Genistein antagonizes inflammatory damage induced by β-amyloid peptide in microglia through TLR4 and NF-κB

Nutrition. 2014 Jan;30(1):90-5. doi: 10.1016/j.nut.2013.06.006.

Abstract

Objectives: Microglia activation and neuroinflammation have been associated with the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB-mediated signal pathways exert key modulating roles in the inflammatory processes. The aim of the present study was to investigate whether genistein (Gen) has a neuroprotective effect against inflammatory damage induced by β-amyloid peptide25-35 (Aβ25-35) through the TLR4 and NF-κB-mediated signal pathways.

Methods: BV-2 microglia cells were preincubated with Gen for 2 h and then treated with 25 μM Aβ25-35 for another 24 h. The expression of inflammatory mediators, TLR4 and NF-κB and the activity of NF-κB were measured.

Results: The results showed that Gen could attenuate the cytotoxicity and inflammatory damage induced by Aβ25-35. Gen also significantly reversed Aβ25-35-induced up-regulation of TLR4 and NF-κB expression and the DNA binding and transcriptional activities of NF-κB.

Conclusion: These results indicated that Gen could alleviate the inflammation caused by Aβ25-35 treatment, which might be associated with the regulation of the TLR4/NF-κB signal pathway.

Keywords: Genistein; NF-κB; Neuroinflammation; TLR4; β-amyloid peptides 25-35.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / adverse effects*
  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Genistein / pharmacology*
  • Inflammation / drug therapy
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neuroprotective Agents / pharmacology*
  • Peptide Fragments / adverse effects*
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Up-Regulation

Substances

  • Amyloid beta-Peptides
  • NF-kappa B
  • Neuroprotective Agents
  • Peptide Fragments
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • amyloid beta-protein (25-35)
  • Genistein