Therapeutic effect of epigallocatechin-3-gallate in a mouse model of colitis.
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.
Abboud
Patricia A
PA
Cincinnati Children's Hospital Medical Center, Division of Critical Care Medicine, College of Medicine, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
Hake
Paul W
PW
Burroughs
Timothy J
TJ
Odoms
Kelli
K
O'Connor
Michael
M
Mangeshkar
Prajakta
P
Wong
Hector R
HR
Zingarelli
Basilia
B
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D000975:Antioxidants; D016207:Cytokines; D016328:NF-kappa B; D013662:Tea; D018808:Transcription Factor AP-1; D002392:Catechin; D014302:Trinitrobenzenesulfonic Acid; C045651:epigallocatechin gallate; D009195:Peroxidase