scholarly journals Antrodia cinnamomea Confers Obesity Resistance and Restores Intestinal Barrier Integrity in Leptin-deficient Obese Mice

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 726
Author(s):  
Yi-Ting Tsai ◽  
Jhen-Wei Ruan ◽  
Cherng-Shyang Chang ◽  
Mei-Lan Ko ◽  
Hsiu-Chuan Chou ◽  
...  
Keyword(s):  
Intestinal Barrier ◽  
Immunoblot Analysis ◽  
Intestinal Epithelial ◽  
Barrier Integrity ◽  
Antrodia Cinnamomea ◽  
Medicinal Fungus ◽  
Reduced Body ◽  
Diet Induced Obesity ◽  
Leptin Deficiency ◽  
Intestinal Barrier Integrity

Obesity is associated with metabolic disorders. Thus, obesity prevention and treatment are essential for health. Antrodia cinnamomea (AC) is a multifunctional medicinal fungus used for the treatment of various diseases and for preventing diet-induced obesity. Leptin deficiency causes over-eating and spontaneous obesity. The concomitant metabolic symptoms are more severe than diet-induced obesity. Here, we used leptin-deficient (ob/ob) mice as an animal model for over-feeding to study the effect of AC on obesity. We fed C57BL/6 mice (WT, ob+/+) and ob/ob mice with AC for four weeks before performing qRT-PCR and immunoblot analysis to elaborate AC-modulated mechanisms. Further, we used Caco-2 cells as a human intestinal epithelial barrier model to examine the effect of AC on intestinal permeability. Our results suggested that AC reduces lipid deposits of the liver and epididymal white adipose tissue (EWAT) by promoting lipid metabolism and inhibiting lipogenesis-associated genes and proteins in ob/ob mice. Moreover, AC effectively repaired intestinal-barrier injury caused by leptin deficiency and enhanced intestinal barrier integrity in Caco-2 cells. Interestingly, AC significantly reduced body weight and EWAT with no compromise on food intake in ob/ob mice. Thus, AC effectively reduced obesity caused by leptin-deficiency and can potentially be used as a nutraceutical for treating obesity.

scholarly journals Activation of α7nAChR Preserves Intestinal Barrier Integrity and Ameliorates Cholestasis Liver Fibrosis in Mice by Enhancing the HO-1 / STAT3 Signaling to Inhibit NF-κB Activation

2021 ◽  
Author(s):  
Wei Lei ◽  
cheng chang Zhao ◽  
sen jia Sun ◽  
ling yan Jin ◽  
jun zhi Duan
Keyword(s):  
Liver Fibrosis ◽  
Epithelial Cells ◽  
Intestinal Barrier ◽  
Therapeutic Effects ◽  
Intestinal Epithelial ◽  
Barrier Integrity ◽  
Stat3 Signaling ◽  
Stat3 Phosphorylation ◽  
Junction Protein ◽  
Intestinal Barrier Integrity

Abstract Background: Activation of alpha-7 nicotinic acetylcholine receptor (α7nAChR) can inhibit the systemic inflammatory response and preserve intestinal barrier integrity. This study aimed at elucidating the molecular mechanisms by which α7nAChR activation could inhibit intestinal barrier injury and cholestatic liver fibrosis in mice induced by bile duct ligation (BDL).Methods: The intestine-specific HO-1 knockout VillinCreHmox1-/- and control Hmox1floxp/floxp C57BL/6 mice were subjected to BDL. The therapeutic effects of GST-21, a specific ligand for α7nAChR, on systemic and intestinal inflammation, intestinal barrier integrity, liver fibrosis and injury, HO-1 expression, STAT3, AKT and NF-kBp65 activation were examined in these mice and intestinal epithelial cells co-cultured with macrophages. Results: Compared with BDL mice, α7nAChR activation by GST-21 decreased intestinal and liver injury and fibrosis in BDL mice, accompanied by reducing serum cytokine responses. In addition, activation of α7nAChR preserved the tight junction protein expression and intestinal epithelial cell barrier integrity in BDL mice and epithelial cells co-cultured with macrophages. The therapeutic effects of α7nAChR activation were mediated by enhancing HO-1 expression, STAT3 phosphorylation, and reducing the NF-kBp65 activation in intestinal tissues and epithelial cells co-cultured with macrophages. Finally, activation of α7nAChR induced HO-1 expression and STAT3 phosphorylation in an interdependent manner, independent of the PI3K/AKT signaling. Conclusion: Activation of α7nAChR enhanced HO-1 expression and STAT3 signaling to inhibit NF-κB activation, preserving the intestinal barrier integrity, and reducing inflammation and liver fibrosis in cholestasis mice. Therefore, targeting α7nAChR may be a promising interventional strategy for primary biliary cholangitis.

