Animal Model Of Ulcerative Colitis Research Articles

Effect of Huangqin Decoction on pyroptosis pathway of NLRP3/caspase-1 in mice with ulcerative colitis

To explore the effect of Huangqin Decoction on ulcerative colitis(UC) pyroptosis, and to explain the mechanism of pyroptosis based on NOD-like receptor thermoprotein domain 3(NLRP3)/cysteine proteinase 1(caspase-1) pathway. The animal model of UC induced with 3% dextran sodium sulfate(DSS) was established. The experimental animals were divided into control group, model group, low-dose(4.55 g·kg~(-1)), medium-dose(9.1 g·kg~(-1)) and high-dose(18.2 g·kg~(-1)) Huangqin Decoction groups and salazosulfapyridine group(0.45 g·kg~(-1)). While modeling, intragastric administration was given for 7 consecutive days. On the 8 th day, the mice were euthanized, the colon length was collected, and the histopathological changes were observed by HE staining. The content of interleukin-18(IL-18) was observed by ELISA. The content of lactatedehydrogenase(LDH)was determined by microplate method. TUNEL assay kit was used to detect the cell death. The immunohistochemical staining was used to detect the expressions of NLRP3 and apoptosis-associated speck-like protein containing a CARD(ASC). Western blot was used to detect the expressions of interleukin-1β(IL-1β), caspase-1 and gasdermin D(GSDMD).The experimental study showed that compared with normal group, the LDH content, TUNEL positive staining, inflammatory factors(IL-18, IL-1β), and proteins associated with pyroptosis were significantly increased(P<0.05). Compared with model control group, the LDH content, TUNEL positive staining, inflammatory factors(IL-18, IL-1β), and proteins associated with pyroptosis were decreased, and these results were more significant in high-dose groups(P<0.05). The results of HE staining showed that Huangqin Decoction could improve the pathological changes of colon. Huangqin Decoction could inhibit UC cell pyroptosis, and the mechanism may be closely related to NLRP3/caspase-1 signaling pathway.

Application of inulin/Eudragit RS in 5-ASA pellet coating with tuned, sustained-release feature in an animal model of ulcerative colitis

A tunable release of 5-aminosalicylic acid (5-ASA) could bring therapeutic benefits in the treatment of inflammatory bowel disease (IBD).A 32 factorial design was used to achieve a tuned delivery of 5-ASA pellets in the small and large intestine using a coating composed of inulin/Eudragit RS (RS). The ratio of inulin/RS and coating level were independent variables while the dependent variables were the percent of drug release at pH 1.2 in 2 h and total release of drug in 10 h at pH 6.8. 5-ASA release from pellets was examined at different pH levels and the therapeutic efficacy of the optimum pellets was compared to 5-ASA pellets of Pentasa in rats with ulcerative colitis.The inulin/RS of 18/82 at a coating level of 16% was found to be the optimum for delivery of the drug to the small and large intestine. The coated pellets offered a superior therapeutic outcome compared to uncoated pellets and Pentasa in terms of colitis activity index (CAI), and the colon's tissue enzymes of GSH and MDA.The optimum coating composed of inulin and RS could offer a tuned sustained release of 5-ASA throughout the small and large intestine with the sensitivity of drug release to microbial degradation.

Analysis of animal models of ulcerative colitis based on characteristics of clinical symptoms of traditional Chinese and Wes-tern medicine

This article aims to provide a good experimental method for the study of drug treatment of ulcerative colitis. According to the characteristics of ulcerative colitis's clinical symptoms, common ulcerative colitis animal models were analyzed. Based on the characteristics of clinical symptoms of traditional Chinese medicine and Western medicine for ulcerative colitis disease, the existing commonly used animal models of ulcerative colitis were analyzed to summarize the current matching degree, advantages and disadvantages of the exi-sting animal models of ulcerative colitis and clinical symptoms. At present, studies on ulcerative colitis mainly adopt four types of induction modeling methods, such as immunization, chemical stimulation, compound method and gene model. There are many reported methods of colitis modeling, but no model can reflect the characteristics of clinical symptoms of ulcerative colitis treated with Western or Chinese medicine. This article summarizes the characteristics, clinically relevant symptoms and applicable scope of immunization, chemical stimulation, compound method, and gene model, so as to provide a reliable animal model for subsequent studies of prevention and treatment of colitis.

