Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
J Mol Model. 2012 Oct;18(10):4657-63. doi: 10.1007/s00894-012-1472-6. Epub 2012 May 31.
Flavonoid extracts are widely used for preventing and treating ischemic heart disease. However, because many flavonoid extracts have been verified to inhibit CYP2D6 the main metabolic enzyme for the majority of antiarrhythmics and beta-blockers, co-administration of flavonoid extracts with these drugs may cause adverse herb-drug interaction in clinic. Here, we evaluated 43 common flavonoids on CYP2D6 inhibition in sillico and four commercial flavonoid extracts in vivo on the pharmacokinetics and pharmacodynamics of metoprolol in rats. Surprisingly, we found that the core skeletons of flavonoids instead of their substituents determine the extent of inhibiting CYP2D6 by a flavonoid extract. Isoflavones are less likely to inhibit CYP2D6, compared with other categories of flavonoids. Consistently, co-administration of soy extract that mainly contains isoflavones did not significantly increase plasma concentration of metoprolol and alter the systolic blood pressure of rats. Our results have implication in rationally selecting flavonoid extracts for therapeutic application.
类黄酮提取物广泛用于预防和治疗缺血性心脏病。然而，由于许多类黄酮提取物已被证实抑制 CYP2D6，这是大多数抗心律失常药和β受体阻滞剂的主要代谢酶，因此类黄酮提取物与这些药物同时使用可能会导致临床上的不良草药-药物相互作用。在这里，我们在计算机上评估了 43 种常见的类黄酮对 CYP2D6 的抑制作用，并在体内评估了四种商业类黄酮提取物对大鼠美托洛尔药代动力学和药效学的影响。令人惊讶的是，我们发现类黄酮提取物抑制 CYP2D6 的程度取决于类黄酮的核心骨架，而不是取代基。与其他类黄酮相比，异黄酮不太可能抑制 CYP2D6。同样，主要含有异黄酮的大豆提取物的联合使用并没有显著增加美托洛尔的血浆浓度，也没有改变大鼠的收缩压。我们的研究结果对于合理选择类黄酮提取物用于治疗具有重要意义。
