摘要
目的研究葛根素体外对细胞色素P450酶亚型CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4等活性的影响。方法分别以咖啡因、甲苯磺丁脲、美芬妥因、美托洛尔和咪哒唑仑为探针药,采用高效液相色谱法测定探针药与相应代谢产物的浓度,采用重组酶研究葛根素对CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4酶体外活性的影响。结果在体外重组酶反应体系中,葛根素对CYP2C9、CYP2C19及CYP3A4酶活性无明显影响。但低浓度(0.1mmol.L-1)下可使CYP1A2活性降低(48±9)%(P<0.05),使CYP2D6活性降低(61±8)%(P<0.01);高浓度(0.4mmol.L-1)下使CYP1A2活性降低(82±8)%(P<0.01),使CYP2D6活性降低(88±6)%(P<0.01)。结论葛根素对CYP1A2和CYP2D6酶体外活性有较明显的抑制作用;随着葛根素浓度的增高,抑制作用也相应增强。
Objective To investigate the effects of puerarin on activities of cytochrome 1A2 （CYP1A2）, CYP2C9, CYP2C19,CYP2D6 和 CYP3A4 in vitro. Methods Caffeine （a CYP1A2 substrate）, Tolbutamide （a CYP2C9 substrate）, mephenytoin （a CYP2C19 substrate）, Metoprolol （a CYP2D6 substrate） and Midazolam （a CYP3A4 substrate） were used as probes respectively. The concentrations of the probe drugs and their metabolites were determined by HPLC. The effect of puerarin on activities of CYP1A2,CYP2C9 ,CYP2C19,CYP2D6 and CYP3A4 was detected through recombinant enzyme reaction system in vitro. Results Puerarin had no significant effects on the activities of CYP2C9, CYP2C19 and CYP3A4, but the lower concentration （ 0.1 mmol·L^ -1 ） decreased the activities of CYP1 A2 by （ 48 ± 9 ） % （ P 〈 0.05 ）, CYP2D6 by （ 61 ± 8 ） % （ P 〈 0.01 ） ; the higher concentration decreased the activities of CYP1A2 by （ 82 ± 8 ） % P 〈 0.01 ）, CYP2D6 by （ 88 ± 6 ） % （ P 〈 0, 01 ）. Conclusion Puerarin inhibited the activity of CYP CYP1A2 and CYP2D6 in a dose-dependent fashion in vitro,
出处
《医药导报》
CAS
2007年第8期852-856,共5页
Herald of Medicine
