[Effects of Wuji pill compound with different compatibility on cytochrome P450 CYP3A1/3A2 in rat liver microsomes in vitro].
OBJECTIVE
Wuji pill is a prescription of traditional Chinese medicine(TCM) and was composed of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae and Radix Paeoniae Alba. The aim of this research is to investigate the effects of Wuji pill compound with different compatibility on the levels of enzymic activity of cytochrome P450 CYP3A1/3A2 in rat liver microsomes in vitro, and to confirm the compatibility mechanism of Wuji pill from the point of relationships between compound prescription of TCM and metabolism.


METHODS
With testosterone being a probe, the levels of enzymic activity of CYP3A1/3A2 were detected by HPLC, which were suppressed by Wuji pill with different compatibility in vitro.


RESULTS
The IC50 of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae, Radix Paeoniae Alba and 1"-9" of different level Wuji pill is: 38.96, 871.96, 15 519.17, 43.17, 60. 47, 276.12, 133.40, 118.08, 88. 47, 64. 36, 35. 13 and 39. 91 mg x L -', respectively. Rhizoma Coptidis and 1-9" of Wuji pill can suppress the enzymic activity of CYP3A1/3A2 significantly, and the capability of Rhizoma Coptidis in Wuji pill of action on CYP3A1/3A2 can be modified by different composition of Fructus Evodiae Rutaecarpae and Radix Paeoniae in Wuji pill, and there are statistical differences among the IC50 of 1#-9# of Wuji pill. While the ratio of Rhizoma Coptidis raises up in Wuji pill, Wuji pill may suppress the enzymic activity of CYP1A2 largely.


CONCLUSIONS
The reason why Wuji pill with different compatibility has different pharmacodynamics and pharmacokinetics characteristics is likely to lie in the difference of the capability of Wuji pill with different compatibility on CYP3A1/3A2. [Key words] Wuji pill; CYP3A1/3A2; testosterone; HPLC; different compatibility prescription of traditional Chinese medi-cine
Weng
Xiaogang
X
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Li
Yujie
Y
Yang
Qing
Q
Wang
Yiwei
Y
Liu
Xiaoni
X
Han
Xiao
X
Zhang
Ganlin
G
Sui
Feng
F
Zhu
Xiaoxin
X
Liang
Rixin
R
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D039323:Coptis / Q000737:chemistry; D051544:Cytochrome P-450 CYP3A; D004339:Drug Compounding; D004365:Drugs, Chinese Herbal / Q000009:adverse effects* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D032086:Evodia / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D029596:Paeonia / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D001189:Aryl Hydrocarbon Hydroxylases; C465260:Cyp3a2 protein, rat; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A