Inhibition of inflammatory mediators by polyphenolic plant extracts in human intestinal Caco-2 cells

The mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-kappa B) are involved in transduction cascades that play a key role in inflammatory response. We tested the ability of preselected natural polyphenolic extracts (grape seed, cocoa, sugar cane, oak, mangosteen and pomegranate) to modulate intestinal inflammation using human intestinal Caco-2 cells treated for 4 h with these extracts and then stimulated by cytokines for 24 or 48 h. The effect of polyphenolic extracts, at 50 mu mol of gallic acid equivalent/ l, was investigated on inflammation-related cellular events: (i) NF-kappa B activity (cells transfected with a NF-kappa B-luciferase construct), (ii) activation of Erk1/2 and JNK (western blotting), (iii) secretion of interleukin 8 (IL-8) (ELISA), (iv) secretion of prostaglandin (PC) E-2 (ELISA), (v) production of NO (Griess method). Results show that: (i) sugar cane, oak and pomegranate extracts inhibited NF-kappa B activity (from 1.6 to 1.9-fold) (P < 0.001): (ii) pomegranate slightly inhibited Erk1/2 activation (1.3-fold) (P = 0.008); (iii) oak and pomegranate decreased NO synthesis by 1.5-fold (P < 0.001) and that of IL-8 by 10.3 and 6.7-fold respectively: (iv) pomegranate and cocoa decreased PGE(2) synthesis by 4.6 (P < 0.0001) and 2.2-fold (P = 0.001), respectively. We suggest that pomegranate extract could be particularly promising in dietary prevention of intestinal inflammation. (C) 2009 Elsevier Ltd. All rights reserved.