[Modulation of the activities and mRNA expression of cytochrome P450 isoenzymes in rat liver by Panax gingseng and coadministration with Veratrum nigrum].
OBJECTIVE
To study the modulatory effect of Panax gingseng and coadministration with Veratrum nigrum on the activity and mRNA expression of cytochrome P450 isoenzymes in rat liver.


METHODS
Rat liver microsomal cytochrome P450, b5, aminopyrine N-demethylase(APND), p-nitrophenol-hydroxylase(pNPH)activities were quantitated by UV chromatography. The mRNA expression level of five CYP isoenzymes CYP1A1, CYP2B1/2, CYP2C11, CYP2E1 and CYP3A1 were detected by semi-quantitative reverse transcriptase-polymerase chain reaction(RT-PCR).


RESULTS
P. gingseng coadministrated with V. nigrum obviously decreased the P450 contents of liver microsomes, and the b5 contents. Both single and combined used inhibited the activities of aminopyrine N-demethylase. At the mRNA level, the expression of CYP2C11 markedly induced exposure to V. nigrum, but combinative groups decreased the expression of CYP2C11. The combination of P. gingseng and V. nigrum induced the expression of CYP1A1. P. gingseng has inhibitory effect on CYP2B1/2 and inductive effect used with V. nigrum. The combination of P. gingseng with V. nigrum also induced the expression of CYP3A1.


CONCLUSIONS
P. gingseng used singly has some different modulation effects compared with combinative used, which may occur because of drug-drug interaction based on cytochrome P450. To elucidate the drug-drug interaction, it needs further analysis and metabolism research.
Wang
Yu-guang
YG
Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China.
Gao
Yue
Y
Chai
Biao-xin
BX
Chen
Peng
P
Tan
Hong-ling
HL
Zhao
Yong-hong
YH
Xiao
Cheng-rong
CR
Sun
Yuan-yuan
YY
Zhu
Li-jun
LJ
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D015786:Cytochromes b5 / Q000378:metabolism; D004344:Drug Incompatibility; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D005894:Panax / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014703:Veratrum / Q000737:chemistry
D004365:Drugs, Chinese Herbal; D007527:Isoenzymes; D012333:RNA, Messenger; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase