Chronic administration of troxerutin protects mouse brain against D-galactose-induced impairment of cholinergic system

Neurobiol Learn Mem. 2010 Feb;93(2):157-64. doi: 10.1016/j.nlm.2009.09.006. Epub 2009 Sep 17.

Abstract

Previous evidence showed that administration of d-galactose (d-gal) increased ROS production and resulted in impairment of cholinergic system. Troxerutin, a natural bioflavonoid, has been reported to have many benefits and medicinal properties. In this study, we evaluated the protective effect of troxerutin against d-gal-induced impairment of cholinergic system, and explored the potential mechanism of its action. Our results displayed that troxerutin administration significantly improved behavioral performance of d-gal-treated mice in step-through test and morris water maze task. One of the potential mechanisms of this action was decreased AGEs, ROS and protein carbonyl levels in the basal forebrain, hippocampus and front cortex of d-gal-treated mice. Furthermore, our results also showed that troxerutin significantly inhibited cholinesterase (AchE) activity, increased the expression of nicotinic acetylcholine receptor alpha 7 (nAchRalpha7) and enhanced interactions between nAchRalpha7 and either postsynaptic density protein 95 (PSD95) or N-methyl-d-aspartate receptors subunit 1 (NMDAR1) in the basal forebrain, hippocampus and front cortex of d-gal-treated mice, which could help restore impairment of brain function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Avoidance Learning / drug effects
  • Brain / drug effects*
  • Brain / enzymology
  • Brain / metabolism*
  • Disks Large Homolog 4 Protein
  • Frontal Lobe / drug effects
  • Frontal Lobe / enzymology
  • Frontal Lobe / metabolism
  • Galactose / metabolism
  • Galactose / toxicity*
  • Glycation End Products, Advanced / metabolism
  • Guanylate Kinases
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Hippocampus / metabolism
  • Hydroxyethylrutoside / administration & dosage
  • Hydroxyethylrutoside / analogs & derivatives*
  • Hydroxyethylrutoside / pharmacology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Maze Learning / drug effects
  • Membrane Proteins / metabolism
  • Mice
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Neuropsychological Tests
  • Prosencephalon / drug effects
  • Prosencephalon / enzymology
  • Prosencephalon / metabolism
  • Protein Carbonylation / drug effects
  • Random Allocation
  • Reactive Oxygen Species / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, Nicotinic / metabolism
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Chrna7 protein, mouse
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Glycation End Products, Advanced
  • Hydroxyethylrutoside
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NMDA receptor A1
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • troxerutin
  • Guanylate Kinases
  • Acetylcholinesterase
  • Galactose