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  • Title: Lupeol inhibits LPS-induced NF-kappa B signaling in intestinal epithelial cells and macrophages, and attenuates acute and chronic murine colitis.
    Author: Lee C, Lee JW, Seo JY, Hwang SW, Im JP, Kim JS.
    Journal: Life Sci; 2016 Feb 01; 146():100-8. PubMed ID: 26767626.
    Abstract:
    AIMS: Lupeol, a natural pentacyclic triterpene, exhibits anti-inflammatory effects. However, its role in colitis has not been investigated. In the present study, we evaluated the effect of lupeol on the NF-κB signaling pathway and experimental colitis in mice. MAIN METHODS: The human intestinal epithelial cells (IECs) COLO 205 and the murine macrophages RAW 264.7 were pretreated with lupeol and then stimulated with lipopolysaccharide (LPS). The production of inflammatory cytokines (IL-8 from COLO 205; IL-6, IL-12 and TNF-α from RAW 264.7) was determined by ELISA. The effect of lupeol on NF-κB pathway was examined by Western blot analysis of IκBα phosphorylation/degradation and an electrophoretic mobility shift assay (EMSA). For in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis model and chronic colitis model in IL-10(-/-) mice were used. Colitis was quantified by disease activity index, colon length and histologic evaluation. KEY FINDINGS: Lupeol strongly suppressed pro-inflammatory cytokine production in IECs and murine macrophages. It also inhibited LPS-induced IκBα phosphorylation/degradation and the DNA binding activity of NF-κB. The oral administration of lupeol significantly reduced the colitis activity and histologic scores in both acute and chronic murine colitis models. Furthermore, the up-regulation of IκBα phosphorylation in the colonic mucosa was attenuated in lupeol-treated mice. SIGNIFICANCE: Lupeol blocks the NF-κB signaling in IECs and murine macrophages, and attenuate experimental murine colitis. These findings suggest that lupeol is a potential therapeutic agent for inflammatory bowel disease.
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