scholarly journals Activation of Free Fatty Acid Receptor 4 Affects Intestinal Inflammation and Improves Colon Permeability in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2716
Author(s):  
Maciej Salaga ◽  
Adrian Bartoszek ◽  
Agata Binienda ◽  
Julia B. Krajewska ◽  
Adam Fabisiak ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Intestinal Inflammation ◽  
Feeding Habits ◽  
Inflammatory Activity ◽  
Intestinal Barrier Function ◽  
Pharmacological Intervention ◽  
Myeloperoxidase Activity ◽  
Trinitrobenzenesulfonic Acid ◽  
Anti Inflammatory

Diet is considered an important trigger in inflammatory bowel diseases (IBD), as feeding habits can affect intestinal permeability and clearance of bacterial antigens, consequently influencing the immune system. Free fatty acid receptors (FFARs), expressed on the intestinal epithelial cells, belong to the family of luminal-facing receptors that are responsive to nutrients. The objective of this study was to characterize the anti-inflammatory activity and the effect on intestinal barrier function of synthetic FFAR agonists in mouse models of colitis. Therapeutic activity of GW9508 (FFAR1 agonist), 4-CMTB (FFAR2 agonist), AR420626 (FFAR3 agonist), and GSK137647 (FFAR4 agonist) was investigated in two models of semi-chronic colitis: induced by trinitrobenzenesulfonic acid (TNBS), mimicking Crohn’s disease, as well as induced by dextran sulfate sodium (DSS), which recapitulates ulcerative colitis in humans. Moreover, we assessed the influence of FFARs agonists on epithelial ion transport and measured the ion flow stimulated by forskolin and veratridine. Administration of FFAR4 agonist GSK137647 attenuated both TNBS-induced and DSS-induced colitis in mice, as indicated by macroscopic parameters and myeloperoxidase activity. The action of FFAR4 agonist GSK137647 was significantly blocked by pretreatment with selective FFAR4 antagonist AH7614. Moreover, FFAR1 and FFAR4 agonists reversed the increase in the colon permeability caused by inflammation. FFAR4 restored the tight junction genes expression in mouse colon. This is the first evaluation of the anti-inflammatory activity of selective FFAR agonists, showing that pharmacological intervention targeting FFAR4, which is a sensor of medium and long chain fatty acids, attenuates intestinal inflammation.

scholarly journals Intestinal Anti-Inflammatory Activity of the Aqueous Extract from Ipomoea asarifolia in DNBS-Induced Colitis in Rats

2018 ◽  
Vol 19 (12) ◽  
pp. 4016 ◽  
Author(s):  
Valéria da Silva ◽  
Aurigena de Araújo ◽  
Daline Araújo ◽  
Maíra Lima ◽  
Roseane Vasconcelos ◽  
...  
Keyword(s):  
Protective Effect ◽  
Aqueous Extract ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Immunohistochemical Analysis ◽  
Histological Evaluation ◽  
Myeloperoxidase Activity ◽  
Down Regulation ◽  
Anti Inflammatory ◽  
Ipomoea Asarifolia

Inflammatory bowel disease is triggered by an uncontrolled immune response associated with genetic, environmental, and intestinal microbiota imbalance. Ipomoea asarifolia (IA), popularly known as “salsa” or “brave salsa”, belongs to the Convolvulaceae family. The aim of this approach was to study the preventive effect of IA aqueous extract in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Rats pretreated with IA extract or sulfasalazine (SSZ) received intracolonic instillation of DNBS in 50% ethanol (v/v). IA extract presented a protective effect against intestinal inflammation, with improvement in the disease activity index and macroscopic damage. IA or SSZ significantly reduced myeloperoxidase activity, and also down-regulation of the gene expression of JNK1, NF-κβ-p65, STAT3, and decreased levels of TNFα, IL-1β, and increased IL-10, associated with a significant improvement of oxidative stress, in addition to a reduction in MDA and an increase of glutathione in colonic tissue. The protective effect of the extract was also confirmed in histological evaluation, showing preservation of the colonic cytoarchitecture. Immunohistochemical analysis revealed down-regulation of NF-κβ-p65, iNOS, IL-17, and up-regulation of SOCs-1 and MUC-2. IA extract presents antioxidant and anti-inflammatory intestinal properties, and proved to be a potential application for preventing damage induced by DNBS.

