The protective effect of Epimedii Folium and Curculiginis Rhizoma on Alzheimer's disease by the inhibitions of NF-κB/MAPK pathway and NLRP3 inflammasome

Oncotarget. 2017 Jul 4;8(27):43709-43720. doi: 10.18632/oncotarget.12574.

Abstract

The purpose of the current study was to explore the effects of the water extracts of Epimedii Folium and Curculiginis Rhizoma (EX) on Aβ-induced Alzheimer's disease. Aβ1-42 was stereotaxically injected bilaterally into the dorsal hippocampus, and then the rats were orally received EX at the doses of 2 g/kg and 6 g/kg for 30 days. Behavior was monitored through Morris water maze test. The neuroprotective effect of EX were examined with methods of histochemistry and biochemistry. EX reduced the contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and cortex. EX also reduced the levels of malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-Px) in the serum. Immunohistochemical analysis demonstrated that EX inhibited the expressions of NLRP3. In addition, we further confirmed that EX suppressed the expression of the NLRP3 inflammasome. EX inhibited the phosphorylations MAPKs, nuclear factor κB (NF-κB), myeloid differentiation factor 88(MyD88), cathepsin B. In conclusion, these results suggest that EX may be a potential agent for treating Alzheimer's disease.

Keywords: Alzheimer’s disease; Gerotarget; amyloid β; neuroinflammation; the water extracts of Epimedii Folium and Curculiginis Rhizoma (EX).

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Inflammasomes / metabolism*
  • Inflammation Mediators / metabolism
  • Male
  • Memory / drug effects
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Rats
  • Signal Transduction / drug effects*
  • Spatial Learning / drug effects

Substances

  • Amyloid beta-Peptides
  • Cytokines
  • Inflammasomes
  • Inflammation Mediators
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Neuroprotective Agents
  • Plant Extracts
  • Mitogen-Activated Protein Kinases