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Evidence-Based Complementary and Alternative Medicine
Volume 2016, Article ID 9240103, 10 pages
http://dx.doi.org/10.1155/2016/9240103
Research Article

Identification of the Metabolic Enzyme Involved Morusin Metabolism and Characterization of Its Metabolites by Ultraperformance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (UPLC/Q-TOF-MS/MS)

1Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
2Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA
3Department of Internal Medicine/Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
4Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China

Received 12 May 2016; Revised 27 July 2016; Accepted 2 August 2016

Academic Editor: Con Stough

Copyright © 2016 Xianbao Shi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Morusin, the important active component of a traditional Chinese medicine, Morus alba L., has been shown to exhibit many vital pharmacological activities. In this study, six recombinant CYP450 supersomes and liver microsomes were used to perform metabolic studies. Chemical inhibition studies and screening assays with recombinant human cytochrome P450s were also used to characterize the CYP450 isoforms involved in morusin metabolism. The morusin metabolites identified varied greatly among different species. Eight metabolites of morusin were detected in the liver microsomes from pigs (PLMs), rats (RLMs), and monkeys (MLMs) by LC-MS/MS and six metabolites were detected in the liver microsomes from humans (HLMs), rabbits (RAMs), and dogs (DLMs). Four metabolites (M1, M2, M5, and M7) were found in all species and hydroxylation was the major metabolic transformation. CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, and CYP2C19 contributed differently to the metabolism of morusin. Compared to other CYP450 isoforms, CYP3A4 played the most significant role in the metabolism of morusin in human liver microsomes. These results are significant to better understand the metabolic behaviors of morusin among various species.