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

Hexameric procyanidins inhibit TNFα-induced NF-κB 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-κB 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 (TNFα)-induced NF-κB activation as related to oxidation and membrane interactions. In Caco-2 cells, Hex (2.5-20 μM) inhibited TNFα-induced NF-κB activation (IκB phosphorylation and degradation, p50 and RelA nuclear translocation, and NF-κB-DNA binding), inducible nitric oxide synthase expression, and cell oxidant increase. The effects on NF-κB activation persist beyond the period of direct exposition of cells to Hex. N-Acetylcysteine and α-lipoic acid inhibited TNFα-induced oxidant increase but did not affect NF-κB activation. In summary, Hex can inhibit NF-κB activation by interacting with the plasma membrane of intestinal cells, and through these interactions preferentially inhibits the binding of TNFα to its receptor and the subsequent NF-κB activation.