Effects of Alismatis rhizome on rat cytochrome P450 enzymes.
BACKGROUND
Alismatis rhizome (RA) (Water Plantain Family, also called "Zexie" in Chinese), one of the commonly used components of traditional Chinese medicines, is derived from the dried rhizomes of Alisma orientalis (Sam.) Juzep. (Alismataceae).


OBJECTIVE
This study explores the RA influences on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9, CYP2E1 and CYP3A4) by using cocktail probe drugs in vivo.


METHODS
A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (20 mg/kg), tolbutamide (5 mg/kg), chlorzoxazone (20 mg/kg) and midazolam (10 mg/kg), was orally administration to rats treated twice daily with RA (10, 20 and 40 g/kg) for consecutive 14 days. Blood samples (0.2 mL) were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0 (Wenzhou Medical College, Zhejiang, China).


RESULTS
In the experiment, there was a statistically significant difference in the t1/2, Cmax, AUC(0-∞) and CL for phenacetin and midazolam, while there was no statistical pharmacokinetics difference for tolbutamide and chlorzoxazone. Our study showed that treatment with multiple doses of RA had an inductive effect on rat CYP1A2 and an inhibitory effect on rat CYP3A4 enzyme activity. However, RA has no inductive or inhibitory effect on the activities of CYP2C9 and CYP2E1.


CONCLUSIONS
Caution is needed when RA is co-administration with some CYP1A2 or CYP3A4 substrates in clinic, because it may result in treatment failure and herb-drug interactions.
Department of General Surgery of Wenzhou People's Hospital , Wenzhou , China .
Yi
Y
Huang
Shuang-li
SL
Zheng
Zhi-sheng
ZS
Xu
Yao
Y
Hou
D034902:Alisma; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome; D016896:Treatment Outcome
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System
CYP; RA; induce; inhibit