Cellular and Molecular Neurobiology

, Volume 34, Issue 8, pp 1209–1221 | Cite as

Hesperidin Alleviates Cognitive Impairment, Mitochondrial Dysfunction and Oxidative Stress in a Mouse Model of Alzheimer’s Disease

  • Dongmei WangEmail author
  • Ling Liu
  • Xiaoying Zhu
  • Wenlan Wu
  • Yong Wang
Original Research


The role of mitochondrial dysfunction and oxidative stress has been well-documented in Alzheimer’s disease (AD). Bioflavonoids are being utilised as neuroprotectants in the treatment of various neurological disorders, including AD. Therefore, we conducted this current study in order to explore the effects of hesperidin (a flavanone glycoside) against amyloid-β (Aβ)-induced cognitive dysfunction, oxidative damage and mitochondrial dysfunction in mice. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two hesperidin (either 50 or 100 mg/kg per day) groups, or an Aricept (2.5 mg/kg per day) group. After 16 weeks of treatment, although there was no obvious change in Aβ deposition in the hesperidin-treated (100 mg/kg per day) group, however, we found that the administration of hesperidin (100 mg/kg per day) resulted in the reduction of learning and memory deficits, improved locomotor activity, and the increase of anti-oxidative defense and mitochondrial complex I–IV enzymes activities. Furthermore, Glycogen synthase kinase-3β (GSK-3β) phosphorylation significantly increased in the hesperidin-treated (100 mg/kg per day) group. Taken together, these findings suggest that a reduction in mitochondrial dysfunction through the inhibition of GSK-3β activity, coupled with an increase in anti-oxidative defense, may be one of the mechanisms by which hesperidin improves cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD.


Hesperidin APPswe/PS1dE9 mice Cognitive ability Oxidative stress 



Alzheimer’s disease



Adenosine triphosphate


Bovine serum albumin


Ethylene glycol tetraacetic acid




Glycogen synthase kinase-3β


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-H-tetrazolium bromide




Reactive oxygen species


Succinate dehydrogenase


Super oxide dismutase


Thiobarbituric acid reactive substances


Total antioxidant capability



The present work was supported by National Natural Science Foundation of China (U1304806) and the Scientific Research Fund of Henan University of Science and Technology (NO. 09001664).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Dongmei Wang
    • 1
    Email author
  • Ling Liu
    • 2
  • Xiaoying Zhu
    • 1
  • Wenlan Wu
    • 1
  • Yong Wang
    • 1
  1. 1.Department of Pathogen Biology, Medical CollegeHenan University of Science and TechnologyLuoyangPeople’s Republic of China
  2. 2.Department of Pharmacy, Medical CollegeHenan University of Science and TechnologyLuoyangPeople’s Republic of China

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