sepharose and Colitis

Porphyran is known to inhibit immune cell function. Previously, porphyran was shown to prevent lipopolysaccharide-induced sepsis in mice. However, studies on the inhibitory effects of porphyran during colitis are currently lacking. In this study, we evaluated the effects of Pyropia yezoensis-derived porphyran on dextran sodium sulfate (DSS)-induced acute and chronic colitis. The oral or intraperitoneal administration of porphyran inhibited the progression of DSS-induced colitis in mice, with the former also preventing immune cell infiltration in the colon. The levels of intracellular interferon-γ and interleukin-17 in T cells decreased when porphyran was administered orally. Porphyran inhibited T cell activation by suppressing dendritic cells (DCs) and macrophages. Porphyran prevented pathogen-associated molecular pattern and damage-associated molecular pattern-dependent DC and macrophage activation. Finally, porphyran attenuated chronic colitis caused via the long-term administration of DSS. These findings indicate that the oral administration of porphyran can inhibit DSS-induced colitis by suppressing DC and macrophage activation.

Topics: Animals; Colitis; Colon; Dendritic Cells; Dextran Sulfate; Disease Models, Animal; Mice; Mice, Inbred C57BL; Rhodophyta; Sepharose

Agaro- and neoagaro-oligosaccharides with even-numbered sugar units possess a variety of biological activities. However, the effects of the odd-numbered oligosaccharides from Gracilaria agarose (OGAOs) on type 2 diabetes mellitus (T2DM) have not been reported. In this study, we aimed to evaluate the effects of OGAOs on anti-T2DM from different aspects. We found that OGAOs treatment could alleviate oxidative stress, inflammation, and the related hyperglycemia, insulin resistance, lipid accumulation, and obesity in high-fat diet (HFD) induced T2DM. Investigation of the underlying mechanism showed that colitis and colonic microbiota dysbiosis in T2DM mice were ameliorated after OGAOs treatment. First, OGAOs increased the expression of ZO-1, occludin, and AMPK, and suppressed the TLR4/MAPK/NF-κB pathway in colon indicating that OGAOs enhance intestinal integrity and conduct the anti-apoptosis effects to prevent the invasion of toxins and harmful microorganisms. Moreover, the relative abundance of Akkermansia was significantly upregulated in the gut microbiome of T2DM mice associated with a dramatic decrease of the relative abundance of Helicobacter, which are both beneficial for alleviating colitis and T2DM. In addition, Spearman's correlation analysis indicated that changes in the colonic microbiota could regulate oxidative stress, inflammation, and hyperlipidemia. In summary, the underlying mechanism of OGAOs on alleviating colitis and colonic microbiota dysbiosis in T2DM has been intensively studied, illustrating that OGAOs could be further developed as a potential pharmaceutical agent for T2DM.

Topics: Animals; Colitis; Diabetes Mellitus, Type 2; Dysbiosis; Gastrointestinal Microbiome; Gracilaria; Male; Mice; Mice, Inbred C57BL; Oligosaccharides; Sepharose

Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract that affects millions of people worldwide. Although the etiology of IBD is not clear, it is known that products from stressed cells and enteric microbes promote intestinal inflammation. High mobility group box 1 (HMGB1), originally identified as a nuclear DNA binding protein, is a cytokine-like protein mediator implicated in infection, sterile injury, autoimmune disease, and IBD. Elevated levels of HMGB1 have been detected in inflamed human intestinal tissues and in feces of IBD patients and mouse models of colitis. Neutralizing HMGB1 activity by administration of anti-HMGB1 antibodies or HMGB1-specific antagonist improves clinical outcomes in animal models of colitis. Since HMGB1 binds to DNA with high affinity, here we developed a novel strategy to sequester HMGB1 using DNA immobilized on sepharose beads. Screening of DNA-bead constructs revealed that B2 beads, one linear form of DNA conjugated beads, bind HMGB1 with high affinity, capture HMGB1 ex vivo from endotoxin-stimulated RAW 264.7 cell supernatant and from feces of mice with colitis. Oral administration of B2 DNA beads significantly improved body weight, reduced colon injury, and suppressed colonic and circulating cytokine levels in mice with spontaneous colitis (IL-10 knockout) and with dextran sulfate sodium-induced colitis. Thus, DNA beads reduce inflammation by sequestering HMGB1 and may have therapeutic potential for the treatment of IBD.

Topics: Animals; Caco-2 Cells; Colitis; Colon; Cytokines; Feces; HeLa Cells; HMGB1 Protein; Humans; Interleukin-10; Mice; Mice, Inbred C57BL; Mice, Knockout; Microspheres; Sepharose

Agarose is hydrolyzed easily to yield oligosaccharides, designated as agaro-oligosaccharides (AGOs). Recently, it has been demonstrated that AGOs induce heme oxygenase-1 (HO-1) expression in macrophages and that they might lead to anti-inflammatory property. Nevertheless, the molecular mechanism of AGO-mediated HO-1 induction remains unknown, as does AGOs' ability to elicit anti-inflammatory activity in vivo. This study was undertaken to uncover the mechanism of AGO-mediated HO-1 induction and to investigate the therapeutic effect of AGOs on intestinal inflammation.. Mice were treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. The respective degrees of mucosal injury of mice that had received AGO and control mice were compared. We investigated HO-1 expression using Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry. The expression of tumor necrosis factor-α (TNF-α) was measured using qRT-PCR and enzyme-linked immunosorbent assay.. AGO administration induced HO-1 expression in colonic mucosa. The induction was observed mainly in F4/80 positive macrophages. Increased colonic damage and myeloperoxidase activity after TNBS treatment were inhibited by AGO administration. TNBS treatment induced TNF-α expression, and AGO administration suppressed induction. However, HO inhibitor canceled AGO-mediated amelioration of colitis. In RAW264 cells, AGOs enhanced HO-1 expression time-dependently and concentration-dependently and suppressed lipopolysaccharide-induced TNF-α expression. Furthermore, agarotetraose-mediated HO-1 induction required NF-E2-related factor 2 function and phosphorylation of c-jun N-terminal kinase.. We infer that AGO administration inhibits TNBS-induced colitis in mice through HO-1 induction in macrophages. Consequently, oral administration of AGOs might be an important therapeutic strategy for inflammatory bowel disease.

Topics: Animals; Anti-Inflammatory Agents; Blotting, Western; Cell Line; Colitis; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Heme Oxygenase-1; Inflammation; Macrophages; Male; Mice; Mice, Inbred C57BL; Oligosaccharides; Real-Time Polymerase Chain Reaction; Sepharose; Time Factors; Trinitrobenzenesulfonic Acid