title: Identification and characterization of naturally occurring inhibitors against human carboxylesterase 2 in White Mulberry Root-bark.
abstract: White Mulberry Root-bark (WMR) is an edible Chinese herbal used for the treatment of inflammation, nephritis and asthma. This study aimed to investigate the inhibitory effects of ethanol extract from WMR against human carboxylesterase 2 (hCE2), as well as to identity and character natural hCE2 inhibitors in this herbal. Our results demonstrated that the ethanol extract of WMR displayed potent inhibitory effects against hCE2, while three major bioactive constitutes in WMR were identified on the basis of LC fingerprinting combined with activity-based screening of LC fractions. Three bioactive compounds including SD, KG and SC were efficiently identified by comparison of LC retention times, UV and MS spectral data, with the help of authentic standards. The inhibition potentials and inhibition types of these natural compounds against hCE2 were further investigated in human liver microsomes. The results demonstrated that these bioactive compounds are potent non-competitive inhibitors against hCE2, with the Kivalues ranging from 0.76μM to 1.09μM. All these findings suggested that three abundant natural compounds in WMR displayed potent inhibitory effects against hCE2, which could be used as lead compounds to develop more potent hCE2 inhibitors for the alleviation of hCE2-mediated severe delayed-onset diarrhea.
authors.affiliation: Dalian Medical University, Dalian 116044, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Shi-Yang
authors.initials: SY
authors.lastname: Li
authors.affiliation: Dalian Medical University, Dalian 116044, China; State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hou
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wang
authors.affiliation: Dalian Medical University, Dalian 116044, China; The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. Electronic address: yongshanj@hotmail.com.
authors.forename: Yong-Shan
authors.initials: YS
authors.lastname: Jiang
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China. Electronic address: geguangbo@dicp.ac.cn.
authors.forename: Guang-Bo
authors.initials: GB
authors.lastname: Ge
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Xin-Miao
authors.initials: XM
authors.lastname: Liang
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
mesh_terms: D043182:Carboxylesterase / Q000037:antagonists & inhibitors*; D002853:Chromatography, Liquid; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects*; D015394:Molecular Structure; D031625:Morus / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C517204:CES2 protein, human; D043182:Carboxylesterase
keywords: Human carboxylesterase 2 (hCE2); Inhibitory effects; Kuwanon G; Sanggenone C; Sanggenone D; White Mulberry Root-bark