative stress, leukocyte infiltration and upregulation of proinflammatory cytokines. In this study, we aim to investigate the effects of crocetin and its protective mechanism on 2,4,6- trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice model.Materials and Methods:Intestinal lesions (judged by macroscopic and histological score) were associated with neutrophil infiltration (measured as increase in myeloperoxidase (MPO) activity in the mucosa), and high levels of malondialdehyde MDA (an indicator of lipid peroxidation).Results:Dose-response studies revealed that treatment of mice with crocetin (50 mg/kg/day) i.g. for 8 days) significantly ameliorated diarrhea and the disruption of colonic architecture. Higher and lower doses (100 and 25 mg/kg/day) did not exhibit comparable effects. In crocetin-treated mice, a significant reduction was noted in the degree of both neutrophil infiltration (measured as decrease in myeloperoxidase activity) and lipid peroxidation (measured as decrease in malondialdehyde activity) in the inflamed colon. Crocetin also reduced the levels of nitric oxide (NO) associated with the favorable expression of TH1 and TH2 cytokines and inducible NO synthase along with the down regulation of nuclear factor-kB (NFkB).Conclusion:These findings suggest that crocetin exerts beneficial effects in experimental colitis, and therefore we propose that this carotenoid may have therapeutic implications for human UC and can be administered along with the conventional therapy of UC

N,N′-Bis(5-aminosalicyl)-L-Cystine is a Potential Colon-specific 5-aminosalicylic Acid Prodrug with Dual Therapeutic Effects in Experimental Colitis

To evaluate N,N′-bis(5-aminosalicyl)-L-cystine (5-ASA-Cys) as a potential colon-specific 5-aminosalicylic acid prodrug with dual therapeutic effects in experimental colitis, the pharmacokinetics and therapeutic activity were investigated after oral administration of 5-ASA-Cys and amelioration of experimental colitis was compared after rectal administration of 5-aminosalicylic acid (5-ASA) and/or cysteine. In addition, the gluthathione (GSH) level in the inflamed colonic tissue was examined after administration of cysteine or 5-ASA-Cys. Oral administration of 5-ASA-Cys delivered much greater amount of 5-ASA to the large intestine and excreted lower amount of 5-ASA via urine than that of free 5-ASA. Oral administration of 5-ASA-Cys ameliorated experimental colitis of rats induced by TNBS, which was more effective than that of sulfasalazine. Although cysteine administered rectally was not significantly effective, intracolonic treatment with both 5-ASA and cysteine showed a synergic effect in alleviating the rat colitis. Furthermore, not only 5-ASA-Cys administered orally but also cysteine administered rectally increased the glutathione level in the inflamed colonic tissue. Taken together, these results suggest that 5-ASA-Cys is a potential colon specific 5-ASA prodrug with dual therapeutic effects on experimental colitis and cysteine modulation of the glutathione level may be relevant to the dual effects of the prodrug. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:159–168, 2009

Prebiotics in Chronic Intestinal Inflammation

Prebiotics are nondigestible fermentable fibers that are reported to have health benefits for the host. Older as well as more recent studies show beneficial effects in experimental colitis and lately also in human inflammatory bowel diseases (IBD), such as Crohn's disease, ulcerative colitis, and chronic pouchitis. In this review we give an overview of the benefits of prebiotics in rodent IBD models and in IBD patients and discuss their possible protective mechanisms. Commensal intestinal bacteria induce and perpetuate chronic intestinal inflammation, whereas others are protective. However, most of the current medications are directed against the exaggerated proinflammatory immune response of the host, some of them toxic and costly. Feeding prebiotics changes the composition of the intestinal microflora toward more protective intestinal bacteria and alters systemic and mucosal immune responses of the host. Therapy for IBD targeting intestinal bacteria and their function is just emerging. Prebiotics have the promise to be relatively safe, inexpensive, and easy to administer. Unraveling their protective mechanisms will help to develop rational applications of prebiotics. However, the initial promising results with dietary prebiotics in preclinical trials as well as small studies in human IBD will need to be confirmed in large randomized controlled clinical trials.

