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Berberine attenuates cognitive impairment and ameliorates tau hyperphosphorylation by limiting the self-perpetuating pathogenic cycle between NF-κB signaling, oxidative stress and neuroinflammation

Pharmacol Rep. 2017 Dec;69(6):1341-1348. doi: 10.1016/j.pharep.2017.06.006. Epub 2017 Jun 15.

Abstract

Background: Berberine (BBR) plays an important role in the prevention and treatment of Alzheimer's disease (AD). The present work was to explore whether BBR ameliorates cognitive deficits in AD and to investigate whether its underlying mechanism involves inhibiting hyperphosphorylated tau protein.

Methods: The cognitive function was measured by the Morris water maze (MWM) test. The levels of hyperphosphorylated tau proteins were determined by Western blot. The biomarkers of NF-κB signaling pathway and oxidative stress were detected by Western blot and biochemical assays. The biomarkers of neuroinflammation were determined by Western blot and immunohistochemistry.

Results: BBR improved learning and memory in APP/PS1 mice. BBR decreased the hyperphosphorylated tau protein in the hippocampus of APP/PS1 mice. BBR lowered the activity of NF-κB signaling in the hippocampus of AD mice. BBR-administration promoted the activity of glutathione (GSH) and inhibited lipid peroxidation in the hippocampus of AD mice.

Conclusion: BBR attenuated cognitive deficits and limited hyperphosphorylation of tau via inhibiting the activation of NF-κB signaling pathway, and by retarding oxidative stress and neuro-inflammation.

Keywords: Berberine; Cognitive dysfunction; Inflammation; Oxidative stress; Tau hyperphosphorylation.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Animals
  • Berberine / pharmacology*
  • Biomarkers / metabolism
  • Blotting, Western
  • Cognitive Dysfunction / drug therapy*
  • Glutathione / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Immunohistochemistry
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Lipid Peroxidation / drug effects
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Mice
  • Mice, Transgenic
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects*
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects
  • tau Proteins / metabolism

Substances

  • Biomarkers
  • NF-kappa B
  • tau Proteins
  • Berberine
  • Glutathione