Bovine Lactoferrin Protects Dextran Sulfate Sodium Salt Mice Against Inflammation and Impairment of Colonic Epithelial Barrier by Regulating Gut Microbial Structure and Metabolites

Background: Ulcerative colitis is characterized by relapsing and remitting mucosal inflammation. Bovine lactoferrin (BL) is a multifunctional protein that could regulate the intestinal flora and has anti-inflammatory effects. The aim of this study was to investigate the therapeutic effect of BL on colitis.Methods: Dextran sulfate sodium salt (DSS) was utilized to establish a mouse model of colitis. BL was administered to treat DSS mice. The weight, the activity, and fecal status of the mice were recorded every day. Disease activity index was calculated. After the mice were euthanized, the colon length was measured. Hematoxylin and eosin staining was used to observe the pathological changes of the colon, and histological activity index was calculated. The myeloperoxidase (MPO) activity of colon tissue was measured. Western blot and immunohistochemistry were used to detect the expressions of Claudin-1, Occludin, and ZO-1. The expressions of IL-1β, IL-6, IL-10, TNF-α, and TGF-β in colon tissue were detected by ELISA. The protein expressions of MUC2, Reg3γ, β-defensin (HBD-2), and cAMP were detected by immunofluorescence (IF). 16S rDNA sequencing determined the type and structure of intestinal flora. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) measured the metabolites of the intestinal flora.Results: Compared with the DSS group, the mice's weight in the BL group was higher and the length of the colon was longer. At the 14th day, MPO activity was higher in the BL group. The expressions of Claudin-1, Occludin, and ZO-1 in the colon were up-regulated in the BL group compared with the DSS group. The expressions of IL-1β, IL-6, and TNF-α were lower. The expressions of IL-10 and TGF-β were higher. IF showed that the expressions of MUC2 and β-defensin (HBD-2) were down-regulated, and the expressions of Reg3γ and cAMP were up-regulated. The 16S rDNA sequencing results showed that the alpha diversity and beta diversity were notably changed in the DSS mice treated with BL. Metabolomics results showed that BL changed purine metabolism in the DSS mice.Conclusion: BL alleviated colitis in mice by improving the inflammatory response and the structure of the colon barrier in the colon. BL changed the composition and metabolites of the intestinal flora. Thus, BL might be an effective nutritional supplement for colitis treatment.

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Xanthoangelol Isolated from Angelica keiskei Roots Prevents Dextran Sulfate Sodium-Treated Colitis in Mice

The Natural Products Journal ◽

10.2174/2210315510999200515100203 ◽

2020 ◽

Vol 10 (5) ◽

pp. 655-663

Author(s):

Yoshiyuki Kimura ◽

Kimye Baba

Keyword(s):

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Gastrointestinal Diseases ◽

Gastric Ulcers ◽

Eosinophil Infiltration ◽

Full Blood Count ◽

Therapeutic Effects ◽

Tnf Α ◽

Angelica Keiskei

Background: The therapeutic effects of a number of natural products on Inflammatory Bowel Disease (IBD) have recently been examined in detail. The whole herb and roots of Angelica keiskei (Umblliferae) have traditionally been used as a diuretic, to treat gastrointestinal diseases such as gastric ulcers and diarrhea in Japan. Objectives: The present study was performed to investigate the effects of xanthoangelol, a major chalcone of Angelica keiskei roots, on diarrhea and inflammation in the large intestine of IBD model mice. Methods: Xanthoangelol (10 & 25 mg/kg) was orally administered to mice with 3% Dextran Sulfate Sodium (DSS)-induced colitis. Blood samples were collected during the experimental period, subjected to a full blood count test, and colonic cytokine and chemokine levels were measured. Results: Xanthoangelol (25 mg/kg) reduced the Disease Activity Index (DAI) of colitis. It also attenuated DSS-induced reductions in red blood cell and platelet counts as well as Hb and Ht levels. A histological examination of the colon using direct fast scarlet staining showed that xanthoangelol prevented DSS-induced mucosal ulceration and eosinophil infiltration. Xanthoangelol also reduced DSS-induced increases in colonic MCP-1, IL-1β, and TNF-α levels. Conclusions: Xanthoangelol reduced DSS-induced increases in colonic IL-1β, TNF-α, and MCP-1 levels and prevented eosinophil infiltration, which supports its potential as a treatment for IBD.

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

Microorganisms ◽

10.3390/microorganisms9102093 ◽

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.

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

Frontiers in Pharmacology ◽

10.3389/fphar.2021.693982 ◽

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.

