scholarly journals Protective Effects of Zerumbone on Colonic Tumorigenesis in Enterotoxigenic Bacteroides fragilis (ETBF)-Colonized AOM/DSS BALB/c Mice

2020 ◽  
Vol 21 (3) ◽  
pp. 857 ◽  
Author(s):  
Soonjae Hwang ◽  
Minjeong Jo ◽  
Ju Eun Hong ◽  
Chan Oh Park ◽  
Chang Gun Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Activity Index ◽  
Oral Treatment ◽  
Bacteroides Fragilis ◽  
Disease Activity Index ◽  
Colonic Polyp ◽  
Spleen Weight ◽  
Protective Agent ◽  
Protective Effects ◽  
Murine Models

Chronic inflammation has been linked to colitis-associated colorectal cancer in humans. The human symbiont enterotoxigenic Bacteroides fragilis (ETBF), a pro-carcinogenic bacterium, has the potential to initiate and/or promote colorectal cancer. Antibiotic treatment of ETBF has shown promise in decreasing colonic polyp formation in murine models of colon cancer. However, there are no reported natural products that have shown efficacy in decreasing polyp burden. In this study, we investigated the chemopreventive effects of oral administration of zerumbone in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. Zerumbone significantly reduced the severity of disease activity index (DAI) scores as well as several parameters of colonic inflammation (i.e., colon weight, colon length, cecum weight and spleen weight). In addition, inflammation of the colon and cecum as well as hyperplasia was reduced. Zerumbone treatment significantly inhibited colonic polyp numbers and prevented macroadenoma progression. Taken together, these findings suggest that oral treatment with zerumbone inhibited ETBF-promoted colon carcinogenesis in mice indicating that zerumbone could be employed as a promising protective agent against ETBF-mediated colorectal cancer.

scholarly journals Grape Pomace Inhibits Colon Carcinogenesis by Suppressing Cell Proliferation and Inducing Epigenetic Modifications in an AOM/DSS Mouse Model

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 358-358
Author(s):  
Qiyu Tian ◽  
Xhixin Xu ◽  
Xiaofei Sun ◽  
Jeanene Deavila ◽  
Min Du ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Wnt Signaling ◽  
Activity Index ◽  
Control Diet ◽  
Disease Activity Index ◽  
Experimental Period ◽  
Dna Demethylation ◽  
Grape Pomace ◽  
Protective Effects

Abstract Objectives Grape pomace (GP), a by-product of the wine and juice industry, is rich in bioflavonoids and dietary fibers. We hypothesized that grape pomace has protective effects against colitis-associated colorectal cancer (CRC). Methods Nine-week-old female mice were fed a control diet (CON) or CON with 5% grape pomace (GP) for 2 weeks, when mice were subjected to azoxymethane (AOM)/dextran sulfate sodium (DSS) for colorectal cancer (CRC) induction. All animals were received 1% DSS in drinking water for 7 days followed by a 21-day recovery in a 3-cycle experimental period, while receiving their respective diet. Results GP supplementation ameliorated the disease activity index (DAI) score, reduced tumor number, tumor size and pathological scores in AOM/DSS treated mice. Furthermore, dietary GP suppressed colonic expression of inflammatory cytokines, IL-1β and TNF-α, and inhibited NF-κB inflammatory signaling. Colorectal inflammation is known to enhance Wnt signaling and cell proliferation. In agreement, the content of β-catenin, a key downstream mediator of Wnt signaling, was reduced so for the expression of Cyclin D1 phosphorylation and content of p53 and PCNA level in GP-fed mice.  In addition, GP reduced the expression of ALDH1, a marker of cell stemness, and increased the expression of Cdx2, a key transcription factor initiating epithelial cell differentiation. Consistently, DNA methylation of the promoter region of Cdx2 gene and hypermethylation of GpG island methylator phenotype (CIMP), which commonly occurs during CRC carcinogenesis, was alleviated in GP group. Conclusions GP supplementation suppressed colitis-associated CRC carcinogenesis associated with the suppression of inflammation and cell proliferation and the enhancement of DNA demethylation in Cdx2 and CIMP genes in the colon. Funding Sources USDA-NIFA 2018–67,017-27,517.

