Neuroprotective effects of salidroside through PI3K/Akt pathway activation in Alzheimer's disease models

Drug Des Devel Ther. 2016 Apr 6:10:1335-43. doi: 10.2147/DDDT.S99958. eCollection 2016.

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by deposits of aggregated amyloid-β (Aβ) peptide and neurofibrillary tangles in the brain parenchyma. Despite considerable research to elucidate the pathological mechanisms and identify therapeutic strategies for AD, effective treatments are still lacking. In the present study, we found that salidroside (Sal), a phenylpropanoid glycoside isolated from Rhodiola rosea L., can protect against Aβ-induced neurotoxicity in four transgenic Drosophila AD models. Both longevity and locomotor activity were improved in Sal-fed Drosophila. Sal also decreased Aβ levels and Aβ deposition in brain and ameliorated toxicity in Aβ-treated primary neuronal culture. The neuroprotective effect of Sal was associated with upregulated phosphatidylinositide 3-kinase (PI3K)/Akt signaling. Our findings identify a compound that may possess potential therapeutic benefits for AD and other forms of neurodegeneration.

Keywords: Alzheimer’s disease; Drosophila; amyloid-β; neuroprotective effect; salidroside.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism*
  • Animals
  • Disease Models, Animal*
  • Drosophila
  • Glucosides / chemistry
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Phenols / chemistry
  • Phenols / isolation & purification
  • Phenols / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rhodiola / chemistry
  • Signal Transduction / drug effects

Substances

  • Glucosides
  • Neuroprotective Agents
  • Phenols
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • rhodioloside