Jujuboside A, a neuroprotective agent from semen Ziziphi Spinosae ameliorates behavioral disorders of the dementia mouse model induced by Aβ 1-42

Eur J Pharmacol. 2014 Sep 5:738:206-13. doi: 10.1016/j.ejphar.2014.05.041. Epub 2014 Jun 2.

Abstract

Semen Ziziphi Spinosae (SZS) has been used as a hypnotic-sedative medicine for thousands of years. Recently, SZS has also shown notable neuroprotective activities via anti-oxidative and anti-inflammatory effects in dementia animals. Jujuboside A (JuA), isolated from SZS, has been proved to be a major hypnotic-sedative component of SZS. In the present study, we firstly evaluated the effects of intracerebroventricular (ICV) injection of JuA (0.02 and 0.2mg/kg) for five consecutive days on cognitive impairment induced by ICV injection of Aβ 1-42. The results showed that ICV treatment with JuA significantly mitigated learning and memory impairment in mice induced by Aβ 1-42 as measured by the Y-maze, active avoidance and Morris water maze. Furthermore, ICV treatment with JuA reduced the level of Aβ 1-42 in hippocampus, significantly inhibited the activities of acetylcholinesterase (AChE) and NO, and decreased the amount of the increased malondialdehyde (MDA) in the hippocampus and cerebral cortex of mice treated with ICV injection of Aβ 1-42. Shrinkage of nuclei, swollen and eccentrically dispersed neuronal bodies were observed in hippocampus of AD mice induced by Aβ 1-42, however, JuA noticeably improved the histopathological damage. Cumulatively, the present study indicates that JuA may serve as a potential therapeutic agent for the treatment of Alzheimer' disease.

Keywords: Alzheimer׳s disease; Anti-inflammation; Antioxidant; Aβ(1–42); Jujuboside A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Amyloid beta-Peptides / adverse effects*
  • Amyloid beta-Peptides / biosynthesis
  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • Cognition / drug effects
  • Dementia / chemically induced*
  • Dementia / drug therapy*
  • Dementia / metabolism
  • Dementia / physiopathology
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Male
  • Maze Learning / drug effects
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Nitric Oxide / metabolism
  • Peptide Fragments / adverse effects*
  • Peptide Fragments / biosynthesis
  • Saponins / pharmacology*
  • Saponins / therapeutic use
  • Ziziphus / chemistry*

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • Saponins
  • amyloid beta-protein (1-42)
  • Nitric Oxide
  • jujuboside A
  • Acetylcholinesterase