Psoralen alleviates ulcerative colitis by suppressing inflammation, modulating oxidative stress, and regulating ferroptosis.

IntroductionInflammatory bowel disease (IBD), including ulcerative colitis (UC), is characterized by disturbances in the intestinal barrier, immune system dysfunction, and an altered gut microbiota composition. Lyophyllum decastes, a medicinal mushroom known for its bioactive polysaccharides, has shown potential anti-inflammatory properties. However, its therapeutic effects on ulcerative colitis have not been studied. This study investigates the effects of L. decastes polysaccharides (LDP) on dextran sulfate sodium (DSS)-induced colitis in mice.MethodsUlcerative colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days. Mice were then treated orally with LDP at doses of 200 or 400 mg/kg for 14 days. Disease activity index (DAI), histopathological analysis, cytokine levels, myeloperoxidase (MPO) activity, tight junction protein expression (occludin and ZO-1), and gut microbiota composition were assessed.Results and discussionLDP treatment significantly reduced DAI scores and preserved colonic histological structure. It modulated cytokine levels, decreasing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and increasing anti-inflammatory cytokines (IL-10, IL-4, TGF-β). Additionally, LDP improved intestinal barrier function by reducing MPO activity and enhancing occludin and ZO-1 expression. 16S rRNA sequencing revealed a significant restoration of gut microbiota diversity, with an increase in beneficial bacteria Muribaculaceae, Lactobacillus, and Lachnospiraceae, and a reduction in pathogenic bacteria Escherichia-Shigella. these findings suggest that LDP exhibits therapeutic effects in DSS-induced colitis through anti-inflammatory properties, enhancement of intestinal barrier function, and modulation of gut microbiota. These findings suggest that LDP may serve as a promising novel therapeutic agent for the management of ulcerative colitis.

Ulcerative colitis (UC) has been identified as one of the inflammatory diseases. Intestinal mucosal barrier function and microflora play major roles in UC. Modified-chitosan products have been consumed as effective and safe drugs to treat UC. The present work aimed to investigate the effect of chitosan (CS) on intestinal microflora and intestinal barrier function in dextran sulfate sodium (DSS)-induced UC mice and to explore the underlying mechanisms. KM (Kunming) mice received water/CS (250, 150 mg/kg) for 5 days, and then received 3% DSS for 5 days to induce UC. Subsequently, CS (250, 150 mg/kg) was administered daily for 5 days. Clinical signs, body weight, colon length, and histological changes were recorded. Alterations of intestinal microflora were analyzed by PCR-DGGE, expressions of TNF-α and tight junction proteins were detected by Western blotting. CS showed a significant effect against UC by the increased body weight and colon length, decreased DAI (disease activity index) and histological injury scores, and alleviated histopathological changes. CS reduced the expression of TNF-α, promoted the expressions of tight junction proteins such as claudin-1, occludin, and ZO-1 to maintain the intestinal mucosal barrier function for attenuating UC in mice. Furthermore, Parabacteroides, Blautia, Lactobacillus, and Prevotella were dominant organisms in the intestinal tract. Blautia and Lactobacillus decreased with DSS treatment, but increased obviously with CS treatment. This is the first time that the effect of original CS against UC in mice has been reported and it is through promoting dominant intestinal microflora such as Blautia, mitigating intestinal microflora dysbiosis, and regulating the expressions of TNF-α, claudin-1, occludin, and ZO-1. CS can be developed as an effective food and health care product for the prevention and treatment of UC.

Probiotic Bacteria Induce Maturation of Intestinal Claudin 3 Expression and Barrier Function

