Effect of glycyrrhetinic acid C-18 epimerides on P-glycoprotein function and expression in Caco-2 cells / 中国药学杂志

ABSTRACT

OBJECTIVE: The aim of our work was to study the effects of C-18 epimers of glycyrrhetinic acid, 18α-glycyrrhetinic acid (α-GA) and 18β-glycyrrhetinic acid (β-GA) on the function and expression of P-gp in Caco-2 cell monolayers. METHODS: Caco-2 cells were cultured, the effects of P-gp function were analyzed by means of rhodamine accumulation test, real-time PCR was used to measure the expression of MDR1 mRNA and western blot was used to analysis P-gp expression in Caco-2 cell. RESULTS: In the rhodamine accumulation test, middle and high concentrations (1 and 10 μmol · L-1) α-GA and high concentration (10 μmol · L-1) β-GA decreased the cellular rhodamine concentration. At high concentrations (10 μmol · L-1), α-GA up-regulated the expression of MDR1 mRNA while β-GA has no effect on the expression of MDR1 mRNA at three test concentrations. α-GA up-regulated the expression of P-gp protein at high concentrations (10 μmol · L-1) while β-GA has no effect on the expression of P-gp protein at three test concentrations. CONCLUSION: Our findings provide experimental evidence that α-GA up-regulated both function and expression of P-gp while β-GA only up-regulate the function of P-gp.