title: Inhibition behavior of fructus psoraleae's ingredients towards human carboxylesterase 1 (hCES1).
abstract: 1. Fructus psoraleae (FP) is the dried ripe seeds of Psoralea corylifolia L. (Fabaceae) widely used in Asia, and has been reported to exert important biochemical and pharmacological activities. The adverse effects of FP remain unclear. The present study aims to determine the inhibition of human carboxylesterase 1 (CES1) by FP's major ingredients, including neobavaisoflavone, corylifolinin, coryfolin, psoralidin, corylin and bavachinin. 2. The probe substrate of CES1 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) was derived from 2-(2-hydroxy-3-methoxyphenyl) benzothiazole (HMBT), and human liver microsomes (HLMs)-catalyzed BMBT metabolism was used to phenotype the activity of CES1. In silico docking method was employed to explain the inhibition mechanism. 3. All the tested compounds exerted strong inhibition towards the activity of CES1 in a concentration-dependent behavior. Furthermore, the inhibition kinetics was determined for the inhibition of neobavaisoflavone, corylifolinin, coryfolin, corylin and bavachinin towards CES1. Both Dixon and Lineweaver-Burk plots showed that neobavaisoflavone, corylifolinin, coryfolin and corylin noncompetitively inhibited the activity of CES1, and bavachinin competitively inhibited the activity of CES1. The inhibition kinetic parameters (Ki) were calculated to be 5.3, 9.4, 1.9, 0.7 and 0.5 μM for neobavaisoflavone, corylifolinin, coryfolin, corylin and bavachinin, respectively. In conclusion, the inhibition behavior of CES1 by the FP's constituents was given in this article, indicating the possible adverse effects of FP through the disrupting CES1-catalyzed metabolism of endogenous substances and xenobiotics.
authors.affiliation: a School of Traditional Chinese Medicine, Shenyang Pharmaceutical University , Shenyang , China .
authors.forename: Dong-Xue
authors.initials: DX
authors.lastname: Sun
authors.affiliation: b Laboratory of Pharmaceutical Resource Discovery , Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian , China .
authors.forename: Guang-Bo
authors.initials: GB
authors.lastname: Ge
authors.affiliation: c Institute of Integrative Medicine, College of Pharmacy, Dalian Medical University , Dalian , China .
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Dong
authors.affiliation: d Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and the First Affiliated Hospital of Liaoning Medical University , Dalian , China .|e Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and the Affiliated Zhongshan Hospital of Dalian University , Zhongshan , Dalian , China .
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Cao
authors.affiliation: d Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and the First Affiliated Hospital of Liaoning Medical University , Dalian , China .|e Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and the Affiliated Zhongshan Hospital of Dalian University , Zhongshan , Dalian , China .
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Fu
authors.affiliation: f School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University .
authors.forename: Rui-Xue
authors.initials: RX
authors.lastname: Ran
authors.affiliation: d Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and the First Affiliated Hospital of Liaoning Medical University , Dalian , China .|e Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and the Affiliated Zhongshan Hospital of Dalian University , Zhongshan , Dalian , China .
authors.forename: Xue
authors.initials: X
authors.lastname: Wu
authors.affiliation: d Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and the First Affiliated Hospital of Liaoning Medical University , Dalian , China .|g The First Affiliated Hospital of Liaoning Medical University , Jinzhou , Liaoning , China .
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: a School of Traditional Chinese Medicine, Shenyang Pharmaceutical University , Shenyang , China .
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Hua
authors.affiliation: h Department of Pharmacy , Tianjin Union Medicine Centre , Tianjin , China , and.
authors.forename: Zhenying
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: i Department of Toxicology , School of Public Health, Tianjin Medical University , Heping , Tianjin , China.
authors.forename: Zhong-Ze
authors.initials: ZZ
authors.lastname: Fang
mesh_terms: D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D007887:Fabaceae; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D029907:Psoralea / Q000737:chemistry*
chemical_list: C000612485:Cullen corylifolium extract; D005419:Flavonoids; D010936:Plant Extracts; C459211:corylin; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human
keywords: Fructus psoraleae; herb–drug interaction; human carboxylesterase 1 (CES1); toxicity