Search Results (237)

Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracaseiL21 (L. paracaseiL21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracaseiL21 decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracaseiL21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-κB signaling while activating HIF1α/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracaseiL21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracaseiL21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies. Full article

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) that has been associated with overconsumption of calories and lipids, compared to the healthy population, and summer temperatures have been reported to be closely related to the prevalence of UC. To evaluate the effects of dietary and lifestyle factors on UC, a combination of 2.0% dextran sulfate sodium (DSS), a high-fat/high-sugar diet, and exposure to high temperature and humidity was used to construct mouse models of UC. Changes in body weight, disease activity index (DAI) scores, histopathological analysis, serum lipid levels, serum diamine oxidase (DAO), and D-Lactate (D-LA) levels, as well as the expression of inflammatory cytokines and tight junction proteins in colonic tissue, were all assessed to study the impacts of the high-fat/high-sugar diet and high-temperature/high-humidity exposure on the progression of UC. The symptoms observed in the UC mouse model induced by 2.0% DSS alone were similar to those seen in patients with UC, while the high-fat and high-sugar diet, along with humid and hot exposure, exacerbated DSS-induced UC in the mice. This included more severe histopathological damage to the colon tissue, increased expression of pro-inflammatory cytokines (IL-6, IL-17A, and IL-1β), and a more significantly compromised intestinal barrier, characterized by the destruction of ZO-1 and elevated levels of DAO and D-LA. Additionally, the high-fat/high-sugar diet and high-temperature/high-humidity exposure led to further disturbances in glucose and lipid metabolism in the mice, which were not observed in those treated with DSS alone. This study is the first to investigate the effects of a high-fat/high-sugar diet and high-temperature/high-humidity exposure on the progression of UC. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease driven by immune dysregulation, microbiota imbalance, and intestinal barrier dysfunction. Despite its global burden, effective therapies remain limited. This study explores the therapeutic potential of Agrocybe cylindracea polysaccharides (ACP) in a dextran sulfate sodium (DSS)-induced murine colitis model. High-performance liquid chromatography (HPLC)-characterized ACP was administered orally to BALB/c mice following colitis induction. ACP treatment significantly reduced Disease Activity Index (DAI) scores, preserved colon length, and restored intestinal barrier integrity by upregulating tight junction proteins. Mechanistically, ACP modulated immune homeostasis, suppressing pro-inflammatory cytokines (IL-17, IL-23, CRP) while enhancing anti-inflammatory mediators (IL-4, TGF-β). Furthermore, ACP inhibited hepatic TLR4/MyD88/NF-κB signaling, attenuated systemic inflammation, and reshaped gut microbiota composition by enriching beneficial taxa and reducing pathogenic Bacteroides. These findings demonstrate ACP multi-target efficacy in colitis, positioning it as a promising natural therapeutic for UC. Full article

Patients with ulcerative colitis exhibit an increased risk for supraventricular arrhythmia during the active disease phase of the disease and show signs of atrial electrophysiological remodeling in remission. The goal of this study was to determine the basis for colitis-induced changes in atrial excitability. In a mouse model (C57BL/6; 3 months) of dextran sulfate sodium (DSS)-induced active colitis (3.5% weight/volume, 7 days), electrocardiograms (ECG) revealed altered atrial electrophysiological properties with a prolonged P-wave duration and PR interval. ECG changes coincided with a decreased atrial conduction velocity in Langendorff perfused hearts. Action potentials (AP) recorded from isolated atrial myocytes displayed an attenuated maximal upstroke velocity and amplitude during active colitis, as well as a prolonged AP duration (APD). Voltage clamp analysis revealed a colitis-induced shift in the voltage-dependent activation of the Na-current (I_Na) to more depolarizing voltages. In addition, protein levels of Na_v1.5 protein and connexin isoform Cx43 were reduced. APD prolongation depended on a reduction in the transient outward K-current (I_to) mostly generated by K_v4.2 channels. The changes in ECG, atrial conductance, and APD were reversible upon remission. The change in conduction velocity predominantly depended on the reversibility of the reduced Cx43 and Na_v1.5 expression. Treatment of mice with inhibitors of Angiotensin-converting enzyme (ACE) or Angiotensin II (AngII) receptor type 1 (AT1R) prevented the colitis-induced atrial electrophysiological remodeling. Our data support a colitis-induced increase in AngII signaling that promotes atrial electrophysiological remodeling and puts colitis patients at an increased risk for atrial arrhythmia. Full article

