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Scope: A study is conducted to determine the anti-inflammatory effects of cocoa and polyphenol-rich cocoa fractions in the dextran sulfate sodium (DSS)-induced mouse model of acute colonic inflammation., Methods and Results: Male C57BL/6J mice are treated with dietary cocoa powder, an extractable cocoa polyphenol fraction, or a non-extractable cocoa polyphenol fraction for 2 weeks prior to treatment with 2.5% DSS in the drinking water for 7 days to induce colonic inflammation. Cocoa treatment continues during the DSS period. Cocoa and/or cocoa fractions exacerbate DSS-induced weight loss and fail to mitigate DSS-induced colon shortening but do improve splenomegaly. Cocoa/cocoa fraction treatment fails to mitigate DSS-induced mRNA and protein markers of inflammation. Principal component analysis shows overlap between cocoa or cocoa fraction-treated mice and DSS-induced controls, but separation from mice not treated with DSS., Conclusion: The results suggest cocoa and cocoa polyphenols may not be useful in mitigating acute colonic inflammation., (© 2024 Wiley‐VCH GmbH.)

Abstract Background Dextran sulfate sodium (DSS) replicates ulcerative colitis (UC)-like colitis in murine models. However, the microbial characteristics of DSS-triggered colitis require further clarification. To analyze the changes in gut microbiota associated with DSS-induced acute and chronic colitis. Methods Acute colitis was induced in mice by administering 3% DSS for 1 week in the drinking water, and chronic colitis was induced by supplementing drinking water with 2.5% DSS every other week for 5 weeks. Control groups received the same drinking water without DSS supplementation. The histopathological score and length of the colons, and disease activity index (DAI) were evaluated to confirm the presence of experimental colitis. Intestinal microbiota was profiled by 16S rDNA sequencing of cecal content. Results Mice with both acute and chronic DSS-triggered colitis had significantly higher DAI and colon histopathological scores in contrast to the control groups (P

Abstract Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis (UC) and Crohn's Disease, are most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. Strategies that target the microbiota have emerged as potential therapies and, of these, probiotics have gained the greatest attention. Herein, we isolated a strain of Lactobacillus paracasei R3 (L.p R3) with strong biofilm formation ability from infant feces. Interestingly, we also found L.p R3 strain can ameliorate the general symptoms of murine colitis, alleviate inflammatory cell infiltration and inhibit Th17 while promote Treg function in murine dextran sulfate sodium (DSS)-induced colitis. Overall, this study suggested that L.p R3 strain significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.

The purpose of this study was to investigate the effect that Glycine max hydrolyzed with enzymes from Bacillus velezensis KMU01 has on dextran-sulfate-sodium (DSS)-induced colitis in mice. Hydrolysis improves functional health through the bioconversion of raw materials and increase in intestinal absorption rate and antioxidants. Therefore, G. max was hydrolyzed in this study using a food-derived microorganism, and its anti-inflammatory effect was observed. Enzymatically hydrolyzed G. max (EHG) was orally administered once daily for four weeks before DSS treatment. Colitis was induced in mice through the consumption of 5% (w/v) DSS in drinking water for eight days. The results showed that EHG treatment significantly alleviated DSS-induced body weight loss and decreased the disease activity index and colon length. In addition, EHG markedly reduced tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 production, and increased that of IL-10. EHG improved DSS-induced histological changes and intestinal epithelial barrier integrity in mice. Moreover, we found that the abundance of 15 microorganisms changed significantly; that of Proteobacteria and Escherichia coli, which are upregulated in patients with Crohn’s disease and ulcerative colitis, decreased after EHG treatment. These results suggest that EHG has a protective effect against DSS-induced colitis and is a potential candidate for colitis treatment.

Ornithine α-ketoglutarate (OKG), a nutritional compound, is an amino acid salt with anti-oxidative and anti-inflammatory effects on humans and animals. Ulcerative colitis (UC), as an inflammatory bowel disease (IBD), leads to chronic intestinal inflammatory dysfunction. This study evaluated the optimal dosage of OKG in healthy mice. Then, a mouse model of acute colitis was established using dextran sodium sulfate (DSS), and the preventive effect of OKG on DSS-induced colitis in mice was explored through analysis of serum inflammatory cytokines and fecal microbiota. Initially, the mice were randomly divided into a control group, a group given a low dose of OKG (LOKG: 0.5%), a group given a medium dose of OKG (MOKG: 1%), and a group given a high dose of OKG (HOKG: 1.5%); they remained in these groups for the entire 14-day experimental period. Our results demonstrated that 1% OKG supplementation increased body weight, serum growth hormone (GH), insulin (INS), alkaline phosphatase (ALP), Tyr, and His and decreased urea nitrogen (BUN), NH3L, and Ile. Then, a 2 × 2 factor design was used for a total of 40 mice, with diet (a standard diet or a 1% OKG diet) and challenge (4% DSS or not) as the main factors. During days 14 to 21, the DSS mice were administered 4% DSS to induce colitis. The results revealed that OKG alleviated weight loss and reversed the increases in colonic histological damage induced by DSS. OKG also increased serum IL-10 secretion. Moreover, OKG enhanced the abundance of Firmicutes and decreased that of Bacteriodetes at the phylum level and particularly enhanced the abundance of Alistipes and reduced that of Parabacterioides at the genus level. Our results indicated that OKG promotes growth performance and hormone secretion and regulates serum biochemical indicators and amino acid concentrations. Furthermore, 1% OKG supplementation prevents DSS-induced colitis in mice via altering microbial compositions and reducing the secretion of inflammatory cytokines in serum.

Irritable bowel disease (IBD), which results in an elevated risk of colitis-associated colorectal cancer (CAC), is characterized by inflammation and barrier disruption of the gut. The genus Rumex has anti-oxidative and anti-inflammatory effects, and the roots of Rumex japonicus Houtt (RJ) have been traditionally used in East Asia to treat digestive problems. We investigated the protective effect of RJ against azoxymethane (AOM)-and dextran sulfate sodium (DSS)-induced CAC in C57BL/6N male mice. The mice were intraperitoneally injected with AOM on the first day and orally treated with 2% DSS for 2 weeks (on the third and sixth weeks). RJ extract (100 mg/kg) was administered to the mice in the RJ group for 4 weeks (from the third to sixth week), and all mice were sacrificed on the final day of the eighth week. Changes in morphology, tight junctions (TJs), inflammation-related factors in the colon and serum inflammatory cytokine levels were measured. The colons of AOM/DSS-treated mice were shorter and heavier than those of normal mice. The number of tumors in the colons of AOM/DSS-treated mice increased; however, RJ suppressed these changes. RJ also reduced the levels of tumor necrosis factor-a, interleukin (IL)-6, and IL-1 β in the colon and serum, and it increased the level of IL-10 in the colon. Moreover, RJ inhibited the barrier disruption and apoptosis in the colons of AOM/DSS-treated mice. RJ effectively suppressed AOM/DSS-induced CAC by inhibiting tumor formation, inflammation, disruption of TJ, and apoptosis in the colon. [ABSTRACT FROM AUTHOR]

