Dextran Sulfate Sodium-induced Colitis Research Articles

Immunomodulatory Effects of Lactiplantibacillus plantarum Strain RW1 During Salmonella Infection in Murine Intestinal Epithelial Cells and Dextran Sulfate Sodium-Induced Murine Colitis.

Inflammatory diseases resulting from bacterial infections or inflammatory bowel disease pose significant threats to the health of both animals and humans. Although probiotics have emerged as a crucial preventive and adjunctive therapy for these conditions, the precise mechanisms through which probiotics regulate inflammatory diseases remain incompletely understood. In our previous study, animal-derived Lactiplantibacillus plantarum strain RW1 (L. plantarum RW1) with probiotic potential was isolated and characterized. In this study, the signaling pathway of L. plantarum RW1 inhibiting the inflammatory response of mouse intestinal epithelial cells caused by Salmonella infection was studied. Our results revealed that infection of Salmonella enterica subsp. enterica serovar Typhimurium strain ATCC14028 (S. Typhimurium ATCC14028) and Salmonella enterica subsp. enterica serovar Typhimurium strain SL1344 (S. Typhimurium SL1344) significantly increased NF-κB/p65 and TLR4 mRNA levels while decreasing IκB and TLR2 mRNA levels. Whereas L. plantarum RW1 treatment significantly reversed these changes. Western blotting confirmed these findings. Additionally, we explored the protective effects of L. plantarum RW1 in a murine colitis model induced by dextran sulfate sodium (DSS). Treatment with L. plantarum RW1 significantly increased both intestinal length and body weight compared to DSS-treated mice. 16S rRNA sequencing analysis demonstrated that L. plantarum RW1 restored the dysbiosis caused by DSS. Flow cytometry analyses further revealed that L. plantarum RW1 specifically increased regulatory T-cell proportions in Peyer's patches while reducing macrophage and neutrophil proportions, indicating the modulatory effects of L. plantarum RW1 on immune responses in gut-associated lymphatic tissue in the context of colitis. This study sheds light on the intricate interaction between probiotics and hosts, offering valuable insights into their potential application for treating inflammatory diseases in animals and humans.

Optimization of a green tea seed oil-loaded double-layer emulsion and its preventive effects on dextran sulfate sodium-induced colitis in mice.

Green tea seed oil (GTSO; Camellia sinensis) is rich in bioactive compounds and has great potential for preventing intestinal inflammation. Conversely, high-fat diets have been shown to promote or aggravate gastrointestinal inflammation, and the bioactive ingredients of GTSO face difficulty passing through the gastrointestinal tract while remaining intact. This study employed whey protein isolate (WPI) and sodium carboxymethyl cellulose (CMC-Na) to prepare a GTSO-loaded double-layer emulsion. The optimal parameters were as follows: WPI (2% w/w) and 35% oil phase for the primary emulsion preparation, CMC-Na (0.8% w/w) for the final emulsion, and 450W of ultrasonic power for homogenization. No significant changes in particle size or coalescence in the emulsions were observed after 30days of storage at 4°C. In addition, in a simulated gastrointestinal digestion system, more than 60% of the encapsulated GTSO was able to remain intact while passing through the gastric and small intestinal environment. In mice with dextran sulfate sodium-induced colitis, pretreatment with the GTSO emulsion significantly prevented the further development of colitis, whereas an empty-carrier-plus-free-GTSO treatment had no such protective effects and even tended to aggravate the disease. The results of the present study suggest that encapsulated GTSO is a reliable alternative approach for colitis prevention. PRACTICAL APPLICATION: The green tea seed oil-loaded double-layer emulsion demonstrates good storage stability when kept at 4°C, exhibits excellent slow-release performance, and achieves superior outcomes in the prevention of colitis. Our current study provides a reliable alternative approach for the prevention of colitis.

The Hydrophobic Amino Acid-Rich Fish Collagen Peptide Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice via Repairing the Intestinal Barrier, Regulating Intestinal Flora and AA Metabolism.

