α-Isocubebenol alleviates scopolamine-induced cognitive impairment by repressing acetylcholinesterase activity

Neurosci Lett. 2017 Jan 18:638:121-128. doi: 10.1016/j.neulet.2016.12.012. Epub 2016 Dec 7.

Abstract

α-Isocubebenol (ICO) isolated from Schisandra chinensis fruit was recently shown to exert neuroprotective properties with significant anti-neuroinflammatory effects. Here, we present evidence of the novel effects of ICO on alleviation of cognitive impairment. To confirm these effects, ICR mice were pretreated with two different doses of ICO for 3 weeks and scopolamine (SP) to induce memory impairment for the last 7days of the period. A passive avoidance test showed that ICO pretreatment recovered memory impairment in SP treated mice, although there was no difference between the two doses. Acetylcholinesterase (AChE) activity was significantly decreased in the SP+ICO treated group compared with the SP+Vehicle treated group. Additionally, significant recovery of the number of apoptotic cells and the ratio of apoptosis proteins (Bcl-2/Bax) were detected in the SP+ICO treated group than the SP+Vehicle treated group. Moreover, ICO treatment attenuated the decrease of ERK phosphorylation by SP treatment. These results indicate that ICO from S. chinensis fruit could be applied as an active pharmaceutical ingredient for cognitive improvement in Alzheimer's disease (AD).

Keywords: Acetylcholinesterase; Cognitive impairment; Scopolamine; α-iso-cubebenol.

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Avoidance Learning / drug effects
  • Cell Survival / drug effects
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / enzymology
  • Cognition Disorders / pathology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Hippocampus / pathology
  • Male
  • Memory, Long-Term / drug effects
  • Mice, Inbred ICR
  • Neurons / pathology
  • Neuroprotective Agents / therapeutic use*
  • Phosphorylation
  • Scopolamine*
  • Sesquiterpenes / therapeutic use*

Substances

  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Sesquiterpenes
  • alpha-iso-cubebenol
  • Scopolamine
  • Extracellular Signal-Regulated MAP Kinases
  • Acetylcholinesterase