scholarly journals Cherry Polyphenol Extract Ameliorated Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice by Suppressing Wnt/β-Catenin Signaling Pathway

Foods ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 49
Author(s):  
Fuhua Li ◽  
Huiming Yan ◽  
Ling Jiang ◽  
Jichun Zhao ◽  
Xiaojuan Lei ◽  
...  

Ulcerative colitis (UC) is a chronic and nonspecific inflammatory disease of the colon and rectum, and its etiology remains obscure. Cherry polyphenols showed potential health-promoting effects. However, both the protective effect and mechanism of cherry polyphenols on UC are still unclear. This study aimed to investigate the potential role of the free polyphenol extract of cherry in alleviating UC and its possible mechanism of action. Our study revealed that the free polyphenol extract of cherry management significantly alleviated UC symptoms, such as weight loss, colon shortening, the thickening of colonic mucous layer, etc. The free polyphenol extract of cherry treatment also introduced a significant reduction in levels of malondialdehyde (MDA), myeloperoxidase (MPO) and nitric oxide (NO), while causing a significant elevation in levels of catalase (CAT), glutathione (GSH-Px), superoxide dismutase (SOD), as well as the downregulation of pro-inflammatory cytokines. This indicated that such positive effects were performed through reducing oxidative damage or in a cytokine-specific manner. The immunofluorescence analysis of ZO-1 and occludin proteins declared that the free polyphenol extract of cherry had the potential to prompt intestinal barrier function. The reduced expression levels of β-catenin, c-myc, cyclin D1 and GSK-3β suggested that the cherry extract performed its positive effect on UC by suppressing the Wnt/β-ctenin pathway. This finding may pave the way into further understanding the mechanism of cherry polyphenols ameliorating ulcerative colitis.

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 273 ◽  
Author(s):  
Chiara Di Lorenzo ◽  
Francesca Colombo ◽  
Simone Biella ◽  
Creina Stockley ◽  
Patrizia Restani

Polyphenols are a group of phytochemicals with potential health-promoting effects. They are classified as flavonoid (flavonols, flavanols, flavones, flavanones, isoflavones, and anthocyanins) and non-flavonoid molecules (phenolic acids, hydroxycinnamic acids, lignans, stilbenes, and tannins). Although an increasing number of trials have shown a correlation among polyphenol consumption and a reduction in risk factors for chronic diseases, discrepancies in explaining their positive effects have been found in terms of the bioavailability. In fact, polyphenols show a low bioavailability due to several factors: interaction with the food matrix, the metabolic processes mediated by the liver (phase I and II metabolism), intestine and microbiota. On the other hand, the biological activities of phenol compounds may be mediated by their metabolites, which are produced in vivo, and recent studies have confirmed that these molecules may have antioxidant and anti-phlogistic properties. This review discusses the studies performed in vivo, which consider the polyphenol bioavailability and their different food sources. Factors influencing the biological effects of the main classes of polyphenols are also considered.


Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  

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.


Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 959 ◽  
Author(s):  
Jefferson Antônio Leite ◽  
Gabriela Pessenda ◽  
Isabel C. Guerra-Gomes ◽  
Alynne Karen Mendonça de Santana ◽  
Camila André Pereira ◽  
...  

Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2−/−) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2−/− mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2−/− mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing β cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.


Author(s):  
I. O. Pasichna ◽  
V. I. Vdovychenko

The recent scientific researches provide evidence of the important role of microbiota for human health. The microbiome is a very complex system, that exists in an equilibrium state and performs multiple functions. The intestinal microflora is disturbed under the influence of iatrogenic factors, and products of microbial origin are used to correct this. The first group of such drugs include probiotics. Their positive effect is associated with immunological and non‑immunological effects. The results of many studies proved the positive effects of probiotics in clinical practice, however publications of recent years outline their low effectiveness and transient nature of the effect, even with prolonged use. Another group of preparations refers to prebiotics, which selectively stimulate the growth of colon microflora. A combination of probiotics and prebiotics, called synbiotics, also in use. Currently, much attention is paid to metabiotics. This group includes various low molecular weight molecules with various chemical manifestations. The components of metabiotics are cellular elements, metabolites and signaling molecules of probiotic cultures. Metabiotics provide the optimal conditions of homeostasis in the contact zone, which are necessary for the normal interaction of the epithelium and microflora, as well as directly affect the physiological functions and biochemical reactions of the macroorganism. The antibacterial properties of metabiotics allow to fight pathogenic and opportunistic flora, without affecting the beneficial microorganisms of the intestine. Creation of targeted metabiotics is a novel promising direction in this area. The possibility of creating a programmed metabiotic drug is considered, depending on the type of disorders of the intestinal microbiocenosis and the peculiarities of the life of specific pathogenic or opportunistic strains.


2020 ◽  
Vol 218 ◽  
pp. 04014
Author(s):  
Yixing Jin ◽  
Peiying Wu ◽  
Cheng Lin ◽  
Yingda Wang

This study investigated the impact of emotional leadership of leaders on organizational commitment of hotel employees, as well as the mediating role of job satisfaction. The results indicate that: (1) Emotional leadership and job satisfaction have positive effects on organizational commitment. (2) Emotional leadership has a positive effect on job satisfaction. (3) Job satisfaction plays a mediating role between emotional leadership and organizational commitment.