Background and Aims: NLRP3 inflammasomes have been reported to have a key role in the initiation and perpetuation of inflammatory bowel diseases (IBD). Here we investigated the effects of OLT1177, a selective inhibitor of NLRP3 inflammasomes, in mice with dextran sulfate sodium (DSS)-induced colitis. Methods: C57BL/6J mice were given drinking water containing 3% DSS for 5 days. OLT1177 was administered for 5 days during the induction phase (simultaneously with DSS treatment) or the recovery phase (after the DSS treatment ended). The body weight and disease activity index were monitored daily. The mice were sacrificed 10 days after the start of the experiment, and the severity of inflammation in the colon was determined based on histological and biochemical analyses. Results: Administration of OLT1177 during the induction phase effectively suppressed DSS colitis in terms of weight loss, disease activity index, histological score, and expression of inflammatory cytokines compared to the DSS group. In contrast, OLT1177 administration during the recovery phase did not significantly affect the colitis disease course or the results of histological analyses. Conclusions: OLT1177 was effective in preventing the onset of DSS colitis in mice. These results could guide the use of OLT1177 as a therapy for human IBD. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is one of the two main forms of inflammatory bowel disease (IBD) and is an idiopathic, chronic inflammatory disease of the colonic mucosa with an unclear etiology. Interleukin (IL)-10 has been reported to play a crucial role in the maintenance of immune homeostasis in the intestinal environment. Type 1 regulatory T (Tr1) cells are a subset of CD4+Foxp3− T cells able to secrete high amounts of IL-10 with potent immunosuppressive properties. In this study, we found that the combination of anti-GITR antibody (G3c) and CD28 superagonist (D665) treatment stimulated the generation of a large amount of Tr1 cells. Furthermore, G3c/D665 treatment not only significantly relieved severe mucosal damage but also reduced the incidence of colonic shortening, weight loss, and hematochezia. Dextran sodium sulfate (DSS) upregulated the mRNA levels of IL-6, IL-1β, IL-17, IL-12, tumor necrosis factor-alpha, C-C chemokine receptor type 5, and Bax in splenic lymphocytes (SPLs) and colon tissues, while G3c/D665 treatment conversely inhibited the increase in mRNA levels of these genes. In addition, G3c/D665 treatment altered the proportion of CD4+ and CD8+ T cells and increased CD4+CD25+Foxp3+ regulatory T cells in SPLs, mesenteric lymph nodes (MLNs), and lamina propria lymphocytes (LPLs). Thus, the combination of G3c and D665 treatment showed efficacy against DSS-induced UC in mice by inducing a large amount of Tr1 cell generation via the musculoaponeurotic fibrosarcoma pathways in vivo and relieving inflammatory responses both systematically and locally. The combination of G3c and D665 treatment showed efficacy against DSS-induced UC in mice by inducing a large amount of Tr1 cell generation via the musculoaponeurotic fibrosarcoma pathways in vivoand relieving inflammatory responses both systematically and locally. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with a low cure rate. Periplaneta americana is a traditional American Cockroach and reportedly has potential therapeutic roles for UC treatment; however, its mechanisms remain unclear. To address this, we investigated the therapeutic effects and underlying molecular mechanisms of Ento-A, a Periplaneta americana extract, in a dextran sulfate sodium (DSS)-induced chronic and recurrent UC mouse model. Ento-A treatment decreased pro-inflammatory cytokine secretion, disease activity index (DAI), colon mucosa damage index (CMDI), histopathological scores (HS), and increased colon length. Additionally, Ento-A effectively increased interleukin-4 (IL-4), and forkhead transcription factor protein 3 (Foxp3) expression levels, while it abated interferon-γ (IFN-γ) and IL-17 levels in spleen lymphocytes. Conversely, in mesenteric lymph nodes, IL-4 and Foxp3 expression were decreased, while IFN-γ and IL-17 expression was increased. Furthermore, Ento-A blocked p-PI3K, p-AKT,*and p-NF-κB activation. In conclusion, Ento-A improved UC symptoms and exerted therapeutic effects by regulating immune responses and inhibiting PI3K/AKT/NF-κB signaling. [ABSTRACT FROM AUTHOR]

Hydroxysafflower yellow A (HSYA) protects against acute kidney injury through TLR4/NF‐κB pathway. However, the effect and potential mechanism of HSYA in ulcerative colitis (UC) have been rarely reported, which is thus investigated in this research. An in vivo UC model was established by oral administration of 5% dextran sulfate sodium (DSS) in Sprague–Dawley rats. After HSYA treatment, the daily body weight and colon length of rats were measured. Then rat colon tissues, myeloperoxidase (MPO) activity, and the levels of inflammatory cytokines were examined by histopathological examination (HE) staining, immunohistochemistry, ultraviolet spectrophotometry, and enzyme‐linked immune sorbent assay (ELISA) respectively. The activated TLR4/NF‐κB pathway was detected by Western blot. RAW 264.7 cell viability was detected by MTT assay after lipopolysaccharide (LPS) treatment, and ELISA and Western blot were performed again to investigate the effects of HSYA on LPS‐treated cells. DSS administration increased body weight and colon length of rats and induced colon tissue injury. DSS or LPS treatment up‐regulated the levels of TNF‐α, IL‐1β, and IL‐6 and activated TLR4/NF‐κB pathway of colon tissues and cells, respectively. HSYA partially reversed the above effect of DSS and LPS treatment, and the effects of the drug were improved with the dosage. Taken together, HSYA alleviates UC by suppressing TLR4/NF‐κB signaling pathway, which may provide a new insight for the treatment of UC. [ABSTRACT FROM AUTHOR]

Colitis is one of the inflammatory states that affect the intestinal wall and may even predispose to malignancy due to chronic irritation. Although the etiology of colitis is not yet fully explored, a combination of genetic and environmental factors is strongly incriminated. Perindopril is an angiotensin-converting enzyme inhibitor that is used for the management of a wide range of cardiovascular diseases. Ambrosin is a sesquiterpene lactone that was proven to have beneficial effects in disorders characterized by inflammatory nature. The objective of this study is to make a comparison between the effects of perindopril or ambrosin on dextran sulfate sodium (DSS)-induced colitis in mice and to explore the effect of their combination. The present findings indicate that each ambrosin or perindopril alone or in combination is able to ameliorate oxidative stress and suppress the proinflammatory pathways in the colonic tissues of DSS-treated mice via mechanisms related to toll-like receptor 4/nuclear factor kappa B signaling and modulation of peroxisome proliferator-activated receptor gamma/sirtuin-1 levels. In addition, each ambrosin or perindopril alone or in combination inhibits apoptosis and augments the mediators of autophagy in DSS-treated mice. These effects are reflected in the amelioration of the histopathological and electron microscopic changes in the colonic tissues. Interestingly, the most remarkable effects are those encountered with the perindopril/ambrosin combination compared to the groups treated with each of these agents alone. In conclusion, the perindopril/ambrosin combination might represent an effective modality for mitigation of the pathogenic events and the clinical sequelae of colitis. [ABSTRACT FROM AUTHOR]

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Abstract Background Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and thus mouse models of CRC are of significant value to study the pathogenesis. The Azoxymethane/Dextran sulfate sodium (AOM/DSS) model is a widely used, robust initiation-promotion model for chemical induction of colitis-associated CRC in rodents. However, the dosage of chemicals, treatment regimens and outcome measures vary greatly among studies employing this model. Thus, the aim of this study was to examine an AOM/DSS model involving a reduced (1%) dose of DSS for induction of carcinogenesis in A/J and C57BL/6J (B6) mice. Results We show that colonic preneoplastic lesions can be reliably detected in A/J and B6 mice by use of a AOM/DSS model involving a single injection of 10 mg/kg AOM followed by three 7-day cycles of a low-dose (1%) DSS administration. Supporting existing evidence of A/J mice exhibiting higher susceptibility to AOM than B6 mice, our AOM/DSS-treated A/J mice developed the highest number of large colonic lesions. Clinical symptoms in both strains subjected to the AOM/DSS treatment did not persist in-between treatment cycles, demonstrating that the animals tolerated the treatment well. Conclusions Our findings suggest that a reduced dose of DSS in the AOM/DSS model can be considered in future studies of early phase colorectal carcinogenesis in the A/J and B6 mouse strains using preneoplastic lesions as an outcome measure, and that such regimen may reduce the risk of early trial terminations to accommodate human endpoints. Overall, our data emphasize the importance of devoting attention towards choice of protocol, outcome measures and mouse strain in studies of CRC in mice according to the study purpose.

