Journal
LIFE SCIENCES
Volume 146, Issue -, Pages 100-108Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2016.01.001
Keywords
Lupeol; Pentacyclic triterpenes; NF-kappa B; Inflammatory bowel diseases; Mice
Funding
- SK Telecom Research Fund through Seoul National University Hospital [34-2014-0230]
- National Research Foundation of Korea (NRF) - Korea government (MSIP) [NRF-2015R1A2A2A04002733]
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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-kappa B 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-alpha from RAW 264.7) was determined by ELISA. The effect of lupeol on NF-kappa B pathway was examined by Western blot analysis of I kappa B alpha 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 I kappa B alpha phosphorylation/degradation and the DNA binding activity of NF-kappa B. 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 I kappa B alpha phosphorylation in the colonic mucosa was attenuated in lupeol-treated mice. Significance: Lupeol blocks the NF-kappa B 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. (C) 2016 Elsevier Inc. All rights reserved.
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