Effects of the Water Extract from Traditional Chinese Medicines Angelica sinensis (Oliv.) Diels and Codonopsis pilosula (Franch.) Nannf.on Rat Liver Cytochrome P450 Activity and mRNA Expression
Objective:To study the effects of the water extract of Angelica sinensis (Oliv.) Diels.and Codonopsis pilosula (Franch.) Nannf.on rat liver cytochrome P450 isoenzymes activity and mRNA expression.Methods:After the administration of once daily for consecutive 7 days,the rat livers were removed rapidly and weighed,with which liver microsomes were prepared.The contents of liver microsomal cytochrome P450 (CYP450),cytochrome b5 (Cytb5) and the activities of Erythromycin N-demethylase (ERD) were measured by ultraviolet spectrophotometry.The activities of phenacetin O-deethylase (PHD) and p-nitrophenol-hydroxylase (pNPH) were determined by high performance liquid chromatography (HPLC).The mRNA expression levels of the five CYP isoenzymes (CYP1A1,CYP1A2,CYP2E1,CYP3A1 and CYP3A2) were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).Results:There is no significant difference in the liver index between all groups,compared with physiological saline control group.In Angelica group the contents of Cytb5 and P450 were significantly increased,with the significantly increased activities of PHD,pNPH and ERD.In Codonopsis group there is a significantly increase in the contents of Cytb5 and P450 contents,with the significantly increased pNPH and ERD activities.In the mRNA level,the CYP1A1 gene was not detected in each group.It showed Angelica group had the inhibition of CYP1 A2 expression and the induction of CYP2E 1 expression,while Codonopsis group had the induction of CYP2E 1 expression.In both groups,the mRNA level of CYP2E 1 expression was largely consistent with the results of the enzyme activity.Conclusion:With the results that the Angelica water extract induced the activities of CYP2E 1,CYP2E 1 and CYP3A,that the Codonopsis water extract induced the activities of CYP2E 1 and CYP3A,and that the combined extract induced the activity of CYP2E1,it could be supposed that the change in enzyme activity may be attribute to the effects on the gene transcription.It indicated that when medicines,which was metabolized by CYP 1A2,CYP2E 1 and CYP3A,were used simultaneously with Angelica,or when drugs,which was metabolized by CYP2E1 and CYP3A,were used with Codonopsis,the actual efficacy of above drugs would be influenced.Therefore,cautious consideration should be paid to possible drug interactions in the clinical application.
Angellica sinensis(Oliv) Diels Codonopsispilosula(Franch.) Nannf cytochrome P450 enzyme activity RT-PCR Drug-Drug Interaction
LIU Ping WU Bai-ling GAO Yue WANG Yu-guang
Department of pharmaceutical care,PLA General Hospital,Beijing(100853),China Institute of Radiation Medicine,Academy of Military Medical Science,Beijing(100850),China
国内会议
北京
英文
114-120
2013-04-01（万方平台首次上网日期，不代表论文的发表时间）