4-O-galloylalbiflorin inhibits the activity of CYP3A, 2C9, and 2D in human liver microsomes

Abstract

The effect of 4-O-galloylalbiflorin on the activity of cytochrome P450 enzymes (CYP450s) is an important factor that may induce drug-drug interaction. The effect of 4-O-galloylalbiflorin on the activity of CYP450s was evaluated in the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM 4-O-galloylalbiflorin in pooled human liver microsomes. The inhibition model and corresponding parameters were assessed b fitting with Lineweaver-Burk plots. The time-dependent study was performed with the incubation time of 0, 5, 10, 15, and 30 min. 4-O-galloylalbiflorin significantly inhibited the activity of CYP3A, 2C9, and 2D in a concentration-dependent manner with the IC50 values of 8.2, 13, and 11 μM, respectively. The inhibition of CYP3A was found to be non-competitive and time-dependent with the Ki value of 4.02 μM and the KI/Kinact value of 2.2/0.030 (μM·min). The inhibition of CYP2C9 and 2D was not affected by the incubation time but was found to be competitive with the Ki values of 6.7 and 6.6 μM, respectively. The inhibitory effect of 4-O-galloylalbiflorin on the activity of CYP3A, 2C9, and 2D implying the potential drug-drug interaction between 4-O-galloylalbiflorin and the drugs metabolized by these CYP450s.