title: Protection from experimental colitis by theaflavin-3,3'-digallate correlates with inhibition of IKK and NF-kappaB activation.
abstract: OBJECTIVE
  Inflammatory bowel disease (IBD) is associated with activation of nuclear factor kappa B (NF-kappaB) 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-kappaB activation, we investigated if TFDG is beneficial in colonic inflammation by suppressing iNOS and proinflammatory cytokines.
  
  
  METHODS
  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-kappaB activation was determined by electrophoretic mobility shift assay and levels of NF-kappaB inhibitory protein (IkappaBalpha) were analyzed by Western blotting.
  
  
  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-kappaB activation and IkappaBalpha depletion in TNBS-treated mice from Day 2 through Day 8 with a maximum at Day 4, which resulted from increased phosphorylation of IkappaBalpha and higher activity of IkappaB kinase (IKK). Pretreatment with TFDG markedly inhibited TNBS-induced increases in nuclear localization of NF-kappaB, cytosolic IKK activity and preserved IkappaBalpha in colon tissue.
  
  
  CONCLUSIONS
  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-kappaB activation.
authors.affiliation: Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology, Jadavpur, Calcutta, India.
authors.forename: A
authors.initials: A
authors.lastname: Ukil
authors.forename: S
authors.initials: S
authors.lastname: Maity
authors.forename: P K
authors.initials: PK
authors.lastname: Das
mesh_terms: D000818:Animals; D044946:Biflavonoids / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D002392:Catechin / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced* / Q000517:prevention & control*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004986:Ether; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D009195:Peroxidase / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D059808:Polyphenols; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D044946:Biflavonoids; D005419:Flavonoids; D020672:I-kappa B Proteins; D016328:NF-kappa B; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004986:Ether; D018664:Interleukin-12; D009569:Nitric Oxide; C077197:theaflavin digallate; D005707:Gallic Acid; D007371:Interferon-gamma; D002392:Catechin; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II