scholarly journals Protective Effect of Cicer arietinum L. (Chickpea) Ethanol Extract in the Dextran Sulfate Sodium-Induced Mouse Model of Ulcerative Colitis

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 456 ◽  
Author(s):  
Mia Kim ◽  
Kyung-Sook Chung ◽  
Se-Jung Hwang ◽  
Ye Seul Yoon ◽  
Young Pyo Jang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mrna Expression ◽  
Cicer Arietinum ◽  
Inflammatory Mediators ◽  
Clinical Symptoms ◽  
Activity Index ◽  
Disease Activity Index ◽  
Ethanol Extract ◽  
Spleen Weight ◽  
Protective Effects

Inflammatory bowel disease (IBD) is a major risk factor of colorectal cancer. Drugs currently used for IBD exhibit adverse effects including vomiting, nausea, and diarrhea. Naturally derived novel alternative therapies are required to overcome these limitations. In this study, we investigated the protective effects of ethanol extract of Cicer arietinum (CEE) in a dextran sodium sulfate (DSS)-induced mouse model of colitis. CEE markedly improved DSS-induced clinical symptoms and histological status, such as the disease activity index, spleen weight, and colon length. Moreover, CEE-treated mice showed significant recovery of DSS-induced crypt damage and cell death. CEE suppressed myeloperoxidase (MPO) activity and macrophage marker F4/80 mRNA expression in colonic tissue of mice with DSS-induced colitis, indicating neutrophil infiltration and macrophage accumulation, respectively. Although DSS upregulated pro-inflammatory mediators and activated transcription factors, CEE downregulated the mRNA expression of cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α, protein expression of cyclooxygenase-2 and inducible nitric oxide synthase, as well as activation of nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Hence, our findings reveal that the anti-inflammatory properties of CEE, involving the downregulation of the expression of pro-inflammatory mediators by inactivating NF-κB and STAT3 in DSS-induced colitis mice.

scholarly journals The Protection of Crocin Against Ulcerative Colitis and Colorectal Cancer via Suppression of NF-κB-Mediated Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Shanshan Teng ◽  
Jie Hao ◽  
Hui Bi ◽  
Congcong Li ◽  
Yongfeng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Activity Index ◽  
Disease Activity Index ◽  
Protective Effects ◽  
Protein Protein Interactions ◽  
Anti Inflammatory ◽  
Factor Α

Background: In China, the incidence of ulcerative colitis (UC) is increasing every year, but the etiology of UC remains unclear. UC is known to increase the risk of colorectal cancer (CRC). The aim of this study was to investigate the protective effects of crocin against UC and CRC in mouse models.Methods: Crocin was used to treat the dextran sodium sulfate (DSS)-induced UC mice for 3 weeks, and ApcMinC/Gpt mice with colorectal cancer for 8 weeks. Proteomics screening was used to detect changes in the protein profiles of colon tissues of UC mice. Enzyme-linked immunosorbent assays and western blot were used to verify these changes.Results: Crocin strongly reduced the disease activity index scores of UC mice, and improved the pathological symptoms of the colonic epithelium. The anti-inflammatory effects of crocin were indicated by its regulation of the activity of various cytokines, such as interleukins, via the modulation of nuclear factor kappa-B (NF-κB) signaling. Crocin significantly suppressed tumor growth in ApcMinC/Gpt mice and ameliorated pathological alterations in the colon and liver, but had no effects on spleen and kidney. Additionally, crocin significantly decreased the concentrations of interleukins and tumor necrosis factor-α in the sera and colon tissues, suggesting its anti-inflammatory effects related to NF-κB signaling. Finally, 12-h incubation of SW480 cells with crocin caused cell cycle arrest, enhanced the apoptotic rate, promoted the dissipation of mitochondrial membrane potential, and the over-accumulation of reactive oxygen species. From the theoretical analyses, phosphorylated residues on S536 may enhance the protein-protein interactions which may influence the conformational changes in the secondary structure of NF-κB.Conclusion: The protective effects of crocin on UC and CRC were due to its suppression of NF-κB-mediated inflammation.

scholarly journals YYFZBJS Inhibits Colorectal Tumorigenesis by Remodeling Enterotoxigenic Bacteroides Fragilis Mediated M2 Macrophage Polarization in Vivo and in Vitro

