DSS-induced Colitis Research Articles

Lacticaseibacillus casei IB1 Alleviates DSS-Induced Inflammatory Bowel Disease by Regulating the Microbiota and Restoring the Intestinal Epithelial Barrier.

Inflammatory bowel disease (IBD) is becoming an increasingly serious health problem in humans and animals. Probiotics can inhibit the development of IBD. Due to the specificity of the strains, the function and mechanism of action of different strains are still unclear. Here, a DSS-induced colitis mouse model was utilized to investigate the ability and mechanism by which Lacticaseibacillus casei IB1 alleviates colitis. Treatment with L. casei IB1 improved DSS-induced colitis in mice, as indicated by increased body weight, colon length, and goblet cell numbers and decreased disease activity index (DAI), proinflammatory factor (TNF-α, IL-1β, and IL-6) levels, and histopathological scores after intake of IB1. IB1 supplementation also improved the expression of tight junction proteins and inhibited the activation of the MAPK and NF-κB signaling pathways to alleviate intestinal inflammation. In addition, IB1 rebalanced the intestinal microbial composition of colitis mice by increasing the abundance of Faecalibaculum and Alistipes and decreasing the abundance of Bacteroides and Escherichia_Shigella. In summary, L. casei IB1 showed great potential for relieving colitis by regulating the microbiota and restoring the epithelial barrier. It can be used as a potential probiotic for the prevention and treatment of UC in the future.

Walnut peptide ameliorates DSS-induced colitis in mice by inhibiting inflammation and modulating gut microbiota

The incidence of ulcerative colitis (UC) is increasing each year, and its course is characterized by alternating remission-relapse; currently, there is no effective treatment for UC. Peptides produced from the hydrolysis of walnut proteins have physiological functions such as anti-inflammatory and antioxidant properties. The aim of this study was to analyze the preventive effect of walnut polypeptide (WP) on UC and to preliminarily screen bioactive peptides in WP. The results of in vitro experiments showed that WP was able to alleviate the LPS-induced inflammatory response by inhibiting M1 polarization in Raw 264.7 cells and thereby alleviating the LPS-induced inflammatory response. The results of in vivo experiments showed that dietary supplementation with 500 mg/kg WP significantly alleviated dextran sodium sulfate (DSS)-induced weight loss, colon shortening, and elevated DAI scores. WP treatment was able to suppress DSS-induced inflammatory responses in mice by inhibiting macrophage M1 polarization and NF-κB signaling pathway. WP intervention also helped maintain intestinal barrier integrity by promoting tight junction protein expression and mucus secretion. In addition, 16S rDNA sequencing showed that WP ameliorated gut microbial disorder induced by DSS, as evidenced by a decrease in the abundance of harmful bacteria (Erysipelatoclostridium, Helicobacter, and Parasutterella) and an increase in the abundance of beneficial bacteria (Flavonifractor, Anaerotignum, and Alistipes) after WP intervention. In conclusion, this study demonstrates that WP ameliorates DSS-induced colonic inflammation in mice by inhibiting inflammation, modulating the gut microbiota and repairing the intestinal barrier.

Pig-Derived Probiotic Bacillus tequilensis YB-2 Alleviates Intestinal Inflammation and Intestinal Barrier Damage in Colitis Mice by Suppressing the TLR4/NF-κB Signaling Pathway.