Differential protection by anthocyanin-rich bilberry extract and resveratrol against lipid micelle-induced oxidative stress and monolayer permeability in Caco-2 intestinal epithelial cells

2021 ◽  
Vol 12 (7) ◽  
pp. 2950-2961
Author(s):  
Maryam Ershad ◽  
Mark K. Shigenaga ◽  
Brian Bandy
Keyword(s):  
Oxidative Stress ◽  
Dietary Fat ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Differential Protection ◽  
Intestinal Epithelial ◽  
Barrier Integrity ◽  
Intestinal Barrier Integrity ◽  
Monolayer Permeability ◽  
Bilberry Extract

Excess dietary fat, and associated bile acids, can impair intestinal barrier integrity, produce intestinal or systemic inflammation and promote tumorigenesis.

scholarly journals Chronic opioid use modulates human enteric microbiota and intestinal barrier integrity

Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1946368
Author(s):  
Angélica Cruz-Lebrón ◽  
Ramona Johnson ◽  
Claire Mazahery ◽  
Zach Troyer ◽  
Samira Joussef-Piña ◽  
...  
Keyword(s):  
Intestinal Barrier ◽  
Opioid Use ◽  
Barrier Integrity ◽  
Intestinal Barrier Integrity ◽  
Chronic Opioid Use

scholarly journals STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Integrity ◽  
Barrier Integrity ◽  
Gp130 Receptor ◽  
Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

scholarly journals Pharmacokinetic Analysis of Carnosic Acid and Carnosol in Standardized Rosemary Extract and the Effect on the Disease Activity Index of DSS-Induced Colitis

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 773
Author(s):  
Jacob P. Veenstra ◽  
Bhaskar Vemu ◽  
Restituto Tocmo ◽  
Mirielle C. Nauman ◽  
Jeremy J. Johnson
Keyword(s):  
Disease Activity ◽  
Activity Index ◽  
Intestinal Barrier ◽  
Disease Activity Index ◽  
Carnosic Acid ◽  
Rosemary Extract ◽  
Oral Gavage ◽  
Barrier Integrity ◽  
Dietary Phytochemicals ◽  
Intestinal Barrier Integrity

Rosemary extract (RE) is an approved food preservative in the European Union and contains dietary phytochemicals that are beneficial for gastrointestinal health. This study investigated the effects of RE on dextran sodium sulfate (DSS)-induced colitis and also determined the pharmacokinetics of dietary phytochemicals administered to mice via oral gavage. Individual components of rosemary extract were separated and identified by LC–MS/MS. The pharmacokinetics of two major diterpenes from RE, carnosic acid (CA) and carnosol (CL), administered to mice via oral gavage were determined. Then, the effect of RE pre-treatment on the disease activity index (DAI) of DSS-induced colitis in mice was investigated. The study determined that 100 mg/kg RE significantly improved DAI in DSS-induced colitis compared to negative control. Sestrin 2 protein expression, which increased with DSS exposure, was reduced with RE treatment. Intestinal barrier integrity was also shown to improve via fluorescein isothiocyanate (FITC)–dextran administration and Western blot of zonula occludens-1 (ZO-1), a tight junction protein. Rosemary extract was able to improve the DAI of DSS-induced colitis in mice at a daily dose of 100 mg/kg and showed improvement in the intestinal barrier integrity. This study suggests that RE can be an effective preventative agent against IBD.