The incidence of ulcerative colitis (UC) is increasing annually, but treatment option is limited. Fish collagen peptide (FCP) is a food source collagen peptide that has shown promise in alleviating UC symptoms. However, its impact on the intestinal barrier and intestinal metabolic homeostasis in UC remains unclear. This study aimed to analyze the peptide sequences and absolute amino acid (AA) content of FCP, assessing its effects on UC in mice induced by dextran sulfate sodium (DSS). FCP was examined by liquid chromatography and tandem mass spectrometry (LC-MS/MS) analysis. The 3% DSS was utilized to induce UC in murine models, followed by the assessment of the therapeutic efficacy of FCP. Clinical manifestations of UC mice were meticulously evaluated and scored. Subsequently, samples were procured for histological examination and intestinal epithelial barrier integrity analysis as well as macrogenomic and metabolomic profiling. Here, it shows that abundant peptide sequences and AAs were in FCP, particularly enriched in hydrophobic AAs (HAAs). Furthermore, it was observed that FCP effectively reversed colon shortening and reduced the extent of histological damage. Additionally, FCP suppressed the abnormal expression of inflammatory factors and intestinal barrier proteins and modulated the dysbiosis of gut microbiota toward a balanced state. These alterations led to the activation of intestinal alkaline AA and various AA metabolisms, ultimately contributing to the mitigation of UC symptoms. In summary, the diverse peptide sequences and high AAs in FCP, particularly rich in HAAs, can alleviate DSS-induced UC via preserving intestinal barrier integrity, regulating gut microbiota, and modulating AA metabolism.

Functional analysis of antigen presentation by enteric glial cells during intestinal inflammation.

The Enteric Nervous System is composed of a vastly interconnected network of neurons and glial cells that coordinate to regulate homeostatic gut function including intestinal motility, nutrient sensing, and mucosal barrier immunity. Enteric Glial Cells (EGCs) are a heterogeneous cell population located throughout the gastrointestinal tract and have well described roles in regulating intestinal immune responses. Enteric Glial Cells have been suggested to act as nonconventional antigen presenting cells via the Major Histocompatibility Complex II (MHC II), though this has not been confirmed functionally. Here, we investigate the capability of EGCs to present antigen on MHC I and MHC II using in vitro antigen presentation assays performed with primary murine EGC cultures. We found that EGCs are capable of functional antigen presentation on MHC I, including antigen cross-presentation, but are not capable of functional antigen presentation on MHC II. We also determined EGC cell surface MHC I and MHC II expression levels by flow cytometry during intestinal inflammation during Dextran Sodium Sulfate-induced colitis or acute Toxoplasma gondii infection. We found that EGCs upregulate MHC I during acute T. gondii infection and induce low-level MHC II expression. These findings suggest that EGCs may be important in the regulation of CD8+ T cell responses via MHC I mediated antigen (cross) presentation but may not be relevant for MHC II-mediated antigen presentation.

Elegant approach to intervention of homogalacturonan from the fruits of Ficus pumila L. in colitis: Unraveling the role of methyl esters and acetyl groups.

Oral administration of homogalacturonan (HG) has shown significant potential in anti-colitis activity, yet the therapeutic efficacy of naturally sourced HG still requires enhancement. Herein, HG from the fruits of Ficus pumila L. was modified by chemical methods and the intervention effect of modified HG with different degrees of methyl-esterification (DM) and acetylation (DA) on dextran sulfate sodium-induced colitis in mice was explored. Our results indicated that low-DM HG (DM3 and DM25) primarily mitigated colitis by reducing inflammation (TNF-α, IL-1β, IL-17, and IL-6), while high-DM HG (DM54 and DM94) primarily repaired the intestinal barrier. These effects may be attributed to the differential regulation of gut microbiota by HG with varying DM, such as Lachnospiraceae_NK4A136_group, Lactobacillus, Mucispirillum, Escherichia-Shigella, Bifidobacterium, and Bacteroides. Increased DA reduced the solubility of HG, showing limited anti-inflammatory response but unique advantages in intestinal barrier repair and microbiome regulation (Bifidobacterium, Candidatus_Saccharimonas, Lachnospiraceae_NK4A136_group, Mucispirillum, and Escherichia-Shigella). Furthermore, various structural parameters and substitution degrees showed no significant impact on HG's regulation of oxidative stress reactions. This study emphasized the importance of substituent effect in determining HG's functional role, providing a robust foundation for the design and development of functional polysaccharides for the prevention of intestinal inflammation and other related conditions.