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Protective Effect of Spirulina platensis Extract against Dextran-Sulfate-Sodium-Induced Ulcerative Colitis in Rats

Nutrients ◽

10.3390/nu11102309 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2309 ◽

Cited By ~ 4

Author(s):

Mohamed A. Morsy ◽

Sumeet Gupta ◽

Anroop B. Nair ◽

Katharigatta N. Venugopala ◽

Khaled Greish ◽

...

Keyword(s):

Ulcerative Colitis ◽

Drinking Water ◽

Spirulina Platensis ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Control Group ◽

Protective Effects ◽

Hydroalcoholic Extract ◽

Tnf Α

Inflammatory bowel disease is a multifactorial inflammatory condition. This study aimed to test the protective effects of Spirulina platensis against ulcerative colitis (UC). UC was induced in thirty-six male Wistar rats by adding dextran sulfate sodium (DSS) to their drinking water, while a control group received only drinking water. UC rats were equally-divided into six groups that received a single oral daily dose of vehicle (DSS), sulfasalazine (SSZ, 50 mg/kg/day), chloroform or the hydroalcoholic extracts of Spirulina platensis (100 or 200 mg/kg/day) for 15 days, and then blood and colon samples were harvested for determination of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), myeloperoxidase (MPO), and histopathology. At the end of the study, compared to time-matched controls, UC rats showed increased TNF-α (1.64-fold), IL-6 (5.73-fold), ESR (3.18-fold), and MPO (1.61-fold), along with loss of body weight (24.73%) and disease activity index (1.767 ± 0.216 vs. 0 ± 0), p < 0.001. These effects were prevented by SSZ treatment (p < 0.001 vs. DSS). The hydroalcoholic extract of Spirulina platensis dose-dependently modulated all DSS-induced inflammatory changes. However, the chloroform extract significantly lowered only IL-6 and ESR, but not TNF-α or MPO levels. The protective effects of the hydroalcoholic extract of Spirulina platensis against experimental UC involved mitigation of DSS-induced inflammation.

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Protective Effect of Lycium barbarum Polysaccharides and Capsaicin in Rats With Dextran Sulfate Sodium-Induced Ulcerative Colitis via Anti-inflammation and Antioxidation

Current Developments in Nutrition ◽

10.1093/cdn/nzab037_016 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 306-306

Author(s):

Yu-Shan Chen ◽

Yu Zhi Lian ◽

Jane Chao

Keyword(s):

Ulcerative Colitis ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Elevated Serum ◽

Control Group ◽

Lycium Barbarum ◽

Tnf Α ◽

Anti Inflammation ◽

Lycium Barbarum Polysaccharides

Abstract Objectives Ulcerative colitis (UC) is a chronic inflammatory disease in the colon, and the prevalence of UC is increasing worldwide. Lycium barbarum polysaccharides (LBP) from wolfberry extract has immunomodulatory effects, and act as a prebiotics candidate. Capsaicin (CAP) as an active ingredient of chili peppers has the potential for anti-inflammation and antioxidation. This study investigated the effects of LBP and CAP on anti-inflammation and antioxidation in rats with dextran sulfate sodium (DSS)-induced UC. Methods Male Sprague-Dawley rats were divided into five groups: control, UC (DSS), UC treated with 100 mg/kg bw LBP (LBP), UC treated with 12 mg/kg bw CAP (CAP), and UC treated with a combination of 50 mg/kg bw LBP and 6 mg/kg bw CAP (MIX) groups. The treatment of LBP and/or CAP was daily given by oral gavage from week 1 to week 4, and UC was induced by 5% DSS in drinking water for 6 days during week 3. Results The DSS group significantly increased disease activity index (DAI) scores, the levels of pro-inflammatory cytokines interleukin-6 (IL-6) in the serum and tumor necrosis factor-α (TNF-α) in the colon, and serum lipid peroxidation malondialdehyde (MDA) levels compared with the control group. While the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) in the serum were significantly decreased in the DSS group. The LBP, CAP, and MIX groups significantly decreased DAI scores on day 6 during the DSS-induced period. Compared with the DSS group, the LBP group significantly decreased serum IL-6 and serum MDA levels, but increased serum CAT activity. The CAP group significantly decreased serum IL-6 levels. The MIX group significantly reduced serum IL-6 and colon TNF-α levels, but elevated serum SOD activity. Conclusions The results suggest that administration of LBP and/or CAP attenuate DSS-induced UC symptoms in rats through the anti-inflammatory and antioxidant activities. Funding Sources This study was supported by the Ministry of Science and Technology, Taiwan (grant no. MOST 108–2320-B-038–052-MY3).

