Abstract

1. The effect of 4-O-galloylalbiflorin on the activity of cytochrome P450 enzymes (CYP450s) is an important factor that may induce drug-drug interaction.

2. 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.

3. 4-O-galloylalbiflorin significantly inhibited the activity of CYP3A, 2C9, and 2 D 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 4.0 μM and the KI/Kinact value of 2.2/0.030 (μM·min). The inhibition of CYP2C9 and 2 D 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.

4. The inhibitory effect of 4-O-galloylalbiflorin on the activity of CYP3A, 2C9, and 2 D implying the potential drug-drug interaction between 4-O-galloylalbiflorin and the drugs metabolized by these CYP450s.

摘要

1. 4-O-galloylalbiflorin 对细胞色素 P450 酶 (CYP450s) 活性的影响是可能诱发药物相互作用的重要因素。

2. 在混合的人肝微粒体中，在 0、2.5、5、10、25、50 和 100 μM 4-O-galloylalbiflorin 存在的情况下，评估了 4-O-galloylalbiflorin 对 CYP450 活性的影响。通过与 Lineweaver-Burk 图拟合来评估抑制模型和相应参数。时间依赖性研究以 0、5、10、15 和 30 分钟的孵育时间进行。

3. 4-O-galloylalbiflorin 以浓度依赖性方式显着抑制 CYP3A、2C9 和 2D 的活性，IC50 值分别为 8.2、13 和 11 μM。发现CYP3A 的抑制是非竞争性和时间依赖性的，Ki 值为4.0 μM，KI/Kinact 值为2.2/0.030 (μM·min)。CYP2C9 和 2 D 的抑制不受孵育时间的影响，但发现分别与 6.7 和 6.6 μM 的 Ki 值具有竞争性。

4. 4-O-galloylalbiflorin 对 CYP3A、2C9 和 2D 活性的抑制作用表明 4-O-galloylalbiflorin 与这些 CYP450 代谢的药物之间存在潜在的药物相互作用。