Curcumin Prevents Brain Damage and Cognitive Dysfunction During Ischemic-reperfusion Through the Regulation of miR-7-5p

Curr Neurovasc Res. 2019;16(5):441-454. doi: 10.2174/1567202616666191029113633.

Abstract

Objective: This study was to investigate the potential protective effects of curcumin in cerebral ischemia-reperfusion (CIR) and its regulation of miR-7.

Methods: Rats were occluded by middle cerebral artery occlusion (MCAO) for 1.5 h and reperfused for 2 h to establish a local CIR model. After 24 hours of model establishment, MCAO rats were given curcumin for 3 days by intragastric administration. PC12 cells were cultured for 6 h in oxygen-glucose deprivation medium and then reoxygenated for 24 h to establish an oxygenglucose deprivation/reoxygenation (OGD/R) model. The OGD/R model cells were treated with curcumin for 48 h.

Results: Curcumin inhibited the decrease of miR-7-5p expression and an increase of RelA p65 expression induced by CIR and ODG/R. RelA p65 was a target of miR-7-5p. MiR-7-5p antagonists were able to counteract the effect of curcumin on the expression of RelA p65 in ischemic brain tissue of MCAO rats and OGD/R model cells. Curcumin improved OGD/R-induced inhibition of cell activity, necrosis and apoptosis. Curcumin significantly reduced the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the activity of superoxide dismutases (SOD) and catalase (CAT) in OGD/R-induced cells. Curcumin may inhibit OGD/R-induced cell damage by regulating miR-7-5p. Curcumin improved cerebral infarction, nerve damage and cognitive dysfunction in rats with CIR, which may be related to the regulation of miR-7-5p/RelA p65 axis.

Conclusion: Curcumin exerts cerebral protection by attenuating cell necrosis and apoptosis, inflammatory response and oxidative stress following CIR, which may be related to its regulation of the miR-7/RELA p65 axis.

Keywords: Cerebral ischemia-reperfusion; curcumin; miR-7-5p/RelA p65 axis; middle cerebral artery occlusion; oxygen-glucose deprivation/reoxygenation model; tumor necrosis factor..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cognition Disorders / metabolism
  • Cognition Disorders / prevention & control*
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Gene Expression Regulation / drug effects
  • Infarction, Middle Cerebral Artery / metabolism*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects
  • Rats
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*

Substances

  • MicroRNAs
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Curcumin