scholarly journals Short-Chain Naphthoquinone Protects Against Both Acute and Spontaneous Chronic Murine Colitis by Alleviating Inflammatory Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Sonia Shastri ◽  
Tanvi Shinde ◽  
Krystel L. Woolley ◽  
Jason A. Smith ◽  
Nuri Gueven ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Inflammatory Responses ◽  
Activity Index ◽  
Critical Role ◽  
Intestinal Barrier ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Sodium Sulphate ◽  
Short Chain ◽  
Cytokines And Chemokines

Ulcerative colitis (UC) is characterised by chronic, relapsing, idiopathic, and multifactorial colon inflammation. Recent evidence suggests that mitochondrial dysfunction plays a critical role in the onset and recurrence of this disease. Previous reports highlighted the potential of short-chain quinones (SCQs) for the treatment of mitochondrial dysfunction due to their reversible redox characteristics. We hypothesised that a recently described potent mitoprotective SCQ (UTA77) could ameliorate UC symptoms and pathology. In a dextran sodium sulphate- (DSS-) induced acute colitis model in C57BL/6J mice, UTA77 substantially improved DSS-induced body weight loss, disease activity index (DAI), colon length, and histopathology. UTA77 administration also significantly increased the expression of tight junction (TJ) proteins occludin and zona-occludin 1 (ZO-1), which preserved intestinal barrier integrity. Similar responses were observed in the spontaneous Winnie model of chronic colitis, where UTA77 significantly improved DAI, colon length, and histopathology. Furthermore, UTA77 potently suppressed elevated levels of proinflammatory cytokines and chemokines in colonic explants of both DSS-treated and Winnie mice. These results strongly suggest that UTA77 or its derivatives could be a promising novel therapeutic approach for the treatment of human UC.

scholarly journals Arbutin Ameliorates Murine Colitis by Inhibiting JAK2 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Wang ◽  
Yuntao Feng ◽  
Jianwen Wang ◽  
Tenglong Luo ◽  
Xinyue Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Activity Index ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Protective Role ◽  
Docking Studies ◽  
Janus Kinase ◽  
Jak2 Inhibitor ◽  
Murine Colitis

Background and objective: Abnormal activation of Janus kinase 2 (JAK2) promotes the pathogenesis and progress of inflammatory bowel disease (IBD) by stimulating the cytokine traffic. Based on docking studies, arbutin, a natural product extracted from a traditional medicinal plant bearberry, was found to bind to JAK2. The study aimed to investigate the effects and mechanisms of regulating JAK2 by arbutin on colitis in mice.Methods: A mice colitis model was established to mimic human IBD. The mice freely drank water containing dextran sulfate sodium. Inflammation in epithelial (IEC6) and immune (RAW264.7) cells was analyzed following treatment with lipopolysaccharides (LPS).Results: Colitis symptoms, including body weight loss, increased disease activity index, and increased colon weight/length ratio, were significantly alleviated by arbutin. Mediators of colonic pro-inflammatory cytokines as well as apoptosis markers in colitis were suppressed by the glycoside. High expression of phosphorylated JAK2 in colitis was significantly reversed by arbutin. The effects of arbutin treatment on colitis were considerably inhibited by the JAK2 inhibitor AG490. LPS-induced inflammatory responses were also suppressed by arbutin, which was notably inhibited by the JAK2 inhibitor AG490.Conclusion: The findings obtained herein suggest the protective role of arbutin and provide novel insights into alternative colitis treatments, which involve inhibition of the JAK2 signaling pathway.

scholarly journals Ficus pandurata Hance Inhibits Ulcerative Colitis and Colitis-Associated Secondary Liver Damage of Mice by Enhancing Antioxidation Activity

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Weibo Dai ◽  
Xinyi Zhan ◽  
Weijie Peng ◽  
Xin Liu ◽  
Weiwen Peng ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Liver Damage ◽  
Activity Index ◽  
Critical Role ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
The Body ◽  
Diamine Oxidase Activity ◽  
Inflammatory Bowel ◽  
Antioxidative Stress

