TNFα-induced NF-κB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells

Hexameric procyanidins inhibit TNF alpha-induced NF-kappa B activation in Caco-2 cells. Most of the physiological actions of high molecular weight procyanidins could be limited to the gut lumen. Transcription factor NF-kappa B plays a central role in inflammation including human intestinal bowel disease. We investigated the capacity of a hexameric procyanidin fraction (Hex) to prevent tumor necrosis factor alpha (TNF alpha)-induced NF-kappa B activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5-20 mu M) inhibited TNF alpha-induced NF-kappa B activation (I kappa B phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-kappa B-DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-kappa B activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and alpha-lipoic acid inhibited TNF alpha-induced oxidant increase but did not affect NF-kappa B activation. In summary, Hex can inhibit NF-kappa B activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNF alpha to its receptor and the subsequent NF-kappa B activation. (C) 2008 Published by Elsevier Inc.