Scopolamine-Induced Memory Impairment Is Alleviated by Xanthotoxin: Role of Acetylcholinesterase and Oxidative Stress Processes

ACS Chem Neurosci. 2018 May 16;9(5):1184-1194. doi: 10.1021/acschemneuro.8b00011. Epub 2018 Feb 9.

Abstract

Xanthotoxin, popularly occurring furanocoumarin, which can be found in plants from the Apiaceae family, was isolated from fruits of Pastinaca sativa L. by mean of high-performance countercurrent chromatography, and its effects on the scopolamine-induced cognitive deficits in male Swiss mice using the passive avoidance (PA) test were evaluated. To measure the acquisition of memory processes, xanthotoxin (1, 2.5, 5 mg/kg) was administered 30 min before PA test and scopolamine was administered 10 min after xanthotoxin. To measure the consolidation of memory processes, xanthotoxin (1 and 2.5 mg/kg) was injected immediately after removing the mouse from the apparatus and 10 min after scopolamine was administered. In subchronic experiments, mice were injected with xanthotoxin (1 mg/kg) or saline, 6 days, twice daily. At 24 h after the last injection of the drugs, the hippocampus and the prefrontal cortex were removed for biochemical assays. The results demonstrated that either single (2.5 and 5 mg/kg) or repeatable (1 mg/kg) administration of xanthotoxin significantly increased index of latency (IL) in both acquisition and consolidation of memory processes, showing some procognitive effects. The behavioral tests also showed that an acute (2.5 mg/kg) and subchronic (1 mg/kg) administration of xanthotoxin prevent memory impairment induced by injection of scopolamine (1 mg/kg). Observed effects could be due to the inhibition of acetylcholinesterase activities and amelioration of oxidative stress processes in the hippocampus and the prefrontal cortex. It was suggested that xanthotoxin could show neuroprotective effect in scopolamine-induced cognitive impairment connected to cholinergic neurotransmission and oxidative stress in the brain structures.

Keywords: Apiaceae; malondialdehyde; memory impairment; methoxypsoralen; mice; oxidative stress; scopolamine; total antioxidant capacity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / drug effects*
  • Animals
  • Brain / drug effects
  • Male
  • Memory / drug effects*
  • Memory Disorders / drug therapy*
  • Methoxsalen / pharmacology
  • Mice
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects*
  • Scopolamine / chemistry
  • Scopolamine / pharmacology*

Substances

  • Neuroprotective Agents
  • Scopolamine
  • Acetylcholinesterase
  • Methoxsalen