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Galectin-1 reduces the severity of ulcerative colitis induced by dextran sulfate sodium via suppressing inflammatory and oxidative mediators

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2019.4539 ◽

2020 ◽

Cited By ~ 1

Author(s):

Pelin Arda-Pirincci ◽

Guliz Aykol-Celik

Keyword(s):

Ulcerative Colitis ◽

Cell Proliferation ◽

Body Weight ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Proliferation Index ◽

Tnf Α ◽

Anti Oxidant ◽

Anti Inflammatory

Ulcerative colitis is an inflammatory bowel disease and many people suffers from this disease across the word. Dextran sulfate sodium (DSS) is a synthetic sulfated polysaccharide that is used to produce ulcerative colitis in rodents. Galectin-1 is a β-galactoside binding animal lectin which plays key roles in many biological events. In this study, we investigated the role of galectin-1 on colon morphology, cell proliferation, oxidative stress, anti-oxidant system, inflammatory and anti-inflammatory mediators in the model of experimental ulcerative colitis induced by DSS in mice. C57BL/6 mice were fed orally 3% DSS in their drinking water for 5 days for acute colitis induction. Animals were injected with 1 mg/kg recombinant human galectin-1 for 7 consecutive days. Oral DSS application resulted in colitis injury by causing histopathological changes; an increase in disease activity index (DAI), lipid peroxidation (MDA), myeloperoxidase (MPO) and TNF-α levels; a decrease in body weight, colon length, cell proliferation index, catalase (CAT), glutahione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, gluathione (GSH) and IL-10 levels. However, treatment with galectin-1 prevented DSS-induced colitis injury through the reduction of DAI, MDA, MPO and TNF-α levels, and the increase of body weight, colon length, cell proliferation, antioxidant enzymes activities, GSH and IL-10 levels. As a result, this study showed that galectin-1 has proliferative, anti-oxidant, anti-inflammatory, and cytoprotective effects against DSS-induced colitis in mice. In addition, galectin-1 reduces the severity of ulcerative colitis via suppressing inflammatory and oxidative mediators.

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Grape Seed Polyphenols Ameliorated Dextran Sulfate Sodium-Induced Colitis via Suppression of Inflammation and Apoptosis

Pharmacology ◽

10.1159/000501897 ◽

2019 ◽

Vol 105 (1-2) ◽

pp. 9-18 ◽

Cited By ~ 5

Author(s):

Yunxia Wang ◽

Yunan Wang ◽

Wanli Shen ◽

Yandi Wang ◽

Yini Cao ◽

...

Keyword(s):

Body Weight ◽

Mrna Expression ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Grape Seed ◽

Bloody Stool ◽

Inflammatory Infiltration ◽

Tnf Α ◽

Grape Seed Polyphenols

Background: Ulcerative colitis (UC) is an inflammatory bowel disease. Its onset is typically gradual, usually followed by periods of spontaneous remission and subsequent relapses. Grape seed polyphenols (GSP), a natural product extracted from grape seeds, have strong anti-inflammatory functions. Objectives: In this study, we investigated whether GSP has an inhibitory effect on UC and its related mechanism or not. Methods: We induced UC by 2.5% dextran sulfate sodium (DSS) and GSP at different doses (500 and 750 mg/kg body weight per day) was administrated to the mice by gavage. Body weight, diarrhea, and bloody stool were recorded every day to evaluate disease activity index. Hemotoxylin-eosin staining and immunohistochemical staining were used to identify the histological damages and inflammatory infiltration in colon tissues. Real-time polymerase chain reaction was used to evaluate mRNA expression of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and the expression of phosphorylated-signal transducer and activator of transcription 3 (STAT3) and STAT3 were assessed by western blot. The immunofluorescent assay was used to evaluate the apoptosis of intestinal epithelial cells (IECs). Results: GSP could alleviate the loss of body weight, diarrhea, bloody stool, the mucosal damage, and inflammatory infiltration. GSP could also downregulate the mRNA expression of inflammatory cytokines IL-6, IL-1β, and TNF-α as well as the phosphorylation of STAT3 and ameliorate the apoptosis of IECs. Conclusions: Our study suggests that GSP has protective effects against DSS-induced UC, which may through suppression of inflammation and apoptosis.

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Lactobacillus fermentum ZS40 Ameliorates Inflammation in Mice With Ulcerative Colitis Induced by Dextran Sulfate Sodium

Frontiers in Pharmacology ◽

10.3389/fphar.2021.700217 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zixia Chen ◽

Long Yi ◽

Yanni Pan ◽

Xingyao Long ◽

Jianfei Mu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Cytokines ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Flora ◽