Inflammatory bowel disease (IBD), a global disease threatening human health, is commonly accompanied by secondary liver damage (SLD) mediated by the gut-liver axis. Oxidative stress acts a critical role in the onset of IBD, during which excessive oxidation would destroy the tight junctions between intestinal cells, promote proinflammatory factors to penetrate, and thereby damage the intestinal mucosa. Ficus pandurata Hance (FPH) is widely used for daily health care in South China. Our previous study showed that FPH protected acute liver damage induced by alcohol. However, there is no study reporting FPH treating ulcerative colitis (UC). This study is designed to investigate whether FPH could inhibit UC and reveal its potential mechanism. The results showed that FPH significantly alleviated the UC disease symptoms including the body weight loss, disease activity index (DAI), stool consistency changing, rectal bleeding, and colon length loss of UC mice induced by dextran sulfate sodium (DSS) and reversed the influences of DSS on myeloperoxidase (MPO) and diamine oxidase activity (DAO). FPH suppressed UC via inhibiting the TLR4/MyD88/NF-κB pathway and strengthened the gut barrier of mice via increasing the expressions of ZO-1 and occludin and enhancing the colonic antioxidative stress property by increasing the levels of T-SOD and GSH-Px and the expressions of NRF2, HO-1, and NQO1 and reducing MDA level and Keap1, p22-phox, and NOX2 expressions. Furthermore, FPH significantly inhibited SLD related to colitis by reducing the abnormal levels of the liver index, ALT, AST, and cytokines including TNFα, LPS, LBP, sCD14, and IL-18 in the livers, as well as decreasing the protein expressions of NLRP3, TNFα, LBP, CD14, TLR4, MyD88, NF-κB, and p-NF-κB, suggesting that FPH alleviated UC-related SLD via suppressing inflammation mediated by inhibiting the TLR4/MyD88/NF-κB pathway. Our study firstly investigates the anticolitis pharmacological efficacy of FPH, suggesting that it can be enlarged to treat colitis and colitis-associated liver diseases in humans.

scholarly journals Protective Effect of Probiotics Isolated from Traditional Fermented Tea Leaves (Miang) from Northern Thailand and Role of Synbiotics in Ameliorating Experimental Ulcerative Colitis in Mice

Nutrients ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 227
Author(s):  
Napapan Kangwan ◽  
Sarawut Kongkarnka ◽  
Nitsara Boonkerd ◽  
Kridsada Unban ◽  
Kalidas Shetty ◽  
...  
Keyword(s):  
Protective Effect ◽  
Clinical Symptoms ◽  
Activity Index ◽  
Intestinal Barrier ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Experimental Period ◽  
Tea Leaves ◽  
Barrier Integrity ◽  
Intestinal Barrier Integrity

This study aimed to investigate the protective effect of probiotics and synbiotics from traditional Thai fermented tea leaves (Miang) on dextran sulfate sodium (DSS)-induced colitis in mice, in comparison to sulfasalazine. C57BL/6 mice were treated with probiotics L. pentosus A14-6, CMY46 and synbiotics, L. pentosus A14-6 combined with XOS, and L. pentosus CMY46 combined with GOS for 21 days. Colitis was induced with 2% DSS administration for seven days during the last seven days of the experimental period. The positive group was treated with sulfasalazine. At the end of the experiment, clinical symptoms, pathohistological changes, intestinal barrier integrity, and inflammatory markers were analyzed. The probiotics and synbiotics from Miang ameliorated DSS-induced colitis by protecting body weight loss, decreasing disease activity index, restoring the colon length, and reducing pathohistological damages. Furthermore, treatment with probiotics and synbiotics improved intestinal barrier integrity, accompanied by lowing colonic and systemic inflammation. In addition, synbiotics CMY46 combined with GOS remarkedly elevated the expression of IL-10. These results suggested that synbiotics isolated from Miang had more effectiveness than sulfasalazine. Thereby, they could represent a novel potential natural agent against colonic inflammation.

