AMPK/SIRT1/p38 MAPK signaling pathway regulates alcohol‑induced neurodegeneration by resveratrol

Mol Med Rep. 2018 Apr;17(4):5402-5408. doi: 10.3892/mmr.2018.8482. Epub 2018 Jan 25.

Abstract

Resveratrol has also been approved for use in enhancing plant disease resistance and reducing pesticide use. A number of studies have shown that the disease resistance of crops treated with resveratrol is markedly improved. The aim of the present study was to examine the protective effect of resveratrol against alcohol‑induced neurodegeneration occurred and its association with AMP‑activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/p38 in rats and humans. ELISA, caspase‑3 activity and western blot analyses were employed in the present study. Sprague‑Dawley rats and human neuroblastoma SH‑SY5Y cells were treated with alcohol to establish the alcohol‑induced model. Resveratrol protected against alcohol‑induced neuron damage in the hippocampus of the rats. Treatment with resveratrol also inhibited the alcohol‑induced inflammatory response, oxidative stress, caspase‑3 activities and B‑cell lymphoma (Bcl‑2)‑associated X protein/Bcl‑2 in the alcohol‑induced rat. Resveratrol also reduced the upregulated protein expression of AMPK and SIRT1, preventing the pro‑apoptotic alcohol‑induced protein expression of p38 in the rats exposed to alcohol. The downregulation of AMPK suppressed the expression of SIRT1 and activated the expression of p38 in the SH‑SY5Y cell model. Taken together, the data obtained suggested that resveratrol protected against alcohol‑induced neurodegeneration via the AMPK/SIRT1/p38 pathway in rats and humans.

Keywords: resveratrol; alcohol; neurodegeneration; AMP-activated protein kinase; sirtuin 1; p38.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Ethanol / adverse effects*
  • Gene Expression Regulation / drug effects
  • Humans
  • Male
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Neurons / drug effects*
  • Neurons / metabolism*
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Rats
  • Resveratrol
  • Signal Transduction / drug effects*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Stilbenes / chemistry
  • Stilbenes / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Neuroprotective Agents
  • Stilbenes
  • Ethanol
  • p38 Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • Sirtuin 1
  • Resveratrol