Crohn's disease and Ulcerative Colitis are chronic idiopathic inflammatory disease of the gastrointestinal tract (IBD). Current medical intervention of IBD consists of anti-inflammatory and immunosuppressive agents. Despite medical intervention, many patients remain refractory. Clearly, new therapeutic modalities are needed to minimize the destructive nature of IBD. Use of alternative medicine is widespread and on the rise in the United States. Patients with IBD frequently use alternative medicine and consider it an important form of therapy. There are a number of alternative medicine therapies that may prove beneficial. These include therapies that have anti-inflammatory properties or alter the bacterial flora in the bowel. However, the scientific evidence for the use of alternative medicines is often lacking or weak, and safety generally has not been assessed. Thus, there is a great need to establish the effectiveness and safety of alternative medicines used in patients. Green tea has potent anti-inflammatory properties. We present evidence that green tea polyphenols decrease the disease activity in interleuken-2 mice model of autoimmunity and IBD. The transcription factor, NF-KappaB and NF-KappaB-inducible inflammatory mediators (e.g. TNF-alpha, interleukin-1) play a critical role in the intestinal injury and the clinical/biochemical abnormalities observed in IBD. We recently showed that polyphenols extracted from green tea are potent inhibitors of NF-KappaB. We have compelling preliminary data showing that the green tea polyphenol and its extract (-)-epigallocatechin-3-gallate (EGCG), inhibit the activity of I-KB kinase (IKK), a pivotal enzyme in the NF-KappaB activation pathway. The overall objectives of this project are to determine whether green tea polyphenols (in doses ranging from functional foods to pharmacological) and/or EGCG modulate intestinal injury and immune cell responses in the Dextran Sulfate Sodium (DSS) model of Ulcerative Colitis. We will also confirm our findings using another IBD model, the interleukin-10 (IL-10) deficient mice that develop spontaneous enterocolitis (similar to Crohn's disease). These studies should provide evidence supporting green tea polyphenols/EGCG as potent anti-inflammatory therapy and provide the basis for a green tea polyphenols/EGCG intervention trials in patients with Inflammatory Bowel Disease.
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