Author(s):  
Myriam MIMOUN-BENARROCH ◽  
Cindy HOGOT ◽  
Larbi RHAZI ◽  
Claude Narcisse NIAMBA ◽  
Flore DEPEINT

Astaxanthin is a marine carotenoid that has a number of potential health benefits, including a very strong antioxidant potential. Present in the flesh of salmonids and shellfish, its natural sources currently on the market for food supplements come from the algae Haematococcus pluvialis and krill. However other natural sources can be found and may be of interest. Cellular uptake studies were performed on Caco-2/TC7 colonic cells. The cells were cultured on a semi-permeable membrane to create a polarized and functional epithelium, representative of the intestinal barrier. Four sources of astaxanthin were selected and compared; synthetic, natural extracts from bacteria, algae or yeast. Astaxanthin was incorporated at a concentration of 5µM into mixed micelles and applied to cultured cells and concentration of astaxanthin measured by HPLC in both apical and basolateral compartments. Small variations in bioavailability were observed at 3 hours. After 6 hours, only the algae source of astaxanthin was still present in the apical compartment as the esterified form. Structure-activity relationships are further discussed. Animal experiments using yeast and algae sources in different types of matrices confirm the role of source and formulation in the bioavailability potential of astaxanthin.


Colitis ◽  
10.5772/25753 ◽  
2012 ◽  
Author(s):  
R.C. Anderson ◽  
J.E. Dalziel ◽  
P.K. Gopal ◽  
S. Bassett ◽  
A. Ellis ◽  
...  

Author(s):  
A. Prysiazhniuk ◽  
T. Dovbynchuk ◽  
B. Kopiyak ◽  
G. Tolstanova

We investigated the involvement of central and peripheral D2 dopaminergic receptors in the mechanism of vascular permeability in rat's colon during experimental ulcerative colitis. Ulcerative colitis was induced in male white inbred rats by 6 % iodoacetamide enema. For the investigation of central and peripheral D2R, separate and joint injections of D2R antagonist domperidone (2 mg/100 g, per os) and D2R agonist quinpirole (1 mg/100 g, per os) were applied. Central D2R were destroyed by neurotoxin injection – 6OHDA. Colonic vascular permeability was measured by colonic extravasation of 1,5 % Evans blue. It was observed that blockade of peripheral D2R decreased colonic vascular permeability, while simultaneous activation of central D2R and inhibition of peripheral D2R have additive positive effect in prevention of increased colonic vascular permeability during experimental colitis.


Planta Medica ◽  
2021 ◽  
Author(s):  
Jiaqi Wu ◽  
Yuzheng Wu ◽  
Yue Chen ◽  
Mengyang Liu ◽  
Haiyang Yu ◽  
...  

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi43-vi44
Author(s):  
Omkar Ijare ◽  
David Conway ◽  
Alan Cash ◽  
David Baskin ◽  
Kumar Pichumani

Abstract Anhydrous enol-oxaloacetate (AEO) has demonstrated the ability to enhance neuronal cell bioenergetics and activate brain mitochondrial biogenesis. Since oxaloacetate has demonstrated positive effects on brain bioenergetics in neurodegenerative diseases we have begun to investigate whether AEO may also have a positive effect on the altered cellular metabolism found in cancer cells, particularly Glioblastoma multiforme. The “Warburg effect” describes an abnormal metabolic state in cancer, distinct from normal tissue, in which energy is generated through enhanced conversion of pyruvate to lactate even in the presence of oxygen during glycolysis. Oxaloacetate (OAA) is a key anaplerotic substrate that is required to maintain TCA cycle flux. The role of oxaloacetate supplementation on the energy metabolism is not known in cancer cells. Goal of this study is to investigate the changes in metabolic fluxes in glucose metabolism with and without the presence of OAA in patient-derived GBM cells. We use GC-MS based 13C isotopomer analysis for this study. GBM cells are grown in 15mM glucose containing DMEM medium supplemented with 2mM oxaloacetate for 10 days. 6 hours prior to harvesting, [U-13C]glucose is introduced to the medium. 13C isotopomer analysis of GC-MS data showed that OAA supplementation for 10 days drastically decreased Warburg glycolysis by reducing 13C labeling (M+3) by 19.7% and 48.8% in pyruvate and lactate pools respectively in comparison with cells not treated with OAA. M+3 13C labeled pyruvate entered TCA cycle via acetyl-CoA, where we also observed reduced levels of M+2 13C labeled citrate (20.5%) and glutamate (23.9%) isotopomers. Pyruvate can also enter TCA cycle via pyruvate carboxylation pathway and this activity was also found to be slightly decreased in the OAA treated cells. All the differences were statistically significant. These results indicate that OAA can be used to alter bioenergetics of GBM cells, specifically glucose oxidation.


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