Chlorogenic acid permeation across intestinal cell monolayers: Influence by circadian rhythms in the presence of other natural polyphenols and by dopaminergic neuronal-like cells

Poor oral bioavailability limits chlorogenic acid (CGA) benefits on the gut-brain axis. In this study we demonstrate the existence of an active circadian-dependent efflux for the CGA intestinal permeation, leading to greater bioavailability in the evening rather than in the morning. As therapeutic/nutraceutical polyphenols can mutually influence their intestinal absorption following circadian rhythms, we also evaluated the effects of other polyphenols on CGA permeation/bioavailability. The results indicate that gallic acid reduced in vitro CGA permeation across IEC-6 cell monolayers, as well as rat oral CGA bioavailability. On the contrary, arbutin, caffeic acid and ferulic acid did not modify in vitro CGA permeation. Finally, 60 mM KCl-evoked dopamine release from PC12 cells significantly increased intestinal CGA permeation, likely by downregulating the expression/activity of efflux transporters, as confirmed by western blot analysis. Dopamine released from the enteric nervous system may therefore increase the dependence of oral bioavailability of CGA on circadian rhythms.