scholarly journals Protective Effect of Iridoid Glycosides of the Leaves of Syringa oblata Lindl. on Dextran Sulfate Sodium-Induced Ulcerative Colitis by Inhibition of the TLR2/4/MyD88/NF-κB Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yifang Zhang ◽  
Dandan Han ◽  
Shen Yu ◽  
Chiying An ◽  
Xin Liu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Proinflammatory Cytokines ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Iridoid Glycosides ◽  
Mrna Levels ◽  
Dependent Manner

Iridoid glycoside (IG) is the major active fraction extracted from the leaves of Syringa oblata Lindl. In view of its antimicrobial and antidiarrheal potential, it could be beneficial for the treatment of ulcerative colitis (UC). In the present study, IG (20, 40, and 80 mg/kg) was administered orally for 14 days to dextran sulfate sodium- (DSS-) induced colitis rats. The anti-inflammatory effects of IG on DSS-induced UC were evaluated by comparing observations in DSS-induced colitis and drug-treated groups using disease activity index (DAI), macroscopic score, histological analysis, and apoptosis assay. To elucidate the antioxidant mechanisms of IG on NOX-dependent ROS production, the activities of 8-OHdG, NOX1, and NOX2 in DSS-induced colitis were determined. The levels of proinflammatory cytokines such as IL-2, IL-4, IL-5, IL-12p40, and IL-13 were detected. The inflammation-associated protein and mRNA expressions of TLR-2, TLR-4, MyD88, and NF-κBp65 were assessed by immunohistochemistry and real-time quantitative PCR, respectively. The results suggested that IG treatment significantly reduced DAI, macroscopic score, and histological damage compared to untreated animals (p<0.01), whereas administration of IG remarkably attenuated the upregulation of 8-OHdG, NOX1, and NOX2 and the expression of proinflammatory cytokines such as IL-2, IL-4, IL-5, IL-12p40, and IL-13 in DSS-treated rats in a concentration-dependent manner. In addition, IG treatment could dose dependently suppress the protein and mRNA levels of TLR-2, TLR-4, MyD88, and NF-κBp65. The dose of IG that produced the most significant protective effect was 80 mg/kg. The above results demonstrate that IG exerts its inhibitory effect on cell apoptosis, oxidative stress, and proinflammatory cytokines in DSS-induced colitis through modulation of the TLR2/4/MyD88/NF-κB signaling pathway.

scholarly journals EGCG Maintains Th1/Th2 Balance and Mitigates Ulcerative Colitis Induced by Dextran Sulfate Sodium through TLR4/MyD88/NF-κB Signaling Pathway in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Xue Bing ◽  
Liu Xuelei ◽  
Dong Wanwei ◽  
Liang Linlang ◽  
Chen Keyan
Keyword(s):  
Ulcerative Colitis ◽  
Flow Cytometry ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Mucosal Injury ◽  
Inflammatory Factors ◽  
Intestinal Mucosal Injury

Objective. To observe the protective effect of epigallocatechin gallate (EGCG) on dextran sulfate sodium- (DSS-) induced ulcerative colitis in rats and to explore the roles of TLR4/MyD88/NF-κB signaling pathway. Methods. Rat models of ulcerative colitis were established by giving DSS. EGCG (50 mg/kg/d) was given to assess disease activity index. HE staining was applied to observe histological changes. ELISA and qPCR detected the expression of inflammatory factors. Flow cytometry was used to measure the percentage of CD4+IFN-γ+ and CD4+IL-4+ in the spleen and colon. TLR4 antagonist E5564 was given in each group. Flow cytometry was utilized to detect CD4+IFN-γ+ and CD4+IL-4+ cells. Immunohistochemistry, qPCR, and western blot assay were applied to measure the expression of TLR4, MyD88, and NF-κB. Results. EGCG improved the intestinal mucosal injury in rats, inhibited production of inflammatory factors, maintained the balance of Th1/Th2, and reduced the expression of TLR4, MyD88, and NF-κB. After TLR4 antagonism, the protective effect of EGCG on intestinal mucosal injury was weakened in rats with ulcerative colitis, and the expressions of inflammatory factors were upregulated. Conclusion. EGCG can inhibit the intestinal inflammatory response by reducing the severity of ulcerative colitis and maintaining the Th1/Th2 balance through the TLR4/MyD88/NF-κB signaling pathway.

Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota

Planta Medica ◽  
2021 ◽  
Author(s):  
Jiaqi Wu ◽  
Yuzheng Wu ◽  
Yue Chen ◽  
Mengyang Liu ◽  
Haiyang Yu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Inflammation ◽  
Activity Index ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Function Evaluation ◽  
Biological Drugs

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.

scholarly journals LUEM PUA RICE EXTRACT ATTENUATES THE SEVERITY OF DEXTRAN SULFATE SODIUMINDUCED ULCERATIVE COLITIS IN RATS THROUGH CHOLINOMIMETIC EFFECTS

2021 ◽  
pp. 5-8
Author(s):  
KORNSUDA THIPART ◽  
KUTCHARIN PHUNIKHOM ◽  
ACHARAPORN NA LAMPANG NOENPLAB ◽  
JINTANA SATTAYASAI
Keyword(s):  
Ulcerative Colitis ◽  
Guinea Pig ◽  
Dextran Sulfate ◽  
Activity Index ◽  
Rice Variety ◽  
Final Concentration ◽  
Spleen Weight ◽  
Dependent Manner ◽  
Protective Effects ◽  
Guinea Pig Ileum

Objective: The objective of the study was to investigate the effect of aqueous extract of unpolished dark purple glutinous Thai rice variety Luem Pua(LP) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in rat and the possible cholinomimetic effects of the extract.Methods: The effect of LP extract (0.5, 1, or 1.5 mg/ml final concentration) on ileum contraction was tested using isolated guinea pig ileum. Certainagonists (acetylcholine, tetramethylammonium, and clonidine) and antagonists (hexamethonium chloride and atropine) were studied to determinethe cholinomimetic effect of the extract. The effects of LP extract (5 g/kg/day) in DSS-induced UC model (drinking water was replaced with 3%DSS in water for 7 days) in rat were evaluated. On each day of treatment, the change of disease activity index (DAI) was recorded. At the end of theexperiments, rats were terminated and disease severity expressed as DAI, colon length, and spleen weight were determined.Results: LP extract at the concentration of 0.5, 1, and 1.5 mg/ml (final concentration) could contract the ileum in a dose-dependent manner and beblocked completely by atropine. Oral administration of LP extract could significantly attenuate the severity of DSS-induced UC as seen by the reductionof DAI, colon length, and spleen weight.Conclusion: Results in isolated guinea pig ileum suggest that LP might contain active substance that could activate muscarinic receptors. In additionto antioxidant activity, through activation of muscarinic receptor, might explain the protective effects of LP extract against DSS-induced UC in rats.

scholarly journals Alleviation Effects of Bifidobacterium animalis subsp. lactis XLTG11 on Dextran Sulfate Sodium-Induced Colitis in Mice

2021 ◽  
Vol 9 (10) ◽  
pp. 2093
Author(s):  
Nana Wang ◽  
Song Wang ◽  
Baofeng Xu ◽  
Fei Liu ◽  
Guicheng Huo ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Intestinal Barrier Function ◽  
Spleen Weight ◽  
Colon Tissue ◽  
Bifidobacterium Animalis

Inflammatory bowel disease (IBD) is a chronic immune-related disease, which can occur through the dysfunction of the immune system caused by the imbalance of gut microbiota. Previous studies have reported the beneficial effects of Bifidobacterium on colitis, while the related mechanisms behind these effects have not been fully elucidated. The aim of our study is to investigate the alleviation effect of Bifidobacterium animalis subsp. lactis XLTG11 (B. lactis) on dextran sulfate sodium (DSS)-induced colitis and its potential mechanism. The results showed that B. lactis XLTG11 significantly decreased weight loss, disease activity index score, colon shortening, myeloperoxide activity, spleen weight, and colon tissue damage. Additionally, B. lactis XLTG11 significantly decreased the levels of pro-inflammatory cytokines and increased the level of anti-inflammatory cytokine. Meanwhile, high doses of B. lactis XLTG11 significantly up-regulated the expression of tight junction proteins and inhibited activation of Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MYD88)/nuclear factor-κB (NF-κB) signaling pathway. Furthermore, B. lactis XLTG11 increased the gut microbiota diversity and modulated gut microbiota composition caused by DSS. Moreover, Spearman’s correlation analysis also found that several specific gut microbiota were significantly correlated with colitis-related indicators. These results demonstrated that B. lactis XLTG11 can alleviate DSS-induced colitis by inhibiting the activation of the TLR4/MYD88/NF-κB signaling pathway, regulating inflammatory cytokines, improving intestinal barrier function, and modulating the gut microbiota.

scholarly journals Resveratrol Alleviates Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in Mice by Mediating PI3K/Akt/VEGFA Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Fang Zhu ◽  
Jujia Zheng ◽  
Fang Xu ◽  
Yiyuan Xi ◽  
Jun Chen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Expression Patterns ◽  
Intestinal Flora ◽  
Inflammatory Factors ◽  
Akt Pathway ◽  
Sham Operation ◽  
Glycerol Phosphate

Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon, and its incidence is on the rise worldwide. Resveratrol (RSV), a polyphenolic compound, was recently indicated to exert anti-inflammatory effects on UC. Consequently, the current study was conducted to investigate the mechanism of RSV on alleviating UC in mice by mediating intestinal microflora homeostasis. First, potential targets that RSV may regulate UC were screened using the TCMSP database. Next, mice were treated differently, specifically subjected to sham-operation and dextran sulfate sodium (DSS) induction, and then treated or untreated with RSV. Disease Activity Index (DAI) and Hematoxylin-Eosin (HE) staining were employed to analyze the pathological changes of mice colon. In addition, the expression patterns of inflammatory factors in spleen tissues were detected using ELISA, while the protein expression patterns of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and vascular endothelial growth factor A (VEGFA) in colon tissues were determined by means of immunohistochemistry (IHC) and Western blot analysis. Moreover, changes in intestinal flora and metabolite diversity in UC were analyzed by metabonomics. It was found that RSV played inhibitory roles in the PI3K/Akt pathway in mice. Meanwhile, the administration of RSV induced downregulated the expressions of TNF-α, IFN-γ, IL-1β, IL-6, and IL-4. The six floras of Haemophilus and Veillonella were significantly enriched in UC, while Clostridium, Roseburia, Akkermansia, and Parabacteroides were found to be enriched in control samples. Lastly, it was noted that Akkermansia could regulate the intestinal flora structure of UC mice through triacylglycerol biosynthesis, glycerol phosphate shuttle, cardiolipin biosynthesis, and other metabolic pathways to improve UC in mice. Altogether, our findings indicate that RSV suppressed the activation of the PI3K/Akt pathway and reduced the VEGFA gene expression to alleviate UC in mice.

Clinical and Structural Effects of Traditional Chinese Medicine and the Herbal Preparation, Iberogast, in a Rat Model of Ulcerative Colitis

2013 ◽  
Vol 19 (1) ◽  
pp. 10-19 ◽  
Author(s):  
Suzanne Mashtoub ◽  
Bang V. Hoang ◽  
Megan Vu ◽  
Kerry A. Lymn ◽  
Christine Feinle-Bisset ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Disease Activity ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Disease Activity Index ◽  
Therapeutic Effects ◽  
Inflammatory Disorder

Plant-sourced formulations such as Iberogast and the traditional Chinese medicine formulation, Cmed, purportedly possess anti-inflammatory and radical scavenging properties. We investigated Iberogast and Cmed, independently, for their potential to decrease the severity of the large bowel inflammatory disorder, ulcerative colitis. Sprague Dawley rats (n = 8/group) received daily 1 mL gavages (days 0-13) of water, Iberogast (100 μL/200 μL), or Cmed (10 mg/20 mg). Rats ingested 2% dextran sulfate sodium or water ad libitum for 7 days commencing on day 5. Dextran sulfate sodium administration increased disease activity index scores from days 6 to 12, compared with water controls ( P < .05). On day 10, 200 μL Iberogast decreased disease activity index scores in colitic rats compared with colitic controls ( P < .05). Neither Iberogast nor Cmed achieved statistical significance for daily metabolic parameters or colonic crypt depth. The therapeutic effects of Iberogast and Cmed were minimal in the colitis setting. Further studies of plant extracts are required investigating greater concentrations and alternative delivery systems.

Protective mechanisms of 6-gingerol in dextran sulfate sodium-induced chronic ulcerative colitis in mice

2018 ◽  
Vol 37 (10) ◽  
pp. 1054-1068 ◽  
Author(s):  
BO Ajayi ◽  
IA Adedara ◽  
EO Farombi
Keyword(s):  
Ulcerative Colitis ◽  
Drinking Water ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Biological Activities ◽  
Disease Activity Index ◽  
Aberrant Crypt Foci ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon, with an increasing incidence worldwide. 6-Gingerol (6G) is a bioactive constituent of Zingiber officinale, which has been reported to possess various biological activities. This study was designed to evaluate the role of 6G in chronic UC. Chronic UC was induced in mice by three cycles of 2.5% dextran sulfate sodium (DSS) in drinking water. Each cycle consisted of 7 days of 2.5% DSS followed by 14 days of normal drinking water. 6G (100 mg/kg) and a reference anti-colitis drug sulfasalazine (SZ) (100 mg/kg) were orally administered daily to the mice throughout exposure to three cycles of 2.5% DSS. Administration of 6G and SZ significantly prevented disease activity index and aberrant crypt foci formation in DSS-treated mice. Furthermore, 6G and SZ suppresses immunoexpression of tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, Regulated on activation, normal T cell expressed and secreted (RANTES), and Monocyte chemoattractant protein-1 (MCP-1) in the DSS-treated mice. 6G effectively protected against colonic oxidative damage by augmenting the antioxidant status with marked decrease in lipid peroxidation levels in DSS-treated mice. Moreover, 6G significantly inhibited nuclear factor kappa B (P65), p38, cyclooxygenase-2, and β-catenin whereas it enhanced IL-10 and adenomatous polyposis coli expression in DSS-treated mice. In conclusion, 6G prevented DSS-induced chronic UC via anti-inflammatory and antioxidative mechanisms and preservation of the Wnt/β-catenin signaling pathway.

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