Inhibitory Effects of Kampo Medicine on Human UGT2B7 Activity
Inhibitory Effects of Kampo Medicine on Human UGT2B7 Activity
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DOI：
10.2133/dmpk.24.490
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发表时间：
2009-01-01
影响因子：
2.1
通讯作者：
Yokoi, Tsuyoshi
中科院分区：
文献类型：
--
作者：
Nakagawa, Nao;Katoh, Miki;Yokoi, Tsuyoshi
贡布药是由中国原产的日本传统药物改装而成的。坎波药是几种草药的混合物，含有许多成分，如糖苷。糖苷在肠道细菌群的作用下被水解成苷元，并被人体吸收。在人体肝脏或小肠中，黄芩素、甘草次酸等苷元可被UDP-葡萄糖醛酸基转移酶(UGT)偶联。UGT2B7是药物结合的主要亚型之一，包括吗啡3-和3‘-叠氮-3’-脱氧胸苷(AZT)葡萄糖醛酸化反应。本文研究了51种甘布药、14种中草药和11种成分对人肝微粒体UGT2B7活性的影响。51种坎布族药物中，有9种对吗啡3-葡萄糖醛酸化反应的抑制作用超过50%。在51种Kampo药物中，有24种对AZT的葡萄糖醛酸化反应有50%以上的抑制作用。大黄、甘草、桂皮等中草药对上述两种糖醛酸化反应均有80%以上的抑制作用。这些中草药的主要成分对低K-I的UGT2B7活性有抑制作用。Kampo药物可抑制UGT2B7活性，并可能通过抑制UGT而引起药物相互作用。
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 Jumihaidoku-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.