Ligand fishing of monoamine oxidase B inhibitors from Platycodon grandiflorus (Jacq.) A.DC. roots by the enzyme functionalised magnetic nanoparticles.

Introduction: As a famous traditional Chinese medicine, roots of Platycodon grandiflorus (Jacq.) A.DC. have shown multiple effects against neurodegenerative diseases. To investigate the components against Parkinson's disease (PD), the roots of P. grandiflora were selected as the research subject.

Objective: Screening and identifying of monoamine oxidase B (MAO-B) inhibitors from the roots of P. grandiflorum via enzyme functionalised magnetic nanoparticles (MNPs)-based ligand fishing combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis.

Method: MAO-B functionalised MNPs have been synthesised for screening MAO-B inhibitors from the roots of P. grandiflorum. The ligands were identified by HPLC-MS and nuclear magnetic resonance (NMR) analysis, and their anti-PD activity was evaluated via MAO-B inhibition assay and cell viability assay in vitro.

Results: Two MAO-B inhibitors were fished out and identified by HPLC-MS as protocatechuic aldehyde (1) and coumarin (2), with the half maximal inhibitory concentrations of 28.54 ± 0.39 and 25.39 ± 0.29 μM, respectively. Among them, 1 could also significantly increase the viability of 6-hydroxydopamine-damaged PC12 cells.

Conclusion: The results are helpful to elucidate the anti-PD activity of the plant, and the ligand fishing method has shown good potential in discovery of MAO-B inhibitors.