Abstract:The present study was designed to investigate the effect of different ratios of 18α-glycyrrhizic acid (18α-GA) and 18β-glycyrrhizic acid (18β-GA) on P-gp function and CYP3A activity. A Caco-2 cell monolayers model was established. The fluorescence intensity of the rhodamine 123 solution in the receiving pool was determined to investigate the effects of different ratios of 18α-GA and 18β-GA on P-gp transport function. Microsomes were made from the liver of rats, and the effects of different concentrations and different ratios of 18α and 18β-GA on the activity of CYP3A were analyzed after incubation. The ratio of 18α-GA and 18β-GA at 6:4 exhibited the strongest inhibitory effect on P-gp, whilst the ratio at 0:10 led to the strongest induction of P-gp. The concentration of 18α-GA in the range of 50~100 μg/mL significantly inhibited the activity of CYP3A, whilst 18β-GA at 10~50 μg/mL significantly induced the activity of CYP3A. The induction of CYP3A was the strongest, when the ratio of 18α-GA and 18β-GA was at 2:8 and the total GA concentration was at 10 μg/mL. Such an induction was greater than that for 18β-GA at the same concentration. As the GA concentration and the 18α-GA to 18β-GA ratio increased, the inhibition of CYP3A enzymatic activity was enhanced. At the 18α-GA to 18β-GA ratio of 10:0 and the total GA concentration of 100 μg/mL, the inhibition of CYP3A enzyme was the strongest. Different ratios of 18α-GA and18β-GA exhibited different effects on P-gp transport function and CYP3A enzymatic activity in rats, which would provide scientific basis for guiding clinical drug therapy.
