Protection from experimental colitis by theaflavin-3,3'-digallate correlates with inhibition of IKK and NF-κB activation

Ukil, A. ; Maity, S. ; Das, P. K. (2006) Protection from experimental colitis by theaflavin-3,3'-digallate correlates with inhibition of IKK and NF-κB activation British Journal of Pharmacology, 149 (1). pp. 121-131. ISSN 0007-1188

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Official URL: http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp....

Related URL: http://dx.doi.org/10.1038/sj.bjp.0706847

Abstract

Background and purpose: Inflammatory bowel disease (IBD) is associated with activation of nuclear factor κ B (NF-κB) involved in regulating the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokine genes. As theaflavin-3,3'-digallate (TFDG), the most potent anti-oxidant polyphenol of black tea, down-regulates NF-κB activation, we investigated if TFDG is beneficial in colonic inflammation by suppressing iNOS and proinflammatory cytokines. Experimental approach: The in vivo efficacy of TFDG was assessed in mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. Both mRNA and protein levels of proinflammatory cytokines and iNOS were analyzed in colon tissue treated with or without TFDG. NF-κB activation was determined by electrophoretic mobility shift assay and levels of NF-κB inhibitory protein (IκBα) were analyzed by Western blotting. Key results: Oral administration of TFDG (5 mg kg-1 daily i.g.) significantly improved TNBS-induced colitis associated with decreased mRNA and protein levels of TNF-α, IL-12, IFN- and iNOS in colonic mucosa. DNA binding and Western blotting revealed increase in NF-κB activation and IκB depletion in TNBS-treated mice from Day 2 through Day 8 with a maximum at Day 4, which resulted from increased phosphorylation of IκB and higher activity of IκB kinase (IKK). Pretreatment with TFDG markedly inhibited TNBS-induced increases in nuclear localization of NF-κBα, cytosolic IKK activity and preserved IκBα in colon tissue. Conclusions and Implications: TFDG exerts protective effects in experimental colitis and inhibits production of inflammatory mediators through a mechanism that, at least in part, involves inhibition of NF-κB activation.

Item Type:Article
Source:Copyright of this article belongs to British Pharmacological Society.
Keywords:Inflammatory Bowel Disease; Theaflavin-3-3'-digallate; TNBS-induced Colitis; Nuclear Factor κB; Proinflammatory Cytokine; Inducible Nitric Oxide Synthase
ID Code:30452
Deposited On:23 Dec 2010 13:32
Last Modified:17 May 2016 13:05

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