2020 ◽  
Author(s):  
Ni Chai ◽  
Yuelei Cheng ◽  
Yibai Xiong ◽  
Wenfei Shi ◽  
Yiqing Yao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Activity Index ◽  
Macrophage Polarization ◽  
Bacteroides Fragilis ◽  
Intragastric Administration ◽  
M2 Macrophage ◽  
Protective Agent ◽  
Dependent Manner ◽  
M2 Macrophages ◽  
Anticancer Activities

Abstract BackgroundThe occurrence of CRC is believed to be related to a variety of factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. Our previous studies indicated that the extract of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS), had potent anticancer activities by significantly inhibiting intestinal tumor development in ApcMin/+ mice. However, knowledge regarding the mechanism and effect of YYFZBJS in the prevention of colorectal cancer is limited.MethodsIn this study, we investigated the preventive effects of oral administration of YYFZBJS in enterotoxigenic Bacteroides fragilis (ETBF)-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. Here, the tumor load, tumor number, histology, and the severity of disease activity index (DAI) scores were reduced as expected.Resultsthe intragastric administration of YYFZBJS in AOM/DSS model significantly decreased ETBF abundance, immunity and some M2 macrophage markers, including CD206, Arg-1, IL-10, and TGF-β. Additionally, reversing polarized macrophages, which has been modified by YYFZBJS, could suppressed CRC cell proliferation and infiltration, as demonstrated by decreasing some tumor proliferation-related proteins in a dose-dependent manner, including c-Met, cyclinD1 and MMPs. Importantly, ETBF dysbiosis can contribute to the development of colon tumor by stimulating p-STAT3 medicated M2 macrophages polarization to promote chronic inflammation and adenoma malignant transformation, which effectively constrained by YYFZBJS.ConclusionAltogether, we demonstrate that ETBF dysbiosis may contribute to M2 macrophages-promoted colon carcinogenesis and progression of CRC cells, and indicating that YYFZBJS could be employed as a promising protective agent against ETBF-mediated colorectal cancer.

scholarly journals Ethanol Extract ofCordyceps militarisGrown on Germinated Soybeans Attenuates Dextran-Sodium-Sulfate- (DSS-) Induced Colitis by Suppressing the Expression of Matrix Metalloproteinases and Inflammatory Mediators

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Dong Ki Park ◽  
Hye-Jin Park
Keyword(s):  
Matrix Metalloproteinases ◽  
Inflammatory Mediators ◽  
Sodium Sulfate ◽  
Activity Index ◽  
Disease Activity Index ◽  
Ethanol Extract ◽  
Treated Group ◽  
Dextran Sodium Sulfate ◽  
Protective Agent ◽  
Colon Tissue

The effect ofCordyceps militaris(CM) grown on germinated soybeans (GSC) in the inflammatory bowel disease (IBD) model was studied. To demonstrate the preventive effect of GSC extract in a dextran-sodium-sulfate- (DSS-) induced acute colitis mouse model, GSC was administered 2 days before DSS coadministration. GSC significantly suppressed DSS-induced disease activity index (DAI) as well as histopathological scores, compared to control or CM-treated group. To elucidate the anti-IBD activity of GSC, we checked the level of matrix metalloproteinases (MMPs) and inflammatory mediators. GSC extract decreased the level of MMP-3 and -9 mRNAs and p53 proteins. The level and activity of LPS-induced MMP-9 were reduced in GSC-treated RAW264.7 cells. It also attenuated the level of inducible nitric oxide synthase (iNOS) and tumor necrosis factor- (TNF-)αmRNAs both in colon tissue and in macrophage cells. These results suggest that GSC can be applied as a protective agent against IBDs.

scholarly journals Brusatol-Enriched Brucea javanica Oil Ameliorated Dextran Sulfate Sodium-Induced Colitis in Mice: Involvement of NF-κB and RhoA/ROCK Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xinghan Zheng ◽  
Liting Mai ◽  
Tongtong Wang ◽  
Ying Xu ◽  
Zireng Su ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Activity Index ◽  
Disease Activity Index ◽  
Protective Effects ◽  
Intestinal Epithelial ◽  
Colon Tissue ◽  
Epithelial Barrier Function ◽  
Brucea Javanica ◽  
Tnf Α ◽  
Brucea Javanica Oil

