Esterification of Quercetin Increases Its Transport Across Human Caco‐2 Cells

Plant polyphenols showed useful biochemical characteristics in vitro; however, the assessments of their clinical applications in vivo are restricted by their limited bioavailability due to their strong resistance to 1st‐pass effects during absorption. In order to improve the bioavailability of quercetin (QU), the ester derivative of QU (3,3′,4′,5,7‐pentahydroxy flavones, TAQU) was synthesized, followed by examining the oil–water partition coefficient as well as the transport mechanisms of QU and its ester derivative (TAQU) using human Caco‐2 cells. The transport characteristics of QU and TAQU transport under different conditions (different concentrations, time, pH, temperature, tight junctions, and potential transporters) were systematically investigated. Results showed that QU had a lower permeability coefficient (2.82 × 10^?6 cm/s) for apical‐to‐basolateral (AP‐BL) transport over 5 to 50 μM, whereas the transport rate for AP to BL flux of TAQU (5.23 × 10^?6 cm/s) was significantly greater than that of QU. Paracellular pathways were not involved during the transport of both QU and TAQU. QU was poorly absorbed by active transport, whereas TAQU was mostly absorbed by passive diffusion. Efflux transporters, P‐glycoproteins, multidrug resistance proteins were proven to participate in the transport process of QU, but not in that of TAQU. These results suggested that improving the lipophicity of QU by esterification could increase the transport of QU across Caco‐2 cells.