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

Abstract

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-3,3 0 -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 (5 mg kg À1 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.

Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-α production and its signaling

“…The results suggest that the action of polyphenol-containing GFW in blocking the migration and adhesion of monocytes to the colon epithelial cells are mediated through regulation of NF-κB activity. These results are consistent with previous findings of the inhibitory effects of polyphenols on NF-κB activity associated with inflammation (Kundu and Surh, 2004;Ukil et al, 2006).…”

Effects of glutamine on proinflammatory gene expression and activation of nuclear factor kappa B and signal transducers and activators of transcription in TNBS-induced colitis

“…[41][42][43][44][45][46] Very recently, it has been shown that glutamine given by intragastric gavage reduces immunohistochemical expression of NF-B in the colon of animals treated with TNBS, 21 and activation of NF-B in rats with acetic acid-induced colitis. 1 Our data further demonstrate that inhibition of the nuclear translocation of p50 and p65 subunits contribute to the protective effect of glutamine in rats with experimental colitis.…”

Black tea polyphenol theaflavin suppresses LPS-induced ICAM-1 and VCAM-1 expression via blockage of NF-κB and JNK activation in intestinal epithelial cells

“…The theaflavins consist of theaflavin, theaflavin-3-gallate, theaflavin-3 0 -gallate and theaflavin-3,3 0 -gallate. Theaflavins have been suggested to reduce oxidative stress and inflammation in studies in vitro and in vivo [8][9][10][11][12][13][14]. However, although black tea is the most widely consumed beverage, the precise mechanisms by which black tea polyphenols exert these protective effects have not yet been as thoroughly elucidated as with green tea.…”