Ochratoxin A challenges the intestinal epithelial cell integrity: results obtained in model experiments with Caco-2 cells

2019 ◽  
Vol 12 (4) ◽  
pp. 399-407 ◽  
Author(s):  
A. Alizadeh ◽  
P. Akbari ◽  
S. Varasteh ◽  
S. Braber ◽  
H. Malekinejad ◽  
...  
Keyword(s):  
Cell Viability ◽  
Ochratoxin A ◽  
Lucifer Yellow ◽  
Intestinal Barrier ◽  
Clinical Importance ◽  
Hazardous Substances ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Cell Integrity ◽  
Barrier Integrity

Contamination of human and animal diets with different mycotoxins have gained significant attention over the past decade. The intestinal barrier is the first site of exposure and a primary target for nutritional contaminants and hazardous substances including mycotoxins. In this study, the potential impact of ochratoxin A (OTA) on intestinal barrier integrity was highlighted using a human intestinal Caco-2 cell line. Cell viability following OTA exposure was determined by lactate dehydrogenase release and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, markers of barrier integrity, such as transepithelial electrical resistance (TEER) as well as the permeability of Lucifer Yellow (LY) and fluorescein isothiocyanate (FITC)-dextran, were assessed. Furthermore, the protein expression of different tight junction (TJ) proteins, as main constituents of barrier integrity, was evaluated by Western blot. Results show that OTA reduces TEER values in a concentration- and time-dependent manner and increase the permeability of LY through the intestinal epithelial layer, while the cell viability did not change significantly. However, the damage was not severe enough to change the permeability to larger molecules, such as FITC-dextran. OTA exposure down-regulated the expression of TJ proteins claudin-1, -3 and -4 and up-regulated the expression of zona occludens 1. The observation that OTA can disrupt the epithelial barrier is of clinical importance as it may lead to an increased passage of luminal antigens into the systemic circulation.

Intestinal barrier integrity and inflammatory bowel disease: Stem cell‐based approaches to regenerate the barrier

2017 ◽  
Vol 12 (4) ◽  
pp. 923-935 ◽  
Author(s):  
Fredrik E.O. Holmberg ◽  
Jannie Pedersen ◽  
Peter Jørgensen ◽  
Christoffer Soendergaard ◽  
Kim B. Jensen ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Stem Cell ◽  
Bowel Disease ◽  
Intestinal Barrier ◽  
Barrier Integrity ◽  
Inflammatory Bowel ◽  
Intestinal Barrier Integrity

scholarly journals HO-1/CO Maintains Intestinal Barrier Integrity through NF-κB/MLCK Pathway in Intestinal HO-1-/- Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhenling Zhang ◽  
Lijing Zhang ◽  
Qiuping Zhang ◽  
Bojia Liu ◽  
Fang Li ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Intestinal Barrier ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Barrier Integrity ◽  
Tnf Α ◽  
Intestinal Barrier Integrity ◽  
Deficient Mice

Background. Intestinal barrier injury is an important contributor to many diseases. We previously found that heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal barrier. This study is aimed at elucidating the molecular mechanisms of HO-1/CO in barrier loss. Materials and Methods. We induced gut leakiness by injecting carbon tetrachloride (CCl4) to wildtype or intestinal HO-1-deficient mice. In addition, we administrated tumor necrosis factor-α (TNF-α) to cells with gain- or loss-of-HO-1 function. The effects of HO-1/CO maintaining intestinal barrier integrity were investigated in vivo and in vitro. Results. Cobalt protoporphyrin and CO-releasing molecule-2 alleviated colonic mucosal injury and TNF-α levels; upregulated tight junction (TJ) expression; and inhibited epithelial IκB-α degradation and phosphorylation, NF-κB p65 phosphorylation, long MLCK expression, and MLC-2 phosphorylation after administration of CCl4. Zinc protoporphyrin completely reversed these effects. These findings were further confirmed in vitro, using Caco-2 cells with gain- or loss-of-HO-1-function after TNF-α. Pretreated with JSH-23 (NF-κB inhibitor) or ML-7 (long MLCK inhibitor), HO-1 overexpression prevented TNF-α-induced TJ disruption, while HO-1 shRNA promoted TJ damage even in the presence of JSH-23 or ML-7, thus suggesting that HO-1 dependently protected intestinal barrier via the NF-κB p65/MLCK/p-MLC-2 pathway. Intestinal HO-1-deficient mice further demonstrated the effects of HO-1 in maintaining intestinal barrier integrity and its relative mechanisms. Alleviated hepatic fibrogenesis and serum ALT levels finally confirmed the clinical significance of HO-1/CO repairing barrier loss in liver injury. Conclusion. HO-1/CO maintains intestinal barrier integrity through the NF-κB/MLCK pathway. Therefore, the intestinal HO-1/CO-NF-κB/MLCK system is a potential therapeutic target for diseases with a leaky gut.

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