School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China.
Phytother Res. 2010 Nov;24(11):1670-5. doi: 10.1002/ptr.3189.
Tiliroside, an active flavonoid extensively found in many medicinal plants including Helichrysum italicum, Geranium mexicanum and Helianthemum glomeratum, has been demonstrated to exert multiple biological effects including antiinflammatory, antimicrobial, antioxidant and antitumor activities. Cytochrome P450 (CYP) enzymes play an important role in the Phase I oxidation metabolism of a wide range of xenobiotics and inhibition of CYP isoforms might influence the elimination of drugs and induce serious adverse drug response. The inhibition of seven CYP isoforms (CYP3A4, CYP1A2, CYP2A6, CYP2D6, CYP2C9, CYP2C8 and CYP2E1) by tiliroside was investigated using in vitro human liver microsomal incubation assays. The results showed that tiliroside strongly inhibited the activity of CYP3A4 (IC(50) = 9.0 ± 1.7 μm), CYP2C8 (IC(50) = 12.1 ± 0.9 μm) and CYP2C9 (IC(50) = 10.2 ± 0.9 μm) with other CYP isoforms negligibly influenced. Further kinetic analysis showed that inhibition of these three CYP isoforms by tiliroside is best fit to a competitive way. The K(i) value was calculated to be 5.5 μm, 3.3 μm, 9.4 μm for CYP3A4, CYP2C9 and CYP2C8, respectively. The relatively low K(i) values suggested that tiliroside might induce drug-drug interactions with many clinically used drugs which are mainly metabolized by these three CYP isoforms. Therefore, attention should be given to the probable drug-drug interaction between tiliroside-containing herbs and substrates of CYP3A4, CYP2C9 and CYP2C8.
三叶豆紫檀苷是一种广泛存在于多种药用植物中的活性类黄酮，包括 Helichrysum italicum、Geranium mexicanum 和 Helianthemum glomeratum，已被证明具有多种生物学作用，包括抗炎、抗菌、抗氧化和抗肿瘤活性。细胞色素 P450（CYP）酶在广泛的外源物质的 I 相氧化代谢中起着重要作用，CYP 同工酶的抑制可能会影响药物的消除并导致严重的药物不良反应。使用体外人肝微粒体孵育试验研究了三叶豆紫檀苷对 7 种 CYP 同工酶（CYP3A4、CYP1A2、CYP2A6、CYP2D6、CYP2C9、CYP2C8 和 CYP2E1）的抑制作用。结果表明，三叶豆紫檀苷强烈抑制 CYP3A4（IC（50）=9.0±1.7μm）、CYP2C8（IC（50）=12.1±0.9μm）和 CYP2C9（IC（50）=10.2±0.9μm）的活性，而对其他 CYP 同工酶的影响可忽略不计。进一步的动力学分析表明，三叶豆紫檀苷对这三种 CYP 同工酶的抑制作用最佳拟合为竞争方式。CYP3A4、CYP2C9 和 CYP2C8 的 K（i）值分别为 5.5μm、3.3μm 和 9.4μm。相对较低的 K（i）值表明，三叶豆紫檀苷可能会与许多主要由这三种 CYP 同工酶代谢的临床用药物发生药物相互作用。因此，应注意含三叶豆紫檀苷的草药与 CYP3A4、CYP2C9 和 CYP2C8 底物之间可能发生的药物相互作用。
