Dataset Information

Homoharringtonine Attenuates Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Signaling.

ABSTRACT: Homoharringtonine (HHT) exhibits an anti-inflammatory activity. The potential protective effects and mechanisms of HHT on dextran sulfate sodium- (DSS-) induced colitis were investigated. DSS-induced colitis mice were intraperitoneally injected with HHT. Body weight, colon length, disease activity index (DAI), and histopathological change were examined. The relative contents of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, IL-6, and the chemokine (C-C motif) ligand 2 (CCL2) in the colon tissues and HHT-treated RAW264.7 cells were detected with the enzyme-linked immunosorbent assay. In the meantime, the levels of p-p65 and p-IκBα were detected by Western blot. The proportion of macrophages (CD11b⁺F4/80⁺) in the colon tissues was detected by flow cytometry. HHT alleviated DSS-induced colitis with downregulated TNF-α, IL-1β, IL-6, and CCL2 expression; reduced activation of nuclear factor-kappa B (NF-κB) signaling; and diminished proportion of recruited macrophages in colon tissues. It was further testified that HHT inhibited lipopolysaccharide-induced macrophage activation with reduced activation of NF-κB signaling. In addition, HHT inhibited the M1 polarization of both human and mouse macrophages, while HHT did not affect the differentiation of human CD4 T cells into Th17, Th1, or Treg cells and did not affect the proliferation and migration of human colon epithelial cells. In summary, HHT attenuates DSS-induced colitis by inhibiting macrophage-associated NF-κB activation and M1 polarization, which could be an option for the treatment of ulcerative colitis.

SUBMITTER: Liu J

PROVIDER: S-EPMC9536985 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Homoharringtonine Attenuates Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Signaling.

Liu Jiangrui J Shi Liangpan L Huang Wenchang W Zheng Zhihua Z Huang Xiaohui X Su Yibin Y

Mediators of inflammation 20220929

Homoharringtonine (HHT) exhibits an anti-inflammatory activity. The potential protective effects and mechanisms of HHT on dextran sulfate sodium- (DSS-) induced colitis were investigated. DSS-induced colitis mice were intraperitoneally injected with HHT. Body weight, colon length, disease activity index (DAI), and histopathological change were examined. The relative contents of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, IL-6, and the chemokine (C-C motif) ligand 2 (CCL ...[more]

PMID: 36211988

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Project description:BackgroundInflammatory bowel disease remains a global burden with rapidly increasing incidence and prevalence in both industrialized countries and developing countries. In this study, we prepared pea albumin from pea seeds and determined its beneficial effects being anti-inflammatory and on gut microbiota modulation in dextran sulfate sodium (DSS)-challenged mice.MethodSix-week-old C57BL/6N male mice received an equivalent volume (200 μL) of sterile phosphate balanced solution, 0.375, 0.75, or 1.50 g/kg body weight (BW) of pea albumin that was subjected to 2.0% DSS for 7 days to induce colitis. On day 17 of the experiment, all mice were sacrificed after blood sample collection, and colon tissue and colon contents were collected. BW change curve, colon length, myeloperoxidase (MPO) activity, mucus staining, immunofluorescence staining of T cells and macrophages, cytokines, pro-inflammatory genes expression, nuclear factor-κB (NF-κB) and signal transducer, and activator of transcription 3 (STAT3) signaling pathways as well as 16S DNA sequence were measured.ResultsOur results show that pea albumin alleviates DSS-induced BW loss, colon length shortening, enhanced MPO activity, cytokines secretion, mucus deficiency, and inflammatory cell infiltration, as well as enhanced pro-inflammatory genes expression. In addition, the overactivation of NF-κB and STAT3 following DSS exposure is attenuated by pea albumin administration. Of particular interest, pea albumin oral administration restored gut microbiota dysbiosis as evidenced by enhanced α-diversity, restored β-diversity, and promoted relative abundance of Lactobacillus and Lachnospiraceae_NK4A136_group.ConclusionTaken together, the data provided herein demonstrated that pea albumin plays a protective role in DSS-induced colitis by reducing inflammatory cell infiltration, pro-inflammatory genes expression and pro-inflammatory cytokines release, inactivation of NF-κB signal, and gut microbiota modulation.

Project description:BackgroundHuman defensin-5 (HD-5) is a key antimicrobial peptide which plays an important role in host immune defense, while the short half-life greatly limits its clinical application. The purpose of this study was to investigate the effects of an engineering probiotic producing HD-5 on intestinal barrier and explore its underlying mechanism METHODS: We constructed the pN8148-SHD-5 vector, and transfected this plasmid into Lactococcus lactis (L. lactis) to create the recombinant NZ9000SHD-5 strain, which continuously produces mature HD-5. NZ9000SHD-5 was administrated appropriately in a dextran sodium sulfate (DSS)-induced colitis model. Alterations in the wounded intestine were analyzed by hematoxylin-eosin staining. The changes of intestinal permeability were detected by FITC-dextran permeability test, the tight junction (TJ) proteins ZO-1 and occludin and cytokines were analyzed by western blotting or enzyme linked immunosorbent assay. In Caco-2 cell monolayers, the permeability were analyzed by transepithelial electrical resistance, and the TJ proteins were detected by western blotting and immunofluorescence. In addition, NF-κB signaling pathway was investigated to further analyze the molecular mechanism of NZ9000SHD-5 treatment on inducing intestinal protection in vitro.ResultsWe found oral administration with NZ9000SHD-5 significantly reduced colonic glandular structure destruction and inflammatory cell infiltration, downregulated expression of several inflammation-related molecules and preserved epithelial barrier integrity. The same protective effects were observed in in vitro experiments, and pretreatment of macrophages with NZ9000SHD-5 culture supernatants prior to LPS application significantly reduced the expression of phosphorylated nuclear transcription factor-kappa B (NF-κB) p65 and its inhibitor IκBα.ConclusionsThese results indicate the NZ9000SHD-5 can alleviate DSS-induced mucosal damage by suppressing NF-κB signaling pathway, and NZ9000SHD-5 may be a novel therapeutic means for ulcerative colitis.

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Homoharringtonine Attenuates Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Signaling.

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Homoharringtonine Attenuates Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-<i>κ</i>B Signaling.

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