Inhibition of P-Glycoprotein Enhances the Suppressive Effect of Kaempferol on Transformation of the Aryl Hydrocarbon Receptor

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  • MUKAI Rie
    Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University
  • SATSU Hideo
    Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo
  • SHIMIZU Makoto
    Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo
  • ASHIDA Hitoshi
    Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University

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説明

Dioxins enter the body mainly through the diet, bind to the aryl hydrocarbon receptor (AhR), and cause various toxicological effects. In this study, we found that oral administration of kaempferol or ginkgo biloba extract (EGb) containing 24% flavonol at 100 mg/kg body weight suppressed AhR transformation induced by 3-methylcholanthrene at 10 mg/kg body weight in the liver of mice. The suppressive effect of kaempferol was enhanced by verapamil, an inhibitor of P-glycoprotein (P-gp), in ex vivo experiments using a hepatic cytosolic fraction and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Enhancement of the suppressive effect by verapamil was also observed in mouse hepatoma Hepa-1c1c7 cells, accompanied by an increase in the uptake of kaempferol into the cells. In conclusion, inhibition of P-gp enhanced the suppressive effect of kaempferol on AhR transformation through an increase in the intracellular kaempferol concentration.

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