Geniposide ameliorates cognitive deficits by attenuating the cholinergic defect and amyloidosis in middle-aged Alzheimer model mice

Neuropharmacology. 2017 Apr:116:18-29. doi: 10.1016/j.neuropharm.2016.12.002. Epub 2016 Dec 6.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory deficits and cognitive decline. Amyloid-β (Aβ) deposition and cholinergic defect are widely thought to be the underlying mechanism of learning and memory impairment. Geniposide, which is the main active component of the traditional Chinese herbal Gardenia jasminoides Ellis, elicits neuroprotective effects by alleviating inflammation responses and oxidative damages. In this study, we investigated the protective effect of geniposide on levels of cholinergic markers, RAGE, RAGE-dependent signalling pathways and amyloid accumulation in the APPswe/PS1dE9 AD model mouse. Geniposide suppressed MAPK signaling over-activation mediated by Aβ-RAGE interaction, resulting in reduced Aβ accumulation and amelioration of cholinergic deficits in the cerebral hippocampus. Furthermore, geniposide inhibited the toxic effect of oligomeric Aβ1-42 induced cholinergic deficit by increasing ChAT levels and activity but decreasing AChE activity in cultured primary hippocampal neurons. These results indicated that geniposide enhanced cholinergic neurotransmission, which likely contributes to its memory enhancing effect.

Keywords: Acetylcholine; Alzheimer's disease; Amyloid β; Cognition; Geniposide; Receptor for advanced glycation end products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / toxicity
  • Amyloidosis / drug therapy*
  • Amyloidosis / pathology
  • Amyloidosis / physiopathology
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / pathology
  • Cognition Disorders / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Iridoids / chemistry
  • Iridoids / therapeutic use*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Male
  • Memory Disorders / drug therapy
  • Memory Disorders / pathology
  • Memory Disorders / physiopathology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Nootropic Agents / chemistry
  • Nootropic Agents / therapeutic use*
  • Peptide Fragments / metabolism
  • Peptide Fragments / toxicity
  • Receptor for Advanced Glycation End Products / metabolism

Substances

  • Ager protein, mouse
  • Amyloid beta-Peptides
  • Iridoids
  • Neuroprotective Agents
  • Nootropic Agents
  • Peptide Fragments
  • Receptor for Advanced Glycation End Products
  • amyloid beta-protein (1-42)
  • geniposide