Brucea javanica oil (BJO) is beneficial for the treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have an anti-UC effect. The present study is aimed at comparing the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO) and at exploring the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function. Balb/C mice received 3% (wt/vol) DSS for one week to establish the UC model. Different doses of BE-BJO, BF-BJO, or BJO were treated. The result illustrated that BE-BJO alleviated DSS-induced loss of body weight, an increase of disease activity index (DAI), and a shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of TNF-α, IFN-γ, IL-6, and IL-1β in the colon tissue, and reversed the decreased expressions of ZO-1, occludin, claudin-1, and E-cadherin induced by DSS but augmented claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice, indicating that the protective effect of BE-BJO is attributed to suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that brusatol is an active component from BJO in the treatment of UC.

The Adipokine Metrnl Ameliorates Chronic Colitis in Il-10–/– Mice by Attenuating Mesenteric Adipose Tissue Lesions During Spontaneous Colitis

2019 ◽  
Vol 13 (7) ◽  
pp. 931-941 ◽  
Author(s):  
Lugen Zuo ◽  
Sitang Ge ◽  
Yuanyuan Ge ◽  
Jingjing Li ◽  
Bing Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Activity Index ◽  
Disease Activity Index ◽  
Experimental Colitis ◽  
Protective Effects ◽  
Systemic Delivery ◽  
Chronic Colitis ◽  
Mesenteric Adipose Tissue ◽  
Proinflammatory Mediators ◽  
Ppar Γ

Abstract Background Crosstalk between mesenteric adipose tissue [MAT] and the intestines affects the progression of Crohn’s disease [CD]. The adipokine metrnl regulates adipocyte function and has anti-inflammatory activity. We aimed to explore metrnl expression in CD MAT, investigate the influence of metrnl on the experimental colitis disease course and determine the mechanism underlying this effect. Methods Metrnl expression in MAT specimens obtained from patients with and without CD was tested by immunohistochemistry. Male Il-10–/– mice with spontaneous enteritis were divided into positive control and metrnl-treated [Metrnl-Fc, 10 mg/kg/d, intraperitoneally, 8 weeks] groups. Age-matched male wild-type [WT] mice were used as negative controls. The effects of metrnl on enteritis and mesenteric lesions and the potential controlling mechanisms were evaluated. Results Metrnl expression was higher in human CD MAT than in control MAT. Systemic delivery of metrnl significantly ameliorated chronic colitis in Il-10–/– mice, as demonstrated by decreases in the disease activity index, inflammatory score and proinflammatory mediators. The protective effects of metrnl on MAT included reduced mesenteric hypertrophy, increased adipocyte size, improved adipocyte intrinsic function and ameliorated inflammation. Metrnl treatment activated STAT5/PPAR-γ signaling and promoted adipocyte differentiation in the MAT. Conclusions Metrnl expression was increased in the MAT of CD patients. Metrnl administration attenuated mesenteric lesions by promoting adipocyte function and differentiation partly through STAT5/PPAR-γ signaling pathway activation, thereby ameliorating CD-like colitis in mice.

scholarly journals Anti-inflammatory Bifidobacterium strains prevent dextran sodium sulfate induced colitis and associated gut microbial dysbiosis in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shashank Singh ◽  
Ruchika Bhatia ◽  
Pragyanshu Khare ◽  
Shikha Sharma ◽  
Sivasubramanian Rajarammohan ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Sodium Sulfate ◽  
Activity Index ◽  
Disease Activity Index ◽  
Dextran Sodium Sulfate ◽  
Raw 264.7 Cells ◽  
Spleen Weight ◽  
Lipocalin 2 ◽  
Weight Percentage ◽  
Microbial Dysbiosis

