scholarly journals Anti-Inflammatory Effects of Urocanic Acid Derivatives in Models Ex Vivo and In Vivo of Inflammatory Bowel Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Arthur Kammeyer ◽  
Charlotte P. Peters ◽  
Sybren L. Meijer ◽  
Anje A. te Velde
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Ex Vivo ◽  
Urocanic Acid ◽  
Ethyl Esters ◽  
Fine Tuning ◽  
Additional Indication ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Urocanic acid (UCA) derivatives were tested for their anti-inflammatory activity in inflammatory bowel disease (IBD) in two models: ex vivo and an experimental mouse model. Ex vivo: inflamed colonic tissue was incubated in culture medium with or without the UCA derivatives. Biopsies, incubated with UCA derivatives, produced lower levels of proinflammatory cytokines IL-6 and IL-8 as compared to control biopsies. The same compounds also showed increased levels of IL-10, providing an additional indication for anti-inflammatory properties. In vivo: a combination of two imidazoles and a combination of two of their ethyl esters were administered to mice while colitis was induced by oral administration of dextran sodium sulfate (DSS). Some parameters did not show conclusive effects, but the imidazoles and their ethyl esters reduced the area of inflammation and the number of infiltrating neutrophils. Fibrosis and the sum of all histological aspects were reduced by the imidazoles, whereas the ethyl esters reduced the colon weight to length ratio. These results suggest that the UCA derivatives have anti-inflammatory effect on IBD. In addition, fine tuning of the ex vivo model may provide an elegant way to predict anti-inflammatory effects of potential drugs in humans, which may decrease the need for animal experiments.

Preparation, characterization, and in vivo evaluation of anti-inflammatory activities of selenium nanoparticles synthesized by Kluyveromyces lactis GG799

2021 ◽  
Author(s):  
Xiao fan Song ◽  
Lei Qiao ◽  
Shuqi Yan ◽  
Yue Chen ◽  
Xina Dou ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Kluyveromyces Lactis ◽  
Selenium Nanoparticles ◽  
Human Diseases ◽  
In Vivo Evaluation ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Selenium (Se) as an essential micronutrient that has implications in human diseases, including inflammatory bowel disease (IBD), especially with respect to Se deficiencies. Recently, selenium nanoparticles (SeNPs) have attracted significant...

scholarly journals Inflammatory Bowel Disease–associated GP2 Autoantibodies Inhibit Mucosal Immune Response to Adherent-invasive Bacteria

2020 ◽  
Vol 26 (12) ◽  
pp. 1856-1868
Author(s):  
Stefanie Derer ◽  
Ann-Kathrin Brethack ◽  
Carlotta Pietsch ◽  
Sebastian T Jendrek ◽  
Thomas Nitzsche ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Ex Vivo ◽  
Expression Patterns ◽  
Mucosal Immune Response ◽  
Disease Manifestation ◽  
Inflammatory Bowel

Abstract Adherent-invasive Escherichia coli have been suggested to play a pivotal role within the pathophysiology of inflammatory bowel disease (IBD). Autoantibodies against distinct splicing variants of glycoprotein 2 (GP2), an intestinal receptor of the bacterial adhesin FimH, frequently occur in IBD patients. Hence, we aimed to functionally characterize GP2-directed autoantibodies as a putative part of IBD’s pathophysiology. Ex vivo, GP2-splicing variant 4 (GP2#4) but not variant 2 was expressed on intestinal M or L cells with elevated expression patterns in IBD patients. The GP2#4 expression was induced in vitro by tumor necrosis factor (TNF)-α. The IBD-associated GP2 autoantibodies inhibited FimH binding to GP2#4 and were decreased in anti-TNFα-treated Crohn’s disease patients with ileocolonic disease manifestation. In vivo, mice immunized against GP2 before infection with adherent-invasive bacteria displayed exacerbated intestinal inflammation. In summary, autoimmunity against intestinal expressed GP2#4 results in enhanced attachment of flagellated bacteria to the intestinal epithelium and thereby may drive IBD’s pathophysiology.