What is the central question of this study? Oxidative stress may play a role in compromising intestinal epithelial barrier integrity in pigs subjected to heat stress, but it is unknown whether an increase of dietary antioxidants (selenium and vitamin E) could alleviate gut leakiness in heat-stressed pigs. What is the main finding and its importance? Levels of dietary selenium (1.0p.p.m.) and vitamin E (200IUkg(-1) ) greater than those usually recommended for pigs reduced intestinal leakiness caused by heat stress. This finding suggests that oxidative stress plays a role in compromising intestinal epithelial barrier integrity in heat-stressed pigs and also provides a nutritional strategy for mitigating these effects. Heat stress compromises the intestinal epithelial barrier integrity of mammals through mechanisms that may include oxidative stress. Our objective was to test whether dietary supplementation with antioxidants, selenium (Se) and vitaminE (VE), protects intestinal epithelial barrier integrity in heat-stressed pigs. Female growing pigs (n = 48) were randomly assigned to four diets containing from 0.2p.p.m. Se and 17 IUkg(-1) VE (control, National Research Council recommended) to 1.0p.p.m. Se and 200 IU kg(-1) VE for 14days. Six pigs from each dietary treatment were then exposed to either thermoneutral (20°C) or heat-stress conditions (35°C 09.00-17.00h and 28°C overnight) for 2days. Transepithelial electrical resistance and fluorescein isothiocyanate-dextran (4kDa; FD4) permeability were measured in isolated jejunum and ileum using Ussing chambers. Rectal temperature, respiratory rate and intestinal HSP70 mRNA abundance increased (all P <0.001), and respiratory alkalosis occurred, suggesting that pigs were heat stressed. Heat stress also increased FD4 permeability and decreased transepithelial electrical resistance (both P<0.01). These changes were associated with changes indicative of oxidative stress, a decreased glutathione peroxidase (GPX) activity and an increased glutathione disulfide (GSSG)-to-glutathione (GSH) ratio (both P<0.05). With increasing dosage of Se and VE, GPX-2 mRNA (P = 0.003) and GPX activity (P = 0.049) increased linearly, the GSSG:GSH ratio decreased linearly (P = 0.037), and the impacts of heat stress on intestinal barrier function were reduced (P<0.05 for both transepithelial electrical resistance and FD4 permeability). In conclusion, in pigs an increase of dietary Se and VE mitigated the impacts of heat stress on intestinal barrier integrity, associated with a reduction in oxidative stress.

Inflammatory bowel disease (IBD), including ulcerative colitis, is marked by intestinal barrier disruptions, immune system dysregulation, and an imbalance in the gut microbiota. The golden chanterelle mushroom, Cantharellus cibarius Fr., a popular edible mushroom, has shown potential therapeutic benefits. This study examines the therapeutic potential of a crude polysaccharide extract obtained from C. cibarius Fr. (CCP) on intestinal barrier integrity, inflammatory cytokine levels, and gut microbiota composition in a murine model of colitis induced by dextran sulfate sodium (DSS). To induce colitis BALB/c mice were provided to consume autoclaved water with 3% DSS for 7days, followed by 14days of CCP supplementation. To assess the effects of CCP, histological analysis of colon tissue was performed, gene expression, inflammatory responses, tight junction proteins expression, gut barrier integrity, and cytokines levels were measured and analyzed and 16S rRNA sequencing were evaluated. CCP treatment alleviates colitis symptoms by improving body weight, and enhancing intestinal integrity through increased mucin-2 and tight junction protein expression. Additionally, CCP administration regulates the altered immune response by mitigating the expression of pro-inflammatory cytokines and upregulating anti-inflammatory cytokines. Furthermore, CCP supplementation effectively modulates DSS-induced dysbiosis as demonstrated by 16S rRNA sequencing results. These findings suggest that crude polysaccharides from the golden chanterelle mushroom, C. cibarius Fr., hold promise for treating colitis, via strengthening the intestinal barrier, regulating inflammatory responses, and reshaping the gut dysbiosis in a DSS-induced colitis model. CCP offers a novel approach for managing colitis, as a chronic inflammatory condition.

This study employed 16S r RNA gene high-throughput sequencing and metabolomics to explore the mechanism of Angelicae Dahuricae Radix polysaccharides(RP) in the treatment of ulcerative colitis(UC). A mouse model of UC was induced with 2. 5% dextran sulfate sodium. The therapeutic effects of RP on UC in mice were evaluated based on changes in body weight, disease activity index( DAI), and colon length, as well as pathological changes. RT-qPCR was performed to assess the m RNA levels of interleukin(IL)-6, IL-1β, tumor necrosis factor(TNF)-α, myeloperoxidase(MPO), mucin 2(Muc2), Occludin, Claudin2, and ZO-1 in the mouse colon tissue. ELISA was employed to measure the expression of IL-1β and TNF-α in the colon tissue. The intestinal permeability of mice was evaluated by the fluorescent dye permeability assay. Immunohistochemistry was employed to detect the expression of Muc2 and occludin in the colon tissue. Changes in gut microbiota and metabolites were analyzed by 16S r RNA sequencing and ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry( UPLC-Q-Exactive Plus Orbitrap MS), respectively. The results indicated that low-dose RP alleviated general symptoms, reduced colonic inflammation and intestinal permeability, and promoted Muc2 secretion and tight junction protein expression in UC mice. In addition, low-dose RP increased gut microbiota diversity in UC mice and decreased the relative abundance of harmful bacteria such as Ochrobactrum and Streptococcus. Twenty-seven differential metabolites were identified in feces, and low-dose RP restored the levels of disturbed metabolites. Notably, arginine and proline metabolism were the most significantly altered amino acid metabolic pathways following lowdose RP intervention. In conclusion, RP can ameliorate general symptoms, inhibit colonic inflammation, and maintain intestinal mucosal barrier integrity in UC mice by modulating gut microbiota composition and arginine and proline metabolism.