The search for new probiotics has been regarded as an important approach to improving intestinal health in animals. Bacillus has many advantages, such as strong resistance to harmful external factors, wide distribution, and easy colonization of the intestine. Hence, this study aims to screen for a probiotic Bacillus strain that improves animal intestinal health and to elucidate its probiotic mechanism so as to provide probiotic resources for the development of feed-using probiotic formulations. In this research, a strain of Bacillus was isolated from adult pig feces and named B. tequilensis YB-2. In vitro probiotic experiments showed that B. tequilensis YB-2 had strong acid and bile salt resistance, indicating that this strain can customize in the intestine. To further explore the effect of B. tequilensis YB-2 upon animal intestinal health, DSS-induced murine colitis models were established, and the body weight, colonic morphology, inflammatory cytokines level, and intestinal-barrier- and TLR4/NF-κB-pathway-related protein were determined. The results showed that mice receiving drinking water with 3% DSS were found to develop colitis symptoms, including body weight loss and increased disease activity index (DAI); colon length and microvilli shedding were shortened; tight junctions were disrupted; goblet cells decreased; anti-inflammatory cytokines were inhibited; and pro-inflammatory cytokines and the TLR4/NF-κB signaling pathway were activated. Notably, orally received B. tequilensis YB-2 alleviated symptoms of DSS-induced colitis in mice. The above results indicated that B. tequilensis YB-2 was capable of improving colitis in mice by weakening inflammation and intestinal barrier damage, and its mechanism may involve the TLR4/NF-κB pathway. Overall, this research suggests that B. tequilensis YB-2 has the potential to serve as an animal feed additive to prevent intestinal inflammation.

Sodium Houttuyfonate Ameliorates DSS-induced Colitis Aggravated by Candida albicans through Dectin-1/NF-κB/miR-32-5p/NFKBIZ Axis Based on Intestinal microRNA Profiling.

Our previous research indicated that Sodium houttuyfonate (SH) can effectively ameliorate dextran sulfate sodium (DSS)-induced colitis exacerbated by Candida albicans. However, the underlying protective mechanism of SH remains unclear. Therefore, in this study, a mice colitis model was infected with C. albicans, and the total colonic miRNAs were assessed. Furthermore, the differentially expressed miRNAs were enriched, clustered, and analyzed. Moreover, based on the dual luciferase analysis of NFKBIZ modulation by miR-32-5p, the in vitro and in vivo therapeutic effects of SH on inflammatory response, fungal burden, oxidative stress, and apoptosis were assessed at transcriptional and translational levels in the presence of agonist and antagonist. A total of 1157 miRNAs were identified, 84 of which were differentially expressed. Furthermore, qRT-PCR validated that SH treatment improved 17 differentially expressed miRNAs with > fourfold upregulation or > sixfold downregulation. Similar to most differentially altered miRNA, C. albicans significantly increased Dectin-1, NF-κB, TNF-α, IL-1β, IL-17A, and decreased miR-32-5p which negatively targeted NFKBIZ. In addition, SH treatment reduced inflammatory response and fungal burden in a colitis model with C. albicans infection. Further analyses indicated that in C. albicans infected Caco2 cells, SH inhibited fungal growth, oxidative stress, and apoptosis by increasing Dectin-1, NF-κB, NFKBIZ, TNF-α, IL-1β, IL-17A, and decreasing miR-32-5p. Therefore, SH can ameliorate the severity of colitis aggravated by C. albicans via the Dectin-1/NF-κB/miR-32-5p/NFKBIZ axis.

Revitalizing gut barrier integrity: role of miR-192-5p in enhancing autophagy via Rictor in enteritis.

Intestinal inflammation and compromised barrier function are critical factors in the pathogenesis of gastrointestinal disorders. This study aimed to investigate the role of miR-192-5p in modulating intestinal epithelial barrier (IEB) integrity and its association with autophagy. A DSS-induced colitis model was used to assess the effects of miR-192-5p on intestinal inflammation. In vitro experiments involved cell culture and transient transfection techniques. Various assays, including dual-luciferase reporter gene assays, quantitative real-time PCR, Western blotting, and measurements of transepithelial electrical resistance, were performed to evaluate changes in miR-192-5p expression, Rictor levels, and autophagy flux. Immunofluorescence staining, H&E staining, TEER measurements, and FITC-dextran analysis were also used. Our findings revealed a reduced expression of miR-192-5p in inflamed intestinal tissues, correlating with impaired IEB function. Overexpression of miR-192-5p alleviated TNF-induced IEB dysfunction by targeting Rictor, resulting in enhanced autophagy flux in enterocytes (ECs). Moreover, the therapeutic potential of miR-192-5p was substantiated in colitis mice, wherein increased miR-192-5p expression ameliorated intestinal inflammatory injury by enhancing autophagy flux in ECs through the modulation of Rictor. Our study highlights the therapeutic potential of miR-192-5p in enteritis by demonstrating its role in regulating autophagy and preserving IEB function. Targeting the miR-192-5p/Rictor axis is a promising approach for mitigating gut inflammatory injury and improving barrier integrity in patients with enteritis.NEW & NOTEWORTHY We uncover the pivotal role of miR-192-5p in fortifying intestinal barriers amidst inflammation. Reduced miR-192-5p levels correlated with compromised gut integrity during inflammation. Notably, boosting miR-192-5p reversed gut damage by enhancing autophagy via suppressing Rictor, offering a potential therapeutic strategy for fortifying the intestinal barrier and alleviating inflammation in patients with enteritis.

