Chemical characterization of small-molecule inhibitors of monoamine oxidase B synthesized from the Acanthopanax senticosus root with affinity ultrafiltration mass spectrometry

Rapid Commun Mass Spectrom. 2020 Apr 30;34(8):e8694. doi: 10.1002/rcm.8694.

Abstract

Rationale: Discovering and identifying new small-molecule inhibitors of monoamine oxidase B (MAO-B) could provide the potential to treat many neurodegenerative diseases.

Methods: We employed affinity ultrafiltration liquid chromatography/tandem mass spectrometry (AUF-LC/MSn ) to identify and characterize small-molecule inhibitors of MAO-B from a 30% ethanolic extract of Acanthopanax senticosus root (ASR). In vitro tests were performed in stimulated BV2 microglia to evaluate the anti-inflammatory effects of the ASR preparation. An in vitro enzyme activity assay, measuring half-maximal inhibitory concentrations (IC50 ) against MAO-B, determined the inhibitory activity of the potential MAO-B ligands.

Results: ASR treatment significantly inhibited NO release (p <0.01) and attenuated tumor necrosis factor (TNF)-α expression in stimulated BV2 microglia. Nine compounds were isolated from the ASR preparation as potential MAO-B inhibitors, identified as quinic acid, chlorogenic acid, isofraxidin, dicaffeoylquinic acid, pinoresinol diglucoside, medioresinol 4'-O-β-D-glucopyranoside, eletutheroside E, syringaresinol O-β-D-glucoside, and trihydroxyoctadecenoic acid, based on their tandem mass spectra.

Conclusions: Our study provides critical data on compounds from ASR extracts which are suitable for the development of new MAO-B inhibitors as potential therapeutics for neurodegenerative diseases.

MeSH terms

  • Animals
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Drug Discovery
  • Eleutherococcus / chemistry*
  • Humans
  • Mice
  • Microglia / drug effects
  • Microglia / metabolism
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plant Roots / chemistry
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Tandem Mass Spectrometry
  • Ultrafiltration

Substances

  • Monoamine Oxidase Inhibitors
  • Plant Extracts
  • Small Molecule Libraries
  • Monoamine Oxidase