Abstract

1. Ophiopogonin D is a commonly used herb in cardiology and pediatrics for its variuos pharmacological effects.

2. It is necessary to investigate the effect of ophiopogonin D on the activity of cytochrome P450 enzymes (CYP450s) to provide more guidance for the clinical application of ophiopogonin D.

3. Eight isoforms of CYP450s, including CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 were incubated with 100 μM ophiopogonin D in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated.

4. Ophiopogonin D exerted a significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 8.08, 12.92, and 22.72 μM, respectively (p < 0.05). The inhibition of CYP3A4 by ophiopogonin D was performed non-competitively and time-dependently with the Ki value of 4.08 μM and the KI/K_inact value of 5.02/0.050 min⁻¹·μM⁻¹. Whereas, ophiopogonin D acts as a competitive inhibitor of CYP2E1 and 2C9 with the Ki value of 6.69 and 11.07 μM, respectively.

5. The inhibitory effect of ophiopogonin D on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between ophiopogonin D and drugs metabolized by these CYP450s, which needs further in vivo investigation and validation.

摘要

1. 麦冬D素因其多种药理作用而成为心脏病学和儿科的常用草药。

2. 有必要研究麦冬色素D对细胞色素P450酶（CYP450s）活性的影响，为麦冬色素D的临床应用提供更多指导。

3. 将CYP450的八种同工型（包括CYP1A2、2A6、2C8、2C9、2C19、2D6、2E1和3A4）与100μMophiopogonin D在合并的人肝微粒体中孵育。还研究了抑制模型和相应的参数。

4. 麦草素D对CYP3A4、2C9和2E1的活性具有剂量依赖性，IC50值分别为8.08、12.92和22.72μM（p  <0.05）。麦草碱D对CYP3A4的抑制作用是非竞争性和时间依赖性的，Ki值为_4.08μM，KI / K_无效 值为5.02 / 0.050 min ^-1 ·μM ^-1。ophophpogonin D作为CYP2E1和2C9的竞争性抑制剂，其Ki值分别为6.69和11.07μM。

5. ophiopogonin D对CYP3A4、2C9和2E1活性的抑制作用表明ophiopogonin D与这些CYP450代谢的药物之间存在潜在的药物相互作用，需要进一步的体内研究和验证。