Dynamics of enterocyte tight junctions: effect of experimental colitis and two different anti-TNF strategies

An alteration of the intestinal barrier is considered to represent an early step in pathogenesis of Crohn's disease. The integrity of intestinal barrier function is guaranteed among other factors by enterocyte tight junction (TJ) proteins. Clinical and experimental data indicate the TNF-alpha to be the major responsible factor for these defects. In the present study we investigated the very early effects of DNBS-ethanol colitis on ileal enterocyte TJ proteins [occludin, zonula occludens-1 (ZO-1), claudin-2] in controls, mice treated with infliximab (IFX) or with etanercept (ETC), and in knockout mice for the TNF-alpha receptor 1 (TNFR-1(-/-)). Circulating TNF-alpha levels were effectively reduced by IFX and ETC (P < 0.01, both) at 3 and at 6 h. DNBS colitis induced disappearance of occludin and ZO-1 from enterocyte cell-cell contact, whereas claudin-2, absent under control conditions, appeared in the ileal epithelium. These alterations were prevented equally by both treatments, IFX and ETC, and in TNFR-1(-/-) animals. DNBS colitis induced a very rapid loss of occludin and ZO-1 from ileal TJ together with an upregulation of claudin-2. Our data are consistent with the hypothesis that TNF-alpha is involved in early TJ rearrangement and that its effects are mediated through TNFR-1. Despite clinical differences, both anti-TNF treatments were equally effective in the present setting.

Immunostimulatory DN A induces indoleamine 2, 3 dioxygenase in both epithelial and classic immune cells to contribute to its protective effects in experimental colitis

Immunostimulatory DN A induces indoleamine 2, 3 dioxygenase in both epithelial and classic immune cells to contribute to its protective effects in experimental colitis

Immunostimulatory DNA induces indoleamine 2, 3 dioxygenase in both epithelial and classic immune cells to contribute to its protective effects in experimental colitis

Immunostimulatory DNA induces indoleamine 2, 3 dioxygenase in both epithelial and classic immune cells to contribute to its protective effects in experimental colitis

Efficacy of butyrate in the treatment of mild to moderate Crohn's disease

Abstract Background Butyrate exerts anti-inflammatory effects in experimental colitis and in lamina propria mononuclear cells of patients with Crohn's disease. Aims To assess the safety and efficacy of butyrate in Crohn's disease. Patients Thirteen patients with mild to moderate Crohn's disease were treated with enteric-release sodium butyrate tablets at a dosage of 4 g/day for eight weeks. Methods Before and after treatment, patients underwent coloscopy with evaluation of the clinical activity of their disease, systemic inflammation index and mucosal expression of interleukin (IL)-1β, IL-6, IL-12, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and nuclear factor (NF)-κB. Results Of the nine patients (69%) responding to treatment, 7 (53%) exhibited complete response and 2 exhibited partial response. Endoscopic and histological evaluation scores were significantly improved ( p p Conclusions Oral administration of butyrate may be effective in inducing clinical improvement or remission in patients with Crohn's disease.

A Hydrogen‐Sulfide Releasing Derivative of Mesalamine Exhibits Markedly Enhanced Anti‐Inflammatory Effects in Experimental Colitis

A Hydrogen‐Sulfide Releasing Derivative of Mesalamine Exhibits Markedly Enhanced Anti‐Inflammatory Effects in Experimental Colitis

PARP inhibition reduces acute colonic inflammation in rats

Poly(ADP-ribose) polymerases (PARP) comprise a family of enzymes which catalyse poly(ADP-ribosyl)ation of DNA-binding proteins. Multiple researches indicate the importance of PARP in promoting cell recruitment and thereby inducing organ injury in various forms of inflammation, such as colitis. We have evaluated the effects of two PARP inhibitors, nicotinamide and 1,5-dihydroxyisoquinoline, in acute colitis induced by trinitrobenzensulfonic acid (TNBS) in rats. Nicotinamide (20–40 mg/kg) and 1,5-dihydroxyisoquinoline (4–8 mg/kg) were administered 48, 24 and 1 h prior to the induction of colitis as well as 24 h later. 48 h after colitis induction the lesions were blindly scored and quantified as ulcer index. Histological study and colonic inflammation were assessed by gross appearance and myeloperoxidase (MPO) activity. Prostaglandin E 2 (PGE 2) synthesis and, cyclooxygenase-1 and cyclooxygenase-2 expressions by Western blotting and immunohistochemistry were also performed. Inflammation following TNBS induction was characterized by increased colonic wall thickness, oedema, diffuse inflammatory cells infiltration in the mucosa and necrosis. Furthermore, increased MPO activity, cyclooxygenase-2 expression and PGE 2 synthesis were significantly augmented after TNBS instillation. On the contrary, treatment with 1,5-dihydroxyisoquinoline significantly reduced the degree of colon injury and also caused a substantial reduction in the rise in MPO activity, in the increase of staining for cyclooxygenase-2, as well as in the up-regulation of PGE 2 caused by TNBS in the colon. Although nicotinamide significantly did not reduce macroscopic damage, it decreased both MPO activity and PGE 2 colonic levels. In conclusion, we demonstrated that PARP inhibition can exert beneficial effects in experimental colitis and may, therefore, be useful in the treatment of ulcerative colitis.

