Protection from experimental colitis by theaflavin- 3,30-digallate correlates with inhibition of IKK and NF-jB activation

Ukil, Anindita and Maity, S and Das, Pijush K (2006) Protection from experimental colitis by theaflavin- 3,30-digallate correlates with inhibition of IKK and NF-jB activation. British Journal of Pharmacology, 149 (1). pp. 121-131.


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    Background and purpose: Inflammatory bowel disease (IBD) is associated with activation of nuclear factor kappa B (NF-kB) involved in regulating the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokine genes. As theaflavin-3,30-digallate (TFDG), the most potent anti-oxidant polyphenol of black tea, down-regulates NF-kB 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-kB activation was determined by electrophoretic mobility shift assay and levels of NF-kB inhibitory protein (IkBa) were analyzed by Western blotting. Key results: Oral administration of TFDG (5mgkg�1 daily i.g.) significantly improved TNBS-induced colitis associated with decreased mRNA and protein levels of TNF-a, IL-12, IFN-g and iNOS in colonic mucosa. DNA binding and Western blotting revealed increase in NF-kB activation and IkBa depletion in TNBS-treated mice from Day 2 through Day 8 with a maximum at Day 4, which resulted from increased phosphorylation of IkBa and higher activity of IkB kinase (IKK). Pretreatment with TFDG markedly inhibited TNBS-induced increases in nuclear localization of NF-kB, cytosolic IKK activity and preserved IkBa 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-kB activation.

    Item Type: Article
    Subjects: Drug Development/Diagnostics & Biotechnology
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Mr Shyamal Nath
    Date Deposited: 01 Nov 2011 17:36
    Last Modified: 22 Jan 2013 15:25
    Official URL: htpp://

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