Bee venom ameliorates lipopolysaccharide-induced memory loss by preventing NF-kappaB pathway

J Neuroinflammation. 2015 Jun 26;12:124. doi: 10.1186/s12974-015-0344-2.

Abstract

Background: Accumulation of beta-amyloid and neuroinflammation trigger Alzheimer's disease. We previously found that lipopolysaccharide (LPS) caused neuroinflammation with concomitant accumulation of beta-amyloid peptides leading to memory loss. A variety of anti-inflammatory compounds inhibiting nuclear factor kappaB (NF-κB) activation have showed efficacy to hinder neuroinflammation and amyloidogenesis. We also found that bee venom (BV) inhibits NF-κB.

Methods: A mouse model of LPS-induced memory loss used administration of BV (0.8 and 1.6 μg/kg/day, i.p.) to ICR mice for 7 days before injection of LPS (2.5 mg/kg/day, i.p.). Memory loss was assessed using a Morris water maze test and passive avoidance test. For in vitro study, we treated BV (0.5, 1, and 2 μg/mL) to astrocytes and microglial BV-2 cells with LPS (1 μg/mL).

Results: We found that BV inhibited LPS-induced memory loss determined by behavioral tests as well as cell death. BV also inhibited LPS-induced increases in the level of beta-amyloid (Aβ), β-and γ-secretases activities, NF-κB and its DNA-binding activity and expression of APP, and BACE1 and neuroinflammation proteins (COX-2, iNOS, GFAP and IBA-1) in the brain and cultured cells. In addition, pull-down assay and molecular modeling showed that BV binds to NF-κB.

Conclusions: BV attenuates LPS-induced amyloidogenesis, neuroinflammation, and therefore memory loss via inhibiting NF-κB signaling pathway. Thus, BV could be useful for treatment of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Bee Venoms / pharmacology*
  • Bee Venoms / therapeutic use*
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Cyclooxygenase 2 / metabolism
  • Glial Fibrillary Acidic Protein
  • In Vitro Techniques
  • Inflammation / chemically induced
  • Inflammation / physiopathology
  • Inflammation / prevention & control
  • Lipopolysaccharides / adverse effects*
  • Lipopolysaccharides / pharmacology
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders / chemically induced*
  • Memory Disorders / physiopathology
  • Memory Disorders / prevention & control*
  • Mice
  • Mice, Inbred ICR
  • Microglia / drug effects
  • Microglia / metabolism
  • Models, Animal
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / drug effects
  • Nerve Tissue Proteins / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology

Substances

  • Amyloid beta-Peptides
  • Bee Venoms
  • Glial Fibrillary Acidic Protein
  • Lipopolysaccharides
  • NF-kappa B
  • Nerve Tissue Proteins
  • glial fibrillary astrocytic protein, mouse
  • Nitric Oxide Synthase Type II
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2