Protection from experimental colitis by theaflavin‐3,3′‐digallate correlates with inhibition of IKK and NF‐κB activation

Inflammatory bowel disease (IBD) is associated with activation of nuclear factor kappa B (NF-kappaB) involved in regulating the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokine genes. As theaflavin-3,3'-digallate (TFDG), the most potent anti-oxidant polyphenol of black tea, down-regulates NF-kappaB activation, we investigated if TFDG is beneficial in colonic inflammation by suppressing iNOS and proinflammatory cytokines. The in vivo efficacy of TFDG was assessed in mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. Both mRNA and protein levels of proinflammatory cytokines and iNOS were analyzed in colon tissue treated with or without TFDG. NF-kappaB activation was determined by electrophoretic mobility shift assay and levels of NF-kappaB inhibitory protein (IkappaBalpha) were analyzed by Western blotting. Oral administration of TFDG (5 mg kg(-1) daily i.g.) significantly improved TNBS-induced colitis associated with decreased mRNA and protein levels of TNF-alpha, IL-12, IFN-gamma and iNOS in colonic mucosa. DNA binding and Western blotting revealed increase in NF-kappaB activation and IkappaBalpha depletion in TNBS-treated mice from Day 2 through Day 8 with a maximum at Day 4, which resulted from increased phosphorylation of IkappaBalpha and higher activity of IkappaB kinase (IKK). Pretreatment with TFDG markedly inhibited TNBS-induced increases in nuclear localization of NF-kappaB, cytosolic IKK activity and preserved IkappaBalpha in colon tissue. TFDG exerts protective effects in experimental colitis and inhibits production of inflammatory mediators through a mechanism that, at least in part, involves inhibition of NF-kappaB activation.

Homeostatic Effects of TLR9 Signaling in Experimental Colitis

The commensal microflora of the intestinal tract confer multiple health benefits to the host, including amelioration of inflammatory bowel disease (IBD). Yet, the exact mechanisms by which it ameliorates experimental colitis in animals and human IBD are largely unknown. We tested whether the attenuation of experimental colitis by probiotic bacteria is mediated by toll-like receptor (TLR) signaling. The severity of colitis was attenuated by delivery of nonviable, gamma-irradiated, or by viable probiotics, but not by heat-killed probiotics, in wild-type mice in mice deficient in TLR2 or TLR4. In contrast we did not observe any inhibition of experimental colitis by probiotics, in mice deficient in MyD88 or TLR9. Furthermore, administration of probiotic DNA ameliorated the severity of experimental colitis, whereas methylated probiotic DNA, calf thymus DNA, and Dnase-treated probiotics had no effect. In subsequent studies, we identified that TLR9-induced type 1 IFN mediates the anti-inflammatory effects in experimental colitis. The addition of neutralization antibodies to type 1 IFN abolished the anti-inflammatory effects, whereas the administration of recombinant IFN-beta mimicked the anti-inflammatory effects induced by TLR9 agonists. Taken together, these results indicate that the protective effects of probiotics are mainly mediated by their own DNA rather than by their metabolites or their ability to colonize the colon. These findings underscore the diverse effects of indigenous microbial TLR ligands in intestinal homeostasis and intestinal inflammation and suggest that strategies, that modulate type 1 IFN may be of therapeutic value for intestinal inflammatory conditions.

Oral butyrate for mildly to moderately active Crohn's disease

Butyrate exerts anti-inflammatory effects in experimental colitis and on Crohn's disease lamina propria mononuclear cells in vitro. To explore the efficacy and safety of oral butyrate in Crohn's disease. Thirteen patients with mild-moderate ileocolonic Crohn's disease received 4 g/day butyrate as enteric-coated tablets for 8 weeks. Full colonoscopy and ileoscopy were performed before and after treatment. Endoscopical and histological score, laboratory data, Crohn's disease activity index and mucosal interleukin (IL)-1beta, IL-6, IL-12, interferon-gamma, tumour necrosis factor-alpha and nuclear factor-kappa B (NF-kappaB) were assessed before and after treatment. One patient withdrew from the study, and three patients did not experience clinical improvement. Among the nine patients (69%) who responded to treatment, seven (53%) achieved remission and two had a partial response. Endoscopical and histological score significantly improved after treatment at ileocaecal level (P < 0.05). Leucocyte blood count, erythrocyte sedimentation rate and mucosal levels of NF-kappaB and IL-1beta significantly decreased after treatment (P < 0.05). Oral butyrate is safe and well tolerated, and may be effective in inducing clinical improvement/remission in Crohn's disease. These data indicate the need for a large investigation to extend the present findings, and suggest that butyrate may exert its action through downregulation of NF-kappaB and IL-1beta.

