Effect of Toosendan Fructus before and after stir-frying process extract on CYP450 enzyme activities in rats in vivo and vitro by cocktail probe drug method  

作　　者：Yu-Feng Hu Si-Yuan Ma Meng-Lin Wang Shuang-Hui Shi Xiao-Tong Wei Ming-Rui Jiang Hui-Nan Wang Jing-Qiu Zhang Qian-Qian Liu Ying-Zi Wang 

机构地区：[1]School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China.

出　　处：《TMR Modern Herbal Medicine》2023年第2期1-8,共8页TMR现代中药

基　　金：supported by Natural Key R&D Program of China(No.2018YFC1707000).

摘　　要：Background:The traditional Chinese medicine Toosendan Fructus has certain hepatotoxicity,which is used after being processed by stir-frying to attenuate toxicity.However,there are few studies on its attenuating toxicity mechanism.The effects of Toosendan Fructus on the activities of CYP450P1A2,CYP2E1 and CYP3A4 were studied in vivo and in vitro and the dose-toxicity mechanism of hepatotoxicity before and after stir-frying was explored to provide the basis for safe,rational use of Toosendan Fructus.Methods:The rat liver microsomes in vitro incubation method and in vivo pharmacokinetics were used to detect the concentrations of phenacetin,chlorzoxazone and dapsone in the liver microsomes in vitro incubation system and the rat plasma to study the effect of stir-frying of Toosendan Fructus on the activity of CYP450P1A2,CYP2E1,CYP3A4.Results:The results of pharmacokinetics in vivo showed that the AUC of phenacetin and dapsone in different groups was lower,and CL value was higher than those of the normal group.At the same dose,the AUC of stir-fried Toosendan Fructus was higher than that of the raw,while CL value was lower.For the same processed product,AUC value was high-dose>low-dose>middle-dose group,CL value was high-dose<low-dose<middle-dose.AUC and CL values of chlorzoxazone showed no difference from those of the normal group.The results of pharmacokinetics in vivo showed that Toosendan Fructus can induce the activity of CYP3A4 in a dose-dependent manner and the induction effect will decrease after stir-frying in vitro.Conclusion:The toxicity attenuation of Toosendan Fructus may be related to the decrease of induction effect after stir-frying.These results would provide the basis for safe,rational use of Toosendan Fructus.

关 键 词：Toosendan Fructus TOXICOLOGY pharmacokinetics CYP450 

分 类 号：R285[医药卫生—中药学]