Alpha-MSH Targeted Liposomal Nanoparticle for Imaging in Inflammatory Bowel Disease (IBD)

2020 ◽  
Vol 26 (31) ◽  
pp. 3840-3846 ◽  
Author(s):  
Tuula Peñate-Medina ◽  
Christabel Damoah ◽  
Miriam Benezra ◽  
Olga Will ◽  
Kalevi Kairemo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Ex Vivo ◽  
Activity Index ◽  
Disease Activity Index ◽  
Delivery Vehicle ◽  
Disease Treatment ◽  
Melanocortin 1 Receptor ◽  
Inflammatory Bowel

Background: The purpose of our study was to find a novel targeted imaging and drug delivery vehicle for inflammatory bowel disease (IBD). IBD is a common and troublesome disease that still lacks effective therapy and imaging options. As an attempt to improve the disease treatment, we tested αMSH for the targeting of nanoliposomes to IBD sites. αMSH, an endogenous tridecapeptide, binds to the melanocortin-1 receptor (MC1-R) and has anti-inflammatory and immunomodulating effects. MC1-R is found on macrophages, neutrophils and the renal tubule system. We formulated and tested a liposomal nanoparticle involving αMSH in order to achieve a specific targeting to the inflamed intestines. Methods: NDP-αMSH peptide conjugated to Alexa Fluor™ 680 was linked to the liposomal membrane via NSuccinyl PE and additionally loaded into the lumen of the liposomes. Liposomes without the αMSH-conjugate and free NDP-αMSH were used as a control. The liposomes were also loaded with ICG to track them. The liposomes were tested in DSS treated mice, which had received DSS via drinking water order to develop a model IBD. Inflammation severity was assessed by the Disease Activity Index (DAI) score and ex vivo histological CD68 staining of samples taken from different parts of the intestine. The liposome targeting was analyzed by analyzing the ICG and ALEXA 680 fluorescence in the intestine compared to the biodistribution. Results: NPD-αMSH was successfully labeled with Alexa and retained its biological activity. Liposomes were identified in expected regions in the inflamed bowel regions and in the kidneys, where MC1-R is abundant. In vivo liposome targeting correlated with the macrophage concentration at the site of the inflammation supporting the active targeting of the liposomes through αMSH. The liposomal αMSH was well tolerated by animals. Conclusions: This study opens up the possibility to further develop an αMSH targeted theranostic delivery to different clinically relevant applications in IBD inflammation but also opens possibilities for use in other inflammations like lung inflammation in Covid 19.

scholarly journals A Gut-Ex-Vivo System to Study Gut Inflammation Associated to Inflammatory Bowel Disease (IBD)

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 605
Author(s):  
Mara Gagliardi ◽  
Romina Monzani ◽  
Nausicaa Clemente ◽  
Luca Fusaro ◽  
Valentina Saverio ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Dynamic Condition ◽  
Transglutaminase 2 ◽  
Effective Manner ◽  
Junction Protein ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a complex, chronic, and dysregulated inflammatory condition which etiology is still largely unknown. Its prognosis and disease progression are highly variable and unpredictable. IBD comprises several heterogeneous inflammatory conditions ranging from Ulcerative Colitis (UC) to Crohn’s Disease (CD). Importantly, a definite, well-established, and effective clinical treatment for these pathologies is still lacking. The urgent need for treatment is further supported by the notion that patients affected by UC or CD are also at risk of developing cancer. Therefore, a deeper understanding of the molecular mechanisms at the basis of IBD development and progression is strictly required to design new and efficient therapeutic regimens. Although the development of animal models has undoubtedly facilitated the study of IBD, such in vivo approaches are often expensive and time-consuming. Here we propose an organ ex vivo culture (Gut-Ex-Vivo system, GEVS) based on colon from Balb/c mice cultivated in a dynamic condition, able to model the biochemical and morphological features of the mouse models exposed to DNBS (5–12 days), in 5 h. Indeed, upon DNBS exposure, we observed a dose-dependent: (i) up-regulation of the stress-related protein transglutaminase 2 (TG2); (ii) increased intestinal permeability associated with deregulated tight junction protein expression; (iii) increased expression of pro-inflammatory cytokines, such as TNFα, IFNγ, IL1β, IL6, IL17A, and IL15; (iv) down-regulation of the anti-inflammatory IL10; and (v) induction of Endoplasmic Reticulum stress (ER stress), all markers of IBD. Altogether, these data indicate that the proposed model can be efficiently used to study the pathogenesis of IBD, in a time- and cost-effective manner.

New probiotic strains for inflammatory bowel disease management identified by combining in vitro and in vivo approaches

2018 ◽  
Vol 9 (2) ◽  
pp. 317-331 ◽  
Author(s):  
J. Alard ◽  
V. Peucelle ◽  
D. Boutillier ◽  
J. Breton ◽  
S. Kuylle ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Chronic Colitis ◽  
Acute Colitis ◽  
Probiotic Strains ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Alterations in the gut microbiota composition play a key role in the development of chronic diseases such as inflammatory bowel disease (IBD). The potential use of probiotics therefore gained attention, although outcomes were sometimes conflicting and results largely strain-dependent. The present study aimed to identify new probiotic strains that have a high potential for the management of this type of pathologies. Strains were selected from a large collection by combining different in vitro and in vivo approaches, addressing both anti-inflammatory potential and ability to improve the gut barrier function. We identified six strains with an interesting anti-inflammatory profile on peripheral blood mononuclear cells and with the ability to restore the gut barrier using a gut permeability model based on Caco-2 cells sensitized with hydrogen peroxide. The in vivo evaluation in two 2,4,6-trinitrobenzene sulfonic acid-induced murine models of colitis highlighted that some of the strains exhibited beneficial activities against acute colitis while others improved chronic colitis. Bifidobacterium bifidum PI22, the strain that exhibited the most protective capacities against acute colitis was only slightly efficacious against chronic colitis, while Bifidobacterium lactis LA804 which was less efficacious in the acute model was the most protective against chronic colitis. Lactobacillus helveticus PI5 was not anti-inflammatory in vitro but the best in strengthening the epithelial barrier and as such able to significantly dampen murine acute colitis. Interestingly, Lactobacillus salivarius LA307 protected mice significantly against both types of colitis. This work provides crucial clues for selecting the best strains for more efficacious therapeutic approaches in the management of chronic inflammatory diseases. The strategy employed allowed us to identify four strains with different characteristics and a high potential for the management of inflammatory diseases, such as IBD.

scholarly journals 5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 578
Author(s):  
Vipul Yadav ◽  
Yang Mai ◽  
Laura E. McCoubrey ◽  
Yasufumi Wada ◽  
Motoyasu Tomioka ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Heme Oxygenase ◽  
Bowel Disease ◽  
Aminolevulinic Acid ◽  
Heme Oxygenase 1 ◽  
Aminosalicylic Acid ◽  
Colonic Tissue ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

5-Aminolevulinic acid (5-ALA) is a naturally occurring nonprotein amino acid licensed as an optical imaging agent for the treatment of gliomas. In recent years, 5-ALA has been shown to possess anti-inflammatory and immunoregulatory properties through upregulation of heme oxygenase-1 via enhancement of porphyrin, indicating that it may be beneficial for the treatment of inflammatory conditions. This study systematically examines 5-ALA for use in inflammatory bowel disease (IBD). Firstly, the ex vivo colonic stability and permeability of 5-ALA was assessed using human and mouse fluid and tissue. Secondly, the in vivo efficacy of 5-ALA, in the presence of sodium ferrous citrate, was investigated via the oral and intracolonic route in an acute DSS colitis mouse model of IBD. Results showed that 5-ALA was stable in mouse and human colon fluid, as well as in colon tissue. 5-ALA showed more tissue restricted pharmacokinetics when exposed to human colonic tissue. In vivo dosing demonstrated significantly improved colonic inflammation, increased local heme oxygenase-1 levels, and decreased concentrations of proinflammatory cytokines TNF-α, IL-6, and IL-1β in both plasma and colonic tissue. These effects were superior to that measured concurrently with established anti-inflammatory treatments, ciclosporin and 5-aminosalicylic acid (mesalazine). As such, 5-ALA represents a promising addition to the IBD armamentarium, with potential for targeted colonic delivery.

