Ellagic acid: Insights into its neuroprotective and cognitive enhancement effects in sporadic Alzheimer's disease

Pharmacol Biochem Behav. 2018 Dec:175:33-46. doi: 10.1016/j.pbb.2018.08.007. Epub 2018 Aug 30.


Sporadic Alzheimer's disease (SAD), an age-associated dementia, is described as neuronal loss and marked cognitive impairment. Ellagic acid (EA) is a phenolic phytoconstituent obtained from grains and fruits, having evident antioxidant effects and known to modulate several endogenous molecular signals in humans in a beneficial way. The current study evaluated the safety profile of EA in the SH-SY5Y human neuroblastoma cell line, performing anti-oxidative effect by DPPH assay, and evaluating anti-AchE (acetylcholinesterase) effect against AchE enzyme from Electrophorus electricus. The observations were further confirmed by in vivo therapeutic effects in streptozotocin (STZ)-induced SAD rats in the context of altered biochemical and behavioral features. Treatment with EA (50 mg/kg, p.o.) for 30 days revealed reduction in STZ (3 mg/kg i.c.v.) prompted SAD and associated biochemical abnormalities in experimental rats which included diminished oxidative stress profile, pro-inflammatory markers i.e. GFAP and CRP; AchE level, and amyloid-β plaque level. Moreover, an elevated level of synaptophysin indicated improved synaptic connectivity, and intact neural architecture showed neuroprotection in the EA group. Furthermore, the behavioral investigation by maze paradigms revealed reduced locomotor behavior, irregular spontaneous alternation, declination in memory score and increased memory errors in SAD rats. EA treatment normalized these SAD-associated abnormal behavioral representations in rats. Hence our findings suggest neuroprotective effects of EA and improvement in cognitive behavior in SAD rats.

Keywords: Acetylcholinesterase; Alzheimer's disease; Cognition; Ellagic acid; Neurodegeneration; Neuroprotection; Oxidative stress.

MeSH terms

  • Acetylcholinesterase / drug effects
  • Alzheimer Disease / prevention & control*
  • Alzheimer Disease / psychology
  • Animals
  • Cell Line, Tumor
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use
  • Cognition / drug effects*
  • Donepezil / pharmacology*
  • Donepezil / therapeutic use
  • Ellagic Acid / pharmacology*
  • Female
  • Free Radical Scavengers / pharmacology
  • Humans
  • Male
  • Maze Learning / drug effects
  • Molecular Docking Simulation
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxazines / chemistry
  • Rats
  • Rats, Wistar
  • Xanthenes / chemistry


  • Cholinesterase Inhibitors
  • Free Radical Scavengers
  • Neuroprotective Agents
  • Oxazines
  • Xanthenes
  • Ellagic Acid
  • resazurin
  • Donepezil
  • Acetylcholinesterase