Aucuboside Inhibits the Generation of Th17 Cells in Mice Colitis

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.

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The protective effect of curcumin on rats with DSS-induced ulcerative colitis and its mechanisms

10.21203/rs.3.rs-191627/v1 ◽

2021 ◽

Author(s):

Jing Guo ◽

Yan-yan Zhang ◽

Mei Sun ◽

Ling-fen Xu

Keyword(s):

Ulcerative Colitis ◽

Th17 Cells ◽

Dextran Sulfate ◽

Activity Index ◽

Disease Activity Index ◽

Treg Cells ◽

Enzyme Linked Immunosorbent Assay ◽

T Helper ◽

T Helper 17 ◽

Inflammatory Bowel

Abstract Aim This study aimed to explore effect of curcumin on inflammatory bowel disease (IBD) in rats and its mechanism.Methods: A dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) rat model was established. The disease activity index (DAI) scores were calculated. The histopathological damage scores were determined by haematoxylin-eosin (H&E) staining. Regulatory T (Treg) cells and T helper 17 (Th17) cells in the spleen were analysed by flow cytometry. The levels of interleukin (IL)-10 and IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Results: Compared with the DSS model group, the curcumin group exhibited significantly reduced DAI scores and improvements in histopathological damage. The expression of CD4+IL-17+ Th17 cells was significantly lower and the expression of CD4+CD25+Foxp3+ Treg cells was significantly higher in the curcumin group than in the DSS group.Conclusion: Curcumin may be a new and effective treatment for IBD by regulating the balance of Treg/Th17 cells and the expression of IL-10 and IL-17A.

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

Mediators of Inflammation ◽

10.1155/2013/982383 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 18

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.

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

BioMed Research International ◽

10.1155/2021/4192451 ◽

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.

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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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00264.2009 ◽

2010 ◽

Vol 298 (2) ◽

pp. G255-G266 ◽

Cited By ~ 22

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.

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

Nutrients ◽

10.3390/nu10111684 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1684 ◽

Cited By ~ 2

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.

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A moderately elevated soy protein diet mitigates inflammatory changes in gut and in bone turnover during chronic TNBS-induced inflammatory bowel disease

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0514 ◽

2019 ◽

Vol 44 (6) ◽

pp. 595-605 ◽

Cited By ~ 4

Author(s):

Corinne E. Metzger ◽

S. Anand Narayanan ◽

David C. Zawieja ◽

Susan A. Bloomfield

Keyword(s):

Inflammatory Bowel Disease ◽

Bone Turnover ◽

Soy Protein ◽

Bowel Disease ◽

Protein Diet ◽

Trinitrobenzene Sulfonic Acid ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

The Impact ◽

Colitis Model

Inflammatory bowel disease is a condition that leads to gut pathologies such as abnormal lymphatic architecture, as well as to systemic comorbidities such as bone loss. Furthermore, current therapies are limited to low efficacy and incur side effects. Dietary interventions have been explored minimally, but may provide a treatment for improving gut outcomes and comorbidities. Indeed, plant-based soy protein has been shown to exert anti-inflammatory effects. Here, we tested the impact of a moderately elevated soy protein diet in a chronic, 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model on gut and bone inflammatory-mediated pathophysiological adaptations. Colitis was induced by intrarectal administration of TNBS. Gut histopathology was scored, and lymphatic structural changes and the local inflammatory state were assessed via immunofluorescence. In addition, the effects of gut inflammation on bone turnover and osteocyte proteins were determined via histomorphometry and immunohistochemistry, respectively. The moderately elevated soy protein diet produced improvements in both colonic and bone tissues. In TNBS animals given the soy protein intervention, colon histological scores were reduced and the abnormal lymphatic architecture resolved. There were also improvements in bone formation and reduced bone resorption. In addition, TNBS increased inflammatory cytokines such as tumor necrosis factor-α and receptor activator of nuclear factor κ-B ligand in the gut and bone, but this was resolved in both tissues with the dietary soy protein intervention. The moderately elevated soy protein diet mitigated gut and bone inflammation in a chronic, TNBS-induced colitis model, demonstrating the potential for soy protein as a potential anti-inflammatory dietary intervention for inflammatory bowel disease.

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Validation of the “German Inflammatory Bowel Disease Activity Index (GIBDI)”: An Instrument for Patient-Based Disease Activity Assessment in Crohn’s Disease and Ulcerative Colitis

Zeitschrift für Gastroenterologie ◽

10.1055/a-0605-4080 ◽

2018 ◽

Vol 56 (10) ◽

pp. 1267-1275 ◽

Cited By ~ 1

Author(s):

Angelika Hüppe ◽

Jana Langbrandtner ◽

Winfried Häuser ◽

Heiner Raspe ◽

Bernd Bokemeyer

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Activity Index ◽

Disease Activity Index ◽

Inflammatory Bowel ◽

Activity Indices

Abstract Introduction Assessment of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC) is usually based on the physician’s evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDICD) and UC (GIBDIUC) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians’ documented activity indices. Methods Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements. Results Rank correlations were 0.56 (pMS, GIBDIUC) and 0.57 (HBI, GIBDICD), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories). Discussion There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information.