Reveal the pharmacodynamic substances and mechanism of an edible medicinal plant Rhodiola crenulate in DSS-induced colitis through plasma pharmacochemistry and metabolomics

Rhodiola crenulate is the edible medicinal herbal medicine widely used for altitude sickness in China. Interestingly, our previous work has found that R. crenulate extract (RCE) could significantly improve the pathology associated with dextran sulfate sodium-induced colitis. Thus, the current research aims to reveal the pharmacodynamic material basis of RCE, as well as its mechanism against colitis. The chemical characterization of RCE was performed by UHPLC-HR-MS, through which a total of 88 constituents were identified. Meanwhile, our results also found 29 constituents absorbed into blood and 8 metabolized absorbable compounds. The decreased flavonoids prototype and the elevated sulfated products of phenols were observed under pathophysiological conditions of colitis. The metabolomics study revealed that colitis caused the alternation of fatty acid metabolism, steroid hormone biosynthesis and bile acid metabolism. Correspondingly, RCE could prevent colitis by improving fatty acid metabolism and secondary bile acid metabolism.

Puerariae radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

Ulcerative colitis (UC) is a common inflammatory disease of the gastrointestinal tract. Traditional Chinese medicine (TCM) has long been used in Asia as a treatment for UC and Puerariae radix (PR) is a reliable anti-diarrheal therapy. The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt (DSS)-induced UC model in mice and identify molecular mechanisms of PR action. The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology (NP) approach were obtained to guide mouse experiments. A total of 180 peaks were identified from PR including 48 flavonoids, 46 organic acids, 14 amino acids, 8 phenols, 8 carbohydrates, 7 alkaloids, 6 coumarins and 43 other constituents. NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC. A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice. PR also alleviated intestinal mucosal shedding, inflammatory cell infiltration and mucin loss. PR treatment suppressed upregulation of NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate-specific proteases-1 (caspase-1), apoptosis-associated speck-like (ASC) and gasdermin D (GSDMD) at both the protein and mRNA expression levels. The addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of PR. These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.

Therapeutic effect and mechanism of Ento-PB on ulcerative colitis in BALB/c mice induced by sodium dextran sulfate

The traditional Chinese medicine (TCM) formula Ento-PB containing Periplaneta americana (Linnaeus) (Blattidae) and Taraxacum mongolicum Hand.-Mazz. (Compositae) has great potential for treating inflammation. Thus, this study aimed to explore the pharmacodynamic effect of Ento-PB on DSS-induced ulcerative colitis in BALB/c mice, and its effects on immune function, JAK2/STAT3-related signaling pathways and intestinal flora in UC mice. It was identified that the extract Ento-PB mainly contained 20 compounds, accounting for 78.50 % of the total peak area. Compared with the model group, each dose group of Ento-PB could reduce the DAI score, colon index, CMDI score and colon HS score of mice to varying degrees (P < 0.05 or P < 0.01). Ento-PB can reduce the content of IL-1β, TNF-α, IFN-γ in serum and IL-7 and IL-17 in colonic tissue, and increase IL-2, IL-10 in serum and EGF in colonic mucosa, TGF-β1 expression level (P < 0.05 or P < 0.01). In conclusion, Ento-PB has a good therapeutic effect on DSS-induced UC mice. Its mechanism of action may be to up-regulate the levels of IL-2, IL-10, EGF, IL-22 and TGF-β1, and down-regulate the levels of TNF-α,IFN-γ, IL-7 and IL-17 in UC mice. This provides sufficient experimental basis for the clinical treatment of UC with Ento-PB.

