Activation of intracellular signaling pathways by polyphenols: potential significance for gastrointestinal disease

C. G. FRAGA; A. G. ERLEJMAN; G. JAGGERS; N.P. DECKER; P. I. OTEIZA

Beijing, China

Congreso; The XIV Biennial Meeting of the Society for Free Radical Research International (14th SFRR); 2008

Colon cancer is the third most prevalent form of cancer, and the second most frequent malignancy in developed countries. Epidemiological studies suggest that risk can be reduced by diminishing the consumption of meat and fats, and by increasing the intake of vegetables and fruits. In addition, the association of ulcerative colitis with an increased risk of developing colon cancer, and the benefits of anti-inflammatory drugs in retarding intestinal tumors afford the basis for considering the participation of inflammation in colon cancer. Furthermore, being inflammation tightly related to oxidative stress it is possible that antioxidant conditions can finally benefit gastrointestinal health. Plant polyphenols in general, and flavonoids in particular, have been claimed as major responsible for the overall health benefits provided by a high consumption of fruits and vegetables. The possibility that flavanols and related compounds, e.g. procyanidins, could act at the gastrointestinal level to prevent pro-inflammatory conditions and to act as antioxidants is strongly suggested by the chemical structure of these compounds, for the relatively high concentration that flavanols (and other flavonoids) and procyanidins can reach in the gastrointestinal tract, and for the several actions that these compounds exert under different experimental situations. Using Caco-2 cells as a model of intestinal epithelium we investigated the effects of high molecular weight procyanidins to prevent the loss of epithelia physiology, cell oxidation and proinflammatory events, associated with the regulation of intracellular signaling, i.e. NF-kB and NFAT pathways. We observed that at physiologically significant concentrations, hexamer and dimer procyanidins can act at different levels in cell signaling preventing  proinflammatory conditions and the lost of epithelial functions. These protective effects were observed when the cells were challenged by bile acids, oxidants or proinflammatory conditions. In conclusion, dietary procyanidins, inclusive that are not absorbed at the gut lumen can protect the intestinal mucosa from oxidant and pro-inflammatory stimuli. These effects stress the potential capacity of plant flavan-3-ols and derived procyanidins to ameliorate the colonic inflammatory processes associated with inflammatory bowel disease and cancer.