Kai Xin San aqueous extract improves Aβ1-40-induced cognitive deficits on adaptive behavior learning by enhancing memory-related molecules expression in the hippocampus

J Ethnopharmacol. 2017 Apr 6:201:73-81. doi: 10.1016/j.jep.2016.10.002. Epub 2016 Oct 14.

Abstract

Ethnopharmacological relevance: Kai Xin San (KXS), a traditional formula of Chinese medicine, has been used to treat dementia.

Aim of the study: The present study aimed to investigate its ameliorating effects on Aβ1-40-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning tasks, and to determine its possible mechanism of action.

Materials and methods: Rats were pretreated with KXS aqueous extract (0.72 and 1.44g/kg, p.o.) for 10 days, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aβ1-40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of memory-related biochemical parameters and molecules.

Results: Our findings first demonstrated that KXS can improve Aβ1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should be attributed to the modulation of memory-related molecules in the hippocampus.

Conclusion: In conclusion, KXS has the potential to prevent and/or delay the deterioration of cognitive impairment in AD.

Keywords: Aβ(1-40); Cognitive deficits; Kai Xin San; Memory-related molecules; Reward-directed instrumental learning.

MeSH terms

  • Acetylcholine / metabolism
  • Amyloid beta-Peptides
  • Animals
  • Behavior, Animal / drug effects
  • Cognition / drug effects
  • Cognition Disorders / drug therapy*
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Glutamic Acid / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Learning / drug effects
  • Male
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Peptide Fragments
  • Phytotherapy
  • Rats, Wistar
  • Reward

Substances

  • Amyloid beta-Peptides
  • Drugs, Chinese Herbal
  • Kai-Xin-San
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • Glutamic Acid
  • Acetylcholine