title: Lipase ligands in Nelumbo nucifera leaves and study of their binding mechanism.
abstract: Lotus (Nelumbo nucifera) leaves have been widely used in weight-loss foods to prevent obesity in China. In this work, a facile procedure based on ligand fishing was developed to isolate and identify lipase inhibitors present in lotus leaves. Highly stable and active lipase-Fe3O4 superparamagnetic nanoparticle conjugates (LMNPs) were prepared and used as baits. Two flavonoids in lotus leaf extract were found to bind to the baits and were identified as quercetin-3-O-β-d-arabinopyranosyl-(1→2)- β-d-galactopyranoside (1) and quercetin-3-O-β-d-glucuronide (4) based on electrospray ionization-mass spectrometric analyses. Their 50% inhibitory concentrations on lipase (IC50) were 52.9 ± 3.2 and 17.1 ± 1.5 μg/mL, respectively. In addition, they were found to significantly quench the fluorescence of lipase, suggesting their strong affinities with this enzyme, which was further evidenced by molecular docking. Ligand fishing based on LMNPs shows great power for fast screening and identification of lipase inhibitors present in edible and medicinal plants.
authors.affiliation: Chengdu Institute of Biology, Chinese Academy of Sciences , Chengdu 610041, China.
authors.forename: Yuan-Ting
authors.initials: YT
authors.lastname: Zhu
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Jia
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Ding
authors.forename: Xun
authors.initials: X
authors.lastname: Liao
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D062105:Molecular Docking Simulation; D031653:Nelumbo / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification; D018515:Plant Leaves / Q000737:chemistry*; D011794:Quercetin / Q000737:chemistry / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D008024:Ligands; D010936:Plant Extracts; D011794:Quercetin; D008049:Lipase
keywords: Nelumbo nucifera leaves; fluorescence quenching; ligand fishing; lipase inhibitors; molecular docking