Target Molecular-Based Neuroactivity Screening and Analysis of Panax ginseng by Affinity Ultrafiltration, UPLC-QTOF-MS and Molecular Docking

Am J Chin Med. 2019;47(6):1345-1363. doi: 10.1142/S0192415X19500691. Epub 2019 Sep 9.

Abstract

Panax ginseng exerts good neuroprotective activity at the cell and animal level, but the specific bioactive compounds and action mechanism are needed to be investigated, verified, and confirmed. In this work, affinity ultrafiltration (AUF), UPLC-QTOF-MS, and molecular docking were integrated into one strategy to screen, identify, and evaluate the bioactive compounds in ginseng at the molecular level. Three biological macromolecules (AChE, MAO-B, and NMDA receptor) were selected as the target protein for AUF-MS screening for the first time, and 16 potential neuroactive compounds were found with suitable binding degree. Then, the bioactivity of ginseng and its components were evaluated by AChE-inhibitory test and DPPH assay, and the data indicate that ginseng extract and the screened compounds have good neuroactivity. The interaction between the three targets and the screened compounds was further analyzed by molecular docking, and the results were consistent with a few discrepancies in comparison with the AUF results. Finally, according to the corresponding relation between component-target-pathway, the action mechanism of ginseng elucidated that ginseng exerts a therapeutic effect on AD through multiple relations of components, targets, and pathways, which is in good accordance with the TCM theory.

Keywords: AChE; Affinity Ultrafiltration; Alzheimer’s Disease; Drug Screening; MAO-B; Molecular Docking; NMDA Receptor; Panax ginseng; UPLC-QTOF-MS.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Animals
  • Antioxidants
  • Cholinesterase Inhibitors
  • Chromatography, High Pressure Liquid*
  • Drug Evaluation, Preclinical / methods*
  • Humans
  • Molecular Docking Simulation*
  • Molecular Targeted Therapy
  • Monoamine Oxidase
  • Neuroprotective Agents*
  • Panax / chemistry*
  • Phytotherapy
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Receptors, N-Methyl-D-Aspartate
  • Tandem Mass Spectrometry*
  • Ultrafiltration*

Substances

  • Antioxidants
  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Plant Extracts
  • Receptors, N-Methyl-D-Aspartate
  • Monoamine Oxidase