Cellular assays combined with metabolomics highlight the dual face of phenolics: From high permeability to morphological cell damage

The Caco-2 cellular permeability of phenolic aqueous extracts from blackcurrant press cake (BC), Norway spruce bark (NS), scots pine bark (SP), and sea buckthorn leaves (SB) was evaluated by combining high-resolution mass spectrometry and atomic force microscopy. Besides, Caco-2 and HepG2 cells allowed the study of intracellular oxidative stress assessed in both apical and basolateral domains. Overall, BC and NS showed the highest total phenolic contents, 4.38 and 3.76 µg/mL, respectively. Multivariate statistics discriminated NS and BC from SP and SB extracts because of their phenolic profile. Polyphenols were classified as highly permeable, thus suggesting their potentially high bioavailability through the gastrointestinal tract. All the phenolic subclasses showed efflux ratio values < 1, except for BC flavonols, flavan-3-ols, and stilbenes. Regarding cellular damage, NS and BC extracts, when acting on the basolateral cellular side, caused epithelial leakage and morphological shape cell damage on Caco-2 cells associated with ROS production.