Effects of Wu-chu-yu-tang and its component herbs on drug-metabolizing enzymes.
The compound herbal medicine Wu-chu-yu-tang is used for the treatment of migraine and vomiting accompanying a cold. To assess the interactions of herb and drug metabolism, effects of Wu-chu-yu-tang on hepatic and renal cytochrome P450 (CYP), UDP-glucuronosyl transferase (UGT) and glutathione S-transferase (GST) were studied in C57BL/6J mice. Treatment of mice with 5 g/kg per day Wu-chu-yu-tang for 3 days caused 2.5-fold and 2.9-fold increases of liver microsomal 7-ethoxyresorufin O-deethylation (EROD) and 7-methoxyresorufin O-demethylation activities, respectively. However, CYP activities toward 7-ethoxycoumarin, benzphetamine, N-nitrosodimethylamine, erythromycin and nifedipine, and conjugation activities of UGT and GST were not affected. In kidney, Wu-chu-yu-tang-treatment had no effects on Cyp, UGT and GST activities. Among the four component herbs of Wu-chu-yu-tang, only Evodiae Fructus (Wu-chu-yu) extract increased EROD activity and CYP1a2 protein level. In E. Fructus, rutaecarpine, evodiamine and dehydroevodiamine are the main active alkaloids. At the doses corresponding to their contents in Wu-chu-yu-tang, rutaecarpine-treatment increased hepatic EROD activity, whereas evodiamine and dehydroevodiamine had no effects. These results demonstrated that ingestion of Wu-chu-yu-tang elevated mouse hepatic Cyp1a2 activity and protein level. E. Fructus and rutaecarpine contributed at least in part to the CYP1a2 induction by Wu-chu-yu-tang. Patients should be cautioned about the drug interaction of Wu-chu-yu-tang and CYP1A2 substrates.
National Research Institute of Chinese Medicine, Taipei, Taiwan. ueng@cma23.nricm.edu.tw
Yune-Fang
YF
Ueng
Ming-Jaw
MJ
Don
Hsiao-Chi
HC
Peng
Shu-Yun
SY
Wang
Jong-Jing
JJ
Wang
Chieh-Fu
CF
Chen
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D032086:Evodia; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010936:Plant Extracts; D011804:Quinolines / Q000494:pharmacology*
D000470:Alkaloids; D004365:Drugs, Chinese Herbal; C406544:Gosyuyu; D010936:Plant Extracts; D011804:Quinolines; C105819:Wu-Hu-Tang; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2