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

Chlorogenic acid (CGA) is a natural polyphenol potentially health-promoting along the gutbrain axis, limited by poor oral bioavailability. Therapeutics or nutraceuticals polyphenols can influence each other’s intestinal absorption following circadian rhythms. We have evaluated, via HPLC-UV analysis, how arbutin, gallic, caffeic and ferulic acids, and circadian entrainment by horse-serum shock, influence CGA permeability across IEC-6 cell monolayers, as intestinal-barrier model. Moreover, neuronal influence on CGA intestinal permeability was investigated mimicking dopaminergic component of enteric nervous system (ENS) by coculture with PC12 cells. Our results indicate the presence of a circadian-dependent active efflux for CGA intestinal permeation, suggesting its higher bioavailability in the evening rather than in the morning. Among the tested polyphenols, only gallic acid influenced and reduced CGA permeation. These results were consistent with data obtained by orally administration to rats of CGA and gallic acid, where CGA induced an increase of the gallic acid bioavailability, whereas gallic acid decreased the CGA bioavailability both at the bloodstream and central levels. Finally, 60 mM KCl-evoked dopamine release from PC12 cells significantly increased CGA intestinal permeation, downregulating efflux transporters expression/activity, as confirmed by western blot analysis. ENS-released dopamine may enhance CGA oral bioavailability dependence on circadian rhythms.