Anti-inflammatory Effects of Lycium barbarum Polysaccharides and/or Bifidobacterium longum in Rats With DSS-Induced Ulcerative Colitis

Anti-inflammatory Effects of Lycium barbarum Polysaccharides and/or Bifidobacterium longum in Rats With DSS-Induced Ulcerative Colitis

Atlantic Mackerel Is Protective in DSS-Induced Colitis Rat Models

Atlantic Mackerel Is Protective in DSS-Induced Colitis Rat Models

Effect of fermented Rosa roxburghii tratt fruit juice on gut microbiota in a dextran sulfate sodium (DSS)-induced colitis mouse model

This study mainly investigated the regulatory effect of Rosa roxburghii Tratt fruit juice fermented by Lacticaseibacillus paracasei SR10-1 (LAB-RRTJ) on modulating gut microbiota in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. Compared to control group, DSS induction decreased body weight of mice, indexes of Shannon, Simpson, Chao 1 and Faith_pd, and increased disease activity index (DAI) and levels of interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ); And this induction also led to an increase in Proteobacteria, Verrucomicrobia and Actinobacteria at phylum level, harmful bacterial species richness at genus level, and relative richness of S. sciuri, desulfovibrio C21_c20, R. gnavus and Akkermansia muciniphila at species level, and a decrease in Firmicutes at phylum level and relative richness of B. acidifaciens in mice. LAB-RRTJ increased body weight of mice with DSS induced ulcerative colitis (UC) and indexes of Shannon, Simpson, Chao 1 and Faith_pd, reduced DAI and the content of four inflammatory factors and improved gut microbiota imbalance in DSS induced UC mice. Besides, the number of OTUs increased, alpha diversity and beta diversity were restored and similar to those in mice in the Control group after LAB-RRTJ treatment. Compared with the positive drug treatment group, LAB-RRTJ has a better effect on regulating gut microbiota diversity in colitis mice. Correlation analysis showed that inflammatory factors were positively correlated with harmful bacteria and negatively correlated with beneficial bacteria which commonly found in some colitis mice. Taken together, our study demonstrated that LAB-RRTJ could alleviate DSS-induced colitis in mice through the modulation of inflammatory cytokines and gut microbiota composition.

Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials.

This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

A thiolated oxidized guar gum and sodium alginate dual-network microspheres with enhanced gastric acid resistance and mucoadhesion for delivery of probiotics

Probiotics offer numerous beneficial functions for human bodies, while the low survival rate under gastric acid and short retention time in the intestine are the major obstacles to their utilization. To address these issues, we designed a novel dual-network hydrogel microsphere that combines gastric acid resistance with enhanced mucoadhesion, aiming for the targeted delivery of probiotics. Thiolated oxidized guar gum (SOGG) was disulfide-linked to form the first network, and sodium alginate (SA) was cross-linked with Ca2+ to form the second network. Under the protection of the interpenetrating dual network microspheres, a much higher viability of Lactobacillus rhamnosus (LGG) (8.73 log CFU/mL) was achieved in simulated gastric fluid, compared to the zero-survival rate of free LGG. Mucoadhesion tests showed that the adhesion rate of SOGG/SA microspheres to the intestinal mucosa was 1.75 times higher than that of thiol-free microspheres. In vivo studies revealed that LGG-loaded microspheres significantly enhanced intestinal barrier function, remodeled the gut microbiome, and alleviated DSS-induced colitis in mice. Overall, SOGG/SA microspheres provide an effective strategy to the challenges of probiotic reduction in the stomach and rapid expulsion from the intestines, enhancing their health benefits.

Hydroethanolic Extract of Lepidium apetalum Willdenow Alleviates Dextran Sulfate Sodium-Induced Colitis by Enhancing Intestinal Barrier Integrity and Inhibiting Oxidative Stress and Inflammasome Activation.