Effects of Centella asiatica-isolated pectic polysaccharide on dextran sulfate sodium-induced colitis

Dietary supplementation of polysaccharides demonstrates strong therapeutic actions on inflammatory bowel disease (IBD). Centella asiatica (CA) has traditionally been used in Ayurveda and Chinese medicine. However, the effects of CA-isolated pectic polysaccharides on IBD remain unknown. This study determined the effect of a CA-isolated pectic polysaccharide on IBD. The crude polysaccharide (CA-CP), isolated from a hot-water extract of CA, is a typical pectic polysaccharide composed mainly of galacturonic acid (40.6 %), galactose (27.6 %), arabinose (13.5 %), and rhamnose (8.5 %). CA-CP improved clinical symptoms in a DSS-induced colitis murine model, including weight change (9.9–12.0 %), disease activity index (31.6–51.9 %), colon length (13.2–21.5 %), and spleen weight (21.8–26.3 %). CA-CP effectively regulated the levels of inflammatory and junctional factors by mediating the MAPK and NF-κB pathways. CA-CP partially alleviated DSS-induced crypt destruction, submucosal edema, inflammatory infiltration, and mucin secretion. The content of total short-chain fatty acids increased substantially (cecum 29.8–53.7 %, feces 75.4–109.3 %) with oral CA-CP administration compared to the DSS group. Cecal microbial community analysis revealed that CA-CP administration regulated DSS-induced colitis by reducing the abundance of Escherichia (5.0–10.9 %) and Clostridium (0.3–0.4 %), while increasing the abundance of Bacteroidetes (6.8–8.5 %), Ligilactobacillus (2.7–6.0 %), and Bilophilia (0.3–0.6 %). The findings provide fundamental data for developing novel functional therapeutic agents for the prevention and treatment of colitis, using CA-isolated pectic polysaccharides. Furthermore, to the best of our knowledge, our study is the first to demonstrate the effects of pectic polysaccharides isolated from CA on IBD.

Curcumin alleviated dextran sulfate sodium-induced ulcerative colitis via inhibition of the Wnt/β-catenin signaling pathway and regulation of the differentiation of intestinal stem cells

In this study, we investigated the regulatory role of curcumin in the differentiation of intestinal stem cells (ISCs) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) model mice and explored whether this effect was mediated by the Wnt/β-catenin signaling pathway. We conducted experiments in DSS-induced UC model mice to observe changes in intestinal morphology through HE staining and detect the expression of key proteins in the Wnt/β-catenin signaling pathway. According to these findings, curcumin was found to have a significant impact on the differentiation of ISCs. These results indicated that curcumin inhibited the Wnt/β-catenin signaling pathway and restored ISC differentiation. The effects of curcumin on the Wnt/β-catenin signaling pathway were further confirmed using Wnt/β-catenin agonists. These findings provide a new perspective for understanding the behavior of ISCs in the context of inflammation and offer new insights into the development of novel therapeutic strategies and drugs for UC.

Poria cocos polysaccharides alleviate dextran sulphate sodium-induced ulcerative colitis in mice by modulating intestinal inflammatory responses and microbial dysbiosis

