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《Chinese Journal of New Drugs》 2014-04
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Effect of continuous oral cycloastragenol on the activity of cytochrome P450 enzymes in rats

WEI Bao-hong;YE Jing;XUE Bao-juan;SUN Gui-xia;YANG Xiao-yan;ZHANG Yu-jie;School of Chinese Materia Medica,Beijing University of Chinese Medicine;  
Objective: To determine the effect of cycloastragenol( CAG) on cytochrome P450 enzyme subtypes of rat liver microsomes. Methods: Rats were treated with CAG( 40 mg·kg- 1·d- 1) for 7 days to induce hepatic microsomal enzyme. Cocktail probe substrates were incubated with liver microsomes in vitro. Then,the metabolic elimination percentages of the five probe substrates metoprolol,aminophenylsulfone,chlorzoxazone,phenacetin and tolbutamide were determined by HPLC. The effect of CAG on the enzymatic activity of rat liver microsomal CYP450s was evaluated. Results: Compared with the control,CAG obviously activated CYP2E1,and remarkably inhibited CYP3A4. However,CAG did not significantly affect CYP2D6,CYP1A2 and CYP2C9. The IC50of CYP3A4 was 12. 13 μmol·L- 1,and inhibition type was competitive inhibition. Conclusion: CAG can remarkably inhibit CYP3A4 and activate CYP2E1.
【Fund】: 北京中医药大学研究生自主课题(5320100604286)
【CateGory Index】: R969.1
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