Biol. Pharm. Bull. 29(10) 2065—2069 (2006)

in the declined mortality rate in industrialized countries, while the number of patients suffering from particular chronic diseases such as hypertension, diabetes, or allergic diseases has been increasing. Since most of the modern medicines are allopatic and cannot cure chronic diseases, and since they sometimes have the possibility of side effects, many patients choose to explore complementary/alternative medicines, including herbal medicines in particular. In Japan, kampo medicine (Japanese traditional herbal medicine) has been attracted as an alternative source of medicinal treatments for chronic diseases, having the potential to treat patients holistically by supporting the patient’s own healing power. Since kampo medicine and modern medicine have their own characteristics, it is desiable that these medicines should be combined, making up for defects of each other and expecting their synergistic action. As the combined therapy using both modern and traditional herbal medicines is getting popular, the possibilities of the interaction between them have been described. Since Bailey et al. first found that grapefruit juice augments the blood concentration of nifedipine in clinical study, a number of reports claiming that herbal medicine may disturb usual medicinal treatments have been published. Among these reports, some insisted the possible dangerousness of herbal medicines based on their in vitro inhibitory effects with high concentration on drug metabolizing enzymes including cytochrome P450 (CYP). Furthermore, the assays were sometimes carried out by using methanol extracts of herbal medicines. However, these approaches have some limitations because (1) most of herbal medicines are used as the extract with boiled water and the solubilized compounds in the decoctions are much different from those extracted or dissolved in organic solvent, (2) most of herbal medicines are administered by oral route, and (3) some of the compounds in herbal extracts are absorbed from intestine to circulation after metabolized by intestinal bacteria, e.g. glycosides are hydrolyzed to give aglycones. In order to provide correct drug information about herb–drug interaction to physicians and pharmacists, it is necessary to use the same dosage form of herbal medicine as patients take, and to conduct in vivo experiments in which the decoctions of herbal medicines are orally administered. Recently, Iwata et al. found that methanol fraction of the water extract of schisandra fruit (五味子) has strong inhibitory effect on human liver microsomal CYP3A4 and CYP2D6 among 78 herbal medicine in vitro, and identified the active ingredients in the alkaloid fraction of the decoction. Shoseiryuto (小青竜湯) contains schisandra fruit as one of eight herbal medicines, and is frequently used to treat common cold with nasal drip, allergic rhinitis and pollinosis in Japan. Kimura et al. evaluated in vitro inhibitory effect of shoseiryuto on rat CYP3A, and they found that the active herbal ingredients were not only schisandra fruit but also ephedra herb (麻黄) and cinnamon bark (桂皮). However, in their in vitro study, the concentrations of shoseiryuto and each herbal constituent were much higher than their clinical usage. Therefore, more accurate drug information is required to use shoseiryuto safely in clinics or pharmacies. In this study, we compared the inhibitory effects of shoseiryuto on rat CYP3A in vitro and in vivo with those of grapefruit juice, a well-characterized natural CYP3A inhibitor studied in patients and experimental animals.