Xenobiotica ( IF 1.3 ) Pub Date : 2020-11-16 , DOI: 10.1080/00498254.2020.1842941 Xiaofei Ji 1 , Baodong Ding 1 , Xiaoyou Wu 1 , Fengyi Liu 2 , Fengqi Yang 3
Abstract
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Ophiopogonin D is a commonly used herb in cardiology and pediatrics for its variuos pharmacological effects.
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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.
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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.
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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/Kinact 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.
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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.
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
麦冬色素D对细胞色素P450酶活性影响的体外研究
摘要
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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。
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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。
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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。
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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。
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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。