Probiotic Bacillus Spores Together with Amino Acids and Immunoglobulins Exert Protective Effects on a Rat Model of Ulcerative Colitis.

In inflammatory bowel disease (IBD), experimental models have proven to be important tools for evaluating potential therapeutic agents and for investigating the mechanisms of pathogenesis. Oxidative stress and the immune response have been associated with acetic acid (AA)-induced ulcerative colitis (UC). Our study aimed to evaluate, for the first time, the ability of a spore-based probiotic and an amino acid and immunoglobulin supplement in reducing tissue damage and inflammatory responses in an experimental animal model of UC. Forty-two Wistar rats were divided into six groups, receiving 1% carboxymethylcellulose, 4% AA, MegaSporeBiotic™ (MSB; 1 × 109 colony forming units/day) and MegaMucosa™ (MM; 70 mg/100 g/day). Pretreatment with MSB or MM alone and in combination significantly lowered inflammation and reduced damage to the colonic mucosa. Pretreatment with these agents resulted in levels of proinflammatory cytokines, vascular tight junction proteins, and measures of oxidative stress similar to those reported for methylprednisolone, one of the first-line therapies for moderate to severe activity of UC. The protection was further confirmed by histologic analysis of the colon tissue. In conclusion, pretreatment with probiotic spore-forming Bacillus strains and a supplement of amino acids in combination with immunoglobulins exhibited anti-inflammatory and antioxidant effects in an AA-induced rat model of UC.

Imperatorin Relieved Ulcerative Colitis by Regulating the Nrf-2/ARE/HO-1 Pathway in Rats.

Ulcerative colitis is a common intestinal inflammatory disease. Imperatorin (IMP) has been reported to alleviate mast cell-mediated allergic responses by suppressing the expression of Nrf-2, ARE, and HO-1. However, whether IMP can relieve ulcerative colitis by regulating Nrf-2/ARE/HO-1 pathway is unclear. Thus, this study aims to investigate the effect of IMP on ulcerative colitis in rats and elucidate the potential mechanism. In our study, rats were treated with 2,4,6-trinitro-benzenesulfonic acid (TNBS) to induce the animal model of ulcerative colitis. Next, these rats were treated with diverse doses of IMP (15mg/kg, 30mg/kg, and 60mg/kg) and sacrificed at different time points (3days, 7days, and 14days). The levels of inflammatory factors (TNF-α and IL-6) in colon tissues were detected with ELISA kits. H&E staining was performed to observe the pathologic changes of the colon tissues. The expression of Nrf-2, ARE, and HO-1 in colon tissues was determined with the immunofluorescence and Western blotting. The results showed that application of IMP alleviated the symptoms of ulcerative colitis and inhibited the secretion of TNF-α and IL-6. Besides, treatment of IMP promoted the expression of Nrf-2, ARE, and HO-1 in the early stage of this disease (the third day), but suppressed the expression of Nrf-2, ARE, and HO-1 in the advanced stage of the ulcerative colitis (the fourteenth day). Collectively, IMP relieved the symptoms of ulcerative colitis by regulating the Nrf-2/ARE/HO-1 pathway, which might provide a new therapeutic drug to support the clinical treatment of ulcerative colitis.

