title: Metabolic profiling of five flavonoids from Dragon's Blood in human liver microsomes using high-performance liquid chromatography coupled with high resolution mass spectrometry.
abstract: Although much is known about the pharmacological activities of Dragon's Blood (DB, a traditional Chinese herb), its metabolism in human liver microsomes (HLMs) and the cytochrome P450 (CYP) enzymes has not been studied. This study aims to identify the metabolic profile of five flavonoids (loureirin A, loureirin B, loureirin C, 7,4'-dihydroxyflavone and 5,7,4'-trihydroxyflavanone) from DB in HLMs as well as the CYP enzymes that are involved in the metabolism of them. High-resolution mass spectrometry was used to characterize the structures of their metabolites and 10 cDNA-expressed CYP enzymes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5) were used to verify which isozymes mediate in the metabolism of the metabolites. Totally, 29 metabolites including 10 metabolites of loureirin A, 10 metabolites of loureirin B, 4 metabolites of loureirin C, 2 metabolites of 7,4'-dihydroxyflavone and 3 metabolites of 5,7,4'-trihydroxyflavanone were elucidated and identified on the basis of the high-resolution MSndata. The metabolic profile of the five flavonoids in HLMs involved hydroxylation, oxidation and demethylation. Among them, hydroxylation was the predominant biotransformation of the five flavonoids in HLMs, occurring in combination with other metabolic reactions. Assay with recombinant P450s revealed that CYP2C9 and CYP2C19 played an important role in the hydroxylation of flavonoids in HLMs. To the best of our knowledge, this is the first in vitro evaluation of the metabolic profile of loureirin A, loureirin B, loureirin C, 7,4'-dihydroxyflavone and 5,7,4'-trihydroxyflavanone in HLMs.
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing, China. Electronic address: lylyjlzh2006@163.com.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing, China.
authors.forename: Lizhong
authors.initials: L
authors.lastname: Wei
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Institute of Chemistry, Chinese Academy of Sciences, Beijing, China. Electronic address: 18383144552@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D055442:Metabolome; D055432:Metabolomics; D008862:Microsomes, Liver / Q000378:metabolism*; D010936:Plant Extracts / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D010936:Plant Extracts; D003577:Cytochrome P-450 Enzyme System; C525191:dragon's blood
keywords: Dragon's Blood; HPLC-HR-MS; Human liver microsomes; Metabolites