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中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (8): 922-926.

• 临床药理学 • 上一篇    下一篇

和厚朴酚等五种中药有效成分对CYP酶活性的体外抑制作用

张培玉1,2,任 静1,2,职文倩1,2,刘澄铭1,2,郜 娜1   

  1. 1 郑州大学临床药理研究所;2 郑州大学临床医学系,郑州 450052,河南
  • 收稿日期:2016-04-11 修回日期:2016-07-20 出版日期:2017-08-26 发布日期:2017-08-18
  • 通讯作者: 郜娜,女,博士,副教授,研究方向:药动学。 Tel:0371-66658363 E-mail: gaonawei@zzu.edu.cn
  • 作者简介:张培玉,女,本科,研究方向:临床医学。 Tel:18337161729 E-mail:1023352402@qq.com
  • 基金资助:

    河南省高等学校重点科研项目(15A310025);郑州大学全国大学生创新创业训练计划资助项目(2014xjxm340)

Inhibition of CYP450 activity by honokiol and other four components of Chinese traditionalmedicine in vitro

ZHANG Peiyu 1,2, REN Jing 1,2, ZHI Wenqian 1,2, LIU Chengming 1,2, GAO Na1   

  1. 1 Institute of Clinic Pharmacology, Zhengzhou University; 2 Department of Clinical Medicine, Zhengzhou University, Zhengzhou 450052, Henan, China
  • Received:2016-04-11 Revised:2016-07-20 Online:2017-08-26 Published:2017-08-18

摘要:

目的: 观察和厚朴酚等五种中药有效成分对人及大鼠肝微粒体四种药物代谢酶活性的影响,为临床中西药联用进一步的研究提供依据。方法: 采用人、大鼠肝微粒体体外孵育方法,以紫杉醇、甲苯磺丁脲、氯唑沙宗、香豆素分别作为CYP2C8、CYP2C9/CYP2C11、CYP2E1和CYP2A6/CYP2A1/2的探针药物,应用液相色谱仪检测探针药物代谢产物生成量,由此计算抑制率和IC50,分析五种中药有效成分对CYP酶的活性是否具有影响。结果: 和厚朴酚、厚朴酚对人肝CYP2C9 的IC50分别为7.7 μmol/L和7.6 μmol/L,对大鼠肝CYP2C11的IC50分别为13.0 μmol/L和3.8 μmol/L。和厚朴酚、厚朴酚对人肝CYP2C8 的IC50分别为19.2 μmol/L和84.5 μmol/L,对大鼠肝CYP2C8、CYP2E1和CYP2A1/2以及人肝CYP2E1和CYP2A6的IC50均大于100 μmol/L。栀子苷、绿原酸、黄芪甲苷对人及大鼠四种CYP酶的IC50均大于100 μmol/L。结论: 和厚朴酚对人肝CYP2C9、CYP2C8和大鼠肝CYP2C11具有明显抑制作用,厚朴酚对人和大鼠肝CYP2C9/CYP2C11具有明显抑制作用,对人肝CYP2C8有较弱抑制作用。

关键词: 中药有效成分, 细胞色素P450, 肝微粒体, 抑制

Abstract:

AIM: To explore the inhibition of honokiol and other four components of Chinese traditional medicine on four kinds of cytochrome P450 activity in human liver microsomes (HLM) and rat liver microsomes (RLM) in vitro, and to provide foundation for further research of clinical combination of Chinese medicine with western medicine. METHODS: Paclitaxel, tolbutamide, chlorzoxazone and coumarin were incubated in vitro as probe drugs of CYP2C8, CYP2C9/CYP2C11, CYP2E1 and CYP2A6/CYP2A1/2 respectively. HPLC was used to detect the amounts of metabolites of the probe drug. The inhibition ratio and the IC50 of the five kinds of effective components of Chinese traditional medicine were calculated and analyzed to find out whether they can affect the enzyme activity. RESULTS:IC50 of honokiol and magnolol on CYP2C9 in HLM were 7.7 μmol/L and 7.6 μmol/L, while IC50 of honokiol and magnolol on CYP2C11 in RLM were 13.0 μmol/L and 3.8 μmol/L separately. IC50 of honokiol and magnolol on CYP2C8 in HLM were 19.2 μmol/L and 84.5 μmol/L, while IC50 of honokiol and magnolol on CYP2C8, CYP2E1, CYP2A1/2 in RLM and CYP2E1, CYP2A6 in HLM were all above 100 μmol/L. IC50 of geniposide, chlorogenic acid and astragaloside on four kinds of CYP enzymes were all above 100 μmol/L. CONCLUSION: Honokiol has obvious inhibition on CYP2C9/CYP2C11 in both HLM and RLM and CYP2C8 in HLM. Magnolol has obvious inhibition on CYP2C9/CYP2C11 in both HLM and RLM and has slightly inhibition on CYP2C8 in HLM.

Key words: effective components of Chinese traditional medicine, cytochrome P450, liver microsomes, inhibition

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