Copaifera malmei Harms leaves infusion attenuates TNBS-ulcerative colitis through modulation of cytokines, oxidative stress and mucus in experimental rats

Ethnopharmacological relevanceEthnobotanical studies show that the infusion of the leaves from Copaifera malmei Harms (Fabaceae) has been utilized in the Brazilian traditional medicine to treat provocative and gastrointestinal diseases, among others. Recently, our research team has shown that an infusion extract of the leaves of C. malmei has a strong antiulcer activity and its oral use gives no indications of toxicity. Aim of the studyThe aim of the study is to evaluate the anti-inflammatory intestinal effect of an infusion extract from the leaves of Copaifera malmei (IECm) in an animal model of ulcerative colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Materials and methodsAcute intestinal inflammation was induced in male Wistar rats by TNBS in 20% EtOH (0.25 mL). IECm was administered by oral gavage (for 72, 48, 24 and 2 h) preceding the induction of ulcerative colitis. The colon damage and degree of inflammation were evaluated by morphological observation scores and colon weight. The improved colonic mucosal injury, oxidative stress and inflammatory response were assessed by histopathological investigation and by estimating myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels and tumor necrosis factor (TNF), interleukin 1β (IL1-β), IL-17 and IL-10 colon tissue concentrations. The histopathological changes were done on the colon tissues by hematoxylin and eosin and Periodic Acid-Schiff staining were utilized to measure the mucus. ResultsPre-treatment (25, 100 and 400 mg/kg) with IECm altogether diminished the intestinal inflammation prompted by TNBS in rats by diminishing colonic score by 69.12% (p < 0.01), 19.87% (p < 0.05) and 67.60% (p < 0.01), individually. Improvement of colonic mucosal injury by treatment with IECm was shown by a decline in MPO activity at dosages 25 and 400 mg/kg by 67.98% and 59.68% (p < 0.001), MDA levels 64.80% and 80.00% (p < 0.01) and an expansion in GSH content at all portions (62.53%, 53.38% and 81.20% p < 0.05) compared with vehicle control group. IECm additionally prevention of intestinal inflammation as confirm by decreased cytokine levels, for example, TNF (31.26%, p < 0.05, 50.68% and 45.95%, p < 0.01), IL1-β (56.41%, 58.83% and 56.65%, p < 0.001), IL-17 (51.66%, p < 0.001, 22.23%, p < 0.05 and 49.67%, p < 0.001) and increased the IL-10 levels at 25 and 400 mg/kg (57.13%, p < 0.01 and 35.83%, p < 0.05) respectively. Histopathological examination of the colon tissue displayed recovery of ulcerative colitis of IECm treated animals by reducing leukocyte infiltrate, epithelial, submucosal and muscular layer damages and maintaining mucus production. ConclusionThese findings revealed that IECm was effective and possess anti-colitic activities in a rodent model of UC and can be useful in inflammatory bowel diseases (IBD). The pre-treatment with IECm decreased intestinal inflammation by reducing macroscopical and microscopical colon injury. In addition, the present study demonstrated that IECm ameliorates TNBS-colitis by promoting antioxidant effect, modulation of cytokines release and restauration of mucus production. The study reinforces the traditional use of the Copaifera malmei leaves infusion to inflammatory gastrointestinal disorders and makes IECm a potential herbal medicine for the treatment of IBD.

Histological and ultrastructural changes of the colon in dextran sodium sulfate-induced mouse colitis.

Ulcerative colitis (UC) is a complex disease that results from a dysregulated immune response in the gastrointestinal tract. A mouse model orally administered with dextran sodium sulfate (DSS) is the most widely used experimental animal model of UC. However, the ultrastructure of the colon in mouse colitis is poorly understood. In the present study, colonic specimens from DSS-induced UC mice underwent hematoxylin and eosin staining, Masson's trichrome staining and Verhoeff's elastic staining. In addition, the ultrastructure of samples was examined by transmission electron microscopy. UC was successfully induced by 7 consecutive days of DSS oral administration. The goblet cell architecture of the UC tissue was damaged in the mucosa. Additionally, a significant number of inflammatory cells infiltrated into the stroma and the structure of the intestinal gland was destroyed. The tissue in the submucosa showed significant edema. Hyperplasia was also identified in the submucosa, promoting a disorganized microstructure within the colon wall. Numerous collagen fibers in the muscular layer were disrupted, and the fiber bundles were thinner compared with those in the normal control group. Furthermore, in the DSS-induced UC group, the smooth muscle cell showed edema, the cell membrane structure was unclear and the shape of the nucleus was irregular. In conclusion, the present study revealed important histological and ultrastructural changes in the colon of DSS-induced UC mice. These features may contribute to improved understanding of the pathogenesis and mechanism of UC.

