Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan, Korea.
Molecules. 2010 Sep 16;15(9):6466-75. doi: 10.3390/molecules15096466.
Eupatilin and jaceosidin are bioactive flavones found in the medicinal herbs of the genus Artemisia. These bioactive flavones exhibit various antioxidant, antiinflammatory, antiallergic, and antitumor activities. The inhibitory potentials of eupatilin and jaceosidin on the activities of seven major human cytochrome P450 enzymes in human liver microsomes were investigated using a cocktail probe assay. Eupatilin and jaceosidin potently inhibited CYP1A2-catalyzed phenacetin O-deethylation with 50% inhibitory concentration (IC(50)) values of 9.4 microM and 5.3 microM, respectively, and CYP2C9-catalyzed diclofenac 4-hydroxylation with IC(50) values of 4.1 microM and 10.2 microM, respectively. Eupatilin and jaceosidin were also found to moderately inhibit CYP2C19-catalyzed [S]-mephenytoin 4'-hydroxylation, CYP2D6-catalyzed bufuralol 1'-hydroxylation, and CYP2C8-catalyzed amodiaquine N-deethylation. Kinetic analysis of human liver microsomes showed that eupatilin is a competitive inhibitor of CYP1A2 with a K(i) value of 2.3 microM and a mixed-type inhibitor of CYP2C9 with a K(i) value of 1.6 microM. Jaceosidin was shown to be a competitive inhibitor of CYP1A2 with a K(i) value of 3.8 microM and a mixed-type inhibitor of CYP2C9 with K(i) value of 6.4 microM in human liver microsomes. These in vitro results suggest that eupatilin and jaceosidin should be further examined for potential pharmacokinetic drug interactions in vivo due to inhibition of CYP1A2 and CYP2C9.
蒙花苷和芹黄素是存在于蒿属药用植物中的生物活性类黄酮。这些生物活性类黄酮表现出各种抗氧化、抗炎、抗过敏和抗肿瘤活性。采用鸡尾酒探针法，研究了蒙花苷和芹黄素对人肝微粒体中 7 种主要人细胞色素 P450 酶活性的抑制潜力。蒙花苷和芹黄素强烈抑制 CYP1A2 催化的苯乙酮 O-去乙基化，半数抑制浓度（IC50）值分别为 9.4 μM 和 5.3 μM，并且分别抑制 CYP2C9 催化的双氯芬酸 4-羟化，IC50 值分别为 4.1 μM 和 10.2 μM。蒙花苷和芹黄素还中度抑制 CYP2C19 催化的[S]-美芬妥因 4'-羟化，CYP2D6 催化的布氟洛尔 1'-羟化和 CYP2C8 催化的氨喹啉 N-去乙基化。人肝微粒体的动力学分析表明，蒙花苷是 CYP1A2 的竞争性抑制剂，K i 值为 2.3 μM，是 CYP2C9 的混合型抑制剂，K i 值为 1.6 μM。芹黄素被证明是 CYP1A2 的竞争性抑制剂，K i 值为 3.8 μM，是 CYP2C9 的混合型抑制剂，K i 值为 6.4 μM，在人肝微粒体中。这些体外结果表明，由于对 CYP1A2 和 CYP2C9 的抑制作用，蒙花苷和芹黄素应进一步在体内研究其潜在的药代动力学药物相互作用。