scholarly journals Free fatty acid receptor 4 is a nutrient sensor that resolves inflammation to maintain cardiac homeostasis

2019 ◽  
Author(s):  
Katherine A. Murphy ◽  
Brian A. Harsch ◽  
Chastity L. Healy ◽  
Sonal S. Joshi ◽  
Shue Huang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Cardiac Myocytes ◽  
Transcriptome Analysis ◽  
Pressure Overload ◽  
Plasma Lipoproteins ◽  
Acid Receptor ◽  
Free Fatty Acid Receptor ◽  
Anti Inflammatory ◽  
Fatty Acid Receptor

AbstractBackgroundNon-­resolving activation of immune responses is central to the pathogenesis of heart failure (HF). Free fatty acid receptor 4 (Ffar4) is a G-protein coupled receptor (GPR) for medium-and long-chain fatty acids (FA) that regulates metabolism and attenuates inflammation in diabetes and obesity. Here, we tested the hypothesis that Ffar4 functions as a cardioprotective nutrient sensor that resolves inflammation to maintain cardiac homeostasis.MethodsMice with systemic deletion of Ffar4 (Ffar4KO) were subjected to pressure overload by transverse aortic constriction (TAC). Transcriptome analysis of cardiac myocytes was performed three days post-TAC. Additionally, Ffar4-mediated effects on inflammatory oxylipin production in cardiac myocytes and oxylipin composition in plasma lipoproteins were evaluated.ResultsIn Ffar4KO mice, TAC induced more severe remodeling, identifying an entirely novel cardioprotective role for Ffar4 in the heart. Transcriptome analysis 3-days post-TAC indicated a failure to induce cell death and inflammatory genes in Ffar4KO cardiac myocytes, as well as a specific failure to induce cytoplasmic phospholipase A2α (cPLA2α) signaling genes. In cardiac myocytes, Ffar4 signaling through cPLA2α-cytochrome p450 ω/ω-1 hydroxylase induced production of the EPA-derived anti-inflammatory oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Systemically, loss of Ffar4 altered oxylipin content in circulating plasma lipoproteins consistent with a loss of anti-inflammatory oxylipins at baseline, and inability to produce both pro-inflammatory and pro-resolving oxylipins following TAC. Finally, we confirmed that Ffar4 is expressed in human heart and down-regulated in HF.ConclusionsOur results identify a novel function for Ffar4 in the heart as a FA nutrient sensor that resolves inflammation to maintain cardiac homeostasis.

scholarly journals Walnut Oil Alleviates Intestinal Inflammation and Restores Intestinal Barrier Function in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1302
Author(s):  
Adrian Bartoszek ◽  
Adam Makaro ◽  
Agnieszka Bartoszek ◽  
Radzisław Kordek ◽  
Jakub Fichna ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Dietary Habits ◽  
Intestinal Inflammation ◽  
Visceral Pain ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Walnut Oil ◽  
Wide Range ◽  
Bowel Diseases ◽  
Anti Inflammatory

