Neuroprotection and mechanisms of atractylenolide III in preventing learning and memory impairment induced by chronic high-dose homocysteine administration in rats

Neuroscience. 2015 Apr 2:290:485-91. doi: 10.1016/j.neuroscience.2015.01.060. Epub 2015 Feb 7.

Abstract

Studies demonstrated that chronic high-dose homocysteine administration induced learning and memory impairment in animals. Atractylenolide III (Aen-III), a neuroprotective constituent of Atractylodis macrocephalae Koidz, was isolated in our previous study. In this study, we investigated potential benefits of Aen-III in preventing learning and memory impairment following chronic high-dose homocysteine administration in rats. Results showed that administration of Aen-III significantly ameliorated learning and memory impairment induced by chronic high-dose homocysteine administration in rats, decreased homocysteine-induced reactive oxygen species (ROS) formation and restored homocysteine-induced decrease of phosphorylated protein kinase C expression level. Moreover, Aen-III protected primary cultured neurons from apoptotic death induced by homocysteine treatment. This study provides the first evidence for the neuroprotective effect of Aen-III in preventing learning and impairment induced by chronic administration of homocysteine. Aen-III may have therapeutic potential in treating homocysteine-mediated cognitive impairment and neuronal injury.

Keywords: ROS; atractylenolide III; homocysteine; learning and memory impairment; neuroprotection; protein kinase C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Hippocampus / drug effects
  • Hippocampus / physiopathology
  • Homocysteine
  • Lactones / pharmacology*
  • Learning Disabilities / drug therapy*
  • Learning Disabilities / physiopathology
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / drug therapy*
  • Memory Disorders / physiopathology
  • Neurons / drug effects
  • Neurons / physiology
  • Neuroprotective Agents / pharmacology*
  • Protein Kinase C / metabolism
  • Random Allocation
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Sesquiterpenes / pharmacology*
  • Spatial Memory / drug effects

Substances

  • Lactones
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Sesquiterpenes
  • atractylenolide III
  • Homocysteine
  • Protein Kinase C
  • Casp3 protein, rat
  • Caspase 3