1,3-Diphenylpropenone ameliorates TNBS-induced rat colitis through suppression of NF-kappa B activation and IL-8 induction

Title
1,3-Diphenylpropenone ameliorates TNBS-induced rat colitis through suppression of NF-kappa B activation and IL-8 induction
Author(s)
김정애박수영구세광[구세광]이응석
Keywords
INFLAMMATORY-BOWEL-DISEASE; MONOCYTE-CHEMOATTRACTANT PROTEIN-1; INTESTINAL EPITHELIAL-CELLS; ULCERATIVE-COLITIS; INTERLEUKIN-8 GENE; PROINFLAMMATORY CYTOKINES; ENHANCED EXPRESSION; IMMUNE-RESPONSES; TOPOISOMERASE-I; CROHNS-DISEASE
Issue Date
201203
Publisher
ELSEVIER IRELAND LTD
Citation
CHEMICO-BIOLOGICAL INTERACTIONS, v.196, no.1-2, pp.39 - 49
Abstract
In the present study, we examined whether newly synthesized phenylpropenone derivatives, by inhibiting NF-kappa B activity, would inhibit IL-8 expression, inflammation and abnormal angiogenesis, resulting in amelioration of disease conditions. The phenylpropenone derivatives inhibited NF-kappa B transcriptional activity, which correlated with their suppressive activity against TNF-alpha-induced adhesion of U937 human monocytic cells to HT-29 human colonic epithelial cells, an in vitro model of IBD. Among the derivatives, 1,3-diphenylpropenone (DPhP) was most efficacious, and it significantly suppressed TNF-alpha-induced production of IL-8 which is a proinflammatory and proangiogenic cytokine. The anti-inflammatory activity of DPhP was also confirmed in the trinitrobenzene sulfonic acid (TNBS)-induced rat colitis model. DPhP was protective against the TNBS-induced inflammatory responses, which included weight loss, increased myeloperoxidase activity and mucosal damage. In the colon tissue, DPhP inhibited TNBS-induced NF-kappa B nuclear translocation, IL-8 and TNF-alpha expressions, and abnormal angiogenesis. In addition, DPhP also suppressed IL-8-induced angiogenesis, which was revealed by an in vivo assay using chick chorioallantoic membrane. Furthermore, the level of IL-6, a pleiotropic cytokine which is implicated in the pathogenesis of IBD and colitis-associated cancer, was suppressed by DPhP in rat colon tissue and serum. In conclusion, the results suggest that DPhP is a potential dual-acting IBD drug candidate targeting both inflammation and abnormal angiogenesis, possibly through the NF-kappa B and IL-8 signaling pathway. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/29693http://dx.doi.org/10.1016/j.cbi.2012.02.002
ISSN
0009-2797
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약학대학 > 약학부 > Articles
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