Detection Of The Effects Of Glycyrrhizin Preparation And Its Principal Component Isomers On The CYP3A Activity And P-gp Function

This paper investigates the effects of glycyrrhizin preparations on the activity of CYP3 A enzymes.It also evaluates the effects of different proportions of 18α-glycyrrhizic and 18β-glycyrrhizic on the P-gp function.Chapter1: In this chapter,firstly,the research backgrounds of glycyrrhizin preparations,CYP3 A enzyme and P-gp are introduced;and then,the purpose and significance of the research are expounded.Chapter2: The effects of four generations of glycyrrhizin preparations on the activity of CYP3 A enzymes of rat liver microsomes by HPLC were analyzed.Rat liver microsomes were incubated with various concentrations of glycyrrhizin preparations and testosterone in vitro.The effects of CYP3 A activity of glycyrrhizin preparations were evaluated by the amount of 6β-hydroxy testosterone,which was determined by HPLC.The result show that this method meets the standard of biological sample.The glycyrrhizin preparations can induce or inhibit the enzyme activity of rat liver CYP3 A in vitro.The first and second generations of glycyrrhizin preparations have an obvious inducing effect on the enzymic activity of CYP3 A in rats.On the contrary,the third and fourth generations of glycyrrhizin preparations have a marked inhibition effect on CYP3 A enzymes.The influences of glycyrrhizin preparations on CYP3 A enzymes activity change with concentrations.The research in this paper indicates that it is important to select a reasonable glycyrrhizin preparation in case of drug interactions.The results of this paper can provide reference for the research of clinical co-administrated drugs and dose adjustment.Chapter3:This chapter discusses the effects of different proportions of 18α-glycyrrhizic acid and 18β-glycyrrhizic acid on membrane transport of P-gp substrate rhodamine 123 in Caco-2 cell monolayers.The results show that : at the proportion of 6:4,the P-gp efflux is weakened.At the proportion of 0:10,the P-gp function is the strongest.The results of this research can be applied to further clinical drug research and development with a basic experiment data.