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)-1β or lipopolysaccharide (LPS) with or without guggulsterone. The effects of guggulsterone on nuclear factor (NF)-κB signaling in IEC were examined by intercellular adhesion molecule (ICAM)-1 real-time reverse-transcription polymerase chain reaction, NF-κB transcriptional activity assay, Western blotting for IκB phosphorylation/degradation, electrophoretic mobility shift assay, and in vitro IκB 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 IκB and IKK in colon mucosa was assessed by Western blotting and immunohistochemistry. RESULTS: Guggulsterone significantly inhibited LPS- or IL-1β-induced ICAM-1 gene expression, NF-κB transcriptional activity, IκB phosphorylation/degradation, and NF-κB 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 IκB and IKK phosphorylation induced by DSS was attenuated in guggulsterone-treated mice. CONCLUSION: Guggulsterone blocks NF-κB 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1152-1161 |
| Number of pages | 10 |
| Journal | Inflammatory Bowel Diseases |
| Volume | 12 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2006 Dec 1 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Gastroenterology
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Plant sterol guggulsterone inhibits nuclear factor-κB signaling in intestinal epithelial cells by blocking IκB kinase and ameliorates acute murine colitis. / Cheon, Jae Hee; Kim, Joo Sung; Kim, Jung Mogg; Kim, Nayoung; Jung, Hyun Chae; Song, In Sung.
In: Inflammatory Bowel Diseases, Vol. 12, No. 12, 01.12.2006, p. 1152-1161.Research output: Contribution to journal › Article
TY - JOUR
T1 - Plant sterol guggulsterone inhibits nuclear factor-κB signaling in intestinal epithelial cells by blocking IκB kinase and ameliorates acute murine colitis
AU - Cheon, Jae Hee
AU - Kim, Joo Sung
AU - Kim, Jung Mogg
AU - Kim, Nayoung
AU - Jung, Hyun Chae
AU - Song, In Sung
PY - 2006/12/1
Y1 - 2006/12/1
N2 - 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)-1β or lipopolysaccharide (LPS) with or without guggulsterone. The effects of guggulsterone on nuclear factor (NF)-κB signaling in IEC were examined by intercellular adhesion molecule (ICAM)-1 real-time reverse-transcription polymerase chain reaction, NF-κB transcriptional activity assay, Western blotting for IκB phosphorylation/degradation, electrophoretic mobility shift assay, and in vitro IκB 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 IκB and IKK in colon mucosa was assessed by Western blotting and immunohistochemistry. RESULTS: Guggulsterone significantly inhibited LPS- or IL-1β-induced ICAM-1 gene expression, NF-κB transcriptional activity, IκB phosphorylation/degradation, and NF-κB 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 IκB and IKK phosphorylation induced by DSS was attenuated in guggulsterone-treated mice. CONCLUSION: Guggulsterone blocks NF-κB 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.
AB - 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)-1β or lipopolysaccharide (LPS) with or without guggulsterone. The effects of guggulsterone on nuclear factor (NF)-κB signaling in IEC were examined by intercellular adhesion molecule (ICAM)-1 real-time reverse-transcription polymerase chain reaction, NF-κB transcriptional activity assay, Western blotting for IκB phosphorylation/degradation, electrophoretic mobility shift assay, and in vitro IκB 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 IκB and IKK in colon mucosa was assessed by Western blotting and immunohistochemistry. RESULTS: Guggulsterone significantly inhibited LPS- or IL-1β-induced ICAM-1 gene expression, NF-κB transcriptional activity, IκB phosphorylation/degradation, and NF-κB 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 IκB and IKK phosphorylation induced by DSS was attenuated in guggulsterone-treated mice. CONCLUSION: Guggulsterone blocks NF-κB 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33751577977&partnerID=8YFLogxK
U2 - 10.1097/01.mib.0000235830.94057.c6
DO - 10.1097/01.mib.0000235830.94057.c6
M3 - Article
C2 - 17119390
AN - SCOPUS:33751577977
VL - 12
SP - 1152
EP - 1161
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
SN - 1078-0998
IS - 12
ER -