Clin Psychopharmacol Neurosci.  2014 Aug;12(2):75-82.

Anti-dementia Activity of Nobiletin, a Citrus Flavonoid: A Review of Animal Studies

  • 1Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
  • 2Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
  • 3Department of Anti-Dementia Functional Food Development, Research Center of Supercritical Fluid Technology, Graduate School of Engineering, Tohoku University, Sendai, Japan.
  • 4Laboratory of Kampo Medicines, Yokohama College of Pharmacy, Yokohama, Japan.
  • 5Kansei Fukushi Research Institute, Tohoku Fukushi University, Sendai, Japan.


Alzheimer's disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function and has a detrimental impact worldwide. Despite intensive laboratory and clinical research over the last three decades, pharmacological options for the prevention and effective long-term treatment of AD are not currently available. Consequently, successful therapeutic and preventive treatments for AD are needed. When researching materials from natural resources having anti-dementia drug activity, we identified nobiletin, a polymethoxylated flavone from the peel of Citrus depressa. Nobiletin exhibited memory-improving effects in various animal models of dementia and exerted a wide range of beneficial effects against pathological features of AD including amyloid-beta (Abeta) pathology, tau hyperphosphorylation, oxidative stress, cholinergic neurodegeneration and dysfunction of synaptic plasticity-related signaling, suggesting this natural compound could become a novel drug for the treatment and prevention of AD.


Nobiletin; Alzheimer's disease; Memory; Amyloid beta; Hyperphosphorylated tau; Oxidative stress; Cholinergic neurodegeneration
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