Studies on effects and mechanisms of P-gp and MRP1 inhibitor on transportation of gastrodin / 中草药

ABSTRACT

Objective: To study the effects and mechanisms of p-glycoprotein (P-gp) inhibitor and MRP1 inhibitor on the transportation of gastrodin (GAS). Methods: Cell toxicity of GAS was detected by MTT assay, molecular Docking was employed to predicted binding mode and effect ability of GAS with P-gp and MRP1. MDCK-MDR1 cell model was employed to study the influences of Ver, a P-gp inhibitor, and Probenecid, a MRP1 inhibitor, on the transportation of GAS. Results: There was no cell cytotoxicity of GAS between the concentration of 100 to 1000 μg/mL. There was hydrogen-bond and hydrophobic interaction between P-gp and GAS, and hydrogen-bond, hydrophobic interaction and electrostatic-interaction between MRP1 and GAS. LibDock Score indicated that both P-gp-verapamil (Ver) and MRP1-Probenecid were more stable than P-gp-GAS and MRP1-GAS. The Papp of GAS BL→AP was greater than that of AP→BL, Efflux ratio (ER) of GAS was about 1.5, which indicated the efflux pump protein might involve the transportation of GAS. The Papp of GAS was significant increased but the ER of GAS was significant decreased when co-administrated with Ver (P<0.05). The Papp of GAS was slightly increased and the ER of GAS was slightly decreased when co-administrated with Probenecid, while there was no significance. Conclusion: The results indicate that GAS is the substrate of P-gp. However, whether GAS is the substrate of MRP1 needs further research. Both Ver and Probenecid could enhance the transportation of GAS by competitive binding with P-gp and MRP1.