• The objective of this study is to demonstrate the therapeutic potential of FGF20 in UC and elucidate its mechanism of action involving modulation of the intestinal microbiota. • A mouse model of UC was established using dextran sodium sulfate (DSS), and the therapeutic effects and mechanism of FGF20 were investigated. • Administration of adeno-associated virus overexpressing FGF20 resulted in a significant improvement in UC-associated phenotypes. • FGF20 significantly ameliorated the dysbiosis of gut microbiota in UC mice by increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria. • The therapeutic effects of FGF20 in UC mice were noticeably attenuated following depletion of microbiota using an antibiotic cocktail. Fecal microbiota transplantation experiments further supported the implication of the gut microbiota in the therapeutic effects of FGF20 on UC mice. Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), presents a significant clinical challenge due to the lack of optimal therapeutic strategies. Emerging evidence suggests that fibroblast growth factor 20 (FGF20) may play a crucial role in mitigating UC symptoms, though the mechanistic underpinnings remain elusive. In this study, a mouse model of UC was established using dextran sodium sulfate (DSS) to investigate the potential role of FGF20. Our findings revealed a marked reduction in FGF20 expression in the serum and colonic tissues of DSS-treated mice. Furthermore, FGF20 knockout did not exacerbate colonic damage in these mice. Conversely, overexpression of FGF20 via adeno-associated virus (AAV) significantly alleviated UC-associated symptoms. This alleviation was evidenced by attenuated intestinal shortening, mitigated weight loss, increased colonic goblet cell density and crypt formation, reduced inflammation severity and inflammatory cell infiltration, and enhanced expression of tight junction and mucin proteins. Moreover, FGF20 significantly ameliorated the dysbiosis of gut microbiota in DSS-treated mice by increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria. The beneficial effects of FGF20 were notably attenuated following gut microbiota depletion with an antibiotic regimen. Fecal microbiota transplantation experiments further supported the critical role of gut microbiota in mediating the effects of FGF20 on DSS-treated mice. In conclusion, these findings highlight the potential involvement of gut microbiota in the therapeutic effects of FGF20 in UC. [ABSTRACT FROM AUTHOR]

Abstract Inflammation is one of the major health threats to humans, and it is associated with various chronic diseases, including metabolic syndrome, type 2 diabetes, cardiovascular diseases, and several types of cancer. For example, colonic inflammation can result in the damage of the intestinal barrier, as indicated by invasion of immune cells and reduced tight junctions. Inflammatory responses can also lead to erythema and edema on skin. The intervention of dietary components offers striking possibilities for the prevention of inflammation by modulating the inflammatory signaling pathways and microbiota–inflammation axis. Thus, the preclinical animal models are of critical importance for investigating the anti‐inflammatory effects of food components. This guideline introduces two inflammatory mouse models: dextran sulfate sodium‐induced colonic inflammation and 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced skin inflammation. These mimic models offer the potential to assess food components in attenuating the colonic and skin inflammation in humans.

Secondary immune damage to the intestinal mucosa due to an influenza virus infection has gained the attention of investigators. The protection of the intestinal barrier is an effective means of improving the survival rate in cases of severe pneumonia. We developed a fusion protein, Vunakizumab-IL22(vmab-IL22), by combining an anti-IL17A antibody with IL22. Our previous study showed that Vunakizumab-IL22 repairs the pulmonary epithelial barrier in influenza virus-infected mice. In this study, we investigated the protective effects against enteritis given its anti-inflammatory and tissue repair functions. The number of goblet cells and the expression of zonula occludens protein 1(ZO-1), Mucin-2, Ki67 and IL-22R were determined by immunohistochemistry (IHC) and quantitative RT-PCR in influenza A virus (H1N1)-infected mice. The expression of NOD-like receptor pyrin domain containing 3 (NLRP3) and toll- like-receptor-4 (TLR4) was assayed by IHC in the lungs and intestine in HIN1 virus-induced mice to evaluate the whole efficacy of the protective effects on lungs and intestines. Consequently, Cytochrome C, phosphorylation of nuclear factor NF-kappaB (p-NF-κB), IL-1β, NLRP3 and Caspase 3 were assayed by Western blotting in dextran sulfate sodium salt (DSS)-treated mice. Treatment with Vunakizumab-IL22 improved the shortened colon length, macroscopic and microscopic morphology of the small intestine (p < 0.001) significantly, and strengthened the tight junction proteins, which was accompanied with the upregulated expression of IL22R. Meanwhile, Vunakizumab-mIL22 inhibited the expression of inflammation-related protein in a mouse model of enteritis induced by H1N1 and DSS. These findings provide new evidence for the treatment strategy for severe viral pneumonia involved in gut barrier protection. The results suggest that Vunakizumab-IL22 is a promising biopharmaceutical drug and is a candidate for the treatment of direct and indirect intestinal injuries, including those induced by the influenza virus and DSS.

Several chemicals, such as dextran sulfate sodium (DSS), oxazolone, acetic acid, and trinitrobenzene sulphonic acid (TNBS), have been used for establishing animal models of ulcerative colitis. These animal models help us to study or explore several factors involved in the etiology or pathogenesis of ulcerative colitis. They are also useful tools to design and develop effective drug delivery strategies. DSS is the most widely used tool to induce colitis in animals. The model of ulcerative colitis developed by this method effectively mimics the colitis condition in humans. The amount of DSS in drinking water can be adjusted to control the severity of colitis, such as acute or chronic inflammation. However, a miscalculation in the amount of DSS produces severe inflammation, which may lead to the death of mice. DSS has been shown to rupture the epithelial lining and induce infiltration of inflammatory markers such as TNF, interferons, and interleukins. The current study aims to study the effects of different amounts of DSS on weight loss, changes in colon length, and histological scoring. Furthermore, the main objective of this study was to find an optimum concentration of DSS to establish a mouse model for ulcerative colitis. Based on the disease index, weight loss, bleeding, histological studies, and colon length, 2.5% w/v DSS for 7 days in water was found to be adequate for the DSS-induced colitis model for a moderate level of colitis, and 3.5% w/v DSS could be used to study severe experimental colitis.

Amikacin sulfate-loaded dextran sulfate sodium nanoparticles were formulated, lyophilized (LADNP), and then analyzed. The LADNP had a −20.9 ± 8.35 mV zeta potential, PDI of 0.256, and % PDI of 67.7. The zeta average nano size of LADNP was 317.9 z. d.nm, while the dimension of an individual particle was 259.3 ± 73.52 nm, and nanoparticle conductivity in colloidal solution was 2.36 mS/cm. LADNP has distinct endothermic peaks at temperatures at 165.77 °C, according to differential scanning calorimetry (DSC). The thermogravimetric analysis (TGA) showed the weight loss of LADNP, which was observed as 95% at 210.78 °C. XRD investigation on LADNP exhibited distinct peaks at 2θ as 9.6°, 10.4°, 11.4°, 18.9°, 20.3°, 24.4°, 28.2°, 33.2°, 38.9°, and 40.4° confirming crystalline structure. The amikacin release kinetics from LADNP revealed zero order kinetics with a linear release showed zero order kinetics with 37% of drug release in 7 h and had an R2 value of 0.99. The antibacterial effect of LADNP showed broad-spectrum activity against tested human pathogenic bacteria. The preset study demonstrated that LADNP is a promising antibacterial agent.

Alginate has been documented to prevent the development and progression of ulcerative colitis by modulating the gut microbiota. However, the bacterium that may mediate the anti-colitis effect of alginate has not been fully characterized. We hypothesized that alginate-degrading bacteria might play a role here since these bacteria could utilize alginate as a carbon source. To test this hypothesis, we isolated 296 strains of alginate-degrading bacteria from the human gut. Bacteroides xylanisolvens AY11-1 was observed to have the best capability for alginate degradation. The degradation and fermentation of alginate by B. xylanisolvens AY11-1 produced significant amounts of oligosaccharides and short-chain fatty acids. Further studies indicated that B. xylanisolvens AY11-1 could alleviate body weight loss and contraction of colon length, reduce the incidences of bleeding and attenuate mucosal damage in dextran sulfate sodium (DSS)-fed mice. Mechanistically, B. xylanisolvens AY11-1 improved gut dysbiosis and promoted the growth of probiotic bacteria, including Blautia spp. And Prevotellaceae UCG-001, in diseased mice. Additionally, B. xylanisolvens AY11-1 showed no oral toxicity and was well-tolerated in male and female mice. Altogether, we illustrate for the first time an anti-colitis effect of the alginate-degrading bacterium B. xylanisolvens AY11-1. Our study paves the way for the development of B. xylanisolvens AY11-1 as a next-generation probiotic bacterium.

