Vitexin prevents Aβ proteotoxicity in transgenic Caenorhabditis elegans model of Alzheimer's disease by modulating unfolded protein response

J Biochem Mol Toxicol. 2021 Jan;35(1):e22632. doi: 10.1002/jbt.22632. Epub 2020 Sep 14.

Abstract

Alzheimer's disease (AD) accounts for an estimated 60% to 80% of all dementia cases. The present study is aimed at evaluating the neuroprotective efficacy of vitexin, an apigenin flavone glycoside using transgenic Caenorhabditis elegans strain (CL2006) of AD. The neuroprotective effect of vitexin was determined using physiological assays, quantitative polymerase chain reaction, and Western blotting. The results of survival and paralysis assay indicate that vitexin (200 μM) significantly extended the lifespan of the nematodes. Vitexin-treated nematodes showed a significant reduction in the expression of Aβ, ace-1, and ace-2 genes when compared to control. Further, vitexin significantly upregulated the expression of acr-8 and dnj-14, and increased the lifespan of the nematodes. Vitexin was also found to modulate the unfolded protein response genes (hsp-4, pek-1, ire-1, and xbp-1) and suppress the expression of Aβ. Overall, the results show that vitexin acts as a neuroprotective agent and protects transgenic C. elegans strains from Aβ proteotoxicity.

Keywords: Alzheimer's disease; Aβ; C. elegans; dnj-14; vitexin.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / metabolism*
  • Apigenin / pharmacology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Disease Models, Animal
  • Humans
  • Unfolded Protein Response / drug effects*
  • Unfolded Protein Response / genetics

Substances

  • Amyloid beta-Peptides
  • Caenorhabditis elegans Proteins
  • Apigenin
  • vitexin