Improvement of the Intestinal Absorption of Dihydroquercetin (DHQ) by Flavonoids via Inhibiting P-Glycoprotein (P-gp)-Mediated Efflux in P-gp Overexpressed KB/MDR1 Cells and Caco-2 Monolayers

Effects of four flavonoid inhibitors (FIs, quercetin, kaempferol, luteolin, and flavone) at different concentrations on dynamically increasing dihydroquercetin (DHQ) uptakes and regulating P-glycoprotein (P-gp)’s mRNA and protein levels were evaluated in KB/MDR1 cells. DHQ’s bidirectional transport was measured in Caco-2 monolayers. The low uptakes of DHQ were dynamically increased by four FIs (better than elacridar) in the order of quercetin > luteolin > kaempferol > flavone. Four FIs significantly increased DHQ40’s uptakes in a dose-independent manner. Four FIs alone or with DHQ significantly decreased P-gp’s mRNA and protein expressions. DHQ was poorly absorbed (efflux ratios >20) in Caco-2 monolayers, especially at high concentrations. Four FIs improved DHQ’s absorption by significantly increasing (reversing) its influx (efflux) at most time points (1, 2, 4, and 6 h), especially for DHQ100 rather than DHQ40. Docking results explained that quercetin competitively occupies DHQ’s binding site or binds to the inhibitor site of P-gp. These results were valuable for improving DHQ absorption.