Abstract Crohn’s and ulcerative colitis are common inflammatory conditions associated with Inflammatory bowel disease. Owing to the importance of diet based approaches for the prevention of inflammatory gut conditions, the present study was aimed to screen the human isolates of Bifidobacterium strains based on their ability to reduce LPS-induced inflammation in murine macrophage (RAW 264.7) cells and to evaluate prioritized strains for their preventive efficacy against ulcerative colitis in mice. Twelve out of 25 isolated strains reduced the production of LPS-induced nitric oxide and inflammatory cytokines. Furthermore, three strains, B. longum Bif10, B. breve Bif11, and B. longum Bif16 conferred protection against dextran sodium sulfate induced colitis in mice. The three strains prevented shortening of colon, spleen weight, percentage body weight change and disease activity index relative to colitis mice. Lower levels of Lipocalin-2, TNF-α, IL-1β and IL-6 and improved SCFA levels were observed in Bifidobacterium supplemented mice relative to DSS counterparts. Bacterial composition of B. longum Bif10 and B. breve Bif11 fed mice was partly similar to the normal mice, while DSS and B. longum Bif16 supplemented mice showed deleterious alterations. At the genus level, Bifidobacterium supplementation inhibited the abundances of pathobionts such as Haemophilus, Klebsiella and Lachnospira there by conferring protection.

scholarly journals Indigo Naturalis Suppresses Colonic Oxidative Stress and Th1/Th17 Responses of DSS-Induced Colitis in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Hai-tao Xiao ◽  
Jiao Peng ◽  
Bo Wen ◽  
Dong-dong Hu ◽  
Xiao-peng Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chinese Medicine ◽  
Th17 Cells ◽  
Molecular Mechanisms ◽  
Activity Index ◽  
Disease Activity Index ◽  
Protective Effects ◽  
Mesenteric Lymph Nodes ◽  
Indigo Naturalis

Indigo naturalis (also known as Qing-dai, or QD), a traditional Chinese medicine, has been widely used as an anticolitis regimen in the clinical practice of Chinese medicine. However, the precise mechanisms behind its efficacy remain unknown. We investigated the protective effects and associated molecular mechanisms of QD in DSS-induced colitis in mice. We found that QD administration attenuated DSS-induced colon shortening, tissue damage, and the disease activity index during the onset of colitis. Moreover, QD administration significantly suppressed colonic MPO activity and increased the activities of colonic T-SOD, CAT, and GSH-Px, as well the expression of p-AMPK and Nrf-2 in colon tissues of colitic mice. In addition, QD was capable of reducing the colonic Th1 and Th17 cell cytokines, the frequencies of Th1 and Th17 cells, and the phosphorylation of p-STAT1 and p-STAT3 in the mesenteric lymph nodes of colitic mice. An in vitro assay showed that QD significantly suppressed the differentiation of Th1 and Th17 cells. These findings suggest that QD has the potential to alleviate experimental colitis by suppressing colonic oxidative stress and restraining colonic Th1/Th17 responses, which are associated with activating AMPK/Nrf-2 signals and inhibiting STAT1/STAT3 signals, respectively. These findings also support QD as an effective regimen in the treatment of IBD.

scholarly journals Suppression of Dextran Sulfate Sodium-Induced Colitis in Mice by Radon Inhalation

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Yuichi Nishiyama ◽  
Takahiro Kataoka ◽  
Keiko Yamato ◽  
Takehito Taguchi ◽  
Kiyonori Yamaoka
Keyword(s):  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Activity Index ◽  
Disease Activity Index ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Activated Neutrophils ◽  
Radon Inhalation ◽  
Activity Index Score

The enhanced release of reactive oxygen species from activated neutrophils plays important role in the pathogenesis of inflammatory bowel disease. We previously reported that radon inhalation activates antioxidative functions in various organs of mice. In this study, we examined the protective effects of radon inhalation on dextran sulfate sodium- (DSS) induced colitis in mice which were subjected to DSS for 7 days. Mice were continuously treated with air only (sham) or radon at a concentration of 2000 Bq/m3from a day before DSS administration to the end of colitis induction. In the results, radon inhalation suppressed the elevation of the disease activity index score and histological damage score induced by DSS. Based on the changes in tumor necrosis factor-alpha in plasma and myeloperoxidase activity in the colon, it was shown that radon inhalation suppressed DSS-induced colonic inflammation. Moreover, radon inhalation suppressed lipid peroxidation of the colon induced by DSS. The antioxidant level (superoxide dismutase and total glutathione) in the colon after DSS administration was significantly higher in mice treated with radon than with the sham. These results suggested that radon inhalation suppressed DSS-induced colitis through the enhancement of antioxidative functions in the colon.

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