This study investigated the therapeutic potential of Bacillus thuringiensis extracellular polysaccharide BPS-2 in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) murine models. BPS-2 demonstrated significant efficacy in ameliorating UC-associated pathologies through three principal mechanisms: (1) attenuating histopathological damage while preserving colon epithelial integrity, (2) modulating immune marker expression patterns in colon tissues, and (3) restoring gut microbiota homeostasis. BPS-2 exhibited multi-faceted protective effects on the gut by mitigating oxidative stress responses and enhancing short-chain fatty acid biosynthesis, leading to an improved gut microbial community structure. Molecular docking analysis displayed strong binding affinity (ΔG = −7.8 kcal/mol) between the BPS-2U fragment and the Nuclear Factor κB (NF-κB) p50/p65 heterodimer, suggesting the potential disruption of NF-κB signaling pathways. Complementary molecular dynamics simulations revealed exceptional conformational stability in the p65-BPS-2U complex. These findings establish BPS-2 as a natural food additive that modulates the microbiota-barrier–inflammation axis through dietary intervention, offering a novel strategy to alleviate UC. Full article

Ulcerative colitis (UC) is a multifactorial disorder, and conventional oral berberine (BBR) suffers from poor colonic targeting. This study aimed to develop a colon-targeted microparticle system (BBR-ES MPs) based on chitosan (CS) and Eudragit S-100 to enhance BBR delivery efficiency and therapeutic efficacy in UC. Methods: BBR-CS nanocarriers were prepared via ionotropic gelation and coated with Eudragit S-100 to form pH/enzyme dual-responsive MPs. Colon-targeting performance was validated through in vitro release assays. SPF-grade male KM mice (Ethics Approval No.: JMSU-2021090301) with dextran sulfate sodium (DSS)-induced UC were divided into normal, model, BBR, and BBR-ES MPs groups. Therapeutic outcomes were evaluated by monitoring body weight, disease activity index (DAI), colon length, histopathology, inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10), and myeloperoxidase (MPO) activity via ELISA. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Results: BBR-ES MP treatment significantly reduced DAI scores (p < 0.01), restored colon length, downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α; p < 0.05), and upregulated anti-inflammatory IL-10. Microbiota analysis revealed that the Bacteroidetes/Firmicutes ratio, which decreased in the model group, was restored post-treatment, with alpha/beta diversity approaching normal levels. BBR-ES MPs outperformed free BBR at equivalent doses. Conclusion: BBR-ES MPs achieved colon-targeted drug delivery via pH/enzyme dual-responsive mechanisms, effectively alleviating UC inflammation and modulating gut dysbiosis, offering a safe and precise therapeutic strategy for UC management. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) associated with recurrent inflammation and ulceration of the colonic mucosa. Conventional treatments, including corticosteroids, have significant side effects, driving the need for safer, effective alternatives. The present study aimed to investigate the mitigating effects of Epilobium angustifolium extract (EAE) in a Dextran sulfate sodium (DSS)-induced colitis mouse model, in a comparative manner to the reference drug dexamethasone (DXM). The severity and progression of colitis were evaluated through disease activity indices and a range of inflammatory and oxidative stress markers, assessed using multiple analytical methods. EAE treatment significantly reduced colonic inflammation, as indicated by decreased myeloperoxidase (MPO) activity, lower levels of malondialdehyde (MDA), and reduced white blood cell counts. EAE also enhanced antioxidant defenses, increasing glutathione (GSH) levels by 64%, and boosting catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities by 36%, 53%, and 70%, respectively. Histopathological analysis confirmed EAE’s efficacy in attenuating colonic injury and inflammation. The blood parameters hemoglobin, erythrocytes, and hematocrit were also improved. Our study shows that EAE has potential as a natural therapeutic candidate for the treatment of UC, demonstrating efficacy comparable to that of conventional pharmacological treatments. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with unmet therapeutic needs. This study investigates the therapeutic potential of Periplaneta americana L. extract (PAE) and its molecular mechanisms, integrating network pharmacology and experimental validation. Liquid chromatography–mass spectrometry identified 1355 compounds in PAE. Network pharmacology analysis revealed that inosine, vidarabine, and adenosine 5′-monophosphate (AMP) were core components and the core components synergistically regulated key targets and acted on inflammation-related pathways, thereby establishing a multi-target anti-inflammatory regulatory network. In vivo experiments demonstrated that these compounds significantly alleviated colitis symptoms in dextran sulfate sodium-induced mice, as evidenced by reduced disease activity index scores, preserved colonic mucosal architecture, and decreased inflammatory infiltration. Mechanistically, core compounds down-regulated granulocyte-macrophage colony-stimulating factor (GM-CSF), inducible nitric oxide synthase (iNOS)/NOS2, monocyte chemoattractant protein 1 (MCP-1), and transforming growth factor beta 1 (TGF-β1), while they up-regulated interleukin-10 (IL-10) and epidermal growth factor (EGF). Additionally, they activated epidermal growth factor receptor (EGFR)-mediated pathways. Molecular docking analysis revealed that adenosine analogs preferentially bound to A1/A2a receptors, triggering signaling cascades essential for epithelial repair and inflammation resolution. This study established the multi-component, multi-pathway mechanism of PAE in UC, highlighting its dual role in suppressing inflammation and promoting mucosal healing. By bridging traditional herbal use with modern molecular insights, these findings provided a translational foundation for developing PAE-based therapies for UC. Full article

