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

Abstract

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.

Keywords

• Chlorogenic acid
• Circadian rhythms
• IEC-6 cells
• Intestinal permeability
• Natural polyphenols
• PC12 cells