a Department of Pharmacy , Yidu Central Hospital of Weifang , Shandong , China.
Pharm Biol. 2018 Dec;56(1):620-625. doi: 10.1080/13880209.2018.1525413.
Bergenin, isolated from the herb of Bergenia purpurascens (Hook. f. et Thoms.) Engl., has anti-inflammatory, antitussive, and wound healing activities. However, whether bergenin affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear.
In this study, the inhibitory effects of bergenin (100 μM) on the eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated, enzyme kinetics and time-dependent inhibition studies were also performed in vitro using human liver microsomes (HLMs).
The results showed that bergenin inhibited the activity of CYP3A4, 2E1 and 2C9, with IC values of 14.39, 22.83 and 15.11 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that bergenin was not only a non-competitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2E1 and 2C9, with K values of 7.71, 11.39 and 8.89 μM, respectively. In addition, bergenin is a time-dependent inhibitor for CYP3A4 with K/K value of 0.025/3.50 μMmin.
The in vitro studies of bergenin with CYP isoforms indicate that bergenin has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, 2E1 and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.
从虎耳草科植物（ Bergenia purpurascens （Hook. f. et Thoms.） Engl.）中分离得到的小檗碱具有抗炎、镇咳和促进伤口愈合的作用。然而，小檗碱是否影响人肝细胞色素 P450（CYP）酶的活性尚不清楚。
在本研究中，研究了小檗碱（100μM）对 8 个人肝 CYP 同工酶（即 1A2、3A4、2A6、2E1、2D6、2C9、2C19 和 2C8）的抑制作用，并用人肝微粒体（HLMs）进行了体外酶动力学和时间依赖性抑制研究。
结果表明，小檗碱抑制 CYP3A4、2E1 和 2C9 的活性，IC 值分别为 14.39、22.83 和 15.11μM，而其他 CYP 同工酶不受影响。酶动力学研究表明，小檗碱不仅是 CYP3A4 的非竞争性抑制剂，也是 CYP2E1 和 2C9 的竞争性抑制剂，K 值分别为 7.71、11.39 和 8.89μM。此外，小檗碱是 CYP3A4 的时间依赖性抑制剂，K/K 值为 0.025/3.50μMmin。
小檗碱与 CYP 同工酶的体外研究表明，小檗碱有可能与其他同时服用的经 CYP3A4、2E1 和 2C9 代谢的药物发生药物相互作用。需要进一步的临床研究来评估这种相互作用的意义。
