黄连解毒汤对人细胞色素P450酶6个亚型的体外抑制作用研究

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (2): 131-136.

黄连解毒汤对人细胞色素P450酶6个亚型的体外抑制作用研究

李丹^1,2, 韩永龙^2,3, 余涛¹, 傅瑶^1,2, 孟祥乐^1,2, 余奇², 郭澄²

¹上海中医药大学, 上海 201203;
²上海交通大学附属第六人民医院药剂科, 上海 200233;
³大庆油田总医院临床药学科, 大庆 163001,黑龙江

收稿日期:2011-09-19 修回日期:2011-12-08 出版日期:2012-02-26 发布日期:2012-03-12
通讯作者: 郭澄,男,博士,教授,主任药师,博士生导师,主要从事中药学与临床药理学研究。Tel: 021-24058098
作者简介:李丹,女,在读博士研究生,主要从事中药药物代谢与药代动力学研究。Tel: 021-24058789 E-mail: lidandorren@126.com;韩永龙,男,共同第一作者,博士,副主任药师,主要从事药物代谢与临床药学研究。Tel: 13836991155 E-mail: yonglongh@sina.com
基金资助:
上海市医院协会科研基金(201002029);上海市药学会(2010-YY-01-03)

In vitro inhibition of Huanglianjiedu Decoction on 6 cytochrome P450 isoforms in human liver microsomes

LI Dan^1,2, HAN Yong-long^1,3, YU Tao¹, Fu Yao^1,2, MENG Xiang-le^1,2, YU Qi², GUO Cheng²

¹Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
²Department of Pharmacy, the Sixth People's Hospital of Shanghai, Affiliated to Shanghai Jiaotong University, Shanghai 200233, China;
³Department of Clinical Pharmacy, Daqing Oilfield General Hospital, Daqing 163001, Heilongjiang, China

Received:2011-09-19 Revised:2011-12-08 Online:2012-02-26 Published:2012-03-12

摘要/Abstract

摘要： 目的: 研究黄连解毒汤对人肝微粒体6个亚型CYP1A2、CYP2C8、CYP2C9、CYP2C19、CYP2D6和CYP3A4的体外抑制作用。方法: 采用液相色谱-串联质谱法(LC-MS/MS)同时测定对乙酰氨基酚、6α-羟基紫杉醇、4-羟基双氯芬酸、4-羟基美芬妥英、右啡烷、1-羟基咪达唑仑和6β-羟基睾酮,分别代表CYP1A2、CYP2C8、CYP2C9、CYP2C19、CYP2D6和CYP3A4的活性;黄连解毒汤提取物和7种混合探针底物在人肝微粒体中共同孵育,并计算其IC₅₀值表示对CYP450酶的抑制程度。结果: 在人肝微粒体体外孵育体系中,黄连解毒汤对CYP2D6的IC₅₀值为 3.54 μg/mL,对CYP1A2的IC₅₀值为 10.8 μg/mL,对CYP2C8、CYP2C9、CYP2C19、CYP3A4_T和CYP3A4_M亚酶的IC₅₀值依次为 67.7、299、530、199和 607 μg/mL。结论: 在正常剂量下,黄连解毒汤对人肝微粒体CYP2D6和1A2可能有抑制作用,对人肝微粒体CYP2C8、CYP2C9、CYP2C19和CYP3A4无明显抑制作用。

关键词: 黄连解毒汤, 细胞色素P450酶, 抑制作用, 药物相互作用

Abstract: AIM: To predict the herb-drug interactions in clinical application, Huanglianjiedu Decoction was evaluated for its in vitro inhibition effect on 6 cytochrome P450 isoforms (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in human liver microsomes.METHODS: Seven metabolites of cytochrome P450 probe substrate (including Paracetamol for CYP1A2, 6α- Hydroxypaclitaxel for CYP2C8, 4-Hydroxydiclofenac for CYP2C9, 4-Hydroxymephenytoin for CYP2C19, Dextrorphan for CYP2D6, 6β-Hydroxytestosterone and 1-Hydroxymidazolam for CYP3A4) were simultaneously measured by LC-MS/MS. Huanglianjiedu Decoction was incubated with human liver microsomes in the presence of seven probe substrates of CYP450 isforms, and the inhibitory effect were evaluated with IC₅₀ values.RESULTS: IC₅₀ value of Huanglianjiedu Decoction on CYP2D6 and CYP1A2 were 3.54 and 10.8 μg/mL, and the other IC₅₀ values were 67.7, 299, 530, 199 and 607 μg/mL with respect to CYP2C8, CYP2C9, CYP2C19, CYP3A4_T and CYP3A4_M isoforms.CONCLUSION: Huanglianjiedu Decoction shows inhibitory effect on CYP2D6 and CYP1A2, but minor inhibitory effects on CYP2C8, CYP2C9, CYP2C19 and CYP3A4.

Key words: Huanglianjiedu Decoction, Cytochrome P450, Inhibition, Drug-drug interactions

中图分类号:

R965.2

李丹, 韩永龙, 余涛, 傅瑶, 孟祥乐, 余奇, 郭澄. 黄连解毒汤对人细胞色素P450酶6个亚型的体外抑制作用研究[J]. 中国临床药理学与治疗学, 2012, 17(2): 131-136.

LI Dan, HAN Yong-long, YU Tao, Fu Yao, MENG Xiang-le, YU Qi, GUO Cheng. In vitro inhibition of Huanglianjiedu Decoction on 6 cytochrome P450 isoforms in human liver microsomes[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(2): 131-136.

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