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

JaeHee Cheon, Joo Sung Kim, Jung Mogg Kim, Nayoung Kim, Hyun Chae Jung, In Sung Song

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)1152-1161
Number of pages10
JournalInflammatory Bowel Diseases
Volume12
Issue number12
DOIs
Publication statusPublished - 2006 Dec 1

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Phytosterols
Colitis
Phosphotransferases
Epithelial Cells
Dextran Sulfate
Phosphorylation
Intercellular Adhesion Molecule-1
Interleukin-1
Inflammatory Bowel Diseases
Lipopolysaccharides
pregna-4,17-diene-3,16-dione
Colon
Anti-Inflammatory Agents
Western Blotting
Caco-2 Cells
Electrophoretic Mobility Shift Assay
Reverse Transcription
Histology
Mucous Membrane
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Cheon, JaeHee ; Kim, Joo Sung ; Kim, Jung Mogg ; Kim, Nayoung ; Jung, Hyun Chae ; Song, In Sung. / Plant sterol guggulsterone inhibits nuclear factor-κB signaling in intestinal epithelial cells by blocking IκB kinase and ameliorates acute murine colitis. In: Inflammatory Bowel Diseases. 2006 ; Vol. 12, No. 12. pp. 1152-1161.
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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.",
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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, JaeHee; 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 journalArticle

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T1 - Plant sterol guggulsterone inhibits nuclear factor-κB signaling in intestinal epithelial cells by blocking IκB kinase and ameliorates acute murine colitis

AU - Cheon, JaeHee

AU - Kim, Joo Sung

AU - Kim, Jung Mogg

AU - Kim, Nayoung

AU - Jung, Hyun Chae

AU - Song, In Sung

PY - 2006/12/1

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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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