Proglumide attenuates experimental colitis in rats

Ulcerative colitis is associated with altered contractile activity and transit time of colon. On the other hand, cholecystokinin (CCK) has been shown to play an important role in regulation of gastrointestinal motor function including colonic contraction and transit. In the present study, an attempt was made to study the effect of proglumide, a CCK receptor antagonist on experimental colitis in rats. Experimental colitis was induced in male Sprague–Dawley rats by instilling 1 ml of 4% acetic acid followed by flushing with 0.5 ml air. The rats were kept in a head-down position for 30 s. Finally, each rat received 1.5 ml colonic wash with 1.5 ml saline. Four groups of rats received proglumide orally (0, 250, 500 and 1000 mg/kg). The first dose of proglumide was given 1 h before acetic acid challenge, whereas the second dose of proglumide was given 25 h after the first dose. Sham control rats received an equal volume of saline instead of acetic acid. Forty-eight hours after the acetic acid challenge, the colon was removed, weighed and split longitudinally and scored for injury. Part of the colon was used for histopathological study as well as analysis of myeloperoxidase (MPO) activity (as a marker of neutrophil activity). Acetic acid produced severe diarrhea and exfoliation of the colonic epithelium accompanied by extensive destruction of the mucosal interstitium. Proglumide dose dependently protected rats against acetic acid-induced increase in colon weight, diarrhea, MPO activity and colonic injury. Inhibition of CCK exerts a beneficial effect in experimental colitis. Further studies are warranted to determine the mechanism of protection and the therapeutic potential of CCK inhibitors.

Selective expression of detoxifying glutathione transferases in mouse colon: effect of experimental colitis and the presence of bacteria.

Glutathione transferases (GSTs) play a central role in the cellular defense against harmful endogenous compounds and xenobiotics in mouse and man. The gastrointestinal channel is constantly exposed to bacteria, bacterial products, and xenobiotics. In the present study the distribution of alpha, mu, and pi class GSTs was examined immunohistologically in the colon of conventional and germ-free (GF) mice subjected to experimental colitis. The tissues samples were from conventional mice with and without colitis induced by dextran sulfate sodium (DSS); GF mice treated with DSS or carrageenan; and GF mice inoculated with normal mouse bacterial flora as well as with Lactobacillus GG. In conventional as well as in GF mice the mu and pi class GSTs showed reduced intestinal expression when colitis was induced. In con-rast, the level of GSTs reacting with antibodies directed against the alpha class, in particular mGST A4-4, was elevated after induction of inflammation. Of special interest is mGST A4-4 because of its high catalytic activity with toxic products of lipid peroxidation. In the colon of conventionalized GF mice that were given mouse intestinal flora, the mGST A4-4 expression was increased with time for several weeks, but then showed a decrease to a normal level. Additionally, the inoculation of GF mice with Lactobacillus GG induced all the intestinal GSTs studied.

Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis.

1 Inflammmatory bowel disease (IBD) is characterized by oxidative and nitrosative stress, leucocyte infiltration and upregulation of proinflammatory cytokines. In this study, we have investigated the protective effects of curcumin, an anti-inflammatory and antioxidant food derivative, on 2,4,6- trinitrobenzene sulphonic acid-induced colitis in mice, a model for IBD. 2 Intestinal lesions (judged by macroscopic and histological score) were associated with neutrophil infiltration (measured as increase in myeloperoxidase activity in the mucosa), increased serine protease activity (may be involved in the degradation of colonic tissue) and high levels of malondialdehyde (an indicator of lipid peroxidation). 3 Dose-response studies revealed that pretreatment of mice with curcumin (50 mg kg(-1) daily i.g. for 10 days) significantly ameliorated the appearance of diarrhoea and the disruption of colonic architecture. Higher doses (100 and 300 mg kg(-1)) had comparable effects. 4 In curcumin-pretreated mice, there was a significant reduction in the degree of both neutrophil infiltration (measured as decrease in myeloperoxidase activity) and lipid peroxidation (measured as decrease in malondialdehyde activity) in the inflamed colon as well as decreased serine protease activity. 5 Curcumin also reduced the levels of nitric oxide (NO) and O(2)(-) associated with the favourable expression of Th1 and Th2 cytokines and inducible NO synthase. Consistent with these observations, nuclear factor-kappaB activation in colonic mucosa was suppressed in the curcumin-treated mice. 6 These findings suggest that curcumin or diferuloylmethane, a major component of the food flavour turmeric, exerts beneficial effects in experimental colitis and may, therefore, be useful in the treatment of IBD.