Effect of glycyrrhetinic acid C-18 epimerides on membrane transport of P-gp substrate rhodamine 123 in Caco-2 cell monolayers / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the effects of C-18 epimers of glycyrrhetinic acid, 18α-glycyrrhetinic acid(α-GA) and 18β-glycyrrhetinic acid(β-GA), on membrane transport of P-gp substrate rhodamine 123 in Caco-2 cell monolayers. METHODS: MTT assay was applied to determine the maximum non-cytotoxic dose of α-GA, β-GA and verapamil to ensure the activity of the cells during the test and to consult the maximum test concentration of each drug; appropriate Caco-2 monolayers were established in Transwell™ plates. ELISA Reader was applied to detect the concentration of Rho-123 in transfer fluid. The bi-directional transport of Rho-123 after being treated by instantaneous action and incubation with α-GA and β-GA for 72 h was studied. RESULTS: High concentration (10 μmol · L-1) of α-GA induced the efflux of Rho-123 both in the instantaneous action test and the incubation test. High concentration (10 μmol · L-1) of β-GA induced the efflux of Rho-123 only in the incubation test. The transport from AP to BL was not affected by any test drugs. CONCLUSION: The results of the transport experiments of P-gp substrates in Caco-2 monolayers indicated that α-GA and β-GA can induce the efflux function of P-gp and accelerate the excretion of P-gp substrates. It may be one of the mechanisms of that glycyrrhizin preparation enhances liver detoxification. Copyright 2012 by the Chinese Pharmaceutical Association.