Browse

Plant sterol guggulsterone inhibits nuclear factor-kappaB signaling in intestinal epithelial cells by blocking IkappaB kinase and ameliorates acute murine colitis

Cited 109 time in Web of Science Cited 121 time in Scopus
Authors
Cheon, Jae Hee; Kim, Joo Sung; Kim, Jung Mogg; Kim, Nayoung; Jung, Hyun Chae; Song, In Sung
Issue Date
2006-11-23
Publisher
Wiley-Blackwell
Citation
Inflamm Bowel Dis. 2006 Dec;12(12):1152-61.
Keywords
AnimalsColitis/chemically induced/*drug therapy/pathologyDNA/metabolismEnterocytes/cytology/*drug effects/pathologyFemaleHumansI-kappa B Kinase/*antagonists & inhibitorsI-kappa B Proteins/metabolismIntercellular Adhesion Molecule-1/geneticsInterleukin-1beta/pharmacologyLipopolysaccharides/pharmacologyMiceMice, Inbred C57BLNF-kappa B/*antagonists & inhibitors/metabolismPhosphorylation/drug effectsPhytosterols/*pharmacology/therapeutic usePhytotherapyPregnenediones/*pharmacology/therapeutic useRNA, Messenger/genetics/metabolismRatsSignal Transduction/*drug effectsTranscription, Genetic/drug effects
Abstract
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)-1beta or lipopolysaccharide (LPS) with or without guggulsterone. The effects of guggulsterone on nuclear factor (NF)-kappaB signaling in IEC were examined by intercellular adhesion molecule (ICAM)-1 real-time reverse-transcription polymerase chain reaction, NF-kappaB transcriptional activity assay, Western blotting for IkappaB phosphorylation/degradation, electrophoretic mobility shift assay, and in vitro IkappaB 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 IkappaB and IKK in colon mucosa was assessed by Western blotting and immunohistochemistry. RESULTS: Guggulsterone significantly inhibited LPS- or IL-1beta-induced ICAM-1 gene expression, NF-kappaB transcriptional activity, IkappaB phosphorylation/degradation, and NF-kappaB 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 IkappaB and IKK phosphorylation induced by DSS was attenuated in guggulsterone-treated mice. CONCLUSION: Guggulsterone blocks NF-kappaB 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.
ISSN
1078-0998 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17119390

https://hdl.handle.net/10371/27824
DOI
https://doi.org/10.1097/01.mib.0000235830.94057.c6
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse