title: 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).
abstract: Morusin, the important active component of a traditional Chinese medicine,Morus albaL., 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.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Xianbao
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China; Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Mackie
authors.affiliation: Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine/Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Shuman
authors.identifier: 0000-0002-9638-0890
authors.initials: S
authors.lastname: Yang
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Song
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Lina
authors.identifier: 0000-0003-1187-9156
authors.initials: L
authors.lastname: Shan