Novel guggulsterone derivative GG-52 inhibits NF-kappa B signaling in intestinal epithelial cells and attenuates acute murine colitisopen access
- Authors
- Kim, Jung Mogg; Kang, Hyoun Woo; Cha, Mi Yeon; Yoo, Doyoung; Kim, Nayoung; Kim, In-Kyoung; Ku, Jeounghun; Kim, Sunil; Ma, Sang-Ho; Jung, Hyun Chae; Song, In Sung; Kim, Joo Sung
- Issue Date
- Jul-2010
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- guggulsterone derivatives; inflammatory bowel disease; murine colitis; NF-kappa B
- Citation
- LABORATORY INVESTIGATION, v.90, no.7, pp.1004 - 1015
- Indexed
- SCIE
SCOPUS
- Journal Title
- LABORATORY INVESTIGATION
- Volume
- 90
- Number
- 7
- Start Page
- 1004
- End Page
- 1015
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/174477
- DOI
- 10.1038/labinvest.2010.54
- ISSN
- 0023-6837
- Abstract
- We already showed that the plant sterol guggulsterone has been reported to inhibit nuclear factor-kappa B (NF-kappa B) signaling in intestinal epithelial cells (IECs) and to attenuate dextran sulfate sodium (DSS)-induced colitis. This study investigates the anti-inflammatory effects of novel guggulsterone derivatives on IEC and preventive and therapeutic murine models of DSS-induced colitis. Novel guggulsterone derivates with high lipophilicity were designed and four derivates, including GG-46, GG-50B, GG-52, and GG-53, were synthesized. Two guggulsterone derivatives, GG-50B and GG-52, significantly inhibited the activated NF-kappa B signals and the upregulated expression of interleukin-8 (IL-8) in COLO 205 cells stimulated with tumor necrosis factor-alpha (TNF-alpha). Pretreatment with GG-50B and GG-52 attenuated the increased I kappa B kinase (IKK) and I kappa B alpha phsophorylation induced by TNF-alpha. In preventive and therapeutic models of murine colitis, administration of GG-52 significantly reduced the severity of DSS-induced colitis, as assessed by disease activity index, colon length, and histology. In contrast, GG-50B did not show a significant reduction in the colitis severity. Moreover, the efficacy on attenuating colitis by GG-52 was comparable to that by sulfasalazine or prednisolone. These results indicate that the novel guggulsterone derivative GG-52 blocks NF-kappa B activation in IEC and ameliorates DSS-induced acute murine colitis, which suggests that GG-52 is a potential therapeutic agent for the treatment of inflammatory bowel diseases.
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