Acetyl-11-keto-β-boswellic acid ameliorates cognitive deficits and reduces amyloid-β levels in APPswe/PS1dE9 mice through antioxidant and anti-inflammatory pathways

Free Radic Biol Med. 2020 Apr;150:96-108. doi: 10.1016/j.freeradbiomed.2020.02.022. Epub 2020 Feb 25.

Abstract

Alzheimer's disease (AD) is a complex disease involved oxidative stress and inflammation in its pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) is an active triterpenoid compound from extracts of Boswellia serrata, which has been widely used as an antioxidant and anti-inflammatory agent. The present study was to determine whether AKBA, a novel candidate, could protect against cognitive and neuropathological impairments in AD. We found that AKBA treatment resulted in a significant improvement of learning and memory deficits, a dramatic decrease in cerebral amyloid-β (Aβ) levels and plaque burden, a profound alleviation in oxidative stress and inflammation, and a marked reduction in activated glial cells and synaptic defects in the APPswe/PS1dE9 mice. Furthermore, amyloid precursor protein (APP) processing was remarkably suppressed with AKBA treatment by inhibiting beta-site APP cleaving enzyme 1 (BACE1) protein expression to produce Aβ in the APPswe/PS1dE9 mice brains. Mechanistically, AKBA modulated antioxidant and anti-inflammatory pathways via increasing nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and via declining phosphorylation of inhibitor of nuclear factor-kappa B alpha (IκBα) and p65. Collectively, our findings provide evidence that AKBA protects neurons against oxidative stress and inflammation in AD, and this neuroprotective effect involves the Nrf2/HO-1 and nuclear factor-kappa B (NF-κB) signaling pathways.

Keywords: AKBA; Alzheimer's disease; Amyloid-β peptide; Cognitive dysfunction; Inflammation; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / genetics
  • Amyloid Precursor Protein Secretases / therapeutic use
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / therapeutic use
  • Aspartic Acid Endopeptidases / therapeutic use
  • Cognition
  • Mice
  • Mice, Transgenic
  • Triterpenes* / pharmacology

Substances

  • Amyloid beta-Protein Precursor
  • Anti-Inflammatory Agents
  • Antioxidants
  • Triterpenes
  • acetyl-11-ketoboswellic acid
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases