scholarly journals Poly-γ-Glutamic Acid Attenuates Angiogenesis and Inflammation in Experimental Colitis

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Munkhtugs Davaatseren ◽  
Jin-Taek Hwang ◽  
Jae Ho Park ◽  
Myung-Sunny Kim ◽  
Shuaiyu Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Glutamic Acid ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Mucosal Inflammation ◽  
Myeloperoxidase Activity ◽  
Inflammatory Bowel ◽  
Colitis Model ◽  
Histopathological Evidence

Poly-γ-glutamic acid (γ-PGA), naturally secreted from various strains ofBacillus, has anti-inflammatory activity. In inflammatory bowel disease (IBD), inflammation is promoted and sustained by angiogenesis; however, the role played byγ-PGA in this condition is unclear. Therefore, we evaluatedγ-PGA effects on angiogenesis and inflammation in a dextran sulfate sodium- (DSS-) induced mouse colitis model. Experimental colitis was induced in male C57BL/6 mice by administering 3% DSS. Disease activity index (DAI), histopathological scores, microvascular density, myeloperoxidase activity, and VEGF-A and VEGFR2 expression were compared among control mice, DSS-treated mice, and mice receiving 3% DSS along withγ-PGA at 50 mg/kg body weight per day or 3% DSS withγ-PGA at 200 mg/kg body weight per day. We found thatγ-PGA significantly attenuated weight loss, DAI, and colon shortening.γ-PGA also significantly reduced histopathological evidence of injury. Moreover,γ-PGA significantly attenuated DSS-induced blood vessel densities. Furthermore,γ-PGA attenuated DSS-induced expression of VEGF-A and its receptor, VEGFR2. In addition,γ-PGA treatment led to reduced recruitment of leukocytes to the inflamed colon. Therefore, our results indicate thatγ-PGA has potential application in conditions marked by inflammatory-driven angiogenesis and mucosal inflammation.

scholarly journals Beneficial Effect of Shikonin on Experimental Colitis Induced by Dextran Sulfate Sodium in Balb/C Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Isabel Andújar ◽  
José Luis Ríos ◽  
Rosa María Giner ◽  
José Miguel Cerdá ◽  
María del Carmen Recio
Keyword(s):  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Myeloperoxidase Activity ◽  
Dependent Manner ◽  
Inflammatory Bowel ◽  
Activity Index Score ◽  
Bloody Stools ◽  
Dose Dependent

The naphthoquinone shikonin, a major component of the root ofLithospermum erythrorhizon, now is studied as an anti-inflammatory agent in the treatment of ulcerative colitis (UC). Acute UC was induced in Balb/C mice by oral administration of 5% dextran sodium sulfate (DSS). The disease activity index was evaluated, and a histologic study was carried out. Orally administered shikonin reduces induced UC in a dose-dependent manner, preventing the shortening of the colorectum and decreasing weight loss by 5% while improving the appearance of feces and preventing bloody stools. The disease activity index score was much lower in shikonin-treated mice than in the colitic group, as well as the myeloperoxidase activity. The expression of cyclooxygenase-2 was reduced by 75%, activation of NF-κB was reduced by 44%, and that of pSTAT-3 by 47%, as well as TNF-α, IL-1β, and IL-6 production. Similar results were obtained in primary macrophages culture. This is the first report of shikonin’s ability to attenuate acute UC induced by DSS. Shikonin acts by blocking the activation of two major targets: NF-κB and STAT-3, and thus constitutes a promising potential therapeutic agent for the management of the inflammatory bowel disease.

scholarly journals High-fat diet promotes experimental colitis by inducing oxidative stress in the colon

2019 ◽  
Vol 317 (4) ◽  
pp. G453-G462 ◽  
Author(s):  
Xue Li ◽  
Xinzhi Wei ◽  
Yue Sun ◽  
Jie Du ◽  
Xin Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Experimental Colitis ◽  
Mucosal Barrier ◽  
Mucosal Inflammation ◽  
High Fat ◽  
Trinitrobenzenesulfonic Acid ◽  
Barrier Permeability ◽  
Inflammatory Bowel ◽  
Colitis Model

Diets high in animal fats are associated with increased risks of inflammatory bowel disease, but the mechanism remains unclear. In this study, we investigated the effect of high-fat diet (HFD) on the development of experimental colitis in mice. Relative to mice fed low-fat diet (LFD), HFD feeding for 4 wk increased the levels of triglyceride, cholesterol, and free fatty acids in the plasma as well as within the colonic mucosa. In an experimental colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS), mice on 4-wk HFD exhibited more severe colonic inflammation and developed more severe colitis compared with the LFD counterparts. HFD feeding resulted in higher production of mucosal pro-inflammatory cytokines, greater activation of the myosin light chain kinase (MLCK) tight junction regulatory pathway, and greater increases in mucosal barrier permeability in mice following TNBS induction. HFD feeding also induced gp91, an NADPH oxidase subunit, and promoted reactive oxygen species (ROS) production in both colonic epithelial cells and lamina propria cells. In HCT116 cell culture, palmitic acid or palmitic acid and TNF-α combination markedly increased ROS production and induced the MLCK pathway, and these effects were markedly diminished in the presence of a ROS scavenger. Taken together, these data suggest that HFD promotes colitis by aggravating mucosal oxidative stress, which rapidly drives mucosal inflammation and increases intestinal mucosal barrier permeability. NEW & NOTEWORTHY This study demonstrates high-fat diet feeding promotes colitis in a 2,4,6-trinitrobenzenesulfonic acid-induced experimental colitis model in mice. The underlying mechanism is that high-fat diet induces oxidative stress in the colonic mucosa, which increases colonic epithelial barrier permeability and drives colonic mucosal inflammation. These observations provide molecular evidence that diets high in saturated fats are detrimental to patients with inflammatory bowel diseases.

Cyclooxygenase-2-derived prostaglandin D2 is an early anti-inflammatory signal in experimental colitis

2000 ◽  
Vol 279 (1) ◽  
pp. G238-G244 ◽  
Author(s):  
Maureen N. Ajuebor ◽  
Anita Singh ◽  
John L. Wallace
Keyword(s):  
Activity Index ◽  
Experimental Colitis ◽  
Cyclooxygenase 2 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Prostaglandin D2 ◽  
Myeloperoxidase Activity ◽  
Granulocyte Infiltration ◽  
Inflammatory Bowel ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The ability of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors to exacerbate inflammatory bowel disease suggests that prostaglandins are important anti-inflammatory mediators in this context. Prostaglandin D2 has been suggested to exert anti-inflammatory effects. We investigated the possibility that prostaglandin D2 derived from cyclooxygenase-2 plays an important role in downregulating colonic inflammation in rats. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid. At various times thereafter (from 1 h to 7 days), colonic prostaglandin synthesis and myeloperoxidase activity (index of granulocyte infiltration) were measured. Prostaglandin D2synthesis was elevated >4-fold above controls within 1–3 h of induction of colitis, preceding significant granulocyte infiltration. Treatment with a selective cyclooxygenase-2 inhibitor abolished the increase in prostaglandin D2 synthesis and caused a doubling of granulocyte infiltration. Colonic granulocyte infiltration was significantly reduced by administration of prostaglandin D2 or a DP receptor agonist (BW-245C). These results demonstrate that induction of colitis results in a rapid increase in prostaglandin D2 synthesis via cyclooxygenase-2. Prostaglandin D2 downregulates granulocyte infiltration into the colonic mucosa, probably through the DP receptor.

scholarly journals Inhibition of PD-1 Protects against TNBS-Induced Colitis via Alteration of Enteric Microbiota

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Hao-ming Xu ◽  
You-lian Zhou ◽  
Jing Xu ◽  
Ying-fei Li ◽  
Chong Zhao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Activity Index ◽  
Alpha Diversity ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Positive Control ◽  
Trinitrobenzene Sulfonic Acid ◽  
Amino Salicylic Acid ◽  
Inflammatory Bowel ◽  
Control Body

