Epigallocatechin-3-gallate (EGCG), a
green tea catechin, has been shown to inhibit signaling pathways involved in
inflammation, including
nuclear factor-kappaB (
NF-kappaB) and
activator protein-1 (AP-1), which are important inducers of pro-inflammatory mediators. Aim of our study was to evaluate the therapeutic efficacy of EGCG in experimental
colitis, which was induced by
rectal administration of
trinitrobenzenesulfonic acid (TNBS) in C57/BL6 mice. Mice were treated twice daily with vehicle or with EGCG (10 mg/kg) intraperitoneally, and sacrificed on days 1, 3, and 7 after TNBS administration. After induction of
colitis, vehicle-treated mice experienced bloody
diarrhea and loss of
body weight. A remarkable colonic damage with
hemorrhage,
ulcers, and
edema was observed and was associated with neutrophil infiltration as evaluated by
myeloperoxidase (MPO) activity. Elevated plasma levels of
tumor necrosis factor alpha,
interleukin (IL)-6,
IL-10 and keratinocyte-derived
chemokine were also found. These events were paralleled by increased
DNA binding of
NF-kappaB and
AP-1 in the colon of the vehicle-treated group. In contrast, the EGCG-treated mice experienced a very mild
diarrhea and no
weight loss. Damage of the colon was characterized by
edema and
hyperemia only. Tissue levels of MPO were also significantly reduced when compared to vehicle-treated mice. These beneficial effects of EGCG were associated with a significant reduction of
NF-kappaB and
AP-1 activation. However, treatment with EGCG did not reduce plasma
cytokine levels. Our data demonstrate that EGCG may be beneficial in
colitis through selective immunomodulatory effects, which may be mediated, at least in part, by inhibition of
NF-kappaB and
AP-1.