Quercetin and naringenin transport across human intestinal Caco-2 cells.
OBJECTIVE
Flavonoids are phenolic compounds found in most edible fruits and vegetables. Previous studies have demonstrated their biological and beneficial effects on human health. However, their bioavailability and, in particular, their intestinal absorption mechanism have not yet been clearly identified. The aim of our work was to quantify and to characterize in vitro the nature of the transport of two flavonoids distinguished by their physicochemical and pharmacological properties: quercetin, a flavan-3-ol, and naringenin, a flavanone.


METHODS
Differentiated and polarized Caco-2 human intestinal epithelial cell lines were used for this purpose.


RESULTS
In our experimental conditions, quercetin and naringenin were poorly absorbed by Caco-2 cells. Quercetin was absorbed by passive diffusion and a pH-dependent mechanism mediated by the organic anion transporting protein B (OATP-B). It was not a multidrug resistance associated protein (MRP)1 substrate, but was substrate of the MRP2 efflux transporter and not P-glycoprotein (P-gp). Intestinal permeability from the apical to the basolateral side was higher for naringenin than for quercetin, which was partly explained by naringenin's physicochemical characteristics. Naringenin, partially absorbed by passive diffusion, was also an ATP-dependent transport substrate mediated by MRP1, but was not an OATP-B substrate. However, naringenin was secreted via active P-gp and MRP2 efflux transporters.


CONCLUSIONS
The contribution of ATP-dependent efflux transporters (MRP2 and P-gp) to the permeability of these compounds in the apical side could explain their low bioavailability. In conclusion, knowledge of the absorption mechanism of these two flavonoids was used to determine the intake level that has a beneficial effect on human health and their putative role in food-drug interactions.
Nait Chabane
Meriem
M
Laboratoire d'Innovation Thérapeutique, Université Louis Pasteur, Faculté de Pharmacie, Strasbourg, France.
Al Ahmad
Abraham
A
Peluso
Jean
J
Muller
Christian D
CD
Ubeaud
Genevieve
G
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport; D018938:Caco-2 Cells; D003106:Colon / Q000378:metabolism*; D004058:Diffusion; D004847:Epithelial Cells / Q000378:metabolism*; D044950:Flavanones / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D027361:Organic Anion Transporters / Q000378:metabolism; D010539:Permeability; D011794:Quercetin / Q000493:pharmacokinetics*; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000255:Adenosine Triphosphate; D044950:Flavanones; D027361:Organic Anion Transporters; D011794:Quercetin; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C005273:naringenin