Effects of Natural Polyphenols on the Expression of Drug Efflux Transporter P-Glycoprotein in Human Intestinal Cells

[Image: see text] The drug efflux transporter P-glycoprotein, which is encoded by MDR1 (ABCB1), plays important roles in drug absorption, distribution, and elimination. We previously reported that dietary polyphenols such as quercetin, curcumin, honokiol, magnolol, caffeic acid phenetyl ester (CAPE), xanthohumol, and anacardic acid inhibit P-glycoprotein-mediated drug transport. In the present study, we investigated the effects of polyphenols on the expression of P-glycoprotein using human intestinal epithelial LS174T cells and a reporter plasmid expressing 10.2 kbp of the upstream regulatory region of MDR1. Honokiol, magnolol, CAPE, xanthohumol, and anacardic acid activated the MDR1 promoter in LS174T cells, and the cellular uptake of rhodamine 123 and calcein-AM, fluorescent substrates of P-glycoprotein, decreased in polyphenol-treated LS174T cells. These results suggest that dietary natural polyphenols can induce the drug efflux transporter P-glycoprotein and have the potential to promote food–drug interactions.