Painong-San extract alleviates dextran sulfate sodium-induced colitis in mice by modulating gut microbiota, restoring intestinal barrier function and attenuating TLR4/NF-κB signaling cascades

Here, we systematically evaluated the therapeutic efficacy and mechanisms of action of in-house synthesized hydroxyethyl starch-curcumin nanoparticles (HES-CUR NPs) in ulcerative colitis (UC). Using a dextran sodium sulfate (DSS)-induced UC mouse model, we analyzed the effect of HES-CUR NPs on colonic tissue and the gut microbiota through the assessment of organ indices and serum biochemical markers, histopathology, immunohistochemistry, Western blot, and 16S rRNA sequencing. We found that HES-CUR NPs significantly suppressed the TLR4/NF-κB inflammatory pathway (downregulated TLR4, p-IKKβ, IL-1β, IL-6, NFKB, MyD88, and p-IKKB/IKKB; p < 0.01), activated the Nrf2/HO-1 antioxidant pathway (enhanced Nrf2 nuclear translocation and HO-1 expression), and upregulated the expression of tight junction proteins (claudin-1, occludin, ZO-1), thereby restoring intestinal barrier integrity. Microbiota analysis revealed that HES-CUR NPs increased gut microbiota diversity (elevated Chao1, Shannon, and ACE indices) and enriched beneficial bacteria abundance (Ligilactobacillus murinus, Lactobacillus johnsonii). Antibiotic intervention partially attenuated the therapeutic effects of the HES-CUR NPs, confirming that their effects involved microbiota-dependent mechanisms. Compared to CUR and SASP, HES-CUR NPs exhibited significantly enhanced bioavailability and efficacy (p < 0.01), attributed to the targeted delivery and sustained-release properties of the hydroxyethyl starch nanocarrier. No toxicity was observed, as indicated by normal spleen, liver, and thymus indices and stable levels of TP, ALT, AST, ALB, GLB, and ALB/GLB. Our findings indicated that HES-CUR alleviates UC through a synergistic, multi-target mechanism involving inflammatory pathway suppression, antioxidant pathway activation, intestinal barrier repair, and microbiota modulation, providing a theoretical foundation for developing efficient and safe natural nanomedicines targeting UC.

Ulcerative colitis (UC) is a multifactorial inflammatory bowel disease associated with intestinal barrier integrity, gut microbiota, and immune homeostasis. According to previous studies, ginsenoside Rk2 (Rk2) demonstrated anti-inflammatory activity in cocultures of Caco-2 and THP-1 cells. This study was the first to demonstrate that Rk2 positively impacted UC by regulating the "barrier-microbiota-immune" axis. Rk2 not only improved inflammatory factor levels and colitis symptoms but also enhanced intestinal epithelial barrier function via increased transepithelial electrical resistance (TEER) values and elevated expressions of tight junction proteins, remodeled gut microbiota via enriching its diversity and composition and increasing short-chain fatty acids (SCFAs) levels, and maintained intestinal homeostasis via restoring Th17/Treg balance. Moreover, the influence of Rk2 on UC might be mediated via the TNFSF14/LTβR/NIK pathway. In summary, Rk2 exerted a beneficial effect on UC by providing multidimensional regulation and was a potential natural therapeutic agent for UC.

When specific gut microbes reveal a possible link between hepatic steatosis and adipose tissue

