Tan Bo, Cai Weimin, Zhang Jinlian, Zhou Ning, Ma Guo, Yang Ping, Zhu Qing, Zhu Yizhun
Department of Pharmacology and.
Xenobiotica. 2014 Sep;44(9):775-84. doi: 10.3109/00498254.2014.898808. Epub 2014 Mar 17.
Leonurine is a potent component of herbal medicine Herba leonuri. The detail information on leonurine metabolism in human has not been revealed so far. Two primary metabolites, leonurine O-glucuronide and demethylated leonurine, were observed and identified in pooled human liver microsomes (HLMs) and O-glucuronide is the predominant one. Among 12 recombinant human UDP-glucuronosyltransferases (UGTs), UGT1A1, UGT1A8, UGT1A9, and UGT1A10 showed catalyzing activity toward leonurine glucuronidation. The intrinsic clearance (CLint) of UGT1A1 was approximately 15-to 20-fold higher than that of UGT1A8, UGT1A9, and UGT1A10, respectively. Both chemical inhibition study and correlation study demonstrated that leonurine glucuronidation activities in HLMs had significant relationship with UGT1A1 activities. Leonurine glucuronide was the major metabolite in human liver microsomes. UGT1A1 was principal enzyme that responsible for leonurine glucuronidation in human liver and intestine microsomes.
益母草碱是草药益母草的一种有效成分。目前尚未揭示益母草碱在人体内代谢的详细信息。在人肝微粒体（HLMs）中观察并鉴定出两种主要代谢产物，益母草碱O-葡萄糖醛酸苷和去甲基益母草碱，其中O-葡萄糖醛酸苷是主要的代谢产物。在12种重组人尿苷二磷酸葡萄糖醛酸转移酶（UGTs）中，UGT1A1、UGT1A8、UGT1A9和UGT1A10对益母草碱葡萄糖醛酸化具有催化活性。UGT1A1的内在清除率（CLint）分别比UGT1A8、UGT1A9和UGT1A10高约15至20倍。化学抑制研究和相关性研究均表明，HLMs中益母草碱葡萄糖醛酸化活性与UGT1A1活性具有显著相关性。益母草碱葡萄糖醛酸苷是人肝微粒体中的主要代谢产物。UGT1A1是负责在人肝和肠微粒体中进行益母草碱葡萄糖醛酸化的主要酶。