Poria cocos polysaccharide (PCP), one of the main active components of P. cocos, is extensively used worldwide and exhibits strong pharmacological effects. However, whether PCP can attenuate inflammatory bowel disease remains unclear. In this study, we assessed the effects of PCP supplementation on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice. We found that PCP supplementation mitigated UC symptoms in DSS-treated mice, as evidenced by reductions in body weight loss, colon length shortening and disease activity index score. Importantly, PCP supplementation enhanced colonic barrier integrity by increasing tight junction protein abundance and exerted anti-inflammatory effects by suppressing nuclear factor-κB (NF-κB) activation in DSS-treated mice. Furthermore, PCP supplementation reversed DSS-induced dysbiosis in colonic microbiota by increasing the colonic abundance of beneficial bacteria (e.g. Akkermansiaceae) and decreasing the colonic abundance of harmful bacteria (e.g. Erysipelotrichaceae) in DSS-treated mice. Although PCP supplementation failed to ameliorate DSS-induced UC in antibiotic-treated mice, faecal microbiota transplantation from PCP-administered mice ameliorated DSS-induced UC in antibiotic-treated mice. In summary, PCP alleviates UC in mice by attenuating intestinal inflammation via the inhibition of NF-κB activation and modulating the intestinal microbiota.

A new strategy for pharmacodynamic substance screening and research on gut microbiota pathway mechanisms based on UPLC-Q-orbitrap-MS and 16S rRNA

ObjectiveTo establish a progressive research strategy for “colonic components analysis - efficacy verification and mechanism exploration - gut microbiota”, screen pharmacodynamic substances, and investigate their mechanism via gut microbiota. MethodsThe pharmacodynamics of Gegen Qinlian decoction (GQD) were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis (UC). Ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC. To analyze the structure and function of characteristic genera of GQD and its active components, 16S rRNA sequencing was performed. ResultsWe identified 67 prototypic and 14 metabolic components of GQD in the UC colon. The primary prototype components are flavonoids and alkaloids, including puerarin (PUE), baicalin (BAI), and berberine (BER). The metabolism was predominantly sulfonation. Efficacy verification showed that the main active components, puerarin, baicalin, and berberine, had good therapeutic effects on UC. The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota. The abundance of gut microbiota involved in the metabolism of the prototype components was influenced by the corresponding components. The function prediction results showed that PUE was the most comparable to GQD, with 24 consistent pathways. BAI and BER showed comparable gut microbiota regulation pathways. Characteristic pathways of BER include glucometabolic processes. ConclusionThis study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components. This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC, as well as changes in the structure and function of the gut microbiota, clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.

Exploring the roles of SPARC as a proinflammatory factor and its potential as a novel therapeutic target against cardiovascular disease.

Cardiovascular disease (CVD) is a leading cause of death worldwide, and the number of patients with CVD continues to increase despite extensive research and developments in this field. Chronic inflammation is a pivotal pathological component of CVD, and unveiling new proinflammatory factors will help devise novel preventive and therapeutic strategies. The extracellular matrix (ECM) not only provides structural support between cells but also contributes to cellular functions. Secreted protein acidic and rich in cysteine (SPARC) is a collagen-binding matricellular protein that is particularly induced during development and tissue remodeling. A proinflammatory role for SPARC has been demonstrated in various animal models, such as in the lipopolysaccharide-induced footpad model and dextran sodium sulfate-induced colitis model. Recent clinical studies reported a positive correlation between elevated plasma SPARC levels and hypertension, obesity, and the inflammatory marker high-sensitive C-reactive protein. In addition, SPARC gene deletion attenuates the cardiac injury induced by aging, myocardial infarction, and pressure load, suggesting that SPARC has deleterious effects on CVD. This review summarizes the regulatory and proinflammatory mechanisms of SPARC on CVD, chronic kidney disease (CKD), and cerebrovascular disease and discusses the rationale behind measuring SPARC as a biomarker of CVD and the effects of inhibition of SPARC in the prevention and treatment of CVD.

Diallyl trisulfide alleviates dextran sulphate sodium-induced colitis in mice by inhibiting NLRP3 inflammasome activation via ROS/Trx-1 pathway.

