Honokiol Attenuates the Memory Impairments, Oxidative Stress, Neuroinflammation, and GSK-3β Activation in Vascular Dementia Rats

J Alzheimers Dis. 2019;71(1):97-108. doi: 10.3233/JAD-190324.


Vascular dementia (VaD) is caused by chronic decreases in brain blood flow and accounts for 15-20% of dementia cases worldwide. In contrast to Alzheimer's disease (AD), no effective drug treatments are currently available for VaD. Previous studies have suggested that oxidative stress and neuroinflammation in the brain play important roles in the pathogenesis of VaD. Honokiol (HKL) is a well-known bioactive and nutraceutical compound that can act as an antioxidant and anti-inflammatory molecule. HKL can protect against memory impairments in AD mouse models. In this study, we explored whether the application of HKL was also protective against the insult of chronic cerebral hypoperfusion (CCH) in rats. We found that HKL supplementation prevented the memory impairments in the inhibitory avoidance step-down and Morris water maze tasks in CCH rats. HKL also suppressed the levels of oxidative stress and inflammation in CCH rats. Moreover, HKL prevented dendritic spines abnormalities in CCH rats. We also found that HKL inhibited the activity of GSK-3β, which may be critical for the neuroprotective activity of HKL. Thus, our study demonstrated the protective role of HKL in VaD.

Keywords: GSK-3β; Honokiol; inflammation; memory impairments; oxidative stress; vascular dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biphenyl Compounds / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism
  • Dementia, Vascular / drug therapy*
  • Dementia, Vascular / metabolism
  • Dementia, Vascular / psychology
  • Disease Models, Animal
  • Enzyme Activation / drug effects
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Inflammation / prevention & control*
  • Lignans / therapeutic use*
  • Maze Learning
  • Memory Disorders / prevention & control*
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar


  • Biphenyl Compounds
  • Lignans
  • Neuroprotective Agents
  • honokiol
  • Glycogen Synthase Kinase 3 beta