Background and Aim. The enteric microbiota is able to cross-talk with factors involved in the blockade of programmed cell death protein 1 (PD-1) and also plays an important role in the predisposition and onset of inflammatory bowel disease (IBD). The current study used a mouse model of experimental colitis to determine the pathogenic connection between PD-1 inhibition, gut microbiota, and IBD. Methods. Colitis was induced in mice using 2,4,6-trinitrobenzene-sulfonic acid (TNBS), and mice were subsequently treated with either a PD-1 inhibitor or 5-amino-salicylic acid (ASA) as a positive control. Body weight, disease activity index (DAI), colon length, and tissue damage were evaluated, and the enteric microbiota was profiled using high-throughput 16S rRNA sequencing of fecal samples from the experimental mice. Results. TNBS caused mice to experience IBD-like symptoms, which were attenuated by the PD-1 inhibitor, as indicated by a decrease in DAI scores ( p = 0.0002 ). Furthermore, in this mouse model of IBD, PD-1 inhibition improved the alpha diversity as well as restored the beta diversity of the enteric microbiome. It also significantly enriched the abundance of short-chain fatty acid- (SCFA-) producing bacteria of the Firmicutes ( p < 0.05 ) and Bacteroidetes ( p < 0.05 ) phyla but depopulated Proteobacteria ( p < 0.05 ). Conclusion. PD-1 inhibition can partly mitigate TNBS-induced colitis and restore the enteric microbiota by enriching the abundance of SCFA-producing bacteria.

scholarly journals A salmon peptide diet alleviates experimental colitis as compared with fish oil

2013 ◽  
Vol 2 ◽  
Author(s):  
Tore Grimstad ◽  
Bodil Bjørndal ◽  
Daniel Cacabelos ◽  
Ole G. Aasprong ◽  
Roald Omdal ◽  
...  
Keyword(s):  
Fish Oil ◽  
Dietary Intervention ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Mrna Levels ◽  
Keratinocyte Chemoattractant ◽  
Male Wistar Rats ◽  
Inflammatory Bowel

AbstractFish oil (FO) has been shown to have anti-inflammatory properties in animal models of inflammatory bowel disease, but how fish peptides (FP) influence intestinal inflammation has been less studied. Male Wistar rats, divided into five groups, were included in a 4-week dietary intervention study. Of the groups, four were exposed in the fourth week to 5 % dextran sulfate sodium (DSS) to induce colitis, while one group was unexposed. The diets were: (1) control, (2) control + DSS, (3) FO (5 %) + DSS, (4) FP (3·5 %) + DSS, (5) FO + FP + DSS. Following DSS intake, weight and disease activity index (DAI) were assessed, and histological combined score (HCS), selected colonic PG, cytokines, oxidative damage markers and mRNA levels were measured. FP reduced HCS, tended to lower DAI (P = 0·07) and reduced keratinocyte chemoattractant/growth-regulated oncogene levels, as compared with the FO diet. FP also reduced mRNA levels of Il-6 and Cxcl1, although not significantly. FO intake increased the DAI as compared with DSS alone. PGE3 levels increased after the FO diet, and even more following FO + FP intake. The FP diet seems to have a protective effect in DSS-induced colitis as compared with FO. A number of beneficial, but non-significant, changes also occurred after FP v. DSS. A combined FO + FP diet may influence PG synthesis, as PGE3 levels were higher after the combined diet than after FO alone.

scholarly journals Aucuboside Inhibits the Generation of Th17 Cells in Mice Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenxue Mei ◽  
Xiao Wang ◽  
Fanxiang Meng ◽  
Xiaoqing Zhang ◽  
Ling Chen ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Inflammatory Responses ◽  
Activity Index ◽  
Biological Activities ◽  
Disease Activity Index ◽  
Treg Cells ◽  
Trinitrobenzene Sulfonic Acid ◽  
Wide Range ◽  
Inflammatory Bowel ◽  
Colitis Model