Diallyl trisulfide (DATS), a sulphur-containing compound isolated from the medicinal food plant garlic, has been previously reported to attenuate experimental colitis induced by either dextran sodium sulphate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice; however, the underlying mechanism remains to be identified. In this study, we deciphered the key mechanism by which DATS alleviates ulcerative colitis (UC). We showed that oral administration of DATS for 10 consecutive days greatly restrained the infiltration of macrophages and the pathological changes in colonic tissues of mice with DSS-induced colitis. DATS treatment notably dampened the content of IL-1β and IL-18 and suppressed NLRP3 inflammasome activation in colon. Mechanistically, DATS effectively diminished the generation of ROS in macrophages. The suppressive effect of DATS on the activation of NLRP3 inflammasome and downregulation of IL-18 and IL-1β levels was blunted by xanthine oxidase. Further studies revealed that DATS inhibited NF-κB pathway activation by suppressing the expression of Trx-1, thereby inhibiting NLRP3 inflammasome activation. Trx-1 overexpression and interference in macrophages promoted and diminished NLRP3 inflammasome activation, respectively. In summary, garlic and its main active ingredient DATS have potentials to prevent and treat UC, and DATS functions by inhibiting NLRP3 inflammasome activation via Trx-1/ROS pathway.

Development of interleukin-27 recombinant Lactococcus lactis and its efficacy in treating psoriasis and colitis in mice

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD.

Osa-miR168a, a Plant miRNA That Survives the Process of In Vivo Food Digestion, Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice by Oral Administration.

Previous studies showed that osa-miR168a, a plant miRNA rich in fruits and vegetables, had cross-kingdom biological effects on immunocytes, silkworms, and rodents. In this study, the effects of miR168a on mouse colitis induced by dextran sulfate sodium (DSS) were investigated. The results showed that miR168a oligomers were resistant during the process of food digestion, ending up with a residual concentration of 67.8 ± 11.2 fM in mouse intestines 4 h after oral gavage. More importantly, direct oral administration of the miRNA to the colitis mice significantly ameliorated the progression of the disease, as evidenced by the reduction in DAI score, histopathological lesions, and proinflammatory cytokines. Repairing intestinal barrier function by promoting the regeneration of TJ proteins and the mucus layer, suppressing oxidative stress and colonic inflammation via modulating Nrf2 and NF-κB signaling pathways, and restoring the imbalanced gut microbiota caused by DSS are proposed mechanisms behind the anticolitis activity of miR168a. This study provided new evidence of the cross-kingdom regulatory effects of dietary miRNAs, suggesting the potential of the plant miRNA for the prevention and treatment of inflammatory bowel diseases.

Acceptable daily intake of aspartame aggravates enteritis pathology and systemic inflammation in colitis mouse model.

In this study, a dextran sodium sulfate-induced ulcerative colitis model in C57BL/6 mice was used to explore the effect of acceptable daily intake (ADI) of aspartame on inflammation in colonic tissues. The effects of aspartame on the inflammatory state of the colon in mice were comprehensively evaluated by comparing the body weight, colon length/colon length index, splenic index, disease activity index (DAI) score, histological activity index (HAI) score, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, claudin-3, and occludin, the infiltration characteristics of macrophage and neutrophil and the composition of the gut microbiota in the control group, aspartame group, ulcerative colitis model group, and aspartame + ulcerative colitis group. We demonstrated that, in a mouse model of dextran sulfate-induced ulcerative colitis, ADI of aspartame caused a significant decrease in body weight, colon length/colon length index, DAI scores, and expression levels of the proteins claudin-3 and occludin. Moreover, ADI of aspartame caused an increase in the splenic index, HAI scores, the levels of proinflammatory factors TNF-α, IL-1β, and IL-6 both in intestinal tissue and serum and infiltration of macrophages and neutrophils in colon tissues. These results showed that ADI of aspartame promoted intestinal pathology and systemic inflammation in a mouse model of colitis.

The Therapeutic Effects of Lactic Acid Bacteria Isolated from Spotted Hyena on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.

Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent episodes and an unclear etiology. Given the limitations of current therapeutic options, which include suboptimal efficacy and significant side effects, there is a pressing need to explore novel treatments. Probiotics derived from diverse species have been identified as a promising approach for managing IBD, owing to their anti-inflammatory properties and their ability to regulate gut flora, among other beneficial effects. In this study, three strains of lactic acid bacteria (LAB) were isolated from the feces of the scavenger spotted hyena (Crocuta crocuta), a scavenging mammal. Based on their capability to survive within and adhere to the gastrointestinal tract, along with their profile of antibiotic resistance, a high-quality strain of Lactobacillus acidophilus (LA) was selected and demonstrated to be safe for mice. Subsequently, the therapeutic efficacy of LA was evaluated using a dextran sulfate sodium (DSS)-induced model of ulcerative colitis in mice. The results indicated that LA restored the disease activity index and improved histopathological lesions in the model group. It also reduced inflammation and oxidative stress and significantly restored the expression of mucins and intestinal tight junction (TJ) proteins (ZO-1, Occludin). Furthermore, LA corrected the DSS-induced disruption of the intestinal flora, leading to a significant decrease in the prevalence of potentially harmful bacterial genera, such as Bacteroides, and an increase in beneficial bacterial genera, including Lactobacillus. In conclusion, Lactobacillus acidophilus LA1, isolated from spotted hyena feces, has potential as a functional supplement for alleviating symptoms of IBD and regulating intestinal flora.

Attenuation by Zhiqiao neohesperidin on dextran sulfate sodium-induced colitis in mice through inhibition of the TLR4/NF-κB pathway

Ulcerative colitis is a chronic inflammatory disease closely associated with immune dysregulation. Zhiqiao (Fructus aurantii), the nearly mature fruit of Citrus aurantium L., is widely used in traditional dietary therapy for intestinal health. Here, we extracted and purified neohesperidin from Zhiqiao and explored its alleviative effects on dextran sulfate sodium-induced colitis and related inflammatory pathways in mice. The results showed that neohesperidin administration significantly ameliorated symptoms of colitis and reduced the accumulation of inflammatory cytokines in mouse tissues and serum. Decreases in the TLR4, MyD88, and NF-κB p65 mRNA expression levels indicated that activity of the TLR4/NF-κB signaling pathway was downregulated. Molecular docking results showed that neohesperidin occupies the lipopolysaccharide-binding pocket of MD-2 and binds to the interacting surface of TLR4/MD-2 and that of the subsequently formed homodimer, thereby disrupting recognition of inflammatory ligands by the TLR4-mediated pathway. Neohesperidin holds promise for the adjunctive treatment of ulcerative colitis.

Staphylea bumalda Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice by Regulating Inflammatory Cytokines, Oxidative Stress, and Maintaining Gut Homeostasis.

Staphylea bumalda is a rare medicine and edible shrub native to the temperate regions of Asia, possessing significant medicinal potential. In this study, the components of S. bumalda tender leaves and buds extract (SBE) were analyzed and identified by HPLC and LC/MS method, and the safety of SBE was evaluated through mouse acute toxicity models. The protective effects of SBE on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were investigated in terms of inflammatory factor levels, oxidative stress, and gut microorganisms. Results showed that hyperoside, kaempferol-3-O-rutinoside, isorhoifolin, and rutin were the main components of the extract, and SBE demonstrated good safety in experimental mice. SBE could alleviate weight losing, disease activity index (DAI) raising, and colon shortening in mice. Pathological section results showed that the inflammatory cell infiltration decreased significantly, and the number of goblet cells increased significantly in the SBE group. After SBE treatment, interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in serum were significantly decreased, and the levels of myeloperoxidase (MPO) and nitric oxide (NO) in colon tissues were significantly decreased. SBE inhibited gut inflammation by increasing Lactobacillus. In summary, SBE played a therapeutic role in UC mice by relieving colon injury, reducing inflammatory factor levels, and maintaining gut flora homeostasis. SBE is expected to become an auxiliary means to participate in the prevention and treatment of UC.

Scutellarein ameliorates dextran sulfate sodium-induced ulcerative colitis by inhibiting colonic epithelial cell proinflammation and barrier disruption.

