title: Transport and metabolism behavior of brazilein during its entrance into neural cells.
abstract: Brazilein, a natural small molecule, shows a variety of pharmacological activities, especially on nervous system and immune system. As a potential multifunctional drug, we studied the distribution and the transport behavior and metabolic behavior of brazilein in vivo and in vitro. Brazilein was found to be able to distribute in the mouse brain and transport into neural cells. A metabolite was found in the brain and in the cells. Positive and negative mode-MS/MS and Q-TOF were used to identify the metabolite. MS/MS fragmentation mechanisms showed the methylation occurred at the 10-hydroxyl of brazilein (10-O-methylbrazilein). Further, catechol-O- methyltransferase (COMT) was confirmed as a crucial enzyme correlated with the methylated metabolite generation by molecular docking and pharmacological experiment.
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Xin-Pei
authors.initials: XP
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Jiang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Yu-Shuang
authors.initials: YS
authors.lastname: Chai
authors.affiliation: Drug Discovery Facility, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Tian-Shi
authors.initials: TS
authors.lastname: Feng
authors.affiliation: Drug Discovery Facility, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Lei
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Xing
authors.affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Du
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000737:chemistry / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D007192:Indenes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008745:Methylation / Q000187:drug effects; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D013696:Temperature; D014466:Ultraviolet Rays
chemical_list: D001578:Benzopyrans; D007192:Indenes; C050295:brazilein; D003576:Electron Transport Complex IV; D002394:Catechol O-Methyltransferase