Screening of Monoamine Oxidase B Inhibitors from Fragaria nubicola by Ligand Fishing and Their Neuroprotective Effects

Fragaria nubicola, known as Tibetan strawberry, is an edible plant possessing various health-promoting effects. However, its functional compositions were rarely studied. In this work, monoamine oxidase B (MAO-B) inhibitors in this plant were rapidly screened using the enzyme-functionalized magnetic nanoparticles coupled with UPLC-QTOF-MS. Two inhibitors, quercetin-3-O-beta-D-glucuronide-6 ''-methyl ester (1) and kaempferol-3-O-beta-D-glucuronide-6 ''-methyl ester (2), were identified from this plant with the IC50 values of 19.44 +/- 1.17 and 22.63 +/- 1.78 mu M, respectively. Enzyme kinetic analysis and molecular docking were carried out to investigate the mechanism of inhibition. Contents of both compounds as well as those of total phenolics and flavonoids were quantified to be 24.76 +/- 1.26, 35.59 +/- 1.17, 837.67 +/- 10.62, and 593.46 +/- 10.37 mu g/g, respectively. In addition, both compounds exhibited significant neuroprotective effects on 6-hydroxydopamine-induced PC12 cells. This is the first report on the neuroprotective components of F. nubicola, suggesting its potential for developing neuroprotective functional food.

Automated summary

In this study, MAO-B inhibitors in Tibetan strawberry were screened using enzyme-functionalized magnetic nanoparticles coupled with UPLC-QTOF-MS. Two inhibitors, quercetin-3-O-beta-D-glucuronide-6''-methyl ester (1) and kaempferol-3-O-beta-D-glucuronide-6''-methyl ester (2), were identified with IC50 values of 19.44 +/- 1.17 and 22.63 +/- 1.78 mu M, respectively. The compounds also exhibited significant neuroprotective effects on PC12 cells.