Probiotics have been shown to possess several properties, depending on the strain. Some probiotics have important roles in preventing infection and balancing the immune system due to the interaction between the intestinal mucosa and cells in the immune system. This study aimed to examine the properties of three probiotic strains using the tumor necrosis factor-alpha (TNF-α) inhibition test in colorectal adenocarcinoma cells (Caco-2 cells). It was revealed that the viable cells and heat-killed cells of the probiotic L. paracasei strain MSMC39-1 dramatically suppressed TNF-α secretion in Caco-2 cells. The strongest strains were then chosen to treat rats with colitis induced by dextran sulfate sodium (DSS). Viable cells of the probiotic L. paracasei strain MSMC39-1 reduced aspartate transaminase and alanine transaminase in the serum and significantly inhibited TNF-α secretion in the colon and liver tissues. Treatment with the probiotic L. paracasei strain MSMC39-1 alleviated the colon and liver histopathology in DSS-induced colitis rats. Furthermore, supplementation with probiotic L. paracasei strain MSMC39-1 increased the genus Lactobacillus and boosted the other beneficial bacteria in the gut. Thus, the probiotic L. paracasei strain MSMC39-1 exhibited an anti-inflammation effect in the colon and modulated the gut microbiota.

Inflammatory bowel disease (IBD) is a specific immune-associated intestinal disease. At present, the conventional treatment for patients is not ideal. Probiotics are widely used in the treatment of IBD patients due to their ability to restore the function of the intestinal mucosal barrier effectively and safely. Lactiplantibacillus plantarum subsp. plantarum is a kind of probiotic that exists in the intestines of hosts and is considered to have good probiotic properties. In this study, we evaluated the therapeutic effect of Lactiplantibacillus plantarum subsp. plantarum SC-5 (SC-5) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice. We estimated the effect of SC-5 on the clinical symptoms of mice through a body weight change, colon length, and DAI score. The inhibitory effects of SC-5 on the levels of cytokine IL-1β, IL-6, and TNF-α were determined by ELISA. The protein expression levels of NF-κB, MAPK signaling pathway, and the tight junction proteins occludin, claudin-3, and ZO-1 were verified using Western Blot and immunofluorescence. 16S rRNA was used to verify the modulatory effect of SC-5 on the structure of intestinal microbiota in DSS-induced colitis mice. The results showed that SC-5 could alleviate the clinical symptoms of DSS-induced colitis mice, and significantly reduce the expression of pro-inflammatory cytokines in the colon tissue. It also attenuated the inflammatory response by inhibiting the protein expression of NF-κB and MAPK signaling pathways. SC-5 improved the integrity of the intestinal mucosal barrier by strengthening tight junction proteins. In addition, 16S rRNA sequencing demonstrated that SC-5 was effective in restoring intestinal flora balance, as well as in increasing the relative abundance and diversity of beneficial microbiota. These results indicated that SC-5 has the potential to be developed as a new probiotic candidate that prevents or alleviates IBD.

Bile acids are major components of bile; they emulsify dietary lipids for efficient digestion and absorption and act as signaling molecules that activate nuclear and membrane receptors. The vitamin D receptor (VDR) is a receptor for the active form of vitamin D and lithocholic acid (LCA), a secondary bile acid produced by the intestinal microflora. Unlike other bile acids that enter the enterohepatic circulation, LCA is poorly absorbed in the intestine. Although vitamin D signaling regulates various physiological functions, including calcium metabolism and inflammation/immunity, LCA signaling remains largely unknown. In this study, we investigated the effect of the oral administration of LCA on colitis in a mouse model using dextran sulfate sodium (DSS). Oral LCA decreased the disease activity of colitis in the early phase, which is a phenotype associated with the suppression of histological injury, such as inflammatory cell infiltration and goblet cell loss. These protective effects of LCA were abolished in VDR-deleted mice. LCA decreased the expression of inflammatory cytokine genes, but this effect was at least partly observed in VDR-deleted mice. The pharmacological effect of LCA on colitis was not associated with hypercalcemia, an adverse effect induced by vitamin D compounds. Therefore, LCA suppresses DSS-induced intestinal injury in its action as a VDR ligand.

Recently, fucoidan has been proposed for use as a potential anti-inflammatory drug. The purpose of this study was to investigate the mechanism of fucoidan in the treatment of ulcerative colitis. We compared the anti-inflammatory effects of fucoidan and fucose induced by dextran sulfate sodium, and the effects of fucoidan and fucose on the gut microbiota of mice. Our results showed that low-dose fucoidan significantly improved weight loss, disease activity index scores, colonic shortening, colonic histopathological damage, intestinal fatty acid binding protein 2 levels, and the expression of Occludin, Claudin-4, and Claudin-1. However, both high-dose fucoidan and fucose did not perform as well as low-dose fucoidan as described above. In addition, 16S rDNA high-throughput sequencing showed that low-dose fucoidan significantly increased the abundance of Alloprevotella, and fucose significantly increased Ruminococcaceae, but neither significantly reversed the imbalance in the gut microbiota. Therefore, we inferred that the regulation of fucoidan on colitis has a unique and complex mechanism, and it is not completely dependent on degradation to fucose to relieve ulcerative colitis, nor is it achieved only by regulating the gut microbiota. The mechanism by which fucoidan treats colitis may also include reducing inflammatory cell infiltration and increasing intestinal barrier function. [ABSTRACT FROM AUTHOR]

Background: Evodiae fructus is a natural plant that is used as a medicinal material in many Asian countries such as Korea and China. However, little is known about its effect on ulcerative colitis. Objectives: Thus, the purpose of this study was to find the improvement effect of Evodiae fructus in mice model with dextran sulfate sodium (DSS)-induced colitis. Materials and Methods: The animal experiments were conducted using ulcerative colitis animals induced by DSS. To induce ulcerative colitis in BALB/c mice used in the experiment, 5% DSS was supplied as drinking water for 7 days. BALB/c mice were divided into five groups (n = 8): Group 1 (normal group), Group 2 (5% DSS control group), Group 3 (5% DSS + sulfasalazine 60 mg/kg treated), Group 4 (5% DSS + Evodiae fructus water extract 50 mg/kg treated), Group 5 (5% DSS + Evodiae fructus water extract 100 mg/kg treated). After the animal experiment, the expression of antioxidant, oxidative stress, inflammatory, and necrosis-related factors in colonic tissues was analyzed by western blotting. Results: As a result, the Evodiae fructus treatment group reduced oxidative stress by increasing the expression of Nrf2, an antioxidant-related transcription factor. Also, the expression of NF-κB, an inflammatory transcription factor, was reduced, thereby reducing the expression of pro-inflammatory proteins and inflammatory cytokines. Conclusion: These results suggest that Evodiae fructus treatment has an inhibitory effect on inflammation against DSS-induced colitis. Therefore, Evodiae fructus has the potential to be used as a natural medicine for ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background: Several rodent models with chemically induced colon cancer have been developed. Among these models, dextran sulfate sodium (DSS), a colitis inducer, combined with azoxymethane as a colon mutagenic carcinogen, is commonly used. We previously reported that although benzo [a] pyrene (BP) is mutagenic but not carcinogenic in the colon, it rapidly develops colon tumors at a high incidence/multiplicity after treatment with DSS. In the present study, we examined whether other colon-mutagenic non-carcinogens (CMNCs) induced colon tumors after treatment with DSS. Results: o-Aminoazotoluene, 7,12-dimethylbenz[a]anthracene, and N-ethyl-N-nitrosourea were selected as CMNCs. Male CD2F1 mice were orally administered CMNC for 5 consecutive days. After a 9-day dose-free period, mice were treated with 4% DSS in drinking water for 1 week. Three months after DSS treatment, colon samples were collected for histopathology and β-catenin immunohistochemistry analyses. All CMNCs in combination with DSS induced colonic adenocarcinomas at a high incidence/multiplicity in the distal and middle parts of the colon, coinciding with the location of colitis. Unlike in normal cells where β-catenin is exclusively located on the cell membrane, in adenocarcinoma cells, it was translocated to both the nucleus and cytoplasm or only to cytoplasm. The translocation of β-catenin is closely associated with colon carcinogenesis in rodents and humans. No colonic tumors or dysplastic lesions were found after exposure to either CMNC or DSS alone. Conclusion: We provided further evidence clearly showing that CMNCs can rapidly induce colonic tumors in mice with DSS-induced colitis, even if they are not colonic carcinogens. [ABSTRACT FROM AUTHOR]