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Predictive value of fibrinogen in identifying inflammatory bowel disease in active stage

BMC Gastroenterology ◽

10.1186/s12876-021-02040-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiao-Fu Chen ◽

Yuan Zhao ◽

Yu Guo ◽

Zhi-Ming Huang ◽

Xie-Lin Huang

Keyword(s):

Inflammatory Bowel Disease ◽

Confidence Interval ◽

Disease Activity ◽

Bowel Disease ◽

Odds Ratio ◽

Activity Index ◽

Characteristic Curve ◽

Disease Activity Index ◽

Mayo Score ◽

Inflammatory Bowel

Abstract Background We aimed to externally validate for the first time the diagnostic ability of fibrinogen to identify active inflammatory bowel disease (IBD). Methods The research totally involved 788 patients with IBD, consisted of 245 ulcerative colitis (UC) and 543 Crohn’ s disease (CD). The Mayo score and Crohn disease activity index (CDAI) assessed disease activity of UC and CD respectively. The independent association between fibrinogen and disease activity of patients with UC or CD was investigated by multivariate logistic regression analyses. Area under the receiver operating characteristic curve (AUROC) assessed the performance of various biomarkers in discriminating disease states. Results The fibrinogen levels in active patients with IBD significantly increased compared with those in remission stage (P < 0.001). Fibrinogen was an independent predictor to distinguish disease activity of UC (odds ratio: 2.247, 95% confidence interval: 1.428–3.537, P < 0.001) and CD (odds ratio: 2.124, 95% confidence interval: 1.433–3.148, P < 0.001). Fibrinogen was positively correlated with the Mayo score (r = 0.529, P < 0.001) and CDAI (r = 0.625, P < 0.001). Fibrinogen had a high discriminative capacity for both active UC (AUROC: 0.806, 95% confidence interval: 0.751–0.861) and CD (AUROC: 0.869, 95% confidence interval: 0.839–0.899). The optimum cut-off values of fibrinogen 3.22 was 70% sensitive and 77% specific for active UC, and 3.87 was 77% sensitive and 81% specific for active CD respectively. Conclusions Fibrinogen is a convenient and practical biomarker to identify active IBD.

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Comparison of Oral Prednisolone, Budesonide and Probiotics in the Treatment of Canine Inflammatory Bowel Disease

Indian Journal of Animal Research ◽

10.18805/ijar.b-4424 ◽

2021 ◽

Author(s):

M. Sandhya Bhavani ◽

S. Kavitha ◽

B. Gowri ◽

Abid Ali Bhat

Keyword(s):

Inflammatory Bowel Disease ◽

Side Effects ◽

Bowel Disease ◽

Activity Index ◽

Disease Activity Index ◽

Oral Prednisolone ◽

Published Data ◽

Inflammatory Bowel ◽

Faecal Score

Background: Inflammatory bowel disease (IBD) is the common cause of chronic gastrointestinal signs in dogs. The treatment possesses numerous difficulties due to the idiopathic nature of the disease. Conventional steroid therapy usually produces side effects on long term usage. Thus, there is a need for alternative therapies. When compared to human medicine, there is no published data on the use of budesonide and probiotic in the treatment of canine IBD in India. The present study was proposed to compare oral prednisolone, budesonide and probiotics in the management of canine inflammatory bowel disease. Methods: Thirty dogs with idiopathic IBD were selected and randomly grouped. They were subjected to therapy involving prednisolone, budesonide or probiotics. Clinical assessment was performed by calculation of the post treatment Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) score, faecal score and endoscopy. Biochemical analysis of alkaline phosphatase and alanine transaminase were done to record side effects of steroid administration. Result: It was observed from the present study that both prednisolone and budesonide are equally effective in the management of IBD in dogs. Probiotics were found to be less effective when compared to prednisolone and budesonide in the treatment of IBD.

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Effects of Deoxyschisandrin on Visceral Sensitivity of Mice with Inflammatory Bowel Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/2986097 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Zhili Xu ◽

Mingbo Zhang ◽

Deqiang Dou ◽

Tingguo Kang ◽

Feng Li

Keyword(s):

Protein Expression ◽

Activity Index ◽

Disease Activity Index ◽

Visceral Hypersensitivity ◽

Colon Mucosa ◽

Visceral Sensitivity ◽

Bdnf Expression ◽

Inflammatory Bowel ◽

Intestinal Hypersensitivity ◽

Colorectal Distention

The aims of this study were to build an IBD mouse model and further to observe the effects of deoxyschisandrin on IBD and visceral sensitivity and to evaluate the relevance of brain-derived neurotrophic factor (BDNF) to intestinal hypersensitivity of IBD mice. The results showed that deoxyschisandrin could depress the contraction of isolated smooth muscle, modulate gastrointestinal function, and efficiently decrease the disease activity index (DAI) of IBD mice, which proved that deoxyschisandrin had antidiarrheal effects on the animals. In the colorectal distention (CRD) experiment, visceral sensibility was increased in the model group. However, abdominal withdrawal reflex (AWR) scores were decreased after deoxyschisandrin intervention, indicating that deoxyschisandrin could reduce the visceral hypersensitivity of IBD mice. Both IHC observation and western blotting analysis showed that BDNF protein expression increased evidently in colon of IBD mice. After the intervention of deoxyschisandrin, colon mucosa BDNF protein expression in IBD mice decreased, indicating that deoxyschisandrin could decrease mouse intestinal sensitivity by reducing colon mucosa BDNF expression. In conclusion, deoxyschisandrin possessed antidiarrheal effects and visceral hypersensitivity inhibitory effects in the mice with IBD induced by TNBS, which was related to the reduction in BDNF expression in the colon.

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