Ulcerative colitis (UC) is the most prevalent inflammatory bowel disease (IBD) in the USA. Current treatments present clinical limitations, underscoring the need for innovative therapeutics that promote an anti-inflammatory immune response. This study evaluates the anti-inflammatory potential of Fh15, a recombinant Fasciola hepatica fatty acid binding protein, in a DSS-induced UC mouse model. Our results demonstrated that Fh15 treatment significantly ameliorated the severity of colitis by reducing the disease activity index (DAI) and histopathological scores. Moreover, Fh15 also decreased the serum levels of myeloperoxidase (MPO) and chitinase-3-like protein 1 (CHI3L1), and the expression of S100A9, a calcium and zinc binding protein, which is an important marker for the pathogenesis of UC. Furthermore, Fh15 downregulated pro-inflammatory cytokines TNFα and IL-1β in the distal colon, suggesting modulation of macrophage activity. Immunohistochemistry analysis revealed significantly reduced neutrophil and macrophage infiltration in UC Fh15-treated mice. These findings highlight the therapeutic potential of Fh15 for UC, as it modulates inflammatory responses, reduces leukocyte infiltration, and preserves colon integrity. Full article

In this study, large yellow croaker (Pseudosciaena crocea) protein isolates/gellan gum (PG) binary hydrogels with dense microstructure were used for embedding and delivery curcumin (Cur). The colitis-relieving effects of PG-Cur were further investigated using the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model. Following PG-Cur treatment, weight loss, diarrhea, and shortening of the colon were significantly alleviated. Compared with the free Cur group, weight loss and colon length in the PG-Cur group increased about 1.05- and 1.12-fold. IL-1β, IL-6, TNF-α, and IL-10 levels in PG-Cur group were not significantly different from those of the normal mice, and the MPO and iNOS activities of the PG-Cur group were 29% and 20% lower than those in the Cur group, respectively. Moreover, fecal microbiota analysis of mice revealed that PG-Cur effectively restored gut dysbiosis in DSS-induced colitis, enriching beneficial bacteria while reducing harmful ones. Overall, the PG hydrogels have the potential to serve as carriers for oral curcumin formulations aimed at alleviating UC. Full article

