Chrysophanol Suppressed Glutamate-Induced Hippocampal Neuronal Cell Death via Regulation of Dynamin-Related Protein 1-Dependent Mitochondrial Fission

Pharmacology. 2017;100(3-4):153-160. doi: 10.1159/000477814. Epub 2017 Jun 23.

Abstract

Chrysophanic acid, or chrysophanol, is an anthraquinone found in Rheum palmatum, which was used in the preparation of oriental medicine in ancient China. The hippocampus plays a major role in controlling the activities of the short- and long-term memory. It is one of the major regions affected by excessive cell death in Alzheimer's disease. Therefore, neuronal cell-death modulation in the hippocampus is important for maintaining neuronal function. We investigated chrysophanol's effects on glutamate-induced hippocampal neuronal cell death. Chrysophanol reduced glutamate-induced cell death via suppression of proapoptotic factors and reactive oxygen species generation. Furthermore, it downregulated glutamate-induced mitochondrial fission by inhibiting dynamin-related protein 1 (Drp1) dephosphorylation. Thus, chrysophanol suppressed hippocampal neuronal cell death via inhibition of Drp1-dependent mitochondrial fission, and can be used as a therapeutic agent for treating neuronal cell death-mediated neurodegenerative diseases.

Keywords: Chrysophanol; Dynamin-related protein 1; Mitochondrial fission; Neuronal cell death; Reactive oxygen species.

MeSH terms

  • Animals
  • Anthraquinones / pharmacology*
  • Cell Death / drug effects*
  • Cell Line
  • Dynamins / antagonists & inhibitors*
  • Glutamic Acid
  • Hippocampus / cytology
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • Mitochondrial Dynamics / drug effects*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Anthraquinones
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Bcl2 protein, mouse
  • Glutamic Acid
  • Dnm1l protein, mouse
  • Dynamins
  • chrysophanic acid