ABSTRACT-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-chuyu-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-yutang 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 (Wuchu-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 Wuchu-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.Keywords: Wu-chu-yu-tang, Evodiae Fructus, Rutaecarpine, Drug-metabolizing enzyme, Liver Due to the increase in the use of herbal remedies, physicians and pharmacists are very much concerned about the toxicity and drug interactions when using herbal medicines. Several medicinal herbs such as Ginkgo biloba and St John's wort have been reported to show interactions with pharmaceutical drugs (1, 2). Modulation of drug-metabolizing enzymes is one of the main causes of drug interactions (3, 4). Oxidation and conjugation are two main reactions involved in drug metabolism. Cytochrome P450 (CYP)-dependent monooxygenases are the primary oxidation enzyme systems involved in the detoxication and bioactivation of a number of drugs and environmental pollutants (5). The oxidations catalyzed by the monooxygenase system require a CYP enzyme, NADPH-CYP reductase and phospholipids. The CYP family comprises a group of enzymes with broad substrate specificity. This substrate specificity leads to the herb-induced drug interactions with selective CYP substrates. For conjugation reactions, UDPglucuronosyl transferase (UGT) and glutathione S-transferase (GST) are important enzymes, which catalyze the glucuronide and glutathione conjugates formation, respectively. Changes of conjugation activities can also affect the detoxication and excretion of drugs (6).Wu-chu-yu-tang (Goshuyu-to in Japanese Kampo medicine) is a traditional Chinese prescription for the treatment of migraine and vomiting accompanying...