The prevalence of ulcerative colitis (UC) has surged in Asian nations recently. The limitations of traditional drug treatments, including biologics, have spurred interest in herbal medicines for managing UC. This study aimed to elucidate the protective mechanisms of hydroethanolic extract from Lepidium apetalum Willdenow (LWE) on intestinal integrity and inflammation in a dextran sodium sulfate (DSS)-induced colitis model of inflammatory bowel disease (IBD). Using UPLC-MS/MS analysis, eleven phytochemicals were identified in LWE, including catechin, vicenin-2, and quercetin. LWE restored transepithelial electrical resistance (TEER) and reduced paracellular permeability in IL-6-stimulated Caco-2 cells, increasing the expression of the tight junction proteins ZO-1 and occludin. LWE treatment alleviated DSS-induced colitis symptoms in mice, reducing body weight loss, disease activity index values, and spleen size, while improving colon length and reducing serum FITC-dextran levels, indicating enhanced intestinal barrier function. LWE suppressed NLRP3 inflammasome activation, reducing protein levels of pro-caspase-1, cleaved-caspase-1, ASC, and NLRP3, as well as mRNA levels of IL-1β, IL-6, and TNF-α. LWE treatment upregulated activity and mRNA levels of the antioxidant enzymes SOD1 and NQO1. Additionally, LWE modulated the Nrf2/Keap1 pathway, increasing p-Nrf2 levels and decreasing Keap1 levels. LWE also restored goblet cell numbers and reduced fibrosis in DSS-induced chronic colitis mice, increasing gene and protein expressions of ZO-1 and occludin. In summary, LWE shows promise as a therapeutic intervention for reducing tissue damage and inflammation by enhancing intestinal barrier function and inhibiting colonic oxidative stress-induced inflammasome activation.

Protective effect of zinc oxide nanoparticles synthesized using Cassia alata for DSS-induced ulcerative colitis in mice model.

The most prevalent form of inflammatory bowel disease (IBD), ulcerative colitis (UC), is characterized by persistent inflammation of the colorectal mucosa. It is asymptomatic, whereas Crohn's disease (CD) causes patchy lesions in the gastrointestinal tract. Men and women suffer equally from ulcerative colitis, which usually strikes in the second and third decades of life and becomes more common in senior citizens. In the present study, we produced zinc oxide nanoparticles using the natural herbal plant, Cassia alata. Zinc oxide nanoparticles have remarkable antimicrobial and antitumor benefits in the field of biomedical science. Furthermore, the synthesized zinc oxide nanoparticles (ZnO NPs) were characterized using UV, XRD, FTIR, and SEM analyses. The XRD analysis confirmed the crystallite nature and purity of the synthesized nanoparticles. Zinc oxide nanoparticles with a uniform size and partially agglomerated morphology were verified by SEM analysis. We investigated the protective effects of environmentally friendly zinc oxide nanoparticles in dextran sodium sulfate-induced ulcerative colitis mouse models. Green synthesized Cassia alata zinc oxide nanoparticles (CA ZnO NPs) reversed weight loss, disease activity index, colon shortening, and colon histological damage. Zinc oxide nanoparticles reduce hypersensitivity, oxidative stress, and inflammation, and protect the mucosal layer. Green synthesized CA ZnO NPs demonstrated protection against dextran sodium sulfate-induced ulcerative colitis via anti-inflammatory activity.

Anti-Inflammatory Effects of Zinc Oxide and Berberine in Rats with Dextran Sulfate Sodium (DSS)-Induced Colitis.

