Protection from experimental colitis by theaflavin-3,3 '-digallate correlates with inhibition of IKK and NF-kappa B activation
Metadata of CSIR Papers
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| Title |
Protection from experimental colitis by theaflavin-3,3 '-digallate correlates with inhibition of IKK and NF-kappa B activation
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| Creator |
Ukil, A
Maity, S Das, PK |
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| Subject |
Pharmacology & Pharmacy
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| Description |
Background and purpose: Inflammatory bowel disease (IBD) is associated with activation of nuclear factor kappa B (NF-kappa B) 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-kappa B 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-kappa B activation was determined by electrophoretic mobility shift assay and levels of NF-kappa B inhibitory protein (I kappa B alpha) 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-alpha, IL-12, IFN-gamma and iNOS in colonic mucosa. DNA binding and Western blotting revealed increase in NF-kappa B activation and I kappa B alpha depletion in TNBS-treated mice from Day 2 through Day 8 with a maximum at Day 4, which resulted from increased phosphorylation of I kappa B alpha and higher activity of I kappa B kinase (IKK). Pretreatment with TFDG markedly inhibited TNBS-induced increases in nuclear localization of NF-kappa B, cytosolic IKK activity and preserved I kappa B alpha 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-kappa B activation.
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| Publisher |
NATURE PUBLISHING GROUPLONDONMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
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| Date |
2011-09-20T12:12:08Z
2011-09-20T12:12:08Z 2006 |
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| Type |
Article
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| Identifier |
BRITISH JOURNAL OF PHARMACOLOGY
0007-1188 http://hdl.handle.net/123456789/14143 |
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| Language |
English
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