Diosgenin (DIO) is a kind of steroid sapogenin derived from natural plants. It exerts strong anti-infection, antiallergy, antiviral, and antishock pharmacological properties. In this article, the protective effects of DIO against dextran sulfate sodium (DSS)-induced colitis in mice were researched. Compared with the 2.5% DSS treatment group, 15 mg/kg body weight of diosgenin alleviated colitis disease, evidenced by the increased body weight, the decrease in the disease activity index, and the histological scores. Furthermore, 16S rRNA high-throughput sequencing results demonstrated that DIO improved the colon homeostasis through modulating the gut microbiota, including increases in the relative abundance of several probiotic bacteria, such as Prevotellaceae (from 1.4% to 5.8%), Lactobacillus (from 12.3% to 29.7%), Mucispirillum (from 0.07% to 0.49%), and decreases in the pathogenic bacteria, such as Streptococcus (from 1.6% to 0.6%) and Pseudomonadaceae (from 0.004% to 0%). In addition, the concentration of gut microbial metabolites, total short-chain fatty acids (SCFAs), acetic acid, and propionic acid were significantly increased after DIO supplementation. In conclusion, our findings suggested that DIO attenuates DSS-induced colitis in mice by means of modulating imbalanced gut microbiota and increases in SCFA generation. [ABSTRACT FROM AUTHOR]

• Androgen synthesis is suppressed in the testis of IBD model mice. • Testicular metabolome and transcriptome are changed by IBD. • 8-oxo-dG is increased and 8-oxoguanine is decreased in testis of IBD mice. • IBD increase the expression of meiosis initiation gene Stra8 in testis. Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are widespread in developed countries and gradually increasing in developing countries. Evidences showed that man with CD has a decrease of serum testosterone, but how IBD take effects on testicular testosterone synthesis is not well elucidated. To investigate the effects of IBD on testis, we analyzed testicular metabolome and transcriptome data of the dextran sulfate sodium (DSS) induced IBD mice. As a result, metabolomic data showed that DSS indeed induced androgen decrease in mouse testis. Correspondingly, androgen synthesis associated genes, especially Lhcgr, were down-regulated in DSS testis. From the metabolomic data, we found vitamin intake associated metabolites vitamin B2 and pyridoxamine were significantly decreased, whereas fatty acid metabolism associated molecules N-lauroylglycine and N-decanoylglycine were increased in DSS testis. In addition, we found 8-hydroxy-deoxyguanosine, a DNA oxidative damage marker, and 8-oxoguanine, a molecule responsible for DNA damage repair, were also changed in DSS testis. Simultaneously, our data also showed that DSS up-regulated the expression of meiosis initiation associated gene Stra8 and oxygen transport associated genes in testis. In summary, these results depicted the complex effects of colitis on testis. These metabolites and transcripts changed in DSS testis could be used as potential targets for IBD treatment or symptom relieve. [ABSTRACT FROM AUTHOR]

Smilax china L. is used not only as a kind of traditional Chinese herbal medicinal ingredients with various pharmacological properties, but also as food in certain parts of China. However, it is by far still unclear whether Smilax china L. polyphenols (SCP), as important bioactive constituents in Smilax china L., have effects on inflammatory bowel diseases (IBD). This study investigated the impact of SCP on the dextran sulfate sodium (DSS)-induced IBD and gut microbiota in mice. SCP treatments ameliorated typical symptoms of IBD as what was reflected through suppressing body weight loss, colonic shortening, intestinal barrier damage, and increasing intestinal disease activity index. SCP treatments simultaneously decreased the release of proinflammatory cytokines and oxidative stress, as well as promoted the release of anti-inflammatory factors. Furthermore, SCP ameliorated the ecological imbalance of gut microbiota and regulated the key bacteria associated with IBD (including Akkermansiaceae, Ruminococcaceae, Acidaminococcaceae, Muribaculaceae, and Anaeroplasmataceae). In general, SCP may improve DSS-induced IBD in mice by regulating inflammatory factors, inhibiting oxidative stress, reducing intestinal tissue damage, and regulating the ecological imbalance of intestinal microbiota. Thus, SCP might serve as a potential therapeutic agent against the inflammation-driven diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitis-related clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

Objective: Ulcerative colitis (UC) is a long-lasting inflammatory disease of the colon. Epidemiological studies showed that the prevalence and incidence of UC are increasing worldwide in recent years. Neferine is a natural alkaloid isolated from Nelumbo nucifera Gaertn that exerts a variety of biological activities. This study was designed to evaluate the protective effect of neferine on dextran sulfate sodium (DSS)-induced experimental UC in mice. Materials and Methods: In this experimental study, 4% DSS was used to induce a mice model of UC. Neferine (5 and 10 mg/kg) was administered by intraperitoneal injection (ip). Clinical symptoms and disease activity index (DAI) scores were recorded and calculated. Pathological changes of colon tissues were detected by Hematoxylin and Eosin (H&E) staining. The levels of inflammatory mediators were detected by ELISA kits. Western blotting and immunohistochemical analysis were used for the evaluation of protein expressions. Results: Neferine treatment significantly alleviated DSS-induced UC by inhibiting weight loss, decreasing DAI scores, and alleviating the pathological changes in colon tissues. Furthermore, neferine significantly decreased serum levels of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 and increased serum levels of anti-inflammatory cytokine IL-10. The increased myeloperoxidase (MPO) activity and nitric oxide (NO) in colon tissues were also inhibited. In addition, neferine significantly down-regulated inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and intercellular cell adhesion molecule-1 (ICAM-1) expression in colon tissues. Conclusion: These results provided evidence that neferine could protect against DSS-induced UC symptoms in an experimental mice model. This effect might be mediated through inhibition of inflammation.

Daily foods contain a great number of self-assembled nanoparticles (NPs) which were incidentally produced during food processing. These food incidental NPs can directly access the human gastrointestinal tract in high frequency and large quantities. Limited reports were focused on whether and how these food incidental NPs affected the gastrointestinal tissues and gut microbiota. In the present study, bone soup and its NPs both significantly ameliorated colitis symptoms in dextran sulfate sodium (DSS)-induced mice and inhibited the release of pro-inflammatory cytokines. They also restored intestinal microbiota dysbiosis by improving the diversity and richness of intestinal microbiota and regulating community composition, such as a remarkable increase in Muribaculaceae, Alistipes, and Alloprevotella, and a decrease in Helicobacter. Moreover, the correlation analysis showed that pro-inflammatory cytokines were negatively correlated with Muribaculaceae, Alloprevotella, and Alistipes, but positively correlated with Helicobacter. These findings suggest that the food incidental NPs can influence human health through regulating the inflammation of the gastrointestinal tissues and the gut microbiota.