Zinc oxide (ZnO) is frequently used in high concentrations to prevent diarrhea in weaning pigs. However, it can produce environmental pollution, because it is not absorbed by the intestines and is excreted in the feces. In studies to identify an alternative substance to ZnO, we used a model of colitis induced by dextran sulfate sodium (DSS) in rats to compare the anti-inflammatory effects of berberine with ZnO. DSS-treated rats displayed weight loss, shortening of the colon, increased fecal water content, and an increase in the disease activity index (DAI). In contrast, DSS + ZnO- and DSS + berberine-treated rats exhibited reduced colon shortening, decreased fecal water content, and a decrease in the DAI. Histological analysis revealed that both ZnO and berberine treatment reduced epithelial cell damage, crypt destruction, and infiltration of inflammatory cells. Moreover, the liver damage index was not significantly different between ZnO and berberine-treated rats. This study indicated that both ZnO and berberine can improve DSS-induced colitis in rats and suggests berberine as an alternative treatment to ZnO that would not cause environmental pollution.

Agrimonolide mitigated DSS-induced colitis by modulating the balance between Treg and Th17 cells through the suppression of the Notch and JAK2/STAT3 signaling pathways

PurposeThe objective of this study was to investigate the effects of agrimonolide (AM) on mice with dextran sulfate sodium (DSS)-induced colitis and elucidate its protective mechanisms. MethodsA 3 % DSS solution was used to induce colitis, and intragastric administration of AM at doses of 25 and 50 mg/kg was performed. A comprehensive assessment was conducted to evaluate inflammatory responses and mucosal integrity in the colon. Inflammatory factors were quantified using enzyme-linked immunosorbent assay (ELISA). The proportions of T helper cell 17 (Th17) and regulatory T cells (Treg) cells in mesenteric lymph nodes (MLNs) was analyzed through RT-qPCR and flow cytometry. Proteins associated with the Notch and JAK2/STAT3 pathways were examined via RT-qPCR, western blotting, and immunofluorescence. Additionally, the impact of AM on Treg and Th17 cell differentiation was investigated in vitro. ResultsPre-treatment with AM significantly alleviated colon inflammation in mice, as evidenced by reduced body weight loss, shorter colon length, lower disease activity index (DAI) score, and decreased myeloperoxidase (MPO) content. Notably, AM pre-treatment attenuated the production of pro-inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6, in mice with DSS-induced colitis. Additionally, AM pre-treatment significantly enhanced the expression of tight junction proteins (Occludin and ZO-1), thereby preserving gut barrier function. Moreover, we observed that AM administration decreased the ratio of Th17 cells while increasing the frequency of colonic Treg cells, thus modulating the Th17/Treg balance both in vivo and in vitro. Furthermore, in the AM-treated group, the expression of Notch-1, Jagged1, delta like 4 (DLL4), phospho-janus kinases 2 (p-JAK2)/JAK2, and p-signal transducer and activator of transcription 3 (STAT3)/STAT3 in colonic tissue was reduced compared to the DSS group. Remarkably, the therapeutic effects of AM in colitis mice were blocked by a Notch activator. ConclusionThese findings underscore the effectiveness of AM in alleviating symptoms and pathological damage in DSS-induced colitis mice by rebalancing Th17/Treg cell homeostasis through modulation of the Notch and JAK2/STAT3 signaling pathways. These insights into AM's mechanisms of action offer potential avenues for novel therapeutic strategies.

Exploring Scopoletin's Therapeutic Efficacy in DSS-Induced Ulcerative Colitis: Insights into Inflammatory Pathways, Immune Modulation, and Microbial Dynamics.