THE ROLE OF MYELOPEROXIDASE AND NEUTROPHIL EXTRACELLULAR TRAPS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S4-S4
Author(s):  
Belal Chami ◽  
Gulfam Ahmad ◽  
Angie Schroder ◽  
Patrick San Gabriel ◽  
Paul Witting
Keyword(s):  
Disease Severity ◽  
Hypochlorous Acid ◽  
Tissue Injury ◽  
Activity Index ◽  
Critical Role ◽  
Neutrophil Migration ◽  
Sodium Sulphate ◽  
Host Tissue ◽  
Neutrophil Extracellular Trap

Abstract Neutrophils are short-lived immune cells that represent the major cell type recruited to the inflamed bowel releasing their azurophilic granules containing enzymes myeloperoxidase (MPO). Fecal and serum MPO levels has previously been shown to correlate to disease severity in IBD patients. MPO, in the presence of H2O2 and free Cl- undergoes a halogenation cycle, yielding the two-electron oxidant, hypochlorous acid (HOCl) - a potent bactericidal agent. However, chronic intestinal exposure to MPO/HOCl due to perpetual inflammation may cause secondary host-tissue injury and cell death. Neutrophil Extracellular Trap (NET)osis is a specialised form of neutrophil death where MPO is entrapped in a DNA scaffold and continues to elicit HOCl activity and may further contribute to host-tissue injury. We investigated the presence of NETs in surgically excised ileum samples from CD and healthy patients using advanced confocal microscopic techniques and found MPO, Neutrophil Elastase (NE) and Citrullinated Histone h3 (CitH3) - critical components of NET formation, individually positively correlate to the severity of histopathological intestinal injury. Furthermore, multiplex Opal™ IHC performed using LMS880 Airyscan-moduled microscopy with z-stacking revealed colocalization of NE, MPO, CitH3 and DAPI indicating the extensive presence of NETs in severely affected CD tissue. Using two pharmacological inhibitors of MPO in a dextran sodium sulphate (DSS) model of murine colitis, we demonstrated the pathological role of MPO in experimental colitis. MPO inhibitors, TEMPOL and AZD3241 delivered via daily i.p significantly rescued the course of colitis by abrogating clinical indices including body weight loss, disease activity index, inhibiting serum peroxidation, and preserving colon length, while significantly mitigating histoarchitectural damage associated with DSS-induced colitis. We also showed that MPO inhibition decreased neutrophil migration to the gut, suggesting MPO may play a role in perpetuating the inflammatory cell by further recruiting cells to the inflamed gut. Collectively, we have shown for the first time that MPO is not only an important clinical marker of disease severity but may also play a critical role in perpetuating host-tissue damage and inflammation.

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.

Blockage of angiotensin II type 1 receptor regulates TNF-α-induced MAdCAM-1 expression via inhibition of NF-κB translocation to the nucleus and ameliorates colitis

2010 ◽  
Vol 298 (2) ◽  
pp. G255-G266 ◽  
Author(s):  
Takashi Mizushima ◽  
Makoto Sasaki ◽  
Tomoaki Ando ◽  
Tsuneya Wada ◽  
Mamoru Tanaka ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Activity Index ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Wild Type ◽  
Inflammatory Conditions ◽  
Tnf Α ◽  
Novel Target ◽  
Colitis Model

Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is an important target in the treatment of inflammatory bowel disease (IBD). Recently, treatment of IBD with an antibody to α4β7-integrin, a ligand for MAdCAM-1, has been an intense focus of research. Our aim was to clarify the mechanism by which MAdCAM-1 is regulated via angiotensin II type 1 receptor (AT1R), and to verify if AT1R might be a novel target for IBD treatment. The role of AT1R in the expression of MAdCAM-1 in SVEC (a murine high endothelial venule cell) and MJC-1 (a mouse colonic endothelial cell) was examined following cytokine stimulation. We further evaluated the effect of AT1R on the pathogenesis of immune-mediated colitis using AT1R-deficient (AT1R−/−) mice and a selective AT1R blocker. AT1R blocker significantly suppressed MAdCAM-1 expression induced by TNF-α, but did not inhibit phosphorylation of p38 MAPK or of IκB that modulate MAdCAM-1 expression. However, NF-κB translocation into the nucleus was inhibited by these treatments. In a murine colitis model induced by dextran sulfate sodium, the degree of colitis, judged by body weight loss, histological damage, and the disease activity index, was much milder in AT1R−/− than in wild-type mice. The expression of MAdCAM-1 was also significantly lower in AT1R−/− than in wild-type mice. These results suggest that AT1R regulates the expression of MAdCAM-1 under colonic inflammatory conditions through regulation of the translocation of NF-κB into the nucleus. Furthermore, inhibition of AT1R ameliorates colitis in a mouse colitis model. Therefore, AT1R might be one of new therapeutic target of IBD via regulation of MAdCAM-1.

