Novel guggulsterone derivative GG-52 inhibits NF-κB signaling in intestinal epithelial cells and attenuates acute murine colitis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-07

AUTHORS

Jung Mogg Kim, Hyoun Woo Kang, Mi Yeon Cha, Doyoung Yoo, Nayoung Kim, In-Kyoung Kim, Jeounghun Ku, Sunil Kim, Sang-Ho Ma, Hyun Chae Jung, In Sung Song, Joo Sung Kim

ABSTRACT

We already showed that the plant sterol guggulsterone has been reported to inhibit nuclear factor-kappaB (NF-kappaB) 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-kappaB 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 IkappaB kinase (IKK) and IkappaBalpha 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-kappaB 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. More... »

PAGES

1004

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/labinvest.2010.54

DOI

http://dx.doi.org/10.1038/labinvest.2010.54

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028780771

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20195240


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