Ulcerative colitis belongs to inflammatory bowel diseases, which is a group of chronic disorders of the gastrointestinal tract. It is a debilitating condition with a wide range of symptoms including rectal bleeding, diarrhea, and visceral pain. Current dietary habits often lead to imbalance in n-6/n-3 polyunsaturated fatty acids (PUFA) in favor of n-6 PUFA. Recent data showed the potential anti-inflammatory advantage of n-3 PUFA. Walnut oil (WO) is rich in those fatty acids and mainly consists of linoleic and linolenic acids that may act via free fatty acids receptors (FFARs). We assessed the anti-inflammatory effect of WO in the mouse model of dextran sulfate sodium (DSS)-induced colitis. Moreover, we examined changes in the expression of tight junction proteins (TJ), pro-inflammatory cytokines, and FFAR proteins in the inflamed mouse colon. WO improves the damage score in inflamed tissue, significantly restoring ion transport and colonic wall permeability. Inflammation caused changes in TJ, FFAR, and pro-inflammatory gene proteins expression, which WO was able to partially reverse. WO has anti-inflammatory properties; however, its exact mechanism of action remains unclear. This stems from the pleiotropic effects of n-3 PUFA ligands associated with receptor distribution and targeted signaling pathways.

Expression and secretion of lipocortin 1 in gut inflammation are not regulated by pituitary-adrenal axis

1997 ◽  
Vol 273 (2) ◽  
pp. R623-R629 ◽  
Author(s):  
N. Vergnolle ◽  
C. Comera ◽  
J. More ◽  
M. Alvinerie ◽  
L. Bueno
Keyword(s):  
Culture Medium ◽  
Experimental Colitis ◽  
Myeloperoxidase Activity ◽  
Trinitrobenzenesulfonic Acid ◽  
Gut Inflammation ◽  
Adrenal Axis ◽  
Histological Damage ◽  
Anti Inflammatory ◽  
Pituitary Adrenal Axis

Lipocortin 1 is considered a mediator of the anti-inflammatory actions of glucocorticoids. We have shown that this protein is overexpressed and secreted during an experimental colitis induced by intraluminal injection of trinitrobenzenesulfonic acid (TNBS) in rats. We studied here the in vivo regulation of lipocortin 1 expression and secretion in this model, either by glucocorticoids using adrenalectomized or dexamethasone-treated (3 mg/24 h) animals or by pituitary factors using hypophysectomized animals. Inflammation was evaluated by measuring myeloperoxidase activity and by histological scoring of the damage. Lipocortin 1 was detected by immunoblotting, and its secretion was studied by incubating colonic specimens in-culture medium. In the colon of TNBS-injected animals, cumulative histological damage scores were increased in adrenalectomized and decreased in dexamethasone-treated animals compared with control and hypophysectomized animals. The colons of all TNBS-injected animals (controls, adrenalectomized, dexamethasone treated, hypophysectomized) overexpressed and secreted lipocortin 1. In conclusion, the induction of lipocortin 1 overexpression and secretion during this colitis occurs independently of glucocorticoids or pituitary factors.

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF KNEMA ATTENUATA (HOOK. F. AND THOMSON) WARB ETHANOLIC STEM BARK EXTRACT IN ALBINO WISTAR RATS

2019 ◽  
pp. 330-334
Author(s):  
SUPRIYA RAJA H
Keyword(s):  
Stem Bark ◽  
Inflammatory Activity ◽  
Assay Method ◽  
Bark Extract ◽  
Raw 264.7 ◽  
Myeloperoxidase Activity ◽  
Stem Bark Extract ◽  
Anti Inflammatory

Objective: Knema attenuata (Myristicaceae), popularly known as “wild nutmeg,” is an endemic tree species from Western Ghats, which has been used in folk medicine. Conventionally, the stem bark of K. attenuata is used for treating inflammatory conditions without any scientific information available for the same. The present study was undertaken to evaluate the anti-inflammatory activity of the ethanolic stem bark extract (ESBE) of K. attenuata using in vivo and in vitro screening models. Methods: The ethanolic extract of stem bark was prepared by soxhlation, and its cytotoxicity in RAW 264.7 cell line was assessed using MTT assay method. In vivo anti-inflammatory effect of extract was estimated in rats using carrageenan-induced paw edema model and cotton pellet-induced granuloma model. The in vitro anti-inflammatory activity of the extract was evaluated by cyclooxygenase and lipoxygenase inhibition assay, estimation of myeloperoxidase activity, and determination of cellular nitrite levels in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Results: Toxic symptoms were not observed for the ESBE. The extract demonstrated significant anti-inflammatory activity in both in vivo and in vitro models. The anti-inflammatory action exhibited by the extract was a result of the inhibition of leukocyte migration and nitric oxide pathway and partially by inhibition of mediators such as prostaglandins and leukotrienes. Conclusion: Findings from the study provide the evidence for the popular use of stem bark extract of K. attenuata as a potential anti-inflammatory agent.

