scholarly journals p-Cymene and Rosmarinic Acid Ameliorate TNBS-Induced Intestinal Inflammation Upkeeping ZO-1 and MUC-2: Role of Antioxidant System and Immunomodulation

2020 ◽  
Vol 21 (16) ◽  
pp. 5870 ◽  
Author(s):  
Rodrigo de Oliveira Formiga ◽  
Edvaldo Balbino Alves Júnior ◽  
Roseane Carvalho Vasconcelos ◽  
Gerlane Coelho Bernardo Guerra ◽  
Aurigena Antunes de Araújo ◽  
...  
Keyword(s):  
Rosmarinic Acid ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Inflammatory Activity ◽  
Cytokine Signaling ◽  
Mesenteric Lymph Nodes ◽  
Communicating Junctions ◽  
Socs3 Expression ◽  
Anti Inflammatory ◽  
Cluster Of Differentiation

p-Cymene (p-C) and rosmarinic acid (RA) are secondary metabolites that are present in medicinal herbs and Mediterranean spices that have promising anti-inflammatory properties. This study aimed to evaluate their intestinal anti-inflammatory activity in the trinitrobenzene sulphonic acid (TNBS)-induced colitis model in rats. p-C and RA (25–200 mg/kg) oral administration reduced the macroscopic lesion score, ulcerative area, intestinal weight/length ratio, and diarrheal index in TNBS-treated animals. Both compounds (200 mg/kg) decreased malondialdehyde (MDA) and myeloperoxidase (MPO), restored glutathione (GSH) levels, and enhanced fluorescence intensity of superoxide dismutase (SOD). They also decreased interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and maintained IL-10 basal levels. Furthermore, they modulated T cell populations (cluster of differentiation (CD)4+, CD8+, or CD3+CD4+CD25+) analyzed from the spleen, mesenteric lymph nodes, and colon samples, and also decreased cyclooxigenase 2 (COX-2), interferon (IFN)-γ, inducible nitric oxide synthase (iNOS), and nuclear transcription factor kappa B subunit p65 (NFκB-p65) mRNA transcription, but only p-C interfered in the suppressor of cytokine signaling 3 (SOCS3) expression in inflamed colons. An increase in gene expression and positive cells immunostained for mucin type 2 (MUC-2) and zonula occludens 1 (ZO-1) was observed. Altogether, these results indicate intestinal anti-inflammatory activity of p-C and RA involving the cytoprotection of the intestinal barrier, maintaining the mucus layer, and preserving communicating junctions, as well as through modulation of the antioxidant and immunomodulatory systems.

scholarly journals Genetic Correction of IL-10RB Deficiency Reconstitutes Anti-Inflammatory Regulation in iPSC-Derived Macrophages

2021 ◽  
Vol 11 (3) ◽  
pp. 221
Author(s):  
Dirk Hoffmann ◽  
Johanna Sens ◽  
Sebastian Brennig ◽  
Daniel Brand ◽  
Friederike Philipp ◽  
...  
Keyword(s):  
Disease Modeling ◽  
Integration Site ◽  
Cytokine Secretion ◽  
Cytokine Signaling ◽  
Stat3 Phosphorylation ◽  
Tnf Α ◽  
Socs3 Expression ◽  
Healthy Control ◽  
Anti Inflammatory ◽  
Inflammatory Regulation