Aucuboside is an iridoid glycoside extracted from traditional Chinese medicine such as Rehmannia glutinosa, possessing a wide range of biological activities, including antioxidant, anti-aging, anti-inflammatory, and anti-fibrotic effects. The effects of aucuboside on inflammatory bowel disease (IBD) have not been studied. Therefore, the effects of aucuboside on the generation of Foxp3+ regulatory T (Treg) cells and IL-17–producing T helper (Th17) cells in colitis were studied. A mouse colitis model was established by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) to mimic human IBD. The generation of Treg and Th17 cells was evaluated by flow cytometry. Aucuboside significantly alleviated colitis symptoms, including weight loss, high disease activity index, and inflammatory responses. The generation of Th17 cells in colitis was significantly inhibited by aucuboside and accompanied by the suppression of IL-17 expression. In Raw264.7 cells, the LPS-induced increase in IL-17 expression was also suppressed by aucuboside, which was significantly blocked by the RORγt inhibitor sr2211. In addition, the decrease in the proportion of Treg cells was also partially reversed by aucuboside, which may reflect the aucuboside-induced inhibition of Th17 cells. This previously unrecognized immunoregulatory function of aucuboside may have clinical applications in IBD.

scholarly journals The therapeutic efficacy of mesenchymal stromal cells on experimental colitis was improved by the IFN-γ and poly(I:C) priming through promoting the expression of indoleamine 2,3-dioxygenase

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  
Keyword(s):  
Weight Loss ◽  
Disease Activity ◽  
Stromal Cells ◽  
Therapeutic Efficacy ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Poly I:C ◽  
Colon Tissue ◽  
Ifn Γ

Abstract Background Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSCs) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 upregulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.

Blockage of angiotensin II type 1 receptor regulates TNF-α-induced MAdCAM-1 expression via inhibition of NF-κB translocation to the nucleus and ameliorates colitis

2010 ◽  
Vol 298 (2) ◽  
pp. G255-G266 ◽  
Author(s):  
Takashi Mizushima ◽  
Makoto Sasaki ◽  
Tomoaki Ando ◽  
Tsuneya Wada ◽  
Mamoru Tanaka ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Activity Index ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Wild Type ◽  
Inflammatory Conditions ◽  
Tnf Α ◽  
Novel Target ◽  
Colitis Model

Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is an important target in the treatment of inflammatory bowel disease (IBD). Recently, treatment of IBD with an antibody to α4β7-integrin, a ligand for MAdCAM-1, has been an intense focus of research. Our aim was to clarify the mechanism by which MAdCAM-1 is regulated via angiotensin II type 1 receptor (AT1R), and to verify if AT1R might be a novel target for IBD treatment. The role of AT1R in the expression of MAdCAM-1 in SVEC (a murine high endothelial venule cell) and MJC-1 (a mouse colonic endothelial cell) was examined following cytokine stimulation. We further evaluated the effect of AT1R on the pathogenesis of immune-mediated colitis using AT1R-deficient (AT1R−/−) mice and a selective AT1R blocker. AT1R blocker significantly suppressed MAdCAM-1 expression induced by TNF-α, but did not inhibit phosphorylation of p38 MAPK or of IκB that modulate MAdCAM-1 expression. However, NF-κB translocation into the nucleus was inhibited by these treatments. In a murine colitis model induced by dextran sulfate sodium, the degree of colitis, judged by body weight loss, histological damage, and the disease activity index, was much milder in AT1R−/− than in wild-type mice. The expression of MAdCAM-1 was also significantly lower in AT1R−/− than in wild-type mice. These results suggest that AT1R regulates the expression of MAdCAM-1 under colonic inflammatory conditions through regulation of the translocation of NF-κB into the nucleus. Furthermore, inhibition of AT1R ameliorates colitis in a mouse colitis model. Therefore, AT1R might be one of new therapeutic target of IBD via regulation of MAdCAM-1.

scholarly journals Isolation and Characterization of Potentially Probiotic Bacterial Strains from Mice: Proof of Concept for Personalized Probiotics

