Involvement of P-glcoprotein in regulating cellular levels of Ginkgo flavonols: quercetin, kaempferol, and isorhamnetin

Quercetin, kaempferol, and isorhamnetin were the most important flavonoid constituents in extracts from Ginkgo biloba leaves. Transport studies of Ginkgo flavonols were performed in Caco-2 cell monolayers. Their apparent permeability in absorptive and secretion directions was determined, and quercetin, kaempferol and isorhamnetin displayed polarized transport, with the P-app,P-B-A being higher than the P-app,P-A-B (P < 0.01 for quercetin, P < 0.001 for kaempferol and isorhamnetin, Student's t-test). Bcap37/MDR1 cells, which were transfected with a P-glycoprotein (P-gp) gene construct, were treated with quercetin, kaempferol or isorhamnetin. The concentrations of Ginkgo flavonol in Bcap37/MDR1 cells were lower than those in parent cells (P < 0.05 for quercetin, P < 0.01 for isorhamnetin, Mann-Whitney U test). The concentrations of the flavonol in transfected cells increased when incubated with the P-gp inhibitor verapamil (P < 0.05 for kaempferol, Mann-Whitney U test). A colorometric assay for ATPase activity was applied to the detection of interaction of flavonol with P-gp. Quercetin and kaempferol inhibited the ATPase activity, and isorhamnetin stimulated the ATPase activity (P < 0.05 for isorhamnetin, Mann Whitney U test). The results indicated that Ginkgo flavonols quercetin, kaempferol and isorhamnetin were substrates of P-gp.The P-gp type efflux pump might limit the bioavailability of Ginkgo flavonols.