title: Soluble epoxide hydrolase inhibitory components from Rheum undulatum and in silico approach.
abstract: Continuous efforts to identify sEH inhibitors using activity-guided fractionation have revealed 12 known compounds, 2-13, from Rheum undulatum. Compounds 2-13 and 1, which was obtained from the in-house library, were tested for inhibitory activity against sEH. Compounds 1-9, 11, and 12 were shown to have inhibitory activity, with IC50values ranging from 2.5 ± 0.5 to 53.2 ± 4.4 μM. They were subjected to enzyme kinetic studies to explore the binding mode between the ligand and receptor. Based on our results, compounds 1, 2, 5-9, and 11 (mixed type) and compounds 3 and 12 (noncompetitive type) had a preferred allosteric site. Compound 4 was identified as a competitive-type interaction in the active site. Molecular docking studies revealed the interacting residues and binding energy between sEH and inhibitors. Additionally, molecular dynamics provided detailed information on the interaction between the ligand and receptor.
authors.affiliation: a College of Pharmacy, Chungnam National University , Daejeon , Republic of Korea.
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Jo
authors.affiliation: b Department of Horticultural Environment , National Institute of Horticultural and Herbal Science, RDA , Wanju-Gun, Republic of Korea , and.
authors.forename: Jang Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: c Shaanxi Key Laboratory of Natural Products & Chemical Biology , College of Science, Northwest A & F University , Yangling , Shaanxi , China.
authors.forename: Xi-Tao
authors.initials: XT
authors.lastname: Yan
authors.affiliation: a College of Pharmacy, Chungnam National University , Daejeon , Republic of Korea.
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Yang
authors.affiliation: a College of Pharmacy, Chungnam National University , Daejeon , Republic of Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D020134:Catalytic Domain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018514:Plant Structures / Q000737:chemistry*; D012250:Rheum / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D010936:Plant Extracts; D004851:Epoxide Hydrolases
keywords: Molecular dynamics; polygonaceae; rheum undulatum; soluble epoxide hydrolase inhibitor