The Influence and Mechanism of Paeoniflorin and Albiflorin on Strychnine and Brucine Transport Through Madin-Darby Canine Kidney/Multidrug Resistance1 Cells In Vitro Model

Abstract

This research sought to study the influence and potentialmechanism of paeoniflorin and albiflorin on strychnine and brucine transport in MDCK-MDR1 cells regulated by P-gp. Cytotoxicity of drugs was tested by MTT assay, and the transport studies were performed in both directions in MDCK-MDR1 cells. The influence of drugs on P-gp ATPase, and the efflux function of P-gp, the expression levels of P-gp and MDR1 mRNA were also estimated. Strychnine and brucine showed well absorption, and the main transport mechanism might be passive diffusion. Verapamil could significantly decrease the efflux rate (ER) of strychnine and brucine, while the ER of strychnine and brucine was increased significantly when co-administrated with paeoniflorin or albiflorin, indicating that paeoniflorin and albiflorin could promote the efflux of these two alkaloids. Strychnine and brucine could activate the activity of P-gp ATPase, suppress the efflux function of P-gp, but have no significant effect on the expression of P-gp. In addition, strychnine could upregulate the expression of MDR1 mRNA. Paeoniflorin and albiflorin could increase the transmembrane transport of strychnine and brucine mediated by P-gp when co-administrated with strychnine or brucine via stimulating the activity of P-gp ATPase, enhancing the efflux function of P-g, increasing the expression levels of MDR1 mRNA and P-gp.