Scutellarein (Scu) is a natural occurring flavonoid found in multiple traditional Chinese medicines such as Oroxylum indicum (L.) Kurz and Scutellaria baicalensis, with various pharmacological activities including anti-inflammation, anti-oxidation and myocardial protection. Here, we investigated the therapeutic efficacy of Scu on ulcerative colitis (UC) and the underlying mechanism. Efficacy of Scu on UC was evaluated in dextran sulfate sodium (DSS) induced colitis mouse model. Inflammation in colonic tissues was assessed by myeloperoxidase activity assay and RT-qPCR. Barrier proteins expression was examined using immunostaining and Western blot. IL-1β-treated HT-29 cells was used for mechanical investigation. Gavage of Scu significantly decreased the DAI score, improved colon shortening, ameliorated the pathological score in DSS-treated mice with better efficacy than the positive drug, 5-aminosalicylic acid. Scu also inhibited the expression levels of cytokines (Il-1β, Tnf-α, Il-1α, Il-6, and Cxcl1) as well as barrier proteins (E-cadherin, Occludin, and ZO-1) in colon tissues of DSS mice. In intestinal epithelial HT-29 cells, Scu attenuated the IL-1β-downregulated expression levels of E-cadherin, occludin, and ZO-1, while reduced IL-1β-upregulated IL-6 and IL-8 mRNA levels. Moreover, Scu inhibited the phosphorylation and nuclear translocation of NF-κB and suppression of NF-κB phosphorylation abolished IL-1β-disrupted epithelial barrier integrity and IL-1β-upregulated proinflammatory mediators expression in HT-29 cells. These data demonstrate that Scu is an efficacious therapeutic agent to treat UC. Inhibition of inflammatory responses and maintenance of epithelial barrier integrity through NF-κB signaling pathway underlines Scu therapeutic effect on UC.

Phage cocktail inhibits inflammation and protects the integrity of the intestinal barrier in dextran sulfate sodium-induced colitis mice model

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by abdominal pain, diarrhea, and rectal bleeding. This study aims to explore the protective effects of a phage cocktail (108 PFU/mL of Clostridium perfringens phage, 108 PFU/mL of Escherichia coli phage, and 108 PFU/mL of Salmonella phage) on a mouse colitis model induced by dextran sulfate sodium (DSS) and its potential toxic effects on normal mice. The results demonstrate that the phage cocktail significantly alleviates clinical symptoms in mice, reduces colon shortening, weight loss, and colonic pathological damage. Furthermore, the phage cocktail markedly suppresses the inflammatory response and safeguards intestinal barrier integrity in the colonic tissues of the mouse colitis model. Preliminary investigation of the toxic effects of the phage cocktail in mice indicates that continuous administration for 14 days does not yield statistically significant differences in hematological and blood biochemical parameters, and specific pathological changes are absent in histopathological examination results. The aforementioned findings suggest that the phage cocktail exhibits anti-inflammatory and intestinal barrier protective effects in the mouse colitis model, and it does not exert significant toxic side effects on mice.

The reverse transsulfuration pathway affects the colonic microbiota and contributes to colitis in mice

Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen Helicobacter pylori. Herein our aim was to investigate the role of CTH in colonic inflammation. First, we found that CTH is induced in the colon mucosa in mice with dextran sulfate sodium-induced colitis. Expression of CTH was completely absent in the colon of Cth–/– mice. We observed that clinical and histological parameters are ameliorated in Cth-deficient mice compared to wild-type animals. However, Cth deletion had no effect on tumorigenesis and the level of dysplasia in mice treated with azoxymethane-DSS, as a reliable model of colitis-associated carcinogenesis. Mechanistically, we determined that the deletion of the gene Slc7a11 encoding for solute carrier family 7 member 11, the transporter of the anionic form of cysteine, does not affect DSS colitis. Lastly, we found that the richness and diversity of the fecal microbiota were significantly increased in Cth–/– mice compared to both WT and Slc7a11–/– mice. In conclusion, our data suggest that the enzyme CTH represents a target for clinical intervention in patients with inflammatory bowel disease, potentially by beneficially reshaping the composition of the gut microbiota.