title: Soluble epoxide hydrolase inhibitors of indolinone alkaloids and phenolic derivatives from Cimicifuga dahurica (Turcz.) Maxim.
abstract: The aim of this study was to search for potential therapeutic agents by identifying novel inhibitors of soluble epoxide hydrolase (sEH) from natural plants using an in silico approach. We found that an ethanolic extract from the roots of Cimicifuga dahurica (Turcz.) Maxim. significantly inhibited sEH in vitro. In a phytochemical investigation using assay-guided fractionation of the dichloromethane extract of C. dahurica, we isolated two new indolinone alkaloids (5 and 6) and five related constituents (1-4, and 7) and established their structures based on an extensive analysis using 1D and 2D NMR, and MS methods. All of the isolated compounds inhibited sEH enzymatic activity in a dose-dependent manner, with IC50values ranging from 0.8±0.0 to 2.8±0.4μM. A kinetic analysis of compounds 1-7 revealed that compound 2 was non-competitive; 1, 3, and 7 were mixed-type; and 4-6 were competitive inhibitors. Molecular docking was employed to further elucidate their receptor-ligand binding characteristics. These results demonstrated that compounds from C. dahurica are potential sEH inhibitors.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea; Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi, Viet Nam.
authors.forename: Nguyen Phuong
authors.initials: NP
authors.lastname: Thao
authors.affiliation: Department of Pharmaceutical Industry, Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, Viet Nam.
authors.forename: Bui Thi Thuy
authors.initials: BT
authors.lastname: Luyen
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Korea Atomic Energy Research Institute, Jeongeup, Jeollabuk-do 580-185, Republic of Korea.
authors.forename: Jang Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D031885:Cimicifuga / Q000737:chemistry; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D007211:Indoles; D010636:Phenols; D004851:Epoxide Hydrolases
keywords: Cimicifuga dahurica; Indolinone alkaloid; Molecular docking; Ranunculaceae; Soluble epoxide hydrolase