Ellagic acid protects the intestinal barrier against inflammation/oxidative stress induced permeabilization

C. G. FRAGA; D. E. IGLESIAS; P. I. OTEIZA

Ferrara

Congreso; Society for Free Radical Research-Europe (SFRR-E) Annual Meeting; 2019

SFRR-E

Chronic intestinal inflammation involves a cycle of oxidative stress, NF-κB activation, and barrier permeabilization. The latter can lead to systemicinflammation and associated co morbidities. Diet is crucial inmodulating intestinal inflammation. Among plant bioactives, ellagic acid(EA) was reported to inhibit inflammatory bowel disease in animalmodels. This work investigated EA capacity to inhibit tumor necrosisalpha (TNFα) induced inflammation, oxidative stress, and myosin lightchain kinase (MLCK) regulated loss of barrier integrity. Caco-2 cellsdifferentiated into an intestinal epithelial cell monolayer were incubatedwith TNFα (10 ng/ml), in the presence of different EA concentrations.TNFα triggered interleukin 6 and 8 release into the medium, which wasinhibited by EA in a dose-dependent manner (IC50¼17.3 μM forinterleukin-6). TNFα also led to: i) increased NOX1 expression; ii)decreased mitochondrial membrane potential; iii) increased oxidantproduction; iv) NF-κB activation; v) MLCK upregulation; and vi) monolayerpermeabilization. EA (10-40 μM) inhibited all these adverse effectsof TNFα. EA mainly acts through NF-κB inhibition breaking the cycle ofoxidative stress, NF κB activation, and intestinal permeabilization. Thissuggests the consumption of EA, via foods or supplements may afford astrategy to mitigate intestinal inflammation and associated comorbidities.Supported by Pfizer Consumer Healthcare, Inc. and NIFAUSDA (CA-D*-xxx-7244-H).