Circadian and dopaminergic influence on chlorogenic acid intestinal permeability

Chlorogenic acid (CGA) is a natural polyphenol potentially health promoting along the gut-brain axis, even if limited by poor oral bioavailability. As components of therapeutic drugs or functional food, polyphenols can influence each other their absorption from the gut according to circadian rhythms. Therefore, we have evaluated, via HPLC-UV analysis, how the permeability of CGA across IEC-6 cell monolayers, as a model of intestinal barrier, is influenced by the presence of arbutin, gallic, caffeic and ferulic acids and by circadian cycles entrainment by horse serum shock. Moreover, dopaminergic neuronal influence on CGA intestinal permeability was investigated by co-culture with rat pheochromocytoma PC12 cell line mimicking dopaminergic component of enteric nervous system (ENS). Our results indicate the presence of a circadian-dependent active efflux for CGA permeation across IEC-6 monolayers, suggesting its higher bioavailability in the evening rather than in the morning. Among the natural polyphenols tested, only gallic acid was able to influence the CGA permeation, causing its reduction. Finally, (60 mM KCl)-evoked dopamine release from PC12 cells induced a significant CGA permeation increase across IEC-6 monolayers, probably by downregulation of efflux transporters expression/activity. Dopamine ENS-evoked may therefore enhance the CGA oral bioavailability dependence on circadian rhythms. Although this is a preliminary study in this field, the results obtained allow us to suggest that the absorption of CGA from an oral administration of a food supplement is not influenced by arbutin, caffeic acid and ferulic acid, whereas it can be enhanced in the absence of gallic acid and by evening intake.