Procyanidin A1 and its digestive products prevent acrylamide-induced intestinal barrier dysfunction via the MAPK-mediated MLCK pathway

Abstract

Procyanidins can alleviate small-intestine damage induced by acrylamide (ACR). However, little is known about whether procyanidins, after gastrointestinal digestion, can prevent ACR-induced intestinal barrier damage and the possible mechanism. Here, Caco-2 cells were differentiated into an intestinal epithelial cell monolayer membrane, which was stimulated with or without ACR in the presence or absence of procyanidin A₁ (A₁) and its digestive products (D–A₁). Our findings show that both A₁ and D–A₁ significantly increased the transepithelial electrical resistance (TEER) value; decreased FITC-dextran 4 kDa (FITC-4 kDa) permeability, apoptosis and lactic dehydrogenase (LDH) release; and enhanced the expression of claudin-1, occludin and zonula occludens-1 (ZO-1) in ACR-induced Caco-2 cell monolayer membrane. In addition, A₁ and D–A₁ suppressed ACR-induced phosphorylation of mitogen-activated protein kinase (MAPK). Finally, A₁ and D–A₁ inhibited the myosin light chain kinase (MLCK) signaling pathway, thereby maintaining normal intestinal barrier functions, similar to the MLCK inhibitor in ACR-induced Caco-2 cell monolayer membrane. These findings indicate that A₁ can alleviate ACR-induced intestinal barrier dysfunction via inhibiting the MAPK/MLCK signaling pathway, and it still has excellent inhibitory effects after digestion.