title: Metabolic study of Angelica dahurica extracts using a reusable liver microsomal nanobioreactor by liquid chromatography-mass spectrometry.
abstract: Highly active and recoverable nanobioreactors prepared by immobilizing rat liver microsomes on magnetic nanoparticles (LMMNPs) were utilized in metabolic study of Angelica dahurica extracts. Five metabolites were detected in the incubation solution of the extracts and LMMNPs, which were identified by means of HPLC-MS as trans-imperatorin hydroxylate (M1), cis-imperatorin hydroxylate (M2), imperatorin epoxide (M3), trans-isoimperatorin hydroxylate (M1') and cis-isoimperatorin hydroxylate (speculated M2'). Compared with the metabolisms of imperatorin and isoimperatorin, it was found that the five metabolites were all transformed from these two major compounds present in the plant. Since no study on isoimperatorin metabolism by liver microsomal enzyme system has been reported so far, its metabolites (M1' and M3') were isolated by preparative HPLC for structure elucidation by (1) H-NMR and MS(2) analysis. M3' was identified as isoimperatorin epoxide, which is a new compound as far as its chemical structure is concerned. However, interestingly, M3' was not detected in the metabolism of the whole plant extract. In addition, a study with known chemical inhibitors on individual isozymes of the microsomal enzyme family revealed that CYP1A2 is involved in metabolisms of both isoimperatorin and imperatorin, and CYP3A4 only in that of isoimperatorin.
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Hai-Li
authors.initials: HL
authors.lastname: Shi
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Jia
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Peng
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Liao
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Ding
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.|Department of Chemistry and Biochemistry, Jackson State University, 1400 Lynch St., Jackson, MS 39217, USA.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Liu
mesh_terms: D029969:Angelica / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D019149:Bioreactors; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000494:pharmacology; D003580:Cytochromes / Q000037:antagonists & inhibitors / Q000378:metabolism; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism; D011564:Furocoumarins / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D058185:Magnetite Nanoparticles; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D003580:Cytochromes; D004852:Epoxy Compounds; D011564:Furocoumarins; D058185:Magnetite Nanoparticles; D010936:Plant Extracts; C055542:isoimperatorin; C017170:Cyp1a2 protein, rat; C465260:Cyp3a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C031534:imperatorin
keywords: Angelica dahurica; HPLC-MS; furocoumarins; immobilized liver microsomes; magnetic nanoparticles; metabolites