(-)-epicatechin and procyanidins in intestinal inflammation

OTEIZA PI; RICCIARDI E; CONTRERAS T; JAGGERS GK; VERSTRAETEN SV; ERLEJMAN AG; FRAGA CG

Siena

Congreso; II International Conference on Environmental Stressors in Biology and Medicine; 2011

Universidad de Siena, Universidad de Ferrara

Inflammatory bowel diseases and colorectal cancer (CRC) are major public health concerns.  Although genetic factors are important, environmental factors, including nutrition, play a significan role in the onset/prevention.  Food extracts containing (-)-epicatechin (EC) and related procyanidins (PCA) show protective effects against colonic inflammation and colorectal cancer (CRC). Epidemiological studies in humans support an anti-inflammatory and anti-CRC action in relationship with the consumption of diets rich in EC and PCA. A diet supplemented with EC and PCA ameliorates colonic inflammation in a rat model of ulcerative colitis.  Both EC and PCA can have distinct but complementary anti-inflammatory actions.  Monomeric EC can be absorbed by intestinal epithelial cells and exert antioxidant and antiinflamatory actions.  EC prevents tumor necrosis alpha (TNF)?induced oxidant production, and the downstream activation of transcription factors NF-κB and AP-1, and of the mitogen activated kinases (MAPK) ERK1/2 and p-38.  Chronic exposure to TNF causes the permeabilization of Caco-2 monolayers differentiated into an intestinal epithelium.  EC (1 µM) prevents the permeabillization of the barrier, in part by downregulating NF-κB which underlies in part TNF-induced altered dynamics of the tight junction proteins.  PCA of more than three EC subunits, are not absorbed by intestinal cells but can exert antioxidant, anti-inflammatory, and anti-CRC actions through their interactions with the cell membrane.  Through these interactions, hexameric PCA (Hex PCA) protect Caco-2 cell monolayers from various pro-inflammatory agents (deoxycholic acid (DCA), TNF, IL-1) that exert their actions in a receptor-independent (DCA) or ?dependent (TNF, IL-1) manner.  In particular, Hex PCA prevents DCA-induced membrane cholesterol redistribution, and the associated calcium influx, NADPH oxidase activation, and oxidant production.  Hex PCA also prevents DCA-mediated activation of the pro-inflammatory and oncogenic signals ERK1/2, p38, AP-1 and Akt.  Hex PCA also delays the onset of DCA-induced apoptosis in differentiated Caco-2 cells, and the permeabilization of the epithelial barrier. From the above, EC and PCA could act synergistically to promote gastrointestinal health.