The pathogenesis of ulcerative colitis (UC) involves genetic, immunological, and environmental factors as well as gut microbiota dysbiosis. As a natural antioxidant with various pharmacological activities widely present in Oleaceae plants, oleuropein (OLE) exhibits anti-inflammatory, anti-tumor, antiviral, hypoglycemic, and cardioprotective effects. It has been validated that OLE extracted from olive oil can ameliorate UC. However, it remains unclear if and how OLE modulates the gut microbiota in the alleviation of UC. Therefore, this study was conducted to explore the mechanisms for OLE to alleviate UC induced by dextran sulfate sodium (DSS), with the focus placed on its regulatory function in the gut microbiota. The results indicated that OLE mitigated DSS-induced UC by enhancing the intestinal barrier function, reshaping the gut microbiota, and modulating bile acid metabolism. The fecal microbiota transplantation (FMT) experiment results further confirmed that the protective effect of OLE against UC could be mediated by alterations in the gut microbiota and their metabolites induced by OLE. Additionally, OLE increased the abundance of Lactobacillus and certain bile acid metabolites in the colon, including hyodeoxycholic acid (HDCA). HDCA could upregulate the expression of ZO-1 and claudin-3, restoring intestinal barrier integrity. Simultaneously, HDCA could inhibit the activation of the nuclear factor kappa-B (NF-κB) signaling pathway in the colon and relieve colonic inflammation. Overall, it was corroborated that OLE alleviated DSS-induced UC by modulating the gut microbiota and altering bile acid metabolism. Full article

The pathogenesis of inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease, remains incompletely understood. Amomum villosum Lour. (Zingiberaceae) is a traditional herbal medicine used across Asia to treat digestive and inflammatory disorders. This study investigated the therapeutic effects of a water extract derived from the fruits of AV (referred to as AVE) in a mouse model of colitis induced by dextran sulfate sodium (DSS). The protective effects of AVE were evaluated by monitoring changes in body weight and colon length, as well as histological and molecular markers of inflammation. Neutrophil infiltration and levels of inflammatory cytokines in colon tissue and serum were assessed, and the integrity of the intestinal epithelial barrier was examined via Western blot analysis. Treatment with AVE significantly alleviated DSS-induced colitis, as evidenced by improved body weight, longer colon length, and reduced inflammatory responses. AVE administration restored tight junction protein expression (zonula occludens-1 [ZO-1] and occludin), suppressed phosphorylation of mitogen-activated protein kinases—specifically, extracellular signal-regulated kinase (ERK) and p38—and inhibited the expression of inflammatory mediators including tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-1β, and myeloperoxidase (MPO) activity. These findings suggest that oral AVE treatment effectively protects against experimental colitis by modulating inflammatory signaling and preserving epithelial barrier integrity. Further studies are warranted to explore the clinical potential and safety of AVE in the management of IBD. Full article

Background/Objectives: Indigo naturalis (IN) is a traditional Chinese medicine concocted from medicinal plants such as Baphicacanthus cusia (Nees) Bremek. IN has multifaceted pharmacological activities. Recent research highlights the remarkable efficacy of IN in treating ulcerative colitis (UC). This study investigates the efficacy of Indigo Naturalis prepared using a novel method (NIN) in ameliorating UC. Methods: We have developed a new IN processing technology without the use of lime. Correspondingly, the content of active ingredients has relatively increased in NIN. In this study, dextran sulfate sodium salt (DSS) induced UC models among male KM mice, and the protective effects of NIN on UC were verified. Results: NIN could significantly improve weight loss, diarrhea and prolapse, bloody stools, elevated Disease Activity Index (DAI) and alleviate the colitis symptoms of mice; it could also improve the shortening of colon, disappearance of intestinal crypts, epithelial cell destruction and inflammatory infiltration caused by UC; and it could also significantly reduce the Histological Index (HI). In addition, NIN relieved the inflammatory response by decreasing the content of pro-inflammatory cytokines TNF-α and IL-1β and elevating the content of anti-inflammatory cytokines IL-10 and IL-22. It also restored the intestinal mucosal barrier by increasing the level of MUC2 protein expression at the site of colonic injury. Conclusions: The significant effects of NIN on UC were verified for the first time, suggesting that NIN was worth further developing into a novel therapeutic drug and, necessarily, further safety evaluations and comparisons with traditional IN will help in the application of NIN. Full article