The glucocorticoid receptor NR3C1 is expressed in multiple cell types in the gut and elsewhere. Intestinal epithelial cells both produce and respond to glucocorticoids in different physiological and pathological contexts. In experimental colitis, glucocorticoids have been shown to exert a dual role, dampening inflammation while producing a deterioration in animal status, including death. Mice with tamoxifen-inducible, intestinal epithelial-specific deletion of NR3C1 (NR3C1ΔIEC mice) are protected against experimental colitis, suggesting glucocorticoid epithelial actions are deleterious. Since glucocorticoids modulate epithelial proliferation, it follows that they may affect the development of colon cancer. In this study, we set out to test this hypothesis using the dextran sulfate sodium-azoxymethane model of colitis-associated cancer. Knockout (KO) mice were found to exhibit a twofold higher tumor load but similar incidence and tumor size. Tumors had a higher trend to extend close to the submucosal layer (36% vs. 0%) in NR3C1ΔIEC mice, and overexpressed Lgr5, Egfr, and Myc, consistent with distinct expression of proliferative/stemness markers. Snai1 and Snai2 were upregulated specifically in tumors of NR3C1ΔIEC mice, suggesting enhanced epithelial to mesenchymal transition in the absence of the intestinal epithelial glucocorticoid (GC) receptor. We conclude that endogenous GC epithelial signaling is involved in colitis-associated cancer. NEW & NOTEWORTHY Mice carrying a tamoxifen-inducible deletion of the glucocorticoid receptor in intestinal epithelial cells (NR3C1ΔIEC mice) and their corresponding controls were subjected to the azoxymethane-dextran sulfate sodium model of colitis-associated cancer. KO mice exhibit a twofold higher tumor load, with a higher trend to extend close to the submucosal layer (36% vs. 0%), but with similar incidence and tumor size. Colonic tumors in NR3C1ΔIEC mice showed signs of increased neoplastic transformation and tumor-associated inflammation. [ABSTRACT FROM AUTHOR]

Bojanggunbi-tang (BGT) is a well-known and widely used herbal prescription in Korea for colon diseases, with well-documented pharmacological effects on the digestive system. The current study aimed to develop a new simple and effective prescription using the original prescription. mBGT, a modified BGT, was developed by mixing the extracts of Lonicera japonica Thunb., Alisma orientalis and Atractylodes macrocephala based on a literature review and screening of 16 kinds of component herbs of BGT. A colitis mouse (Male, BALB/c) model was induced using dextran sulfate sodium (5%). The effects of BGT and mBGT on body weight, histological damage, clinical score, macroscopic score and colon length were compared. The mechanisms of action were analyzed based on cytokine production in colon tissue. mBGT at 300mg/kg showed similar effectiveness to that of BGT on colon shortening (P<0.01), clinical score (P<0.05), macroscopic score (P<0.01) and histological damage (P<0.01). In addition, mBGT decreased cytokines, including Interleukin 1 beta, tumor necrosis factor alpha and Interleukin 17, in a dose-dependent manner. In conclusion, mBGT could be a substitute prescription for BGT in clinics and a candidate for the development of a new BGT-based therapeutic agent against colitis. [ABSTRACT FROM AUTHOR]

Background/Aims The modulation of CD1d-restricted natural killer T (NKT) cells by glycolipids has been considered as a potential therapy against immunologic diseases, including inflammatory bowel disease. A recently identified a glycolipid analog, 7DW8-5, which is derived from α-galactosylceramide (α-GalCer), is as much as 100-fold more active at stimulating both human and mice NKT cells when compared to α-GalCer. We explored the effects of 7DW8-5 in mouse models of acute and chronic colitis. Methods We investigated the effects of 7DW8-5 on intestinal inflammation by assessing the effects of 7dW8-5 on a murine dextran sulfate sodium (DSS)-induced acute colitis model and a chronic colitis-associated tumor model. Results The acute DSS-induced colitis model showed a dose-dependent response to 7DW8-5, as mice administered 7DW8-5 showed a significant improvement in DSS-induced colitis based on their disease activity index, histologic analysis, and serum C-reactive protein levels, when compared to mice administered vehicle alone. However, DSS-induced colitis in CD1d-KO mice showed no response to 7DW8-5. A fluorescence-activating cell sorting analysis revealed an increase in NKT cells in colonic tissues of 7DW8-5-treated mice. RNA-seq and real-time quantitative polymerase chain reaction showed a significant increase in the expression of interleukin (IL)-4, IL-13, and interferon-gamma in 7DW8-5-treated mice. In addition, 7DW8-5 treatment reduced colitis-associated tumor development in an azoxymethane/DSS mouse model. Conclusions 7DW8-5 activates NKT cells through CD1d and provides a protective effect against intestinal inflammation in mice. Therefore, 7DW8-5 may be a promising therapeutic agent for treatment of inflammatory bowel disease.

Objective To investigate the effect of IL-2 on CD4+ regulatory cells (Treg) in inflammatory bowel disease (IBD) mice induced by dextran sulfate sodium (DSS), and to explore its regulatory mechanism in the pathogenesis of IBD. Methods Wild type C57BL/6 (WT) and IL-2 knockout (IL-2-/-) female mice (both at 6 week old) were randomly divided into WT control group, WT DSS treatment group, and IL-2-/- control group and IL-2-/- DSS treatment group, respectively. The mice in the control group had normal drinking water, and those in the treatment group had the water containing 25 g/L DSS. In 1 week after the continuous feeding, all mice were sacrificed and the whole colon was collected for intestinal pathological injury in each group by HE staining. The expression levels of IL-2, TGF-β, IL-10, IFN-γ and TNF-α at mRNA and protein levels were detected by PCR and Western blotting, respectively, and the percentage of CD4+ Treg were counted by flow cytometry. Results There were significant differences in the lesion, inflammation, lesion range and crypt destruction score among the 4 groups, and the pathological scores of colon tissue were the highest in the IL-2-/- DSS treatment group than the other 3 groups, and the scores were significantly higher in the WT DSS treatment group and IL-2-/- control group mice than the WT control group (P < 0.05). Significant differences were seen in the mRNA and protein levels of IL-2, TGF- β, IL-10, IFN-γ and TNF-α in the colon tissues from the 4 groups (P < 0.05). The mRNA and protein levels of IL-2, TGF-β and IL-10 in WT DSS treatment group were significantly higher than those in the other 3 groups, and the levels of IFN-γ and TNF-α in the IL-2-/- DSS treatment group were significantly higher than those in the other 3 groups (P < 0.05). After 7 days' treatment, the percentage of CD4+ Treg was significantly higher in WT DSS treatment group than the other 3 groups (P < 0.05). Conclusion IL-2 can improve DSS-induced IBD and reduce inflammatory response and colon tissue injury by inducing CD4+ Treg to secrete inhibitory inflammatory factors TGF- β and IL-10.

Objective: To assess the anti-inflammatory efficacy of ferruginol on dextran sulfate sodium (DSS) stimulated ulcerative colitis mice. Methods: Ulcerative colitis was induced in C57BL/6J mice by administering 2% of DSS through drinking water for 7 d. The mice in the treatment group were treated with DAA+50 mg/kg/day ferruginol orally. In the positive control group, sulfasalazine (50 mg/kg/day) was used alongside with DSS. After induction, the bodyweight, character of stool and feces occult blood were recorded daily, the disease activity index was calculated, and the colon length, colon weight, and spleen weight were recorded. The myeloperoxidase activity was assayed by spectrophotometry. Interleukin (IL)-6, IL-1β, and tumor necrosis factor-a were determined by ELISA method, and nuclear factor-κB, cyclooxygenase-2, matrix metalloproteinases-9, and inducible nitric oxide synthase by Western blotting assays. Results: Ferruginol significantly increased the bodyweight, colon weight, colon length, and decreased disease activity index and spleen weight. It exhibited anti-inflammatory activity against DSS induced ulcerative colitis in mice by reducing the activities of myeloperoxidase, tumor necrosis factor-α, nuclear factor-κβ, IL-1β, cyclooxygenase-2, matrix metalloproteinases-9, IL-6, and inducible nitric oxide synthase. Conclusions: Ferruginol could be used to treat ulcerative colitis by attenuating the inflammation in colon cells and maintaining colonic mucosal barrier integrity.

