Effects of Wu-chu-yu-tang and its component herbs on drug-metabolizing enzymes

Jpn J Pharmacol. 2002 Jul;89(3):267-73. doi: 10.1254/jjp.89.267.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP1A2 / metabolism
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology*
  • Evodia
  • Kidney / drug effects
  • Kidney / enzymology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology*
  • Plant Extracts
  • Quinolines / pharmacology*


  • Alkaloids
  • Drugs, Chinese Herbal
  • Gosyuyu
  • Plant Extracts
  • Quinolines
  • Wu-Hu-Tang
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2