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.

Screening of lipase inhibitors from Scutellaria baicalensis extract using lipase immobilized on magnetic nanoparticles and study on the inhibitory mechanism

“…Lipase-functionalized MNPs were synthesized following a procedure previously reported with minor modification [30]. Briefly, FeCl 3 ·6H 2 O and FeCl 2 ·4H 2 O (molar ratio = 1:2) were dissolved in deionized water by vigorously stirring under a nitrogen atmosphere, and then ammonia water was injected into the solution to adjust the pH value to 9.…”

“…Orlistat is a powerful inhibitor of lipase and has been approved by the Food and Drug Administration of the USA for treating obesity [30,33]. Samples were dissolved in Tris-HCl buffer and with a little amount of DMSO.…”

Co‐administration of nuciferine reduces the concentration of metformin in liver via differential inhibition of hepatic drug transporter OCT1 and MATE1

“…Nelumbinis Folium, as well as its formulations, has been used not only as food supplements but also as a traditional medicine in Asia (Commission CP, ), especially as weight control dietary supplements (Grienke et al, ; Zhu et al, ). Considering the moderate half‐life time (t 1/2 ) of nuciferine (4.2 ± 2.4 h) in liver and the high plasma clearance (Cl: 22.5 ± 10.4l l/h/kg) in rats after a single oral administration of nuciferine (Xu et al, ), we inferred that nuciferine might not be accumulated in hepatocytes even though the supplements containing nuciferine are given repeatedly.…”

Ligand fishing of anti‐neurodegenerative components from Lonicera japonica using magnetic nanoparticles immobilised with monoamine oxidase B

“…Recently, specific enrichment of target compounds based on solid‐phase and micro solid‐phase extraction have drawn much attention in this field , among which magnetic nanoparticles (MNPs) are of special interest . The MNPs immobilised enzymes not only retains the enzymatic activity, but also bind and separate the enzyme ligands from complex mixture which been called ligand fishing , and thus showing great potential in discovering active components from the complex of herbal extracts.…”