Neuroprotective Effect of Curcumin Against Cerebral Ischemia-Reperfusion Via Mediating Autophagy and Inflammation

J Mol Neurosci. 2018 Jan;64(1):129-139. doi: 10.1007/s12031-017-1006-x. Epub 2017 Dec 15.

Abstract

Curcumin, a polyphenolic compound extracted from Curcuma longa, has drawn attention for its effective bioactivities against ischemia-induced injury. This study aimed to evaluate the neuroprotective effect of curcumin and investigate the underlying mechanism that mediates autophagy and inflammation in an animal model of middle cerebral artery occlusion (MCAO) in rats. Curcumin was delivered to Sprague Dawley male rats at a dose of 200 mg/kg curcumin by intraperitoneal injection 30 min after ischemia-reperfusion (I/R). LY294002, a specific inhibitor of the PI3K/Akt/mTOR pathway, as well as anisomycin, an activator of TLR4/p38/MAPK, was administered by ventricle injection 30 min before MCAO. The same volume of saline was given as a control. Brain infarction and neurological function were determined 24 h post-MCAO. Immunoblotting and immunofluorescence were used to detect alterations in autophagy-relevant proteins Akt, p-Akt, mTOR, p-mTOR, LC3-II, and LC3-I, and inflammation-related proteins TLR4, p-38, p-p38, and IL-1 in the ipsilateral hemisphere. Cerebral I/R injury resulted in significant alterations of LC3-II/LC3-I, IL-1, TLR4, and p-p38. Curcumin in MCAO rats significantly improved brain damage and neurological function by upregulating p-Akt and p-mTOR and downregulating LC3-II/LC3-I, IL-1, TLR4, p-38, and p-p38. However, these protective effects against ischemia could be suppressed when LY294002 or anisomycin was included. Curcumin exerts neuroprotective effects by attenuating autophagic activities through mediating the PI3K/Akt/mTOR pathway, while also suppressing an inflammatory reaction by regulating the TLR4/p38/MAPK pathway. Furthermore, this study indicates that curcumin could be an effective therapy for patients afflicted with ischemia.

Keywords: Autophagy; Cerebral ischemia-reperfusion injury; Crucumin; Inflammation; Signaling pathway.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Autophagy / drug effects*
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Curcumin / administration & dosage
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • MAP Kinase Signaling System
  • Male
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Autophagy-Related Proteins
  • Interleukin-1
  • Neuroprotective Agents
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Curcumin