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Geniposide attenuates mitochondrial dysfunction and memory deficits in APP/PS1 transgenic mice.

Abstract
Oxidative stress and mitochondrial dysfunction appear early and contribute to the disease progression in Alzheimer's disease (AD), which can be detected extensively in AD patients brains as well as in transgenic AD mice brains. Thus, treatments that result in attenuation of oxidative stress and mitochondrial dysfunction may hold potential for AD treatment. Geniposide, a pharmacologically active component purified from gardenia fruit, exhibits anti-oxidative, antiinflammatory and other important therapeutic properties. However, whether geniposide has any protective effect on oxidative stress and mitochondrial dysfunction in AD transgenic mouse model has not yet been reported. Here, we demonstrate that intragastric administration of geniposide significantly reduces oxidative stress and mitochondrial dysfunction in addition to improving learning and memory in APP/PS1 mice. Geniposide exerts protective effects on mitochondrial dysfunction in APP/PS1 mice through suppressing the mitochondrial oxidative damage and increasing the mitochondrial membrane potential and activity of cytochrome c oxidase. These studies indicate that geniposide may attenuate memory deficits through the suppression of mitochondrial oxidative stress. Thus, geniposide may be a potential therapeutic reagent for halting and preventing AD progress.
AuthorsCui Lv, Xiaoli Liu, Hongjuan Liu, Tong Chen, Wensheng Zhang
JournalCurrent Alzheimer research (Curr Alzheimer Res) Vol. 11 Issue 6 Pg. 580-7 ( 2014) ISSN: 1875-5828 [Electronic] United Arab Emirates
PMID25034042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Iridoids
  • Nootropic Agents
  • PSEN1 protein, human
  • Presenilin-1
  • Reactive Oxygen Species
  • geniposide
  • Malondialdehyde
  • Electron Transport Complex IV
Topics
  • Alzheimer Disease (drug therapy, physiopathology)
  • Amyloid beta-Protein Precursor (genetics)
  • Animals
  • Brain (drug effects, physiopathology)
  • Disease Models, Animal
  • Electron Transport Complex IV (metabolism)
  • Humans
  • Iridoids (chemistry, pharmacology)
  • Male
  • Malondialdehyde (metabolism)
  • Maze Learning (drug effects, physiology)
  • Membrane Potential, Mitochondrial (drug effects, physiology)
  • Memory Disorders (drug therapy, physiopathology)
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitochondria (drug effects, physiology)
  • Nootropic Agents (chemistry, pharmacology)
  • Oxidative Stress (drug effects, physiology)
  • Presenilin-1 (genetics)
  • Random Allocation
  • Reactive Oxygen Species (metabolism)

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