Protection from experimental colitis by theaflavin- 3,30-digallate correlates with inhibition of IKK and NF-jB activation
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Protection from experimental colitis by theaflavin-
3,30-digallate correlates with inhibition of IKK and
NF-jB activation
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| Creator |
Ukil, Anindita
Maity, S Das, Pijush K |
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| Subject |
Drug Development/Diagnostics & Biotechnology
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| Description |
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.
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| Date |
2006
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/435/1/BRITISH_JOURNAL_OF_PHARMACOLOGY%2C_149(_1)%2C121%2D131[46].pdf
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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| Relation |
htpp://dx.doi.org/10.1038/sj.bjp.0706847
http://www.eprints.iicb.res.in/435/ |
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