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1684 ◽  
Author(s):  
Larissa Celiberto ◽  
Roseli Pinto ◽  
Elizeu Rossi ◽  
Bruce Vallance ◽  
Daniela Cavallini
Keyword(s):  
Intestinal Inflammation ◽  
Activity Index ◽  
Disease Activity Index ◽  
Bacterial Strains ◽  
Dss Colitis ◽  
Isolation And Characterization ◽  
Inflammatory Bowel ◽  
Commercial Probiotics ◽  
Lower Disease Activity

Modulation of the gut microbiota through the use of probiotics has been widely used to treat or prevent several intestinal diseases. However, inconsistent results have compromised the efficacy of this approach, especially in severe conditions such as inflammatory bowel disease (IBD). The purpose of our study was to develop a personalized probiotic strategy and assess its efficacy in a murine model of intestinal inflammation. Commensal bacterial strains were isolated from the feces of healthy mice and then administered back to the host as a personalized treatment in dextran sodium sulfate (DSS)-induced colitis. Colonic tissues were collected for histological analysis and to investigate inflammatory markers such as Il-1β, Il-6, TGF-β, and Il-10, and the enzyme myeloperoxidase as a neutrophil marker. The group that received the personalized probiotic showed reduced susceptibility to DSS-colitis as compared to a commercial probiotic. This protection was characterized by a lower disease activity index and reduced histopathological damage in the colon. Moreover, the personalized probiotic was more effective in modulating the host immune response, leading to decreased Il-1β and Il-6 and increased TGF-β and Il-10 expression. In conclusion, our study suggests that personalized probiotics may possess an advantage over commercial probiotics in treating dysbiotic-related conditions, possibly because they are derived directly from the host’s own microbiota.

scholarly journals ROLE OF ANTIOXIDANT AND MYELOPEROXIDASE LEVELS IN 7, 12-DIMETHYLBENZ [A] ANTHRACENE INDUCED EXPERIMENTAL RAT MODEL: EVIDENCE FOR OXIDATIVE DAMAGE IN ACTIVE ULCERATIVE COLITIS.

2017 ◽  
Vol 9 (3) ◽  
pp. 282
Author(s):  
P. Geetha ◽  
B. Lakshman Kumar ◽  
U. Indra ◽  
B. Pavithra Sheetal
Keyword(s):  
Ulcerative Colitis ◽  
Body Weight ◽  
Antioxidant Status ◽  
Activity Index ◽  
Disease Activity Index ◽  
The Body ◽  
Unknown Etiology ◽  
Steady Increase ◽  
Tissue Samples ◽  
Significant Change

Objective: Ulcerative colitis known as inflammatory bowel disease (IBD) of unknown etiology. We examined the antioxidant and myeloperoxidase status in a murine model of 7,12-dimethylbenz[a]anthracene induced colitis to elucidate the exact mechanism behind the inflammation.Methods: Male Wistar rats were exposed to ulcerative colitis using various concentration of DMBA (7,12-Dimethylbenz[A]anthracene) were periodically analysed on 4th, 8th, 12th, 24th and 32nd week from the date of induction. To determine the disease activity index changes in body weight, food consumption, the presence of gross blood in stool and consistency of feces and diarrhea were observed. Macroscopic characters were elucidated based on clinical features of the colon and rectum using scoring pattern. Tissue inflammation status was noted through myeloperoxidase (MPO) assay. The antioxidant status in tissue samples was analysed by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total reduced glutathione (GSH).Results: Gavage intubation of DMBA induced colitis showed significant changes from 4th week and severity on 32nd week. The body weight was gradually reduced. Macroscopic scoring showed severe scoring pattern the inflammation was significantly heavier by week 4; and by the end of 32 w, inflammation in rats was double that of the controls, tissue myeloperoxidase (MPO) activity showed the steady increase of neutrophil infiltration and inflammation rate every week. A significant change was noted in tissue antioxidant status and it showed the oxidation level. Statistically, significant change was recorded from 4th week till 32nd week.Conclusion: The conventional biochemical changes in colitis induced animal model revealed the association between the oxidative stress and ulcerative colitis.

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