Herbal Medicine and Acupuncture Combined Treatment Attenuates Colitis in Rats

2021 ◽  
pp. 1-18
Author(s):  
Yu-Mi Lee ◽  
Seung-Ho Seo ◽  
Seong-Young Cho ◽  
Dong-Hee Choi ◽  
Min-Woo Cheon ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Acupuncture Treatment ◽  
Activity Index ◽  
Combined Treatment ◽  
Group Analysis ◽  
Microbial Control ◽  
Body Weight Loss ◽  
Disease Activity Index ◽  
Simultaneous Treatment ◽  
Treatment Groups

This study aimed to verify the efficacy of a combined treatment of Jakyakgamcho-tang (JGT) and acupuncture (CV12, ST25, CV4) on colitis induced by dextrane sulfate sodium (DSS). Changes in immuno-mediated factors and metabolites were investigated. Colitis symptoms such as body weight loss and elevated disease activity index were alleviated by the combined treatment. Moreover, treatment with JGT and acupuncture restored the disturbed architecture of colon by suppressing inflammatory cytokine levels of IFN-[Formula: see text] ([Formula: see text]), IL-5 ([Formula: see text]), and IL-13 ([Formula: see text]) compared with the DSS group. Analysis of metabolic profiles of serum revealed that treatment groups were clearly separated from the DSS group, suggesting that JGT and acupuncture treatment altered serum metabolites. Furthermore, treatments caused opposite metabolite patterns for dimethylbenzimidazole, 1,5-anhydro-D-glucitol, proline, phosphate, glycolic acid, aspartic acid, tryptophan, phthalic acid, ornithine, and glutamic acid compared with the DSS group. The combined treatment group induced more effective metabolite patterns than the JGT group, implying that acupuncture treatment can restore metabolic changes caused by DSS induction. These results indicate that the simultaneous treatment of JGT administration and acupuncture procedure provides better management of the immune function and inflammatory expression of colitis than a single treatment. It is assumed that intestinal microbial control can be achieved by acupuncture stimulation as well as by taking herbal medicine.

Identification of Chemical Compounds from Artemisia gmelinii using UPLC-QTOF-MS/MS and their Regulatory Effects on Immune Responses in DSS-Induced Colitis Mice

2021 ◽  
pp. 1-23
Author(s):  
Yang-Ju Son ◽  
Ji Min Shin ◽  
In Jin Ha ◽  
Saruul Erdenebileg ◽  
Da Seul Jung ◽  
...  
Keyword(s):  
Immune Responses ◽  
High Performance ◽  
Activity Index ◽  
Disease Activity Index ◽  
Ethanol Extract ◽  
Chemical Compounds ◽  
Chronic Inflammatory Disease ◽  
Lymphoid Tissues ◽  
Food Ingredient ◽  
Cytokines And Chemokines

Artemisia gmelinii Web. ex Stechm. (AG), a popular medicinal herb in Asia, has been used as a common food ingredient in Korea and is traditionally known for its anti-inflammatory properties. Therefore, in this study, we aimed to investigate whether AG relieves IBD, a classic chronic inflammatory disease of the gastrointestinal tract. We identified 35 chemical compounds in AG ethanol extract using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. In mice with DSS-induced IBD, AG administration attenuated the disease activity index and the serum and colonic levels of inflammatory cytokines and chemokines. AG treatment decreased nuclear factor-[Formula: see text]B (NF-[Formula: see text]B) signaling, a key mediator of inflammation, in the mouse colons. Additionally, AG extract enhanced immune responses in lymphoid tissues such as spleen and Peyer’s patches. Thus, AG consumption potently ameliorated IBD symptoms and improved immune signaling in lymphoid tissues.

scholarly journals P015 Tricellulin overexpression protects against elevated macromolecule uptake in DSS colitis mice

