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目的:探讨左金丸对人肝细胞色素P450的CYP1A2/2C8/2C9/2C19/2D6/3A4亚型的体外抑制作用。方法:左金丸、黄连和吴茱萸的水提物分别与CYP1A2/2C8/2C9/2C19/2D6/3A4/3A4亚型的7种混合探针底物在人肝微粒体中共同孵育后,采用液相色谱-串联质谱法(LC-MS/MS)同时测定这7种代谢产物(对乙酰氨基酚/6α-羟基紫杉醇/4-羟基双氯芬酸/4-羟基美芬妥英/右啡烷/1-羟基咪达唑仑/6β-羟基睾酮)的浓度,计算其IC_(50)值表示对该亚型的抑制程度。结果:在人肝微粒体体外孵育体系中,左金丸提取物对CYP2D6的IC_(50)值为11.6μg·ml~(-1),对CYP1A2和CYP3A4的IC_(50)值分别为77.4μg·ml~(-1)和97.0μg·ml~(-1),对其他亚型的IC_(50)值从334μg·ml~(-1)到690μg·ml~(-1);黄连提取物对CYP2D6的IC_(50)值为5.8μg·ml~(-1),对CYP1A2和CYP3A4的IC_(50)值分别为36.8μg·ml~(-1)和59.2μg·ml~(-1),对其他亚型的IC_(50)值从163μg·ml~(-1)到476μg·ml~(-1);吴茱萸提取物对CYPs的IC_(50)值均大于107μg·ml~(-1)。结论:左金丸在体外对人肝微粒体CYP2D6活性有抑制作用,对CYP1A2和CYP3A4活性有弱的抑制作用,其君药黄连在该抑制作用中起到了主要作用,在联合用药时应注意左金丸与CYP2D6相关的药物相互作用。
Objective: To investigate the inhibitory effect of Zuojin Pill on CYP1A2 / 2C8 / 2C9 / 2C19 / 2D6 / 3A4 subtypes of human hepatocyte cytochrome P450 in vitro. Methods: The aqueous extracts of Zuojin pill, Coptis chinensis and Evodia rutaecarpa were co-incubated with seven hybrid probe substrates of CYP1A2 / 2C8 / 2C9 / 2C19 / 2D6 / 3A4 / 3A4 subtypes respectively in human liver microsomes. The seven metabolites (acetaminophen / 6α-hydroxy paclitaxel / 4-hydroxy diclofenac / 4-hydroxymerphenomethacin / dextrorphan / 1-hydroxy Midazolam / 6 [beta] -hydroxytestosterone), and calculating its IC50 value indicates the degree of inhibition of this subtype. Results: The IC 50 value of CYP2D6 was 11.6 μg · ml -1 and the IC 50 values of CYP1A2 and CYP3A4 were 77.4 μg · ml -1 and 97.0 μg · ml -1, and the IC 50 values of other subtypes ranged from 334 μg · ml -1 to 690 μg · ml -1. The IC 50 values of CYP2D6 were 5.8 μg · ml -1 and the IC 50 values of CYP1A2 and CYP3A4 were 36.8 μg · ml -1 and 59.2 μg · ml -1, The IC 50 values of other subtypes ranged from 163 μg · ml -1 to 476 μg · ml -1. The IC 50 values of Evodia rutaecarpa extract on CYPs were all above 107 μg · ml -1, . CONCLUSION: Zuojin pills can inhibit the activity of CYP2D6 in human liver microsome in vitro and weakly inhibit the activity of CYP1A2 and CYP3A4. Its main drug, Coptis chinensis, plays a major role in this inhibitory effect. When combined with Zuojin pills, CYP2D6-related drug interactions.