Ulcerative colitis (UC) is a gastrointestinal, autoimmune disease that causes ulceration and inflammation of the colon with an incidence of 10 out of every 100,000 people in North America and Western Europe. Though the specific cause is unknown, several studies have demonstrated that inflammatory cells as well as environmental variables, genetics, and lifestyle behaviors can play a role in the long-term inflammatory response. Researchers have commonly used immunohistochemistry, western blotting and gene sequencing to establish the cellular processes behind UC relapse and remission. However, because these destructive methods necessitate the removal of a sample, they can only be used on non-living tissues. The use of minimally invasive approaches to evaluate the in vivo, longitudinal effects of UC on the mucosa in the colon is gaining popularity among clinicians and researchers. We have created a dextran sulfate sodium-induced model of UC in C57 mice based on the work of Wirtz et al., and a minimally invasive imaging modality to explore the changes in mucosal tissue during “active” and “in remission” UC. Briefly, C57 mice were given dextran sulfate sodium (DSS) dissolved in water in 5-day cycles with a remission/recovery period of 10 days. After 7 days post-DSS treatment and 7 days post-recovery, mice were anesthetized and exploratory endoscopies were performed to assess the mucosal changes that occur during the “active” and “remission” periods of UC. Value of protocol: • Minimally invasive induction of ulcerative colitis in a murine mouse model. • Minimally invasive longitudinal monitoring of “active” and “in remission” ulcerative colitis. • Our endoscopic based imaging modality can be used to validate the induction of ulcerative colitis and the potential treatment response for pre-clinical trials.

Inflammatory bowel disease (IBD) has become a global concern. Proanthocyanidin-rich red rice extract (PRRE) has been shown to suppress the inflammatory response in cellular cultures. However, the anti-colitis effect of PRRE has never been investigated in animals. This study aimed to examine the protective effect of the PRRE against dextran sulfate sodium (DSS)-induced colitis in mice. Male mice were orally administrated with PRRE of 50, 250 and 500 mg/kg/day for 21 days. Acute colitis was subsequently induced by administrated 2.5% DSS in drinking water for the final seven days. Sulfasalazine-treated mice were the positive group. All doses of PRRE and sulfasalazine significantly ameliorated DSS-induced severity of colitis, as indicated by decreasing daily activity index and restoring colon shortening. Treatments with PRRE, but not sulfasalazine, significantly reduced the histopathological index and infiltration of inflammatory cells. Furthermore, the PRRE treatments effectively improved mucous in colonic goblet cells using PAS staining, and suppressed the production of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 induced by DSS, while sulfasalazine reduced only IL-1β and IL-6. This study suggested that PRRE had a greater anti-colitis effect than sulfasalazine. Thus, PRRE has a potential anti-colitis effect, and should be developed in a clinical trial as a natural active pharmaceutical ingredient for IBD.

Ulcerative colitis (UC) is caused by inflammation only in the mucosa of the colon, and its incidence is increasing worldwide. The intake of probiotics is known to have a beneficial effect on the development of UC. In this study, we investigated the alleviating effects of kimchi (KC), a fermented food rich in probiotics, and Leuconostoc mesenteroides DRC 1506 (DRC) isolated from kimchi on UC. A freeze-dried kimchi suspension and DRC were orally given to mice at a dose of 1 × 109 CFU/day for 3 weeks. Furthermore, 3% dextran sulfate sodium (DSS) in drinking water was given to induce UC. The KC and DRC groups reduced symptoms of colitis, such as disease activity index, decrease in colon length, colon weight-to-length ratio, and pathological damage to the colon caused by DSS treatment. The KC and DRC groups decreased the levels of pro-inflammatory cytokine (TNF-α) and increased anti-inflammatory cytokine (IL-10) in the colon tissues. At the mRNA and protein expression levels in the colon tissue, KC and DRC groups downregulated inflammatory factors and upregulated tight junction-related factors. Therefore, DRC, as well as KC supplementation, are potent in alleviating UC by improving the inflammatory response and mucosal barrier function in the colon.

Polysaccharide from the edible alga Enteromorpha clathrata has been demonstrated to exert beneficial effects on human health. However, what effect it has on inflammatory bowel diseases has not been investigated. Here, using a mouse model of dextran sulfate sodium (DSS)-induced ulcerative colitis, we illustrate that Enteromorpha clathrata polysaccharide (ECP) could alleviate body weight loss, reduce incidences of colonic bleeding, improve stool consistency and ameliorate mucosal damage in diseased mice. 16S rRNA high-throughput sequencing and bioinformatic analysis indicated that ECP significantly changed the structure of the gut microbiota and increased the abundance of Parabacteroides spp. in DSS-fed mice. In vitro fermentation studies further confirmed that ECP could promote the growth of Parabacteroides distasonis F1-28, a next-generation probiotic bacterium isolated from the human gut, and increase its production of short-chain fatty acids. Additionally, Parabacteroides distasonis F1-28 was also found to have anti-ulcerative colitis effects in DSS-fed mice. Altogether, our study demonstrates for the first time a beneficial effect of ECP on ulcerative colitis and provides a possible basis for understanding its therapeutic mechanisms from the perspective of symbiotic gut bacteria Parabacteroides distasonis.

Oenanthe javanica, commonly known as water dropwort, has long been used to treat acute and chronic hepatitis, abdominal pain, alcohol hangovers, and inflammation in various traditional medicine systems in Asia. However, whether O. javanica has beneficial effects on colitis-induced intestinal damage remains elusive. This study tested the hypothesis that O. javanica has anti-inflammatory and antioxidant activities in mice with dextran sulfate sodium (DSS)-induced colitis. First, treatment of O. javanica ethanol extract (OJE) inhibited the production of inflammatory cytokines in lipopolysaccharide-affected macrophages. Second, in mice with DSS-induced colitis, OJE administration reduced pathological damage to the colon while alleviating weight gain and decreasing colon length, including inflammation and mucosal necrosis. In addition, OJE significantly (p < 0.01) restricted the activation of nuclear factor-κB (NF-κB) and the secretion of pro-inflammatory mediators and increased the expression of Nrf2-phase 2 antioxidant enzymes. The results of 16S rRNA gene sequencing workflows for taxonomic assignment analysis confirmed that the diversity (richness and evenness) of fecal microbiota was markedly elevated in the OJE group. OJE administration reduced the abundance of Proteobacteria including Escherichia and increased the abundance of the genus Muribaculum. These results suggested that OJE exerts beneficial effects on inflammation and gut microbial composition in a mouse model of colitis.

Ulcerative colitis is an inflammatory bowel disease characterized by symptoms such as abdominal pain, diarrhea, bleeding, and weight loss. Ulcerative colitis is typically treated with anti-inflammatory drugs; however, these drugs are associated with various side effects, limiting their use. β-Caryophyllene (BCP), a natural compound derived from cloves, has antioxidant, antibacterial, and anti-inflammatory activities. In this study, we aimed to investigate the effects of BCP on colitis in a dextran sulfate sodium (DSS)-induced colitis mouse model. BCP was administered for seven days, followed by 2.5% DSS for additional seven days to induce colitis. Changes in stool weight, recovery of gut motility, colon length, colon histology, myeloperoxidase activity, inflammatory cytokines (TNF-α, IL-1β, IL-6, IgA, and IgG), and the gut microbiota were observed. Administration of BCP increased stool weight, restored gut motility, and considerably increased colon length compared to those in the untreated colitis mouse model. In addition, the amount of mucin and myeloperoxidase activity in the colon increased, whereas the concentrations of IL-1β, IL-6, and TNF-α decreased following the administration of BCP. Furthermore, BCP reduced the abundance of Proteobacteria which can cause intestinal immune imbalance. These results suggest that BCP has a potential to be developed as a preventive agent for colitis.

