Effect of honokiol on the induction of drug-metabolizing enzymes in human hepatocytes.
Effect of honokiol on the induction of drug-metabolizing enzymes in human hepatocytes.
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DOI：
10.2147/dddt.s72305
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Lee HS
中科院分区：
文献类型：
--
作者：
Cho YY;Jeong HU;Kim JH;Lee HS
Honokiol，2-(4-羟基-3-丙-2-烯基-苯基)-4-丙-2-烯基-苯酚，是厚朴和广玉兰的活性成分，具有抗肿瘤、抗氧化、抗炎、神经营养和抗血栓等多种药理活性。为了研究和厚朴酚是否在药物相互作用中发挥作用，通过实时逆转录聚合酶链反应分析了 I 期和 II 期药物代谢酶（包括细胞色素 P450 (CYP)、UDP-葡萄糖醛酸基转移酶 (UGT) 和磺基转移酶 2A1 (SULT2A1)）的信使核糖核酸 (mRNA) 水平，如下 三个独立冷冻保存的人肝细胞培养物中和厚朴酚暴露 48 小时。在三种不同的肝细胞培养物中，最高测试浓度 (50 μM) 的和厚朴酚处理使 CYP2B6 mRNA 水平和 CYP2B6 催化的安非他酮羟化酶活性增加两倍以上，表明和厚朴酚在更高浓度下诱导 CYP2B6。然而，和厚朴酚处理（0.5-50 μM）并没有显着改变冷冻保存的人肝细胞培养物中 I 相酶（CYP1A2、CYP3A4、CYP2C8、CYP2C9 和 CYP2C19）或 II 相酶（UGT1A1、UGT1A4、UGT1A9、UGT2B7 和 SULT2A1）的 mRNA 水平。在冷冻保存的人肝细胞中，CYP1A2 催化的非那西丁 O-脱乙基酶和 CYP3A4 催化的咪达唑仑 1'-羟化酶活性不受和厚朴酚处理 48 小时的影响。这些结果表明和厚朴酚是一种弱 CYP2B6 诱导剂，不太可能增加伴随的 CYP2B6 底物的代谢并在人体中引起基于药代动力学的药物相互作用。
Honokiol, 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol, an active component of Magnolia officinalis and Magnolia grandiflora, exerts various pharmacological activities such as antitumorigenic, antioxidative, anti-inflammatory, neurotrophic, and antithrombotic effects. To investigate whether honokiol acts as a perpetrator in drug interactions, messenger ribonucleic acid (mRNA) levels of phase I and II drug-metabolizing enzymes, including cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT), and sulfotransferase 2A1 (SULT2A1), were analyzed by real-time reverse transcription polymerase chain reaction following 48-hour honokiol exposure in three independent cryopreserved human hepatocyte cultures. Honokiol treatment at the highest concentration tested (50 μM) increased the CYP2B6 mRNA level and CYP2B6-catalyzed bupropion hydroxylase activity more than two-fold in three different hepatocyte cultures, indicating that honokiol induces CYP2B6 at higher concentrations. However, honokiol treatment (0.5–50 μM) did not significantly alter the mRNA levels of phase I enzymes (CYP1A2, CYP3A4, CYP2C8, CYP2C9, and CYP2C19) or phase II enzymes (UGT1A1, UGT1A4, UGT1A9, UGT2B7, and SULT2A1) in cryopreserved human hepatocyte cultures. CYP1A2-catalyzed phenacetin O-deethylase and CYP3A4-catalyzed midazolam 1′-hydroxylase activities were not affected by 48-hour honokiol treatment in cryopreserved human hepatocytes. These results indicate that honokiol is a weak CYP2B6 inducer and is unlikely to increase the metabolism of concomitant CYP2B6 substrates and cause pharmacokinetic-based drug interactions in humans.