Ligustilide improves aging-induced memory deficit by regulating mitochondrial related inflammation in SAMP8 mice

Aging (Albany NY). 2020 Feb 16;12(4):3175-3189. doi: 10.18632/aging.102793. Epub 2020 Feb 16.

Abstract

Alzheimer's disease (AD) is an age-related neurodegenerative disease. The main active component in Angelica sinensis, ligustilide, has been reported to have the protective effect on AD. Whether ligustilide could protect against age-induced dementia is still unknown. In this study, we used an aging model, SAMP8 mice to investigate the neuroprotective effect of ligustilide. The behavioral tests (Morris water maze, object recognition task, open field test and elevated plus maze) results showed that ligustilide could improve the memory deficit in SAMP8 mice. For mechanism study, we found that the protein level of P-Drp1 (fission) was decreased and the levels of Mfn1 and Mfn2 (fusion) were increased after ligustilide treatment in animals and cells. Ligustilide increased P-AMPK and ATP levels. Malondialdehyde and superoxide dismutase activity results indicated that ligustilide exerts antioxidant effects by reducing the level of oxidative stress markers. In addition, ligustilide improved neural function and alieved apoptosis and neuroinflammation. These findings have shown that ligustilide treatment improves mitochondrial function in SAMP8 mice, and improves memory loss.

Keywords: Alzheimer’s disease; SAMP8 mice; ligustilide; mitochondrial dysfunction; neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / pharmacology
  • 4-Butyrolactone / therapeutic use
  • Aging / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Male
  • Maze Learning / drug effects*
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Mice
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Spatial Memory / drug effects

Substances

  • Neuroprotective Agents
  • ligustilide
  • 4-Butyrolactone