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S137-S137
Author(s):  
F WEIß ◽  
I F M Lee ◽  
A Fromm ◽  
J C E Hu ◽  
T Breiderhoff ◽  
...  
Keyword(s):  
Weight Loss ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Sodium Sulphate ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Central Tube ◽  
Dss Colitis ◽  
Inflammatory Processes

Abstract Background In Inflammatory bowel disease, intestinal homeostasis cannot be sustained due to an overreaction of the immune system and a disturbed epithelial barrier due to an impaired tight junction (TJ). At tricellular TJs (tTJs), which are formed where three cells meet, the TJ network is basolaterally expanded and forms a central tube which would be potentially large enough to allow for a paracellular passage of macromolecules. Under normal conditions, the tTJ protein tricellulin (Tric) seals the central tube against luminal uptake. However, in ulcerative colitis (UC), Tric is downregulated, resulting in increased uptake of macromolecules including antigens which may further support the inflammatory processes. Thus, we aimed to identify whether or not overexpression of Tric has a protective effect against inflammation. Methods We generated intestinal epithelial cell-specific overexpression of Tric in mice (B6.C-Tg(Vil-cre) Rosa26tgGFP-Tric). In Tric-overexpressing (Tric-OE) and in wild-type (wt) mice experimental colitis was induced by 3% dextran sodium sulphate (DSS) for 6 days. The effect was assessed by determining the disease activity index (DAI: weight loss, stool consistency, and stool bleeding) and the colon dimensions. Using chamber experiments were performed to determine permeabilities for ions and macromolecules of different sizes (4 and 10 kDa). Results No difference in weight loss was observed between wt and Tric-OE mice upon DSS treatment. However, Tric-OE mice suffered less from diarrhoea and had less bloody stools compared with wt mice resulting in a lower DAI. In addition, DSS caused a reduced colon length which was less prominent in Tric-OE mice than in wt mice. Functional analysis revealed higher permeabilities for Na+ and Cl− after DSS treatment with no significant differences between Tric-OE and wt mice. In contrast, permeabilities for macromolecules of both sizes were unchanged after DSS treatment in Tric-OE mice but elevated in wt-mice. Conclusion Tric-overexpression prevents the epithelial barrier from elevated paracellular uptake of macromolecules during DSS colitis without affecting ion permeability. This protects against DSS colitis as indicated by less affected clinical and structural outcome parameters, most likely via a reduction in a load of immunologically active macromolecules in the subepithelium.

Bacillus licheniformis Zhengchangsheng® attenuates DSS-induced colitis and modulates the gut microbiota in mice

2019 ◽  
Vol 10 (5) ◽  
pp. 543-553 ◽  
Author(s):  
Y. Li ◽  
M. Liu ◽  
J. Zhou ◽  
B. Hou ◽  
X. Su ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bacillus Licheniformis ◽  
Activity Index ◽  
Intestinal Barrier ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Valuable Insight ◽  
Microbial Composition ◽  
Gastrointestinal Health ◽  
Human Inflammatory Bowel Disease

Human inflammatory bowel disease (IBD) and experimental colitis models in mice are associated with shifts in gut microbiota composition, and several probiotics are widely used to improve gastrointestinal health. Here, we investigated whether the probiotic Bacillus licheniformis Zhengchangsheng® (BL) ameliorates dextran sulphate sodium (DSS)-induced colitis through alteration of the gut microbiota. Experimental colitis was induced in BALB/C mice by dissolving 3% DSS in their drinking water for 7 days, which were gavaged with 0.2 ml phosphate-buffered saline or BL (3×107 cfu/ml) once a day. Administration of BL attenuated several effects of DSS-induced colitis, including weight loss, increased disease activity index, and disrupted intestinal barrier integrity. In addition, BL mitigated the reduction in faecal microbiota richness in DSS treated mice. Interestingly, BL was found to reduce the elevated circulating endotoxin level in mice with colitis by modulating the microbial composition of the microbiota, and this was highly associated with a proportional decrease in gut Bacteroidetes. Our results demonstrate that BL can attenuate DSS-induced colitis and provide valuable insight into microbiota interactions during IBD.

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