Asiaticoside reduces autophagy and improves memory in a rat model of dementia through mTOR signaling pathway regulation

Mol Med Rep. 2021 Sep;24(3):645. doi: 10.3892/mmr.2021.12284. Epub 2021 Jul 19.

Abstract

Vascular dementia (VD) is one of the leading causes of neurological disorder following Alzheimer's disease. The present study evaluated the possible role of asiaticoside in the treatment of rats with VD and its inhibitory effects on autophagy in hippocampal tissues. Double ligation was used for permanent occlusion of the arteries, and spatial memory was assessed using the T‑maze test. Western blotting was used for determination of protein expression levels and H&E staining for histological analysis. Treatment of rats with VD with asiaticoside significantly alleviated the impairment in spontaneously altered behaviors and significantly reduced escape latency. VD mediated a decrease in distance travelled, swim time and number of platform crossings, whereas this was alleviated by asiaticoside. Furthermore, VD‑mediated hippocampal tissue damage was significantly alleviated by asiaticoside treatment (P<0.05), and asiaticoside alleviated formation of autophagosomes and markedly suppressed the number of primary lysosomes. In asiaticoside‑treated rats, VD‑mediated increases in Beclin 1 and microtubule‑associated protein light chain 3 (LC3) II expression in the hippocampal tissues were alleviated. Asiaticoside treatment also prevented suppression of mammalian target of rapamycin (mTOR) phosphorylation in VD rat hippocampal tissues. Notably, the rapamycin‑mediated suppression of phosphorylated‑mTOR, and elevation of Beclin 1 and LC3II expression in the rat hippocampus could not be alleviated by asiaticoside treatment. In conclusion, asiaticoside effectively prevented cerebral ischemia‑mediated cognitive impairment and neuronal damage in the rats. Moreover, autophagy was inhibited and the mTOR pathway was activated in rats with cerebral ischemia by asiaticoside treatment. Therefore, asiaticoside may warrant further study as a therapeutic agent for the treatment of dementia.

Keywords: autophagy; cerebral ischemia; dementia; neuronal damage; rapamycin.

MeSH terms

  • Alzheimer Disease / metabolism
  • Animals
  • Autophagosomes / metabolism
  • Autophagy / drug effects*
  • Beclin-1 / metabolism
  • Brain Ischemia
  • Cognitive Dysfunction / metabolism
  • Dementia, Vascular / drug therapy
  • Hippocampus / metabolism
  • Male
  • Maze Learning
  • Memory / drug effects*
  • Microtubule-Associated Proteins / metabolism
  • Neurons / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*
  • Triterpenes / pharmacology*

Substances

  • Beclin-1
  • LC3 protein, rat
  • Microtubule-Associated Proteins
  • Triterpenes
  • mTOR protein, rat
  • TOR Serine-Threonine Kinases
  • asiaticoside