scholarly journals Probiotic Cell-Free Supernatants Exhibited Anti-Inflammatory and Antioxidant Activity on Human Gut Epithelial Cells and Macrophages Stimulated with LPS

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Stefania De Marco ◽  
Marzia Sichetti ◽  
Diana Muradyan ◽  
Miranda Piccioni ◽  
Giovanna Traina ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lactobacillus Reuteri ◽  
Intestinal Inflammation ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Human Colon ◽  
Saccharomyces Boulardii ◽  
Inflammatory Activity ◽  
Industrialized Countries ◽  
Anti Inflammatory

The incidence of inflammatory bowel disease is increasing all over the world, especially in industrialized countries. The aim of the present work was to verify the anti-inflammatory activity of metabolites. In particular, cell-free supernatants ofLactobacillus acidophilus, Lactobacillus casei,Lactococcus lactis, Lactobacillus reuteri, andSaccharomyces boulardiihave been investigated. Metabolites produced by these probiotics were able to downregulate the expression of PGE-2 and IL-8 in human colon epithelial HT-29 cells. Moreover, probiotic supernatants can differently modulate IL-1β, IL-6, TNF-α, and IL-10 production by human macrophages, suggesting a peculiar anti-inflammatory activity. Furthermore, supernatants showed a significant dose-dependent radical scavenging activity. This study suggests one of the mechanisms by which probiotics exert their anti-inflammatory activity affecting directly the intestinal epithelial cells and the underlying macrophages. This study provides a further evidence to support the possible use of probiotic metabolites in preventing and downregulating intestinal inflammation as adjuvant in anti-inflammatory therapy.

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF PARTIALLY PURIFIED LECTIN FROM PRAECITRULLUS FISTULOSUS PHLOEM EXUDATES.

2019 ◽  
Vol 12 (1) ◽  
pp. 91
Author(s):  
Madhu Cs ◽  
Sharada Ac
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Activity ◽  
No Production ◽  
Myeloperoxidase Activity ◽  
Mice Model ◽  
Ammonium Sulfate Precipitation ◽  
Edema Volume ◽  
Anti Inflammatory ◽  
Praecitrullus Fistulosus ◽  
Inflammatory Effect

Objective: The objective of the present study is to determine the anti-inflammatory effect of a partially purified lectin from phloem exudates againstpaw edema mice model.Methods: Partially purified lectin was prepared by phloem exudates in phosphate buffer saline followed by ammonium sulfate precipitation anddialysis. Anti-inflammatory activity was determined against carrageenan-induced mice model and inhibition of nitric oxide (NO) production wasdetermined.Results: Partially purified lectin exhibited promising anti-inflammatory activity at 50 mg/kg b.w. by reducing the edema volume significantly up to64% (**p<0.01) against control mice. Decrease in myeloperoxidase activity and NO production in paw exudates was observed up to 55.90 (*p<0.05)and 47.22% (*p<0.05), respectively, and this supports the anti-inflammatory property of the partially purified lectin.Conclusion: This finding indicated that further studies needed to purify and characterize a novel lectin from Praecitrullus fistulosus for elucidating themolecular mechanism of anti-inflammatory activity.

Sign in / Sign up

Export Citation Format

Share Document