Effect of Fuzi(Radix Aconiti Carmichaeli)on P-glycoprotein and Tight Junction Protein and Its Herb-Drug Interaction with Digoxin
Objective:To investigate the effect of Fuzi(Radix Aconiti Carmichaeli)on the efflux activity of P-glycoprotein(P-gp)and tight junction protein in Caco-2 cells,and to study the effect and mechanism of Fuzi(Radix Aconiti Carmichaeli)combined with medication on digoxin.Methods:The effects of Fuzi(Radix Aconiti Carmichaeli)on the efflux activity and function of P-gp were studied by measuring the efflux and uptake of Rh-123 and the changes of ATP level in Caco-2 cells.The effect of Fuzi(Radix Aconiti Carmichaeli)on the expression of tight junction protein was investigated by cell immunofluorescence assay.According to Caco-2 cell model absorption transport experiment and molecular docking,the effect and mechanism of Fuzi(Radix Aconiti Carmichaeli)combined with drugs on the intracellular transport of digoxin were elucidated.Results:Fuzi(Radix Aconiti Carmichaeli)shows a two-way regulatory effect on P-glycoprotein,and it may be related to the action time.Fuzi(Radix Aconiti Carmichaeli)can affect the efflux function of P-gp by regulating ATP level.The long-term effect(72 h)of Fuzi(Radix Aconiti Carmichaeli)may promote the efflux of digoxin.Fuzi(Radix Aconiti Carmichaeli)can increase the expression of tight junction proteins ZO-1 and Occludin in Caco-2 cells,and it is speculated that the absorption of digoxin may be weakened by inhibiting the cell bypass pathway.Conclusion:When Fuzi(Radix Aconiti Carmichaeli)is combined with digoxin,it may affect the blood concentration of digoxin by reducing absorption and promoting efflux.
万方数据
维普