Effect of chemical modulation of toll-like receptor 4 in an animal model of ulcerative colitis.

The partial ineffectiveness and side effects of inflammatory bowel disease (IBD) current therapies drive basic research to look for new therapeutic target in order to develop new drug lead. Considering the pivotal role played by toll-like receptors (TLRs) in gut inflammation, we evaluate here the therapeutic effect of the synthetic glycolipid TLR4 antagonist FP7. The anti-inflammatory effect of FP7, active as TLR4 antagonist, was evaluated on peripheral blood mononuclear cells (PBMCs) and lamina propria mononuclear cells (LPMCs) isolated from IBD patients, and in a mouse model of ulcerative colitis. FP7 strongly reduced the inflammatory responses induced by lipopolysaccharide (LPS) in vitro, due to its capacity to compete with LPS for the binding of TLR4/MD-2 receptor complex thus inhibiting both the MyD88- and TRIF-dependent inflammatory pathways. Colitic mice treated with FP7 exhibit reduced colonic inflammation and decreased levels of pro-inflammatory cytokines. This study suggests that TLR4 chemical modulation can be an effective therapeutic approach to IBD. The selectivity of FP7 on TLR4 makes this molecule a promising drug lead for new small molecules-based treatments.

Effect of egg white and honey enema on ulcerative colitis in an animal model

Egg and honey contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways and have effects on oxidative stress. In this study, the effects of egg white and honey against acetic acid-induced colitis were investigated in rats. Forty adult rats were divided into five groups (n = 7), group I (normal saline), group II (egg white), group III (honey), group IV (Asacol® 100 mg/ml used as a positive control), and group V (combination of honey and egg white 50:50 v/v). Medications (2 cc/day) were administered rectally for a period of 6 days after induction of colitis using 2% acetic acid. Animals were killed on day 7 and colonic biopsies were taken for histopathological scoring. The concentration of malondialdehyde (MDA) and TNF-α was measured on the samples of the colon tissue that were frozen in liquid nitrogen. At 1 week, the histological damage was severe, and the MDA and TNF-α were high throughout the study without any treatment. Honey decreased the TNF-α and MDA tissue levels towards normal levels significantly (P < 0.05). Combination of honey and egg white was not better than honey alone as an anti-inflammatory agent. In the animal model of ulcerative colitis, rectal administration of honey significantly reduced the colonic inflammation. The present study indicates that honey is efficacious in the acetic acid-induced rat colitis model, but these results require further confirmation in human studies and determination of active ingredients.

Bin1 antibody lowers the expression of phosphorylated Tau in Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible, progressive brain disorder responsible for memory loss leading to the inability to carry out the simplest tasks. AD is one of the leading causes of death in the United States. As yet there are no effective medications to treat this debilitating disease. In recent years, a human gene calledbridging integrator 1 (BIN1) has emerged as one of the most important genes in affecting the incidence of sporadic AD. Bin1 can directly bind to Tau and mediates late onset AD risk by modulating Tau pathology. Recently our group found Bin1 antibody could exert drug-like properties in an animal model of ulcerative colitis. We hypothesized that the Bin1 monoclonal antibody (mAb) could be used in the treatment of AD by lowering the levels of Tau in cell culture and animal models. Cell culture studies confirmed that the Bin1 mAb (99D) could lower the levels of phosphorylated Tau (pTau). Multiple mechanisms aided by endosomal proteins and Fc gamma receptors are involved in the uptake of Bin1 mAb into cells. In Tau expressing cell culture, the Bin1 mAb induces the proteasome machinery leading to ubiquitination of molecules thereby preventing cell stress. In vivo studies demonstrated that treatment of P301S mice expressing Tau with the Bin1 mAb survived longer than the untreated mice. Our data confirm that Bin1 mAb lowers the levels of pTau and could be a drug candidate in the treatment of AD.

