土茯苓6种黄酮类成分在CYP2D6中的体外酶促动力学研究  

The Enzyme Kinetics of CYP2D6 to Six Flavonoids of Smilax glabra In Vitro

作　　者：许佳明[1] 谢静 刘桂明 黄晓巍[1] 史玉蕊 陈荣达 李丽 XU Jia-ming;XIE Jing;LIU Gui-ming;HUANG Xiao-wei;SHI Yu-rui;CHEN Rong-da;LI Li(School of Pharmaceutical Science,Changchun University of Chinese Medicine,Changchun 130032,China;College of Chemistry,Changchun Normal University,Changchun 130032,China)

机构地区：[1]长春中医药大学药学院,长春130117 [2]长春师范大学化学学院,长春130032

出　　处：《中国药学杂志》2021年第6期472-477,共6页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(81373899);吉林省科技厅项目资助(20180101153JC,JJKH20181168KJ);吉林省中医药科技项目资助(2018019);长春师范大学研究生创新项目资助(Cscxy2018001,Cscxy2017025)。

摘　　要：目的比较土茯苓中6种黄酮类成分在CYP2D6中的体外酶促动力学过程。方法以表儿茶素、新落新妇苷、落新妇苷、异落新妇苷、黄杞苷、白藜芦醇6种黄酮类成分为底物,研究了不同孵育时间、不同CYP2D6酶浓度对土茯苓中6种黄酮类成分体外代谢的影响。结果6种黄酮类成分在30~90 min内呈线性消除,且代谢消除率随着CYP2D6酶浓度(1.0~3.0 mg·mL^(-1))的增加而增大。表儿茶素、新落新妇苷、落新妇苷、异落新妇苷、黄杞苷、白藜芦醇为底物时,米氏常数分别为1.20、2.14、3.84、2.84、1.86、1.30μmol·L^(-1),表明表儿茶素为CYP2D6最适合底物;最大反应速度分别为0.01、0.02、0.03、0.03、0.02、0.01μmol·L^(-1)·min^(-1);代谢清除率分别为0.0083、0.0093、0.0078、0.0105、0.0107、0.0076 min^(-1),表明CYP2D6对黄杞苷清除能力最大。结论本实验为进一步研究6种黄酮类成分与CYP2D6相互作用提供了实验和理论依据。OBJECTIVE To investigate the enzyme kinetics of CYP2D6 to six flavonoids of Smilax glabra in vitro.METHODS The effects of incubation time and CYP2D6 enzyme concentration on the metabolism of six flavonoids including epicatechin,neoastilbin,astilbin,isoastilbin,engeletin and resveratrol from Smilax glabra were studied in vitro.RESULTS The RESULTS showed that the six flavonoids were eliminated linearly within 30-90 min,and the metabolic elimination rate increased with the increase of CYP2D6 enzyme concentration at 1.0-3.0 mg·mL^(-1).When epicatechin,neoastilbin,astilbin,isoastilbin,engeletin and resveratrol were used as substrates,the Km were 1.20,2.14,3.84,2.84,1.86 and 1.30μmol·L^(-1),respectively,indicating that epicatechin was the most suitable substrate for CYP2D6;the maximum reaction rates were 0.01,0.02,0.03,0.03,0.02 and 0.01μmol·L^(-1)·min^(-1);and the metabolic clearance rates were 0.0083,0.0093,0.0078,0.0105,0.0107,0.0076 min^(-1),respectively,and the RESULTS showed that CYP2D6 had the greatest scavenging ability to engeletin.CONCLUSION This study provides experimental and theoretical basis for further research on the interaction between six flavonoids and CYP2D6.

关 键 词：土茯苓 黄酮 CYP2D6 代谢 酶促动力学 

分 类 号：R945[医药卫生—微生物与生化药学]