Thursday, July 16, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Background and aims: Lupeol, a natural pentacyclic triterpene, is shown to anti-inflammatory effect but its role in colitis has not been investigated. This study evaluated the effect of lupeol on the NF-κB signaling pathways and on experimental colitis.
Methods: The human intestinal epithelial cell (IEC)-line COLO 205, the murine macrophage cell-line RAW264.7 were prepared and subsequently stimulated with lipopolysaccharide (LPS) alone or LPS plus various dose of lupeol. The production of cytokines (IL-8 from COLO 205; TNF-α, IL-6, IL-12 and IL-10 from RAW 264.7) was qualified by ELISA. The effect of lupeol on NF-κB signaling was examined by western blotting and an electrophoretic mobility shift assay (EMSA) to assess the DNA binding activity of NF-κB. In in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis in wild-type mice and chronic colitis in IL-10-/- mice were treated with or without lupeol. Colitis was quantified by histologic scoring, and the phosphorylation of IκBα in the colonic mucosa was assessed using immunohistochemistry.
Results: Lupeol significantly inhibited LPS-induced IκBα phosphorylation, NF-κB binding activity, and pro-inflammatory cytokine production in both IEC and macrophages. The administration of lupeol significantly reduced the severity of colitis, as assessed based on histology in the both murine colitis models. Furthermore, in colon tissue, the up-regulations of IκBα phosphorylation with colitis induction were attenuated in lupeol-treated mice.
Conclusions: Lupeol may block the NF-κB signaling pathways, inhibit the activation of IECs and macrophages, and attenuate experimental murine colitis. These findings suggest that lupeol is a potential therapeutic agent for inflammatory bowel diseases.
Methods: The human intestinal epithelial cell (IEC)-line COLO 205, the murine macrophage cell-line RAW264.7 were prepared and subsequently stimulated with lipopolysaccharide (LPS) alone or LPS plus various dose of lupeol. The production of cytokines (IL-8 from COLO 205; TNF-α, IL-6, IL-12 and IL-10 from RAW 264.7) was qualified by ELISA. The effect of lupeol on NF-κB signaling was examined by western blotting and an electrophoretic mobility shift assay (EMSA) to assess the DNA binding activity of NF-κB. In in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis in wild-type mice and chronic colitis in IL-10-/- mice were treated with or without lupeol. Colitis was quantified by histologic scoring, and the phosphorylation of IκBα in the colonic mucosa was assessed using immunohistochemistry.
Results: Lupeol significantly inhibited LPS-induced IκBα phosphorylation, NF-κB binding activity, and pro-inflammatory cytokine production in both IEC and macrophages. The administration of lupeol significantly reduced the severity of colitis, as assessed based on histology in the both murine colitis models. Furthermore, in colon tissue, the up-regulations of IκBα phosphorylation with colitis induction were attenuated in lupeol-treated mice.
Conclusions: Lupeol may block the NF-κB signaling pathways, inhibit the activation of IECs and macrophages, and attenuate experimental murine colitis. These findings suggest that lupeol is a potential therapeutic agent for inflammatory bowel diseases.