ELR positive CXCL chemokines are highly expressed in an animal model of ulcerative colitis.

Background: The presence of neutrophil-rich inflammation in colon tissues of patients with ulcerative colitis (UC) is one of the most important histological characteristics of this disease. However, the expression of CXCL chemokines governing the infiltration of neutrophils in UC has not been well elucidated.Materials and methods: In this experimental study, the UC model was induced in Wistar rats by administration of 2 mL 4% acetic acid into the large colon through the rectum. Animals were anesthetized after 48 hrs; their colon tissue samples were isolated for macroscopic and histopathological examinations. The expression of CXCL family was assessed by reverse transcription polymerase chain reaction (qRT-PCR) technique.Results: Heavy infiltration of neutrophils, coagulation necrosis, and ulcers were observed in H&E staining, which pathologically proved the UC model. qRT-PCR results showed that ELR+ CXC chemokines such as CXCL6 and CXCL3 had the highest expression in the UC group, which was 49 and 28 times higher than that of the control group, respectively. In addition, other chemokines of this group including CXCL1, CXCL2, and CXCL7 had a significant increase compared to the control group (P≤0.05). However, ELR− CXC chemokines such as CXCL4, CXCL13, and CXCL16 showed a smaller upregulation, while CXCL14 chemokine showed a significant decrease compared to the control group (P≤0.05). However, the expression of CXCL9-12 and CXCL17 did not change.Conclusion: The results showed that the ELR+ CXC chemokines, especially CXCL6 and CXCL3, many involved in the pathogenesis of UC; therefore, CXCL6 and CXCL3 chemokines can be used as therapeutic targets for UC, although more studies using human samples are required.

Su1822 – Np-120 and Np-178: Repurposed Neurological Drugs with Efficacy in Animal Models of Ulcerative Colitis and Crohn’s Disease

Su1822 – Np-120 and Np-178: Repurposed Neurological Drugs with Efficacy in Animal Models of Ulcerative Colitis and Crohn’s Disease

Hydroalcoholic extract of Tagetes erecta L. flowers, rich in the carotenoid lutein, attenuates inflammatory cytokine secretion and improves the oxidative stress in an animal model of ulcerative colitis

Given the role of oxidative stress in ulcerative colitis (UC) etiology, and the amount of lutein (a carotenoid with antioxidant properties) in the dry hydroalcoholic extract of Tagetes erecta flowers (DHETE), this study investigated the intestinal anti-inflammatory properties of DHETE in an animal model of UC. The amount of lutein in the extract was determined by 1H-nuclear magnetic resonance spectroscopy, and total phenols, radical scavenger capability, cytotoxicity, and effects on reactive oxygen species and nitric oxide production were evaluated in vitro. Experimental UC was established by adding 5% dextran sulfate sodium (DSS) to drinking water, with the effects of DHETE (30-300 mg/kg, once a day for 7 days) on the morphological (colon length and weight), clinical (disease activity index and body weight loss), microscopic (histological score and mucin levels), and biochemical parameters analyzed. The lutein concentration found in DHETE was 8.2%, and DHETE scavenged 2,2-diphenyl-1-picrylhydrazyl radicals at 1000 μg/mL The exposure of intestinal epithelial cells to DHETE did not change its viability but reduced reactive oxygen species and nitric oxide production after lipopolysaccharide stimulation. In vivo, DHETE (300 mg/kg) attenuated weight loss, disease activity index, colon shortening, and histopathological changes promoted by DSS intake. Moreover, DHETE increased mucin colonic staining. The treatment with DHETE decreased myeloperoxidase activity as well as tumor necrosis factor and interleukin-6 levels. The extract also increased reduced glutathione levels and catalase activity and normalized superoxide dismutase and glutathione-S-transferase activities. In conclusion, DHETE reduced colitis severity by attenuating inflammatory cytokine secretion and improved the endogenous antioxidant defense in DSS-induced UC in mice.

