Evaluation of the Neuroprotective Effect of Total Glycosides of Cistanche deserticola and Investigation of Novel Brain-Targeting Natural MAO-B Inhibitors

ACS Chem Neurosci. 2024 Dec 18;15(24):4544-4558. doi: 10.1021/acschemneuro.4c00608. Epub 2024 Nov 23.

Abstract

In this study, we investigated the role of total glycosides of Cistanche deserticola (TC) in MPTP-induced neuronal injury. Further, we screened potential inhibitory components of monoamine oxidase B (MAO-B). The study results indicate that TC may improve movement disorders and apoptosis of dopamine (DA) neurons by inhibiting MAO-B activity while reducing the number of glial cells, adjusting the metabolism level of monoamine neurotransmitters, and lowering inflammation and oxidative stress levels. Subsequently, a rapid screening method for drug-containing brain tissue was further constructed, and five candidate components that can cross the blood-brain barrier and bind to MAO-B were screened and submitted for biological activity evaluation and inhibition mechanism research. In summary, we discovered 2'-acetylacteoside as a promising and reversible mixed natural MAO-B inhibitor in TC and developed a rapid screening method for screening central nervous system drugs with blood-brain barrier permeability characteristics, providing potential candidates and an effective screening strategy for neurodegenerative diseases.

Keywords: Parkinson’s disease; glial cells; monoamine oxidase B; neuroinflammation; oxidative stress; total glycosides of Cistanche deserticola.

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Brain* / drug effects
  • Brain* / metabolism
  • Cistanche* / chemistry
  • Glycosides* / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monoamine Oxidase Inhibitors* / pharmacology
  • Monoamine Oxidase* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology

Substances

  • Monoamine Oxidase Inhibitors
  • Neuroprotective Agents
  • Glycosides
  • Monoamine Oxidase