Cognitive dysfunctions induced by a cholinergic blockade and Aβ 25-35 peptide are attenuated by salvianolic acid B

Neuropharmacology. 2011 Dec;61(8):1432-40. doi: 10.1016/j.neuropharm.2011.08.038. Epub 2011 Sep 1.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive cognitive and memory loss and neuronal cell death. Current therapeutic strategies for AD are very limited; thus, traditional herbal medicines or their active constituents receive much attention. The aim of this study was to investigate the cognitive enhancing effects of salvianolic acid B (SalB) isolated from Salvia miltiorrhiza and its ameliorating effects on various drug-induced amnesic models using the passive avoidance, Y-maze, and Morris water maze tasks. Drug-induced amnesia was induced by administering scopolamine, diazepam, muscimol, or amyloid-β (Aβ)(25-35) peptide. SalB (10 mg/kg, p.o.) was found to significantly reverse the cognitive impairments induced by scopolamine (1 mg/kg, i.p.) or Aβ(25-35) (10 nmol/5 μl, i.c.v.) injection. This ameliorating effect of SalB was antagonized by the GABA(A) receptor agonists, muscimol or diazepam, respectively. In addition, SalB alone was capable of improving cognitive performances. Furthermore, SalB (100 μM) was found to inhibit GABA-induced outward Cl(-) currents in single hippocampal CA1 neuron. These results suggest that the observed ameliorations of cholinergic dysfunction- or Aβ(25-35)-induced memory impairment by SalB were mediated, in part, via the GABAergic neurotransmitter system after a single administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / adverse effects*
  • Animals
  • Animals, Newborn
  • Benzofurans / chemistry
  • Benzofurans / therapeutic use*
  • Cholinergic Antagonists / adverse effects*
  • Cholinesterase Inhibitors / adverse effects
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / drug therapy*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Hippocampus / cytology
  • In Vitro Techniques
  • Injections, Intraventricular
  • Male
  • Maze Learning / drug effects
  • Membrane Potentials / drug effects
  • Mice
  • Neurons / drug effects
  • Patch-Clamp Techniques
  • Peptide Fragments / adverse effects*
  • Pregnancy
  • Rats
  • Tacrine / adverse effects
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Amyloid beta-Peptides
  • Benzofurans
  • Cholinergic Antagonists
  • Cholinesterase Inhibitors
  • Peptide Fragments
  • amyloid beta-protein (25-35)
  • Tacrine
  • gamma-Aminobutyric Acid
  • salvianolic acid B