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Novel Guggulsterone Derivative GG-52 inhibits NF-kB Signaling in Intestinal Epithelial Cells and attenuates acute Murine Colitis

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Authors

Kang, H.; Kim, J.; Cha, M.; Lee, J.; Kim, I; Kim, S.; Jung, H.; Kim, J.; Song, I; Ma, S.; Ku, J.; Kim, N.

Issue Date
2009-12
Publisher
JOHN WILEY & SONS INC
Citation
INFLAMMATORY BOWEL DISEASES; Vol.15 12; S50-S50
Abstract
BACKGROUND/AIM: The plant sterol guggulsterone has been reported to inhibit
NF- B signaling in intestinal epithelial cells (IEC) and to ameliorate dextran sulfate
sodium (DSS)-induced colitis in mice. The aim of this study was to investigate the
anti-inflammatory effects of novel guggulsterone derivatives on IEC and preventive
and therapeutic murine models of DSS-induced colitis.
METHODS: Novel guggulsterone derivates with high lipophilicity were designed and
four derivates, including GG-46, GG-50B, GG-52 and GG-53, were synthesized. COLO
205 colon epithelial cells were pre-treated with each derivative and then stimulated
with TNF- . IL-8 expression was measured by real-time RT-PCR and ELISA. I B phosphorylation/
degradation was determined by immunoblotting and NF- B activity by
electrophoretic mobility shift assay, and transcriptional reporter assay. Guggulsterone
derivatives were administered to mice with preventive and therapeutic models of
DSS-induced colitis. Colitis was quantified by body weight, disease activity index (DAI),
colon length and histology.
RESULTS: Two guggulsterone derivatives, GG-50B and GG-52, inhibited IL-8 expression,
I B phosphorylation/degradation and NF- B activity in COLO 205 cells significantly.
In preventive and therapeutic models of murine colitis, administration of GG-52
significantly reduced the severity of DSS-induced colitis, as assessed by DAI, colon
length, and histology. In contrast, GG-50B did not show a significantly reduction in the
colitis severity. Moreover, the efficacy on attenuating colitis by GG-52 was comparable
to that by sulfasalazine or prednisolone.
CONCLUSION: Guggulsterone derivative GG-52 blocks NF- B activation in IEC and
ameliorates DSS-induced acute murine colitis, which suggesting that GG-52 is a potential
therapeutic agent for the treatment of inflammatory bowel diseases.
Key words: Guggulsterone derivatives, nuclear factor- B, inflammatory bowel disease,
intestinal epithelial cells, murine colitis
ISSN
1078-0998
Language
English
URI
https://hdl.handle.net/10371/77546
DOI
https://doi.org/10.1002/ibd.21172
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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