Patient material from rare diseases such as very early-onset inflammatory bowel disease (VEO-IBD) is often limited. The use of patient-derived induced pluripotent stem cells (iPSCs) for disease modeling is a promising approach to investigate disease pathomechanisms and therapeutic strategies. We successfully developed VEO-IBD patient-derived iPSC lines harboring a mutation in the IL-10 receptor β-chain (IL-10RB) associated with defective IL-10 signaling. To characterize the disease phenotype, healthy control and VEO-IBD iPSCs were differentiated into macrophages. IL-10 stimulation induced characteristic signal transducer and activator of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) downstream signaling and anti-inflammatory regulation of lipopolysaccharide (LPS)-mediated cytokine secretion in healthy control iPSC-derived macrophages. In contrast, IL-10 stimulation of macrophages derived from patient iPSCs did not result in STAT3 phosphorylation and subsequent SOCS3 expression, recapitulating the phenotype of cells from patients with IL-10RB deficiency. In line with this, LPS-induced cytokine secretion (e.g., IL-6 and tumor necrosis factor-α (TNF-α)) could not be downregulated by exogenous IL-10 stimulation in VEO-IBD iPSC-derived macrophages. Correction of the IL-10RB defect via lentiviral gene therapy or genome editing in the adeno-associated virus integration site 1 (AAVS1) safe harbor locus led to reconstitution of the anti-inflammatory response. Corrected cells showed IL-10RB expression, IL-10-inducible phosphorylation of STAT3, and subsequent SOCS3 expression. Furthermore, LPS-mediated TNF-α secretion could be modulated by IL-10 stimulation in gene-edited VEO-IBD iPSC-derived macrophages. Our established disease models provide the opportunity to identify and validate new curative molecular therapies and to investigate phenotypes and consequences of additional individual IL-10 signaling pathway-dependent VEO-IBD mutations.

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.

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.

Preparation, optimization, characterization and bioevaluation of rosmarinic acid loaded phytovesicles for anti-inflammatory activity

2020 ◽  
Vol 59 ◽  
pp. 101888
Author(s):  
Abhishek Singh ◽  
Nidhi Srivastava ◽  
Kuldeep Singh Yadav ◽  
Priyam Sinha ◽  
Narayan Prasad Yadav
Keyword(s):  
Rosmarinic Acid ◽  
Inflammatory Activity ◽  
Anti Inflammatory

scholarly journals The Herbal Medicine Scutellaria-Coptis Alleviates Intestinal Mucosal Barrier Damage in Diabetic Rats by Inhibiting Inflammation and Modulating the Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Boxun Zhang ◽  
Rensong Yue ◽  
Yuan Chen ◽  
Xiaoying Huang ◽  
Maoyi Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Diabetic Rats ◽  
Mucosal Barrier ◽  
Inflammatory Factors ◽  
Pathological State ◽  
Intestinal Mucosal Barrier ◽  
Metabolic Inflammation ◽  
Anti Inflammatory

Recent studies have confirmed that increased intestinal permeability and gut-origin lipopolysaccharide (LPS) translocation are important causes of metabolic inflammation in type 2 diabetes (T2D), but there are no recognized therapies for targeting this pathological state. Scutellaria baicalensis and Coptis chinensis are a classic herbal pair often used to treat diabetes and various intestinal diseases, and repair of intestinal barrier damage may be at the core of their therapeutic mechanism. This study investigated the effects of oral administration of Scutellaria-Coptis (SC) on the intestinal mucosal barrier in diabetic rats and explored the underlying mechanism from the perspective of anti-inflammatory and gut microbiota-modulatory effects. The main results showed that, in addition to regulating glycolipid metabolism disorders and inhibiting serum inflammatory factors, SC could also upregulate the expression levels of the tight junction proteins claudin-1, occludin, and zonula occludens (ZO-1), significantly improve intestinal epithelial damage, and inhibit excessive LPS translocation into the blood circulation. Furthermore, it was found that SC could reduce the levels of the inflammatory factors interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) in intestinal tissue and that the anti-inflammatory effects involved the TLR-4/TRIF and TNFR-1/NF-κB signalling pathways. Moreover, SC had a strong inhibitory effect on some potential enteropathogenic bacteria and LPS-producing bacteria, such as Proteobacteria, Enterobacteriaceae, Enterobacter, Escherichia-Shigella, and Enterococcus, and could also promote the proliferation of butyrate-producing bacteria, such as Lachnospiraceae and Prevotellaceae. Taken together, the hypoglycaemic effects of SC were related to the protection of the intestinal mucosal barrier, and the mechanisms might be related to the inhibition of intestinal inflammation and the regulation of the gut microbiota.

