Fruitless Wolfberry-Sprout Extract Rescued Cognitive Deficits and Attenuated Neuropathology in Alzheimer's Disease Transgenic Mice

Curr Alzheimer Res. 2018;15(9):856-868. doi: 10.2174/1567205015666180404160625.

Abstract

Background: Alzheimer's disease (AD) is a neurodegenerative disease featured by memory loss, neuroinflammation and oxidative stress. Overproduction or insufficient clearance of Aβ leads to its pathological aggregation and deposition, which is considered the predominant neuropathological hallmark of AD. Therefore, reducing Aβ levels and inhibiting Aβ-induced neurotoxicity are feasible therapeutic strategies for AD treatment. Wolfberry has been traditionally used as a natural antioxidant and anti-aging product. However, whether wolfberry species has therapeutic potential on AD remains unknown.

Method: The effects of fruitless wolfberry-sprout extract (FWE) on Aβ fibrillation and fibril disaggregation was measured by thioflavin T fluorescence and transmission electron microscope imaging; Aβ oligomer level was determined by dot-blot; Cell viability and apoptosis was assessed by MTT and TUNEL assay. The levels of Aβ40/42, oxidative stress biomarkers and inflammatory cytokines were detected by corresponding kits. 8-month-old male APP/PS1 mice and their age-matched WT littermates were treated with FWE or vehicle by oral administration (gavage) once a day for 4 weeks. Then the cognitive performance was determined using object recognition test and Y-maze test. The Aβ burden and gliosis was evaluated by immunostaining and immunoblotting, respectively.

Results: FWE significantly inhibited Aβ fibrillation and disaggregated the formed Aβ fibrils, lowered Aβ oligomer level and Aβ-induced neuro-cytotoxicity, and attenuated oxidative stress in vitro. Oral administration of FWE remarkably improved cognitive function, reduced Aβ burden, decreased gliosis and inflammatory cytokines release, and ameliorated oxidative stress in the brains of APP/PS1 mice.

Conclusion: These findings indicate that FWE is a promising natural agent for AD treatment.

Keywords: Alzheimer's disease; Fruitless wolfberry-sprout extract; amyloid-β; neuroinflammation; oligomers; oxidative stress..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Calcium-Binding Proteins / metabolism
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology*
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Interleukin-6 / metabolism
  • Lycium / chemistry*
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins / metabolism
  • Mutation / genetics
  • Oxidative Stress / drug effects
  • Peptide Fragments / metabolism
  • Plant Extracts / therapeutic use*
  • Presenilin-1 / genetics
  • Recognition, Psychology / drug effects
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Aif1 protein, mouse
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Interleukin-6
  • Microfilament Proteins
  • Peptide Fragments
  • Plant Extracts
  • Presenilin-1
  • Tumor Necrosis Factor-alpha
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • Superoxide Dismutase
  • Glutathione
  • Glutathione Disulfide