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is characterized by chronic intestinal inflammation and epithelial barrier disruption. Emerging evidence highlights mitochondrial dysfunction as a pivotal contributor to IBD pathogenesis, where impaired mitochondrial homeostasis in intestinal epithelial cells (IECs) disrupts redox balance, exacerbates oxidative stress, and triggers apoptosis, further compromising barrier integrity. This study investigated the therapeutic effects of Engeletin (Eng), a dihydroflavonoid from Smilax glabra Roxb., in dextran sulfate sodium (DSS)-induced colitis mice and colonic organoid models. Eng administration (10, 20, 40 mg/kg) significantly alleviated colitis symptoms, including weight loss, disease activity index (DAI) scores, and colon shortening, while restoring intestinal barrier integrity through the upregulation of tight junction proteins (ZO-1, claudin-1) and goblet cell preservation. Eng suppressed NF-κB-mediated inflammation and activated the Nrf2 antioxidant pathway, as well as reduced oxidative stress markers (MDA, CAT, GSH, and SOD). It attenuated epithelial apoptosis by balancing pro- and anti-apoptotic proteins (Bax/Bcl2, c-caspase3) and ameliorated mitochondrial dysfunction via enhanced ATP production, mtDNA levels, and complex I/IV activity. Mechanistically, Eng activated the AMPK/SIRT1/PGC-1α axis, and pharmacological inhibition of PGC-1α abolished its mitochondrial protective and anti-apoptotic effects. These findings demonstrate that Eng alleviates colitis by targeting mitochondrial homeostasis and oxidative stress through AMPK/SIRT1/PGC-1α signaling, offering a multitargeted strategy for IBD therapy. Full article

Ulcerative colitis (UC) is characterized clinically by intestinal inflammation and gut microbiota dysbiosis. The consumption of biologics, although effective in inflammation control, may lead to adverse effects and is inconvenient for at-home administration. Goat milk-derived extracellular vesicles (GMEVs) have been proposed as a supplement to prevent intestinal inflammation. However, their therapeutic potential for colitis remains elusive. This study aimed to explore the preventive effect of GMEVs on colitis and its underlying mechanisms through the microbiota-immune axis using a dextran sodium sulfate (DSS)-induced colitis mouse model. We found that a pre-treatment of 20 mg/kg/d GMEVs effectively prevented body weight loss, colon shortening, the depletion of colonic goblet cells, and the disappearance of crypts, while enhancing the intestinal mucosal barrier. Consistent with these phenotypes, GMEV pre-treatment increased levels of IL-22 and IL-10 and decreased levels of IL-1β, TNF-α, IL-6, and iNOS. However, GMEVs themselves had no effect on normal mice. Paralleling the alleviation of intestinal inflammation, GMEV pre-treatment also restored the reduction in unclassified Muribaculaceae, Dubosiella, and Lactobacillus and suppressed the expansion of Alistipes and Proteobacteria following DSS treatment. Additionally, GMEV intake significantly downregulated the expression of proteins in the NF-κB signaling pathway induced by DSS. In summary, GMEVs could prevent colitis by regulating intestinal inflammation, the intestinal mucosal barrier, gut microbiota, organ damage, and the immune microenvironment. This study demonstrated that GMEVs have potential application prospects for UC prevention. Full article