Structural elucidation, anti-inflammatory activity and intestinal barrier protection of longan pulp polysaccharide LPIIa

2020 ◽  
Vol 246 ◽  
pp. 116532 ◽  
Author(s):  
Yajuan Bai ◽  
Xuchao Jia ◽  
Fei Huang ◽  
Ruifen Zhang ◽  
Lihong Dong ◽  
...  
Keyword(s):  
Intestinal Barrier ◽  
Structural Elucidation ◽  
Inflammatory Activity ◽  
Anti Inflammatory

scholarly journals Bioaccessibility and Bioactivity of Cereal Polyphenols: A Review

Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1595
Author(s):  
Borkwei Ed Nignpense ◽  
Nidhish Francis ◽  
Christopher Blanchard ◽  
Abishek Bommannan Santhakumar
Keyword(s):  
Barrier Function ◽  
Plasma Concentrations ◽  
Intestinal Barrier ◽  
Inflammatory Activity ◽  
Intestinal Barrier Function ◽  
Mucin Production ◽  
Therapeutic Benefits ◽  
Wide Range ◽  
Anti Inflammatory

Cereal bioactive compounds, especially polyphenols, are known to possess a wide range of disease preventive properties that are attributed to their antioxidant and anti-inflammatory activity. However, due to their low plasma concentrations after oral intake, there is controversy regarding their therapeutic benefits in vivo. Within the gastrointestinal tract, some cereal polyphenols are absorbed in the small intestine, with the majority accumulating and metabolised by the colonic microbiota. Chemical and enzymatic processes occurring during gastrointestinal digestion modulate the bioactivity and bioaccessibility of phenolic compounds. The interactions between the cereal polyphenols and the intestinal epithelium allow the modulation of intestinal barrier function through antioxidant, anti-inflammatory activity and mucin production thereby improving intestinal health. The intestinal microbiota is believed to have a reciprocal interaction with polyphenols, wherein the microbiome produces bioactive and bioaccessible phenolic metabolites and the phenolic compound, in turn, modifies the microbiome composition favourably. Thus, the microbiome presents a key link between polyphenol consumption and the health benefits observed in metabolic conditions in numerous studies. This review will explore the therapeutic value of cereal polyphenols in conjunction with their bioaccessibility, impact on intestinal barrier function and interaction with the microbiome coupled with plasma anti-inflammatory effects.

Rosmarinic acid: A new inhibitor of complement C3-convertase with anti-inflammatory activity

1988 ◽  
Vol 10 (6) ◽  
pp. 729-737 ◽  
Author(s):  
W. Englberger ◽  
U. Hadding ◽  
E. Etschenberg ◽  
E. Graf ◽  
S. Leyck ◽  
...  
Keyword(s):  
Rosmarinic Acid ◽  
Inflammatory Activity ◽  
Complement C3 ◽  
Anti Inflammatory

scholarly journals Idebenone Protects against Spontaneous Chronic Murine Colitis by Alleviating Endoplasmic Reticulum Stress and Inflammatory Response

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 384 ◽  
Author(s):  
Sonia Shastri ◽  
Tanvi Shinde ◽  
Agampodi Promoda Perera ◽  
Nuri Gueven ◽  
Rajaraman Eri
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Goblet Cells ◽  
Inflammatory Activity ◽  
Mrna Levels ◽  
Anti Inflammatory ◽  
The Impact ◽  
Chronic Intestinal Inflammation

Endoplasmic reticulum (ER) stress in intestinal secretory goblet cells has been linked to the development of ulcerative colitis (UC). Emerging evidence suggests that the short chain quinone drug idebenone displays anti-inflammatory activity in addition to its potent antioxidant and mitochondrial electron donor properties. This study evaluated the impact of idebenone in Winnie mice, that are characterized by spontaneous chronic intestinal inflammation and ER stress caused by a missense mutation in the mucin MUC2 gene. Idebenone (200 mg/kg) was orally administered daily to 5–6 weeks old Winnie mice over a period of 21 days. Idebenone treatment substantially improved body weight gain, disease activity index (DAI), colon length and histopathology score. Immunohistochemistry revealed increased expression of MUC2 protein in goblet cells, consistent with increased MUC2 mRNA levels. Furthermore, idebenone significantly reduced the expression of the ER stress markers C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6) and X-box binding protein-1 (XBP-1) at both mRNA and protein levels. Idebenone also effectively reduced pro-inflammatory cytokine levels in colonic explants. Taken together, these results indicate that idebenone could represent a potential therapeutic approach against human UC by its strong anti-inflammatory activity and its ability to reduce markers of ER stress.

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