scholarly journals OP36 Investigating the role of bioactives produced by gut bacteria to modulate immune response in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S037-S038
Author(s):  
R Giri ◽  
K Shamsunnahar ◽  
A Salim ◽  
R Capon ◽  
M Morrison ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Ex Vivo ◽  
Gut Bacteria ◽  
Healthy Controls ◽  
Healthy Human ◽  
Chronic Inflammatory Condition ◽  
Inflammatory Bowel ◽  
Colitis Model

Abstract Background inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract. Although the pathogenesis of IBD is not fully understood, it is believed to result from the interaction between various genetic and environmental factors, including the microbiome, resulting in inappropriate gut inflammation. Under homeostatic conditions, the gut immune system exists in a tolerogenic state with the microbiota. However, microbial dysbiosis and an imbalance of pro- and anti-inflammatory cytokines in the gut characterise IBD and recently faecal microbiota transplantation studies have demonstrated that manipulation of the microbiome can induce remission. In this study, the ability of bioactives produced from single species of anaerobic gut bacteria cultured from healthy human faecal samples to modulate NF-kB activity was investigated, their biochemical properties were assessed and their ability to alleviate colitis was also investigated. Methods The NF-κB suppressive effects of culture supernatants (CSs) from 23 different isolates were tested on colonic epithelial cell lines. Suppressive CSs were also tested on human-derived colonic organoids from IBD patients and healthy controls and IL-8 expression was measured. Furthermore, CS from AHG0001 strain was also tested in spontaneous colitis model Winnie in vivo. The supernatant was further characterised by extraction in multiple solvents and fractionated through reversed-phase analytic HPLC column to test for suppressive fractions and further investigate their chemical characteristics. Results LS174T and Caco-2 reporter cells stimulated with TNFα and IL-1β respectively, resulted in NF-κB activation. Of the 23 isolates screened, CS from five isolates significantly suppressed NF-κB activation. The selected CSs also suppressed IL-8 secretion in PBMCs and gut organoids from both UC and CD patients, as well as healthy controls, with notable individual variation. Rectal gavage of CS from AHG0001 also reduced disease activity, improved histologic inflammation and reduced the pro-inflammatory gene expression in Winnie mice. Furthermore, a potent small molecule (IC50 = 3 nM) produced by AHG0001 was also identified through bioassay-guided solvent extractions and filtrations, followed by UPLC-QTOF and comparative metabolomics. Conclusion Our anaerobic culturing and NF-κB reporter assay system allows for the rapid identification of bacteria producing immunomodulatory bioactives, which could lead to the future development of novel therapeutics. Our in vivo and ex vivo testing utilising spontaneous colitis model and patient-derived organoids demonstrates the potential of precision medicine-based approaches for bacterial based therapeutics.

scholarly journals Intestinal Anti-Inflammatory Effect of a Peptide Derived from Gastrointestinal Digestion of Buffalo (Bubalus bubalis) Mozzarella Cheese