Aggravated mucosal and immune damage in a mouse model of ulcerative colitis with stress.

The aim of the present study was to determine the influence of stress on the colonic mucosa and immune system and to further investigate the association between stress and development and pathogenesis of ulcerative colitis (UC). Mice were treated with 2,4,6-trinitrobenzenesulfonic acid to induce an animal model of UC, and stress was induced by water immersion and restraint. Subsequently, the disease activity index (DAI), secretory immunoglobulin A (sIgA), IgA, interleukin (IL)-6 and -8, tumor necrosis factor-α (TNF-α), complement component (C)3 and C4, and alterations in the colonic mucosa were observed. The DAI scores and the expression levels of IL-6, IL-8 and TNF-α significantly increased in the experimental UC mice compared with the control mice, while the expression levels of IgA and sIgA decreased (all P<0.01). DAI and colonic mucosa damage scores increased in the stress-treated mouse models of UC compared with the untreated mouse models of UC (P<0.05). Expression levels of IgA and sIgA decreased, while IL-6, IL-8 and TNF-α further increased in the stress-treated UC mice (P<0.05). The expression levels of C3 and C4 were not affected by stress or UC (P>0.05). These results indicated that UC may be associated with an immune disorder and that stress can aggravate colonic mucosa injury and alter the immune response. Furthermore, stress and immunity may serve roles in the pathogenesis of UC.

Synergistic effects of hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) administration in ameliorating animal model of ulcerative colitis

This study was done to investigate the synergistic impacts hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) administration in ameliorating animal model of ulcerative colitis (UC). After the induction of UC and with the development of signs, the treatment groups daily received the hydro extract of jujube fruit (200 mg/kg, orally, enema), Mesalazine (30 mg/kg, orally) and Asacol (10 mg/kg, enema). After 10 days, rats were euthanized and were studied. Findings indicated a significant increase in Myeloperoxidase (161.66 ± 10.40), Nitric oxide (216.01 ± 17.55), IL-6 (138.54 ± 7.02), and TNF-α (123.87 ± 9.80) colon tissue levels and pathological damage of positive control group compared with the negative control group. Hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) group represented a higher capability in significantly decreasing Myeloperoxidase (73.33 ± 9.07), Nitric oxide (81.66 ± 10.50), IL-6 (51.69 ± 5.19), TNF-α (30.59 ± 5.50) levels and pathological damage in compared with the other treatment groups. Considering accessibility and affordability of jujube fruit and the side effects of routine drugs, taking a combination of jujube fruit with low doses of routine pharmaceutical drugs can improve and cure ulcerative colitis disease.

The Beneficial Effects of Hypiran in Ameliorating Rat Model of Ulcerative Colitis

Background: Different studies have been done on Hypericum anti-depressant effects, but only a few ones have documented in vivo anti-inflammatory properties of Hypericum following systemic administration. Objectives: This survey was designed to evaluate the potential effects of Hypiran, a hydro-alcoholic extract of St. John’s Wort, for the treatment and controlling inflammation in animal models of ulcerative colitis. Methods: In this experimental study, ulcerative colitis was induced in the male Wistar rats by luminal instillation of acetic acid. Animals in the treatment groups received Hypiran (150 mg/kg PO) or Prednisolone (4 mg/kg PO) daily for 10 consecutive days. At the end, the rats were sacrificed and the disease activity index, the levels of malondialdehyde, myeloperoxidase, nitric oxide, total protein and the concentration of TNF-α, IL-1β and IL-6 were assessed in the colonic homogenized tissue specimens. Results: The results showed that both therapies with Hypiran and Prednisolone could regress the clinical scores and the mortality rate of ulcerative colitis in a comparable manner. The levels of TNF-α, IL-1β and myeloperoxidase activity were down-regulated in the guts of Prednisolone treated rats more than Hypiran groups. Nevertheless, Hypiran decreased the levels of IL-6, nitric oxide and malondialdehyde more significantly than Prednisolone. Conclusions: Collectively, these data suggest that the Hypiran may be used as a natural source to alleviate the signs of rat model of ulcerative colitis.