This study aimed to investigate the therapeutic potential of scopoletin in ulcerative colitis, with a primary focus on its impact on crucial inflammatory pathways and immune responses. A male mouse model of DSS-induced colitis was employed with six distinct groups: a control group, a group subjected to DSS only, three groups treated with varying scopoletin doses, and the final group treated with dexamethasone. The investigation included an assessment of the effects of scopoletin on colitis symptoms, including alterations in body weight, Disease Activity Index (DAI), and histopathological changes in colonic tissue. Furthermore, this study scrutinized the influence of scopoletin on cytokine production, PPARγ and NF-κB expression, NLRP3 inflammasome, and the composition of intestinal bacteria. Scopoletin treatment yielded noteworthy improvements in DSS-induced colitis in mice, as evidenced by reduced weight loss and colonic shortening (p < 0.05, < 0.01, respectively). It effectively diminished TNF-α, IL-1β, and IL-12 cytokine levels (p < 0.01, p < 0.05), attenuated NLRP3 inflammasome activation and the associated cytokine release (p < 0.05, p < 0.01), and modulated the immune response by elevating PPARγ expression while suppressing NF-κB pathway activation (p < 0.05, p < 0.01). Additionally, scopoletin induced alterations in the gut microbiota composition, augmenting beneficial Lactobacillus and Bifidobacteria while reducing E. coli (p < 0.05). It also enhanced tight junction proteins, signifying an improvement in the intestinal barrier integrity (p < 0.05, < 0.01). Scopoletin is a promising therapeutic agent for managing ulcerative colitis, showing benefits that extend beyond mere anti-inflammatory actions to encompass regulatory effects on gut microbiota and restoration of intestinal integrity.

Investigation of Rhizopus oligosporus Metabolites in Fermented Wheat Bran and Its Bio Function in Alleviating Colitis in Mice Model.

Wheat bran (WB) is a low-value by-product of the wheat milling industry. Solid-state fermentation with Rhizopus oligosporus is performed to improve WB's nutritional quality (RH). Twenty-five mice (11-week-old C57BL/6N male mice) were divided into three groups. The first group was fed a control diet (n = 8), the second group a 10% WB-supplemented diet (n = 8), and the last group had a 10% RH-supplemented diet (n = 9). The diet treatment was administered for 4 days before dextran sodium sulfate (DSS, 3% in drinking water) was administered for 9 days. RH supplementation prevented bodyweight loss and reduced the disease activity index in mice. An increase in the level of SCFAs in mouse intestines was detected post-RH supplementation, suggesting that SCFAs might have contributed to its anti-colitis effect. Metabolome analysis was conducted to explore other bioactive compounds in RH. R. oligosporus fermentation significantly increased the amounts of ergothioneine, arginine, branched-chain amino acids, and adenosine in wheat bran. All of these compounds are known to have antioxidant and anti-inflammatory capacities. These bioactive compounds might also have contributed to the RH's ability to ameliorate DSS-induced colitis.

A derivative of 3-(1,3-diarylallylidene)oxindoles inhibits dextran sulfate sodium-induced colitis in mice

BackgroundIA-0130 is a derivative of 3-(1,3-diarylallylidene)oxindoles, which is a selective estrogen receptor modulator (SERM). A previous study demonstrated that SERM exhibits anti-inflammatory effects on colitis by promoting the anti-inflammatory phenotype of monocytes in murine colitis. However, the therapeutic effects of oxindole on colitis remain unknown. Therefore, we evaluated the efficacy of IA-0130 on dextran sulfate sodium (DSS)-induced mouse colitis.MethodsThe DSS-induced colitis mouse model was established by administration of 2.5% DSS for 5 days. Mice were orally administered with IA-0130 (0.01 mg/kg or 0.1 mg/kg) or cyclosporin A (CsA; 30 mg/kg). Body weight, disease activity index score and colon length of mice were calculated and histological features of mouse colonic tissues were analyzed using hematoxylin and eosin staining. The expression of inflammatory cytokines and tight junction (TJ) proteins were analyzed using quantitative real-time PCR and enzyme-linked immunosorbent assay. The expression of interleukin-6 (IL-6) signaling molecules in colonic tissues were investigated using Western blotting and immunohistochemistry (IHC).ResultsIA-0130 (0.1 mg/kg) and CsA (30 mg/kg) prevented colitis symptom, including weight loss, bleeding, colon shortening, and expression of pro-inflammatory cytokines in colon tissues. IA-0130 treatment regulated the mouse intestinal barrier permeability and inhibited abnormal TJ protein expression. IA-0130 down-regulated IL-6 expression and prevented the phosphorylation of signaling molecules in colonic tissues.ConclusionsThis study demonstrated that IA-0130 suppressed colitis progression by inhibiting the gp130 signaling pathway and expression of pro-inflammatory cytokines, and maintaining TJ integrity.