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 610 ◽  
Author(s):  
Gian Tenore ◽  
Ester Pagano ◽  
Stefania Lama ◽  
Daniela Vanacore ◽  
Salvatore Di Maro ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Therapeutic Potential ◽  
Intestinal Barrier ◽  
Bubalus Bubalis ◽  
Epithelial Junctions ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Under physiological conditions, the small intestine represents a barrier against harmful antigens and pathogens. Maintaining of the intestinal barrier depends largely on cell–cell interactions (adherent-junctions) and cell–matrix interactions (tight-junctions). Inflammatory bowel disease is characterized by chronic inflammation, which induces a destructuring of the architecture junctional epithelial proteins with consequent rupture of the intestinal barrier. Recently, a peptide identified by Bubalus bubalis milk-derived products (MBCP) has been able to reduce oxidative stress in intestinal epithelial cells and erythrocytes. Our aim was to evaluate the therapeutic potential of MBCP in inflammatory bowel disease (IBD). We studied the effect of MBCP on (i) inflamed human intestinal Caco2 cells and (ii) dinitrobenzene sulfonic acid (DNBS) mice model of colitis. We have shown that MBCP, at non-cytotoxic concentrations, both in vitro and in vivo induced the adherent epithelial junctions organization, modulated the nuclear factor (NF)-κB pathway and reduced the intestinal permeability. Furthermore, the MBCP reverted the atropine and tubocurarine injury effects on adherent-junctions. The data obtained showed that MBCP possesses anti-inflammatory effects both in vitro and in vivo. These results could have an important impact on the therapeutic potential of MBCP in helping to restore the intestinal epithelium integrity damaged by inflammation.

scholarly journals Resveratrol and inflammatory bowel disease: the evidence so far

2017 ◽  
Vol 31 (1) ◽  
pp. 85-97 ◽  
Author(s):  
Sandra Nunes ◽  
Francesca Danesi ◽  
Daniele Del Rio ◽  
Paula Silva
Keyword(s):  
Inflammatory Bowel Disease ◽  
Intestinal Mucosa ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Human Subjects ◽  
Intestinal Immunity ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

AbstractDespite the fact that inflammatory bowel disease (IBD) has still no recognised therapy, treatments which have proven at least mildly successful in improving IBD symptoms include anti-inflammatory drugs and monoclonal antibodies targeting pro-inflammatory cytokines. Resveratrol, a natural (poly)phenol found in grapes, red wine, grape juice and several species of berries, has been shown to prevent and ameliorate intestinal inflammation. Here, we discuss the role of resveratrol in the improvement of inflammatory disorders involving the intestinal mucosa. The present review covers three specific aspects of resveratrol in the framework of inflammation: (i) its content in food; (ii) its intestinal absorption and metabolism; and (iii) its anti-inflammatory effects in the intestinal mucosa in vitro and in the very few in vivo studies present to date. Actually, if several studies have shown that resveratrol may down-regulate mediators of intestinal immunity in rodent models, only two groups have performed intervention studies in human subjects using resveratrol as an agent to improve IBD conditions. The effects of resveratrol should be further investigated by conducting well-designed clinical trials, also taking into account different formulations for the delivery of the bioactive compound.

scholarly journals The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rayko Evstatiev ◽  
Adam Cervenka ◽  
Tina Austerlitz ◽  
Gunther Deim ◽  
Maximilian Baumgartner ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Models ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Food Additives ◽  
Colorectal Carcinogenesis ◽  
Testing Procedures ◽  
Inflammatory Models ◽  
Inflammatory Bowel

AbstractInflammatory bowel disease is a group of conditions with rising incidence caused by genetic and environmental factors including diet. The chelator ethylenediaminetetraacetate (EDTA) is widely used by the food and pharmaceutical industry among numerous other applications, leading to a considerable environmental exposure. Numerous safety studies in healthy animals have revealed no relevant toxicity by EDTA. Here we show that, in the presence of intestinal inflammation, EDTA is surprisingly capable of massively exacerbating inflammation and even inducing colorectal carcinogenesis at doses that are presumed to be safe. This toxicity is evident in two biologically different mouse models of inflammatory bowel disease, the AOM/DSS and the IL10−/− model. The mechanism of this effect may be attributed to disruption of intercellular contacts as demonstrated by in vivo confocal endomicroscopy, electron microscopy and cell culture studies. Our findings add EDTA to the list of food additives that might be detrimental in the presence of intestinal inflammation, but the toxicity of which may have been missed by regulatory safety testing procedures that utilize only healthy models. We conclude that the current use of EDTA especially in food and pharmaceuticals should be reconsidered. Moreover, we suggest that intestinal inflammatory models should be implemented in the testing of food additives to account for the exposure of this primary organ to environmental and dietary stress.

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