Neuroprotective effect of mogrol against Aβ 1-42 -induced memory impairment neuroinflammation and apoptosis in mice

J Pharm Pharmacol. 2019 May;71(5):869-877. doi: 10.1111/jphp.13056. Epub 2018 Dec 26.

Abstract

Objectives: Cognitive impairment is the main character of Alzheimer's disease (AD). This study mainly focused on whether mogrol, a tetracyclic triterpenoids compound of Siraitia grosvenorii Swingle, can ameliorate the memory impairment induced by Aβ1-42 .

Methods: Memory impairment mice model was made by stereotactic intra-hippocampal microinjection of Aβ1-42 (410 pm/mouse). Mogrol (20, 40, 80 mg/kg) was given to mice by intragastric administration at 3 days after Aβ1-42 injection for totally 3 weeks. Morris water maze test and Y-maze test were operated to evaluate the therapeutic effect of morgrol on Aβ1-42 -induced memory impairments. Immunohistochemical analyses and Hoechst 33258 assay were used to evaluate effect of morgrol on Aβ1-42 -induced microglia overactivation and apoptotic response in hippocampus of mice. Western blotting assay was used to evaluate effect of mogrol on the Aβ1-42 -activated NF-κB signaling.

Key findings: Mogrol could significantly alleviate Aβ1-42 -induced memory impairments, inhibit Aβ1-42 -induced microglia overactivation and prevent Aβ1-42 -triggered apoptotic response in the hippocampus. Mogrol also could suppress Aβ1-42 -activated NF-κB signaling, reduce the production of proinflammatory cytokines.

Conclusions: This study suggested that mogrol would ameliorate the memory impairment induced by Aβ1-42 , which is involved in anti-inflammation and anti-apoptosis in the brain.

Keywords: Alzheimer's disease; NF-κB; apoptosis; inflammation; mogrol.

MeSH terms

  • Alzheimer Disease / chemically induced*
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / administration & dosage*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Apoptosis / drug effects
  • Cognitive Dysfunction / drug therapy*
  • Cytokines / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred ICR
  • Microglia / drug effects
  • NF-kappa B / metabolism
  • Neuroprotective Agents / pharmacology*
  • Peptide Fragments / administration & dosage*
  • Peptide Fragments / toxicity
  • Random Allocation
  • Signal Transduction / drug effects
  • Spatial Learning / drug effects
  • Triterpenes / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Cytokines
  • NF-kappa B
  • Neuroprotective Agents
  • Peptide Fragments
  • Triterpenes
  • amyloid beta-protein (1-42)