Plant sterol guggulsterone inhibits nuclear factor-κB signaling in intestinal epithelial cells by blocking IκB kinase and ameliorates acute murine colitis
Plant sterol guggulsterone inhibits nuclear factor-κB signaling in intestinal epithelial cells by blocking IκB kinase and ameliorates acute murine colitis
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DOI：
10.1097/01.mib.0000235830.94057.c6
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发表时间：
2006-12-01
影响因子：
4.9
通讯作者：
Song, In Sung
中科院分区：
文献类型：
--
作者：
Cheon, Jae Hee;Kim, Joo Sung;Song, In Sung
Background/Aims: The plant sterol guggulsterone has been shown to have anti-inflammatory properties. It remains unknown, however, whether guggulsterone is effective for the treatment of inflammatory bowel disease (IBD). Therefore, we investigated anti-inflammatory effects of guggulsterone on intestinal epithelial cells (IEC) and on experimental murine colitis models and elucidated its molecular mechanisms.Methods: Human Caco-2 cells and rat non-transformed IEC-18 cells were stimulated with interleukin (IL)-1 beta or lipopolysaccharide (LPS) with or without guggulsterone. The effects of guggulsterone on nuclear factor (NF)-kappa B signaling in IEC were examined by intercellular adhesion molecule (ICAM)-1 real-time reverse-transcription polymerase chain reaction, NF-kappa B transcriptional activity assay, Western blotting for I kappa B phosphorylation/degradation, electrophoretic mobility shift assay, and in vitro I kappa B kinase (IKK) assay For in vivo study, dextran sulfate sodium (DSS)-treated mice were fed with or without guggulsterone. Colitis was quantified by disease activity index and evaluation of macroscopic and microscopic findings. Phosphorylation Of I kappa B and IKK in colon mucosa was assessed by Western blotting and immunohistochemistry.Results: Guggulsterone significantly inhibited LPS- or IL-1 beta-induced ICAM-1 gene expression, NF-kappa B transcriptional activity, I kappa B phosphorylation/degradation, and NF-kappa B DNA binding activity in IEC. Moreover, guggulsterone strongly blocked IKK activity. Administration of guggulsterone significantly reduced the severity of DSS-induced murine colitis as assessed by clinical disease activity score, colon length, and histology Furthermore, tissue upregulation of I kappa B and IKK phosphorylation induced by DSS was attenuated in guggulsterone-treated mice.Conclusion: Guggulsterone blocks NF-kappa B signaling pathway by targeting IKK complex in IEC and attenuates DSS-induced acute murine colitis, which suggests that guggulsterone could be an attractive therapeutic option in the treatment of IBD.