Background/Objectives: Ulcerative colitis (UC) incidence has risen alarmingly worldwide, posing significant clinical challenges due to limitations of therapeutic efficacy and side effects of current drugs. While Polygonatum kingianum polysaccharides (PKPs) exhibit anti-inflammatory and antioxidant properties, their anti-colitis potential remains unexplored. This study aimed to validate the protective effects of PKPs against dextran sulfate sodium (DSS)-induced colitis and elucidate its mechanisms. Methods: Acute UC was induced in C57BL/6J mice by 3% DSS. PKPs (125 mg/kg) were administered via gavage for 10 days. Integrated approaches included histopathology, tight junction protein (ZO-1/Occludin/Claudin-1) immunohistochemistry, inflammatory/oxidative markers (ELISA), Nrf2 pathway proteins (Western blot), 16S rRNA gut microbiota sequencing, fecal untargeted metabolomics (UHPLC-MS), short-chain fatty acids (SCFAs) analysis and combined analysis. Results: PKPs significantly alleviated colitis phenotypes: reduced weight loss, lowered disease activity index (DAI), and attenuated colon shortening. They restored intestinal barrier integrity by upregulating tight junction proteins and reducing plasma Diamine Oxidase (DAO)/D-lactate (D-Lac)/Endotoxin (ET). PKPs suppressed pro-inflammatory cytokines (TNF-α/IL-1β/IL-6) while elevating IL-10, activated the Nrf2/HO-1/NQO1 antioxidant pathway, and reduced oxidative stress (MDA decreased, SOD/GSH increased). Multi-omics revealed PKPs enriched beneficial bacteria (Blautia, Odoribacter, Rikenellaceae_RC9_gut_group), restored SCFAs (acetate/propionate/butyrate), and modulated metabolic pathways (sphingolipid/linoleic acid metabolism). Conclusions: PKPs ameliorate DSS-induced colitis through multi-target mechanisms: (1) preserving intestinal barrier function, (2) suppressing inflammation and oxidative stress via Nrf2 activation, (3) restoring gut microbiota balance and SCFA production, and (4) regulating host-microbiota metabolic interactions. These findings support PKPs as a promising dietary supplement for UC management.

Pulsatilla decoction improves DSS-induced colitis via modulation of fecal-bacteria-related short-chain fatty acids and intestinal barrier integrity

Intestinal epithelial barrier dysfunction is deeply involved in the pathogenesis of inflammatory bowel diseases (IBD). Arctigenin, the main active constituent in Fructus Arctii (a traditional Chinese medicine), has previously been found to attenuate colitis induced by dextran sulfate sodium (DSS) in mice. The present study investigated whether and how arctigenin protects against the disruption of the intestinal epithelial barrier in IBD. Arctigenin maintained the intestinal epithelial barrier function of mice with DSS- and TNBS-induced colitis. In Caco-2 and HT-29 cells, arctigenin lowered the monolayer permeability, increased TEER, reversed the abnormal expression of tight junction proteins, and restored the altered localization of F-actin induced by TNF-α and IL-1β. The specific antagonist PHTPP or shRNA of ERβ largely weakened the protective effect of arctigenin on the epithelial barrier function of Caco-2 and HT-29 cells. Molecular docking demonstrated that arctigenin had high affinity for ERβ mainly through hydrogen bonds as well as hydrophobic effects, and the protective effect of arctigenin on the intestinal barrier function was largely diminished in ERβ-mutated (ARG346 and/or GLU305) Caco-2 cells. Moreover, arctigenin-blocked TNF-α induced increase of the monolayer permeability in Caco-2 and HT-29 cells and the activation of myosin light chain kinase (MLCK)/myosin light chain (MLC) pathway in an ERβ-dependent manner. ERβ deletion in colons of mice with DSS-induced colitis resulted in a significant attenuation of the protective effect of arctigenin on the barrier integrity and colon inflammation. Arctigenin maintained the integrity of the intestinal epithelial barrier under IBD by upregulating the expression of tight junction proteins through the ERβ-MLCK/MLC pathway.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), and its pathogenesis is related to intestinal mucosal barrier damage and gut microbiota imbalance. Protopine (PRO), an isoquinoline alkaloid, is one of the main anti-inflammatory ingredients of traditional Chinese medicine Macleaya cordata (Willd.) R. Br. This study investigated the effects of PRO on the intestinal mucosal barrier and gut microbiota in dextran sodium sulfate (DSS)-induced colitis mice. C57BL/6J mice were treated with 3% DSS in drinking water to induce acute colitis, while PRO was administered orally once daily for 7 days. The results showed that PRO administration significantly alleviated the symptoms of DSS-induced colitis in mice and inhibited the expression of inflammation-related genes. In addition, PRO restored the integrity of the intestinal barrier in colitis mice by restoring colonic mucin secretion and promoting the expression of tight junction proteins. Furthermore, PRO alleviated the DSS-induced gut microbiota dysbiosis by decreasing the abundance of Proteobacteria, Escherichia-Shigella and Enterococcus, as well as enhancing the abundance of beneficial bacteria, such as Firmicutes and Akkermansia. These findings suggested that PRO effectively alleviated DSS-induced ulcerative colitis by suppressing the expression of inflammation-related genes, maintaining the intestinal mucosal barrier and regulating the intestinal microbiota.

Mulberry leaf benefits the intestinal epithelial barrier via direct anti-oxidation and indirect modulation of microbiota in pigs