Anthocyanins inhibit tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity

An increased permeability of the intestinal barrier is proposed as a major event in the pathophysiology of conditions characterized by chronic gut inflammation. This study investigated the capacity of pure anthocyanins (AC), and berry and rice extracts containing different types and amounts of AC, to inhibit tumor necrosis alpha (TNF alpha)-induced permeabilization of Caco-2 cell monolayers. Caco-2 cells differentiated into intestinal epithelial cell monolayers were incubated in the absence/presence of TNF alpha, with or without the addition of AC or AC-rich plant extracts (ACRE). AC and ACRE inhibited TNF alpha-induced loss of monolayer permeability as assessed by changes in transepithelial electrical resistance (TEER) and paracellular transport of FITC-dextran. In the range of concentrations tested (0.25-1 mu M), O-glucosides of cyanidin, and delphinidin, but not those of malvidin, peonidin and petunidin protected the monolayer from TNF alpha-induced decrease of TEER and increase of FITC-dextran permeability. Cyanidin and delphinidin acted by mitigating TNF alpha-triggered activation of transcription factor NF-kappa B, and downstream phosphorylation of myosin light chain (MLC). The protective actions of the ACRE on TNF alpha-induced TEER increase was positively correlated with the sum of cyanidins and delphinidins (r(2) = 0.83) content in the ACRE. However, no correlation was observed between TEER and ACRE total AC, malvidin, or peonidin content. Results support a particular capacity of cyanidins and delphinidins in the protection of the intestinal barrier against inflammation-induced permeabilization, in part through the inhibition of the NF-kappa B pathway.