Effects of Zexie Decoction on CYP450 enzyme subtype in hyperlipidemia model mice

JU Aixia; ZHOU Yusheng; SHAN Wanting; LIU Li; LI Qiuhong

doi:10.13506/j.cnki.jpr.2023.12.002

Abstract：Objective To explore the effects of Zexie Decoction and its disassembled prescriptions on CYP450 enzyme subtype in hyperlipidemia model mice.Methods Hyperlipidemia model was established by feeding KM mice with high fat diet.The model mice were randomly divided into model group,Zexie Decoction group,Rhizoma alismatis group and Atrac-tylodes macrocephala Koidz group,and set blank groups with 10 animals in each group.The mice in the Zexie Decoction group,Rhizoma alismatis group and Atractylodes macrocephala Koidz group were administered by gavage once a day(admin-istration doses were 12.0,8.6,3.4 g·kg-1,respectively)for 28 consecutive days,the blank group and model group were given the same volume of normal saline.The enzymatic activity and gene expression levels of CYP1A2,CYP2E1,CYP2C9 and CYP3A4 were detected by"Cocktail"probe drug method and real-time fluorescence quantitative PCR.Results Com-pared with the model group,the CYP3A4 enzymatic activity in the Zexie Decoction group,Rhizoma alismatis group and At-ractylodes macrocephala Koidz group were increased,CYP2E1 enzymatic activity was decreased,while CYP1A2 enzymatic activity in Zexie Decoction group were decreased.Compared with the model group,the mRNA expression levels of CYP1A2 and CYP3A4 in the Zexie Decoction group,Rhizoma alismatis group and Atractylodes macrocephala Koidz group were re-versed,but had no significant effect on CYP2C9,while the mRNA expression level of CYP2E1 was decreased in Zexie De-coction group.Conclusion Zexie Decoction and its disassembled prescriptions can reverse the changes of enzymatic activity and gene expression of CYP3A4 caused by hyperlipidemia,Rhizoma alismatis plays a leading role in Zexie Decoction.