Lactobacillus Fermentum ◽

Mouse Serum ◽

Colon Tissue ◽

Relative Expression ◽

Anti Inflammatory

Ulcerative colitis is an inflammatory disease of the intestine caused by many reasons, and it may even develop into colon cancer. Probiotics are normal bacteria that exist in the human body and have been proven to regulate the balance of intestinal flora and alleviate inflammation. The current study aimed to study the effect of Lactobacillus fermentum ZS40 (ZS40) on dextran sulfate sodium (DSS)-induced ulcerative colitis mice. The length and weight of the colon were measured, and the histopathological morphological changes of colon tissue were observed to evaluate the effects of ZS40 on colitis. Biochemical kits, ELISA kits, real-time quantitative PCR (RT-qPCR), and western blot were also used to detect the effects of ZS40 on serum and colon tissue related oxidative indicators and pro-inflammatory and anti-inflammatory cytokines. We found that ZS40 could reduce colonic inflammatory cell infiltration and goblet cell necrosis, increase total superoxide dismutase and catalase in mouse serum, and reduce myeloperoxidase and malondialdehyde levels. ZS40 could down-regulate the level of proinflammatory cytokines and up-regulate the level of anti-inflammatory cytokines. More importantly, ZS40 down-regulated the relative expression of nuclear factor-κB p65 (NF-κBp65), IL-6, and TNF-α mRNA and protein, up-regulated the relative expression of inhibitor kapa B alpha (IκB-α). By regulating the NF-κB and MAPK pathways to down-regulated the relative expression of p38 and JNK1/2 mRNA and p38, p-p38, JNK1/2, and p-JNK1/2 proteins. Our study suggested that ZS40 may serve as a potential therapeutical strategy for ulcerative colitis.

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Polyphenol Extract of Moringa Oleifera Leaves Alleviates Colonic Inflammation in Dextran Sulfate Sodium-Treated Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/6295402 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Yunjuan Zhang ◽

Lei Peng ◽

Wenyun Li ◽

Tianyi Dai ◽

Long Nie ◽

...

Keyword(s):

Moringa Oleifera ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Disease Activity Index ◽

Experimental Colitis ◽

Mucosal Damage ◽

Tnf Α ◽

Moringa Oleifera Leaves ◽

Moringa Oleifera Lam

Moringa oleifera Lam. is an essential herb used for the treatment of inflammation, diabetes, high blood pressure, and other diseases. In this study, phenolic extracts of M. oleifera leaves were obtained and analyzed. The results showed that the main identifiable phenols were astragalin, chlorogenic acid, isoquercitrin, kaempferitrin, luteolin, quercetin, and rutin. The effects of M. oleifera polyphenol extract (MOPE) on experimental colitis induced by 3% dextran sulfate sodium (DSS) were investigated. The results showed that oral administration of MOPE significantly alleviated the symptoms of DSS-induced colitis. MOPE significantly reduced weight loss, the disease activity index, colon shortening, and mucosal damage. In addition, MOPE attenuated the infiltration of CD3+ T cells, CD177+ neutrophils, and F4/80+ macrophages and significantly inhibited the secretion of IL-6 and TNF-α. After the MOPE administration, the expression of proteins associated with the NF-κB signaling pathway changed. Specifically, compared with that of the DSS group, the protein expression of NF-κB p65 and p-IκBα was downregulated, and the expression of IκBα was upregulated. This study revealed the anti-inflammatory effects and mechanisms of MOPE in the colon, indicating its potential use in preventing inflammation-driven diseases.

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β-Glucan Extracted from Highland Barley Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis in C57BL/6J Mice

Molecules ◽

10.3390/molecules26195812 ◽

2021 ◽

Vol 26 (19) ◽

pp. 5812

Author(s):

Minjie Chen ◽

Shuhua Tian ◽

Shichao Li ◽

Xinyi Pang ◽

Jing Sun ◽

...

Keyword(s):

Ulcerative Colitis ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Intestinal Flora ◽

Disease Activity Index ◽

Gastrointestinal Dysfunction ◽

Genes Encoding ◽

Inflammatory Bowel ◽

Highland Barley

Inflammatory bowel disease (IBD), which significantly affects human health, has two primary presentations: Crohn’s disease and ulcerative colitis (UC). Highland barley is the most common food crop for Tibetans and contains much more β-glucan than any other crop. Highland barley β-glucan (HBBG) can relieve the gastrointestinal dysfunction and promote intestines health. This study aimed to evaluate whether HBBG can relieve UC in mice. A mouse model of UC was established by adding 2% dextran sulfate sodium (DSS) to drinking water for 1 week. UC was alleviated after the introduction of the HBBG diet, as indicated by reductions in the disease activity index (DAI) score, histopathological damage, and the concentration of colonic myeloperoxidase (MPO), along with an improvement in colonic atrophy. Furthermore, we found that HBBG can increase the relative transcriptional levels of genes encoding ZO-1, claudin-1, occludin, and mucin2 (MUC2), thereby reducing intestinal permeability. Additionally, HBBG maintained the balance of proinflammatory and anti-inflammatory cytokines and modulated the structure of the intestinal flora.

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