和厚朴酚对人肝微粒体细胞色素 P450 和 UDP-葡糖醛酸基转移酶活性的影响。
Effect of honokiol on cytochrome P450 and UDP-glucuronosyltransferase enzyme activities in human liver microsomes.
机构信息
College of Pharmacy, the Catholic University of Korea, Bucheon 420-743, Korea.
出版信息
Molecules. 2013 Sep 3;18(9):10681-93. doi: 10.3390/molecules180910681.
Honokiol is a bioactive component isolated from the medicinal herbs Magnolia officinalis and Magnolia grandiflora that has antioxidative, anti-inflammatory, antithrombotic, and antitumor activities. The inhibitory potentials of honokiol on eight major human cytochrome P450 (CYP) enzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4, and four UDP-glucuronosyltransferases (UGTs) 1A1, 1A4, 1A9, and 2B7 in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. Honokiol strongly inhibited CYP1A2-mediated phenacetin O-deethylation, CYP2C8-mediated amodiaquine N-deethylation, CYP2C9-mediated diclofenac 4-hydroxylation, CYP2C19-mediated [S]-mephenytoin 4-hydroxylation, and UGT1A9-mediated propofol glucuronidation with K(i) values of 1.2, 4.9, 0.54, 0.57, and 0.3 μM, respectively. Honokiol also moderately inhibited CYP2B6-mediated bupropion hydroxylation and CYP2D6-mediated bufuralol 1'-hydroxylation with K(i) values of 17.5 and 12.0 μM, respectively. These in vitro results indicate that honokiol has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2, CYP2C8, CYP2C9, CYP2C19, and UGT1A9.
和厚朴酚是从厚朴和凹叶厚朴等药用植物中分离得到的一种生物活性成分，具有抗氧化、抗炎、抗血栓形成和抗肿瘤活性。采用液相色谱-串联质谱法研究了和厚朴酚对人肝微粒体中 8 种主要细胞色素 P450（CYP）酶 1A2、2A6、2B6、2C8、2C9、2C19、2D6 和 3A4 以及 4 种 UDP-葡萄糖醛酸基转移酶（UGT）1A1、1A4、1A9 和 2B7 的抑制作用。和厚朴酚强烈抑制 CYP1A2 介导的苯乙酮 O-去乙基化、CYP2C8 介导的氨苯砜 N-去乙基化、CYP2C9 介导的双氯芬酸 4-羟基化、CYP2C19 介导的[S]-美芬妥因 4-羟基化和 UGT1A9 介导的丙泊酚葡萄糖醛酸化，Ki 值分别为 1.2、4.9、0.54、0.57 和 0.3 μM。和厚朴酚还中度抑制 CYP2B6 介导的丁丙诺啡羟化和 CYP2D6 介导的布福洛尔 1'-羟化，Ki 值分别为 17.5 和 12.0 μM。这些体外结果表明，和厚朴酚有可能与其他同时服用的经 CYP1A2、CYP2C8、CYP2C9、CYP2C19 和 UGT1A9 代谢的药物发生药物相互作用。
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