Transport characteristics of ligustrazine across Caco-2 cell monolayer model and its effect on P-glycoprotein expression

Objective To investigate the transport characteristics of ligustrazine across Caco-2 cell monolayer and the effect on P-glycoprotein(P-gp) expression.Methods Safe concentration range of ligustrazine against Caco-2 cell monolayer model was selected by the MTT method.The mechanism of ligustrazine bidirectional transport was investigated by Caco-2 cell monolayer model.The influences of time,concentration,and P-gp inhibitor Verapamil on the transport of ligustrazine were studied using apparent permeability coefficient(Papp) as index.P-gp expression in Caco-2 cells was analyzed by the Western blotting method.Results The Papp of transport from apical(AP) side to basolateral(BL) side was over 10 6cm/s,which showed a good absorption.In the Caco-2 cell model,the transport amount of ligustrazine was positively correlated with time and concentration,and the transport amount from AP side to BL side was higher than that from BL to AP.The absorption of ligustrazine was not only rejected by P-gp,but also the P-gp expression was inhibited by ligustrazine.Conclusion The transport of ligustrazine across Caco-2 cell monolayer model is deduced as passive transport,ligustrazine is rejected by P-gp,and there is an inhibition of ligustrazine on the expression of P-gp.