title: In vitro metabolism of pyranocoumarin isomers decursin and decursinol angelate by liver microsomes from man and rodents.
abstract: The aim of this study is to investigate and compare the metabolic rate and profiles of pyranocoumarin isomers decursin and decursinol angelate using liver microsomes from humans and rodents, and to characterize the major metabolites of decursin and decursinol angelate in human liver microsomal incubations using LC-MS/MS. First, we conducted liver microsomal incubations of decursin and decursinol angelate in the presence or absence of NADPH. We found that in the absence of NADPH, decursin was efficiently hydrolyzed to decursinol by hepatic esterase(s), but decursinol angelate was not. In contrast, formation of decursinol from decursinol angelate was mediated mainly by cytochrome P450(s). Second, we measured the metabolic rate of decursin and decursinol angelate in liver S9 fractions from mice and humans. We found that human liver S9 fractions metabolized both decursin and decursinol angelate more slowly than those of the mouse. Third, we characterized the major metabolites of decursin and decursinol angelate from human liver microsomes incubations using HPLC-UV and LC-MS/MS methods and assessed the in vivo metabolites in mouse plasma from a one-dose PK study. Decursin and decursinol angelate have different metabolite profiles. Nine metabolites of decursin and nine metabolites of decursinol angelate were identified in human liver microsome incubations besides decursinol using a hybrid triple quadruple linear ion trap LC-MS/MS system, and many of them were later verified to be also present in plasma samples from rodent PK studies.
authors.affiliation: Department of Biomedical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, Amarillo, Texas, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jinhui
authors.initials: J
authors.lastname: Zhang
authors.forename: Chengguo
authors.initials: C
authors.lastname: Xing
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.forename: Junxuan
authors.initials: J
authors.lastname: Lü
mesh_terms: D000818:Animals; D019661:Apiaceae / Q000737:chemistry; D001578:Benzopyrans / Q000302:isolation & purification / Q000378:metabolism*; D002087:Butyrates / Q000302:isolation & purification / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000378:metabolism*; D039681:Pyranocoumarins / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001578:Benzopyrans; D002087:Butyrates; D039681:Pyranocoumarins; C101278:decursin
references.citation: Arch Pharm Res. 2003 Sep;26(9):727-30
references.pmid: 14560921
references.citation: Drug Metab Dispos. 2009 Jan;37(1):221-8
references.pmid: 18948380
references.citation: Mol Cancer Ther. 2007 Mar;6(3):907-17
references.pmid: 17363485
references.citation: Br J Pharmacol. 2009 Jul;157(6):907-21
references.pmid: 19508398
references.citation: Planta Med. 2012 Feb;78(3):252-9
references.pmid: 22116603
references.citation: Curr Drug Metab. 2007 Dec;8(8):822-9
references.pmid: 18220563
references.citation: Breast Cancer Res. 2007;9(6):R77
references.pmid: 17986353
references.citation: Phytother Res. 2012 May;26(5):633-8
references.pmid: 21972114
references.citation: Neurobiol Learn Mem. 2003 Jan;79(1):11-8
references.pmid: 12482674
references.citation: Am J Chin Med. 2009;37(1):127-42
references.pmid: 19222117
references.citation: J Agric Food Chem. 2010 Mar 10;58(5):2931-4
references.pmid: 20155945
references.citation: Phytother Res. 2011 Jul;25(7):959-64
references.pmid: 21170925
references.citation: Anticancer Agents Med Chem. 2012 Dec;12(10):1239-54
references.pmid: 22583405
references.citation: Planta Med. 2012 Jun;78(9):909-13
references.pmid: 22573368
references.citation: J Pharm Biomed Anal. 2008 Jan 22;46(2):258-66
references.pmid: 17997069
references.citation: Drug Metab Dispos. 2007 Oct;35(10):1759-65
references.pmid: 17620343
references.citation: Planta Med. 2013 Mar;79(3-4):275-80
references.pmid: 23364885
references.citation: Biosci Biotechnol Biochem. 2011;75(3):434-42
references.pmid: 21389625