Bacterial Flora Play Important Roles in Acute Dextran Sulphate Sodium-Induced Colitis But Are Not Involved in Gal-3 Dependent Modulation of Colon Inflammation

Abstract An altered immune response to normal gut microflora is important for the pathogenesis of ulcerative colitis (UC). Galectin- 3 (Gal-3) is an endogenous lectin that plays an important pro-inflammatory role in the induction phase of acute colitis by promoting activation of the NLRP3 infl ammasome and production of IL-1β in macrophages. By using dextran sulphate sodium (DSS) induced colitis, a well-established animal model of UC, we determined whether Gal-3 affects the function of colon infiltrating macrophages by interfering with intestinal microfl ora. Our results showed that genetic deletion of Gal-3 significantly attenuates DSS-induced colitis by down-regulating infiltration of phagocytic cells (neutrophils, macrophages and dendritic cells) in colon tissue of DSS-treated mice, and this correlated with differences in bacterial flora of the gut. Antibiotic treatment attenuates DSS-induced colitis in WT and Gal-3-/- mice without affecting differences between the groups. In conclusion, Gram negative bacterial flora play an important role in DSS-induced acute colitis of mice but are not involved in Gal-3 dependent modulation of colon inflammation.

Involvement of PPARγ in the protective action of tropisetron in an experimental model of ulcerative colitis

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal (GI) tract. Tropisetron, a selective 5-HT3 receptor antagonist, is highly used to counteract chemotherapy-induced emesis. Previous studies revealed the anti-inflammatory properties of this drug. The aim of this study was to evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) receptor in the protective effect of tropisetron in an animal model of ulcerative colitis. Experimental colitis was induced by a single intra-colonic instillation of 4% (V/V) acetic acid in male rats. Tropisetron (3 mg/kg) and GW9662 (PPARγ antagonist) (5 mg/kg) were given twice daily for 2 days after colitis induction. Forty-eight hours after induction of colitis, colon was removed and macroscopic and microscopic features were given. Moreover, colonic concentrations of malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, myeloperoxidase (MPO), and PPARγ activity were assessed. Both macroscopic and histopathological features of colonic injury were markedly ameliorated by tropisetron. Likewise, levels of NO, MDA, TNF-α, and IL-1β diminished significantly (p < .05). GW9662 reversed the effect of tropisetron on these markers partially or completely. In addition, tropisetron increased the PPARγ and decreased the MPO activity (p < .05). Tropisetron exerts notable anti-inflammatory effects in acetic acid-induced colitis in rats, which is probably mediated through PPARγ receptors.

Orally available extract from Brassica oleracea var. capitata rubra attenuates experimental colitis in mouse models of inflammatory bowel diseases

Red cabbage is an important source of vitamins, micro- and macroelements and polyphenols. The aim of our study was to evaluate the anti-inflammatory effect of red cabbage extract (RCE) in mouse models of inflammatory bowel disease (IBD). The effect of RCE on experimental colitis was determined using clinical, macro- and microscopic parameters of inflammation. To study the mechanism of RCE action, the expression of pro-inflammatory cytokines and parameters of oxidative stress were assessed. RCE produced a potent anti-inflammatory action in the mouse model of Crohn's disease, as shown by decreased macroscopic damage score in acute (2.70 ± 0.24 vs. 5.78 ± 0.58 for control group) and chronic (1.81 ± 0.38 vs. 2.94 ± 0.29) colitis model. In the animal model of ulcerative colitis, total macroscopic score was decreased after prophylactic and therapeutic administration (11.9 ± 0.5 and 11.2 ± 0.9 vs. 14.2 ± 0.4 in control group, respectively). Red cabbage extract may be applied as a potential dietary supplement in IBD therapy.

Animal models of ulcerative colitis developed with chemicals

Animal models of ulcerative colitis developed with chemicals