Abstract
Kampo is a traditional Japanese herbal medicine and widely used in clinical practice in Japan. Little is known about interactions between Kampo and other medicines. Kampo contains many aglycones, which can be conjugated by UDP-glucuronosyltransferase (UGT). Therefore, in the present study, the effects of Kampo on human UGT1A1 activity were investigated in vitro. Substrates of human UGT1A1, beta-estradiol or 7-ethyl-10-hydroxycamptothecin (SN-38), were incubated with human liver microsomes in the presence of 51 Kampos, 14 medicinal herbs and their components. Beta-estradiol 3-glucuronidation was strongly inhibited by some Kampos such as Bofu-tsusho-san, Mashinin-gan and Otsuji-to. Medicinal herbs such as Daio (Rhei Rhizoma), Kanzo (Glycyrrhizae Radix), Keihi (Cinnamomi Cortex) and Ogon (Scutellariae Radix) exhibited potent inhibition on that activity. On beta-estradiol 3-glucuronidation, the major component of Keihi (cinnamaldehyde) and Ogon (wogonin) exhibited mixed-type inhibition of K(i) with values of 0.7 microM and 2.8 microM, respectively. On SN-38 glucuronidation, the inhibitory potencies of Kampos, medicinal herbs and their components tended to be similar to those on beta-estradiol 3-glucuronidation. In the present study, Kampo was clarified to inhibit beta-estradiol and SN-38 glucuronidation mainly catalyzed by UGT1A1.
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