Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-1192, Japan.
Drug Metab Pharmacokinet. 2009;24(6):490-9. doi: 10.2133/dmpk.24.490.
Kampo medicine is traditional Japanese medicine modified from the Chinese original. Kampo medicine is a mixture of several medicinal herbs and includes many ingredients such as glycosides. Glycosides are hydrolyzed to aglycons by intestinal bacterial flora and absorbed into the body. Aglycons such as baicalein and glycyrrhetinic acid can be conjugated by UDP-glucuronosyltransferase (UGT) in human liver or small intestine. UGT2B7 is one of the major isoforms responsible for drug conjugation including morphine 3- and 3'- azido-3'-deoxythymidine (AZT) glucuronidation. The present study investigates the effects of 51 Kampo medicines, 14 medicinal herbs and 11 ingredients on UGT2B7 activity in human liver microsomes. Morphine 3-glucuronidation was inhibited by more than 50% by 9 of 51 Kampo medicines such as Ryo-kei-jutsu-kan-to. AZT glucuronidation was inhibited by more than 50% by 24 of 51 Kampo medicines such as Jumi-haidoku-to. Medicinal herbs such as Daio (Rhei Rhizoma), Kanzo (Glycyrrhizae Radix) and Keihi (Cinnamomi Cortex) exhibited more than 80% inhibition on both glucuronidations. The major ingredients of these medicinal herbs inhibited UGT2B7 activity with low K(i). Kampo medicines were found to inhibit the UGT2B7 activity and may cause drug interactions via the inhibition of UGT.
汉方药是从中国原方改良的传统日本药。汉方药是由几种草药混合而成，包括许多糖苷类成分。糖苷类在肠道细菌菌群的作用下水解为苷元，被人体吸收。黄芩素和甘草次酸等苷元可被人肝或小肠中的 UDP-葡糖醛酸基转移酶（UGT）结合。UGT2B7 是负责包括吗啡 3-和 3'-叠氮-3'-去氧胸苷（AZT）葡糖醛酸化在内的药物结合的主要同工酶之一。本研究调查了 51 种汉方药、14 种草药和 11 种成分对人肝微粒体中 UGT2B7 活性的影响。9 种汉方药（如柔连解毒汤）使吗啡 3-葡糖醛酸化抑制率超过 50%。24 种汉方药（如九味柴胡汤）使 AZT 葡糖醛酸化抑制率超过 50%。大黄（大黄根茎）、甘草（甘草根）和桂皮（肉桂皮）等草药对这两种葡糖醛酸化的抑制率均超过 80%。这些草药的主要成分以低 K(i) 抑制 UGT2B7 活性。汉方药被发现可抑制 UGT2B7 活性，并可能通过抑制 UGT 引起药物相互作用。
