Effect of the flavonoids biochanin A and silymarin on the P-glycoprotein-mediated transport of digoxin and vinblastine in human intestinal Caco-2 cells

Purpose. The purpose of this study was to investigate the effects of flavonoids biochanin A and silymarin on intestinal absorption of P-gp substrates by determining their effects on P-gp-mediated efflux in Caco-2 cells. Methods. The cellular accumulation and bidirectional transport of digoxin and vinblastine in Caco-2 cells were determined in the presence and absence of flavonoids. Results. The 1.5-h accumulation of digoxin and vinblastine in Caco-2 cells was significantly increased by 50 μM biochanin A or silymarin, and this effect was flavonoid-concentration dependent. The AP-to-BL transport of digoxin was significantly increased, whereas the BL-to-AP transport was significantly decreased by 50 μM biochanin A or 75 μM silymarin. At 150 μM concentrations of biochanin A or silymarin, mean transport ratios (P_app.B-A/P_app.A-B) of 1.62 and 4.48, respectively, compared with the control ratio of 43.4, were obtained. Conclusion. These results indicate that biochanin A and silymarin can inhibit P-gp-mediated efflux in Caco-2 cells, suggesting they could potentially increase the absorption/bioavailability of coadministered drugs that are P-gp substrates.