Background: Dextran sulfate sodium (DSS) replicates ulcerative colitis (UC)-like colitis in murine models. However, the microbial characteristics of DSS-triggered colitis require further clarification. To analyze the changes in gut microbiota associated with DSS-induced acute and chronic colitis. Methods: Acute colitis was induced in mice by administering 3% DSS for 1 week in the drinking water, and chronic colitis was induced by supplementing drinking water with 2.5% DSS every other week for 5 weeks. Control groups received the same drinking water without DSS supplementation. The histopathological score and length of the colons, and disease activity index (DAI) were evaluated to confirm the presence of experimental colitis. Intestinal microbiota was profiled by 16S rDNA sequencing of cecal content. Results: Mice with both acute and chronic DSS-triggered colitis had significantly higher DAI and colon histopathological scores in contrast to the control groups (P < 0.0001, P < 0.0001), and the colon was remarkably shortened (P < 0.0001, P < 0.0001). The gut microbiota α-diversity was partly downregulated in both acute and chronic colitis groups in contrast to their respective control groups (Pielou index P = 0.0022, P = 0.0649; Shannon index P = 0.0022, P = 0.0931). The reduction in the Pielou and Shannon indices were more obvious in mice with acute colitis (P = 0.0022, P = 0.0043). The relative abundance of Bacteroides and Turicibacter was increased (all P < 0.05), while that of Lachnospiraceae, Ruminococcaceae, Ruminiclostridium, Rikenella, Alistipes, Alloprevotella, and Butyricicoccus was significantly decreased after acute DSS induction (all P < 0.05). The relative abundance of Bacteroides, Akkermansia, Helicobacter, Parabacteroides, Erysipelatoclostridium, Turicibacter and Romboutsia was also markedly increased (all P < 0.05), and that of Lachnospiraceae_NK4A136_group, Alistipes, Enterorhabdus, Prevotellaceae_UCG-001, Butyricicoccus, Ruminiclostridium_6, Muribaculum, Ruminococcaceae_NK4A214_group, Family_XIII_UCG-001 and Flavonifractor was significantly decreased after chronic DSS induction (all P < 0.05). Conclusion: DSS-induced acute and chronic colitis demonstrated similar symptoms and histopathological changes. The changes in the gut microbiota of the acute colitis model were closer to that observed in UC. The acute colitis model had greater abundance of SCFAs-producing bacteria and lower α-diversity compared to the chronic colitis model. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The number of patients with non-alcoholic steatohepatitis (NASH) and inflammatory bowel disease (IBD) is increasing. This study elucidates the effect of both NASH and IBD on hepatocellular carcinoma (HCC) using a mouse model combining NASH and IBD. The melanocortin 4 receptor-deficient (Mc4r -KO) mice were divided into four groups with or without a high-fat diet (HFD) and with or without dextran sulfate sodium (DSS) to induce colitis, and the differences in liver damage and occurrence of HCC were analyzed. In the HFD + DSS group, the body weight, liver weight/body weight ratio, and serum levels of albumin and alanine aminotransferase were significantly lower than those in the HFD group. We further found that steatosis was significantly lower and lobular inflammation was significantly higher in the HFD + DSS group than those in the HFD group, and that individual steatosis and lobular inflammation state in the HFD + DSS mice varied. We detected HCC only in the HFD + DSS group, and mice with severe steatosis and mild colitis were found to be at high risk of HCC. Presently, the prediction of HCC is very difficult. In some cases, severe colitis reverses the fat accumulation due to appetite loss. Our findings clearly showed that severe steatohepatitis and mild colitis are simultaneously essential for the occurrence of HCC in patients with NASH and IBD. [Display omitted] •The incidence of NASH and IBD is increasing worldwide. •The melanocortin-4 receptor-deficient mice with DSS models were established. •Hepatocellular carcinomas were detected only in the HFD + DSS group. •Mice with severe steatosis and mild colitis were at high risk of HCC. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis (UC) and Crohn's Disease, are most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. Strategies that target the microbiota have emerged as potential therapies and, of these, probiotics have gained the greatest attention. Herein, we isolated a strain of Lactobacillus paracasei R3 (L.p R3) with strong biofilm formation ability from infant feces. Interestingly, we also found L.p R3 strain can ameliorate the general symptoms of murine colitis, alleviate inflammatory cell infiltration and inhibit Th17 while promote Treg function in murine dextran sulfate sodium (DSS)-induced colitis. Overall, this study suggested that L.p R3 strain significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice. [ABSTRACT FROM AUTHOR]

Empagliflozin and metformin are widely used for the treatment of type 2 diabetes. These drugs showed marked anti-inflammatory effects in different animal models via enhancing AMPK activity. Yet, the protective anti-inflammatory effects of their combination against ulcerative colitis have not been previously investigated. The current study aimed to explore the potential of empagliflozin/metformin combination to mitigate the DSS-induced rat colitis model. The modulating effects of empagliflozin and metformin on the AMPK/mTOR/NLRP3 axis and T cell polarization were delineated. In this study, distal colons were examined for macroscopic and microscopic pathological alterations. ELISA, qRT-PCR, and immunohistochemistry techniques were applied to detect proteins and cytokines involved in AMPK/mTOR/NLRP3 axis and T Cell polarization. Oral administration of empagliflozin (10 mg/kg/day) and metformin (200 mg/kg/day) combination alleviated colitis as revealed by the reduced disease activity index, macroscopic damage index, colon weight/length ratio, and histopathologic scoring values. Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1β, and IL-18. Reduced mTOR expression and reduced IL-6 levels led to a reduction in Th17 cell polarization and maintenance. Together, the current study reveals that the protective effects of empagliflozin and metformin against DSS-induced colitis are fundamentally mediated via enhancing AMPK phosphorylation. Since adult humans with diabetes mellitus are at greater risk for developing inflammatory bowel diseases, clinical application of empagliflozin/metformin combination represents a novel therapeutic approach for treating diabetic patients with ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background and aimLuminal nutrients stimulate enteroendocrine L cells to release gut hormones, including intestinotrophic glucagon-like peptide-2 (GLP-2). Because L cells express the bile acid receptor TGR5 and dipeptidyl peptidase-IV (DPPIV) rapidly degrades GLPs, we hypothesized that luminal TGR5 activation may attenuate intestinal injury via GLP-2 release, which is enhanced by DPPIV inhibition.MethodsIntestinal injury was induced in mice by administration of dextran sulfate sodium (DSS) in drinking water (free access to water containing 5% DSS for 7 days). The selective TGR5 agonist betulinic acid (BTA) and the DPPIV inhibitor sitagliptin phosphate monohydrate (STG) were administered orally for 7 days. Male C57BL/6 mice (6-7 weeks old) were divided into five groups: normal control group, disease control group, BTA low group (drinking water containing 15 mg/L BTA), BTA high group (50 mg/L BTA), and BTA high + STG (3 mg/kg, i.g.) group.ResultsThe selective TGR5 agonist BTA dose-dependently suppressed disease activity index and mRNA expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the colon. Nevertheless, STG administration had little additive effect on BTA-induced protection. Fibroblast activation protein mRNA expression, but not expression of other DPP family members, was increased in the colon of DSS-treated mice with increased mucosal DPPIV. Co-administration of the selective GLP-2 antagonist GLP-2 (3-33) reversed the effect of BTA.ConclusionThe selective TGR5 agonist BTA ameliorated DSS-induced colitis in mice via the GLP-2 pathway with no effect of DPPIV inhibition, suggesting that other DPP enzymatic activity is involved in GLP-2 degradation.

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.

Empagliflozin and metformin are widely used for the treatment of type 2 diabetes. These drugs showed marked anti-inflammatory effects in different animal models via enhancing AMPK activity. Yet, the protective anti-inflammatory effects of their combination against ulcerative colitis have not been previously investigated. The current study aimed to explore the potential of empagliflozin/metformin combination to mitigate the DSS-induced rat colitis model. The modulating effects of empagliflozin and metformin on the AMPK/mTOR/NLRP3 axis and T cell polarization were delineated. In this study, distal colons were examined for macroscopic and microscopic pathological alterations. ELISA, qRT-PCR, and immunohistochemistry techniques were applied to detect proteins and cytokines involved in AMPK/mTOR/NLRP3 axis and T Cell polarization. Oral administration of empagliflozin (10 mg/kg/day) and metformin (200 mg/kg/day) combination alleviated colitis as revealed by the reduced disease activity index, macroscopic damage index, colon weight/length ratio, and histopathologic scoring values. Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1β, and IL-18. Reduced mTOR expression and reduced IL-6 levels led to a reduction in Th17 cell polarization and maintenance. Together, the current study reveals that the protective effects of empagliflozin and metformin against DSS-induced colitis are fundamentally mediated via enhancing AMPK phosphorylation. Since adult humans with diabetes mellitus are at greater risk for developing inflammatory bowel diseases, clinical application of empagliflozin/metformin combination represents a novel therapeutic approach for treating diabetic patients with ulcerative colitis.