A Gastrointestinally Digested Ribes nigrum L. Fruit Extract Inhibits Inflammatory Response in a Co-culture Model of Intestinal Caco-2 Cells and RAW264.7 Macrophages

Blackcurrant fruits are a rich source of polyphenolic compounds with high antioxidant capacity and potent anti-inflammatory properties. In this study, blackcurrant extract digested in an artificial gastrointestinal tract and its intestinal permeable fraction were investigated for their ability to suppress inflammatory responses induced in a two-component cell culture system of intestinal epithelial cells and macrophages. The obtained results showed the capacity of the extract at a concentration of 1 mg of freeze-dried blackcurrant powder per mL to down-regulate the expression of inflammatory mediators, such as IL-8 (54 +/- 7%) and COX-2 (17 +/- 6%) in intestinal cells and IL-1 alpha (76 +/- 4%), IL-1 beta (91 +/- 2%), and IL-6 (61 +/- 5%) in macrophages stimulated with lipopolysaccharides. Inhibited COX-2 (44 +/- 6%) and iNOS (15 +/- 7%) expression played a role in reducing the production of prostaglandin E2 (40 20%) and NO (31 9%), respectively. Decreased TNF-alpha secretion (24 +/- 5%) by activated macrophages was also observed after treatment with blackcurrant extract. Moreover, the gastrointestinal digested extract (0.01-1 mg/mL) dose dependently decreased the enhanced ROS generation (14-54%) and oxidative DNA damage (16-37%) induced in intestinal cells. The increased intestinal permeability caused by proinflammatory mediators, as assessed by transepithelial electrical resistance, was completely counteracted.