Identification of UDP-glucuronosyltransferase isoforms responsible for leonurine glucuronidation in human liver and intestinal microsomes

• DOI: 10.3109/00498254.2014.898808
• Publication Date: 2014-03-17T13:07:38Z
• Authors: Bo Tan; Weimin Cai; Jinlian Zhang; Ning Zhou; Guo Ma; Ping Yang; Qing Zhu; Yizhun Zhu
• Keywords: 0301 basic medicine; Herbal Medicine; 3. Good health; Intestines; 03 medical and health sciences; Glucuronides; Liver; Gallic Acid; Microsomes; UDP-Glucuronosyltransferase 1A9; Microsomes, Liver; Humans; Protein Isoforms; Glucuronosyltransferase

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.