Curcumin alleviates OGD/R-induced PC12 cell damage via repressing CCL3 and inactivating TLR4/MyD88/MAPK/NF-κB to suppress inflammation and apoptosis

J Pharm Pharmacol. 2020 Sep;72(9):1176-1185. doi: 10.1111/jphp.13293. Epub 2020 May 21.

Abstract

Objectives: Curcumin presents some therapeutic effects including anti-cancer and anti-inflammation. Herein, we centred on the functional role of curcumin in cerebral ischaemia injury and its potential molecular mechanisms.

Methods: Microarray analysis was used for excavating crucial genes in cerebral ischaemia. PC12 cells were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) to imitate cerebral ischaemia/reperfusion (I/R) injury in vitro. Cell viability and apoptosis abilities were evaluated by Cell Counting Kit-8 and flow cytometry assays. qRT-PCR, Western blot and enzyme-linked immunosorbent assays were performed to assess the concentrations of related genes.

Key findings: By enquiring GEO dataset, C-C motif chemokine ligand 3 (CCL3) was profoundly upregulated in cerebral I/R injury model. And CCL3 was found to be highly expressed in PC12 cells suffered from OGD/R. Moreover, we found that CCL3 was a potential target of curcumin in cerebral I/R injury. More importantly, the following experiments illustrated that curcumin inhibited the expression of CCL3 in OGD/R model and reduced cell apoptosis and inflammation. Moreover, high expression levels of TLR4, MyD88, p-NF-κB P65, p-P38 MAPK and p-IκBα in OGD/R model were inhibited by curcumin.

Conclusions: Our study manifested that curcumin might be a meritorious drug for the treatment of cerebral ischaemia by acting on CCL3.

Keywords: CCL3; apoptosis; cerebral ischaemia; curcumin; proliferation.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / genetics
  • Chemokine CCL3 / genetics
  • Curcumin / pharmacology*
  • Gene Expression Regulation / drug effects
  • Glucose / metabolism
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Myeloid Differentiation Factor 88 / genetics
  • Oxygen / metabolism
  • PC12 Cells
  • Rats
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / genetics
  • Toll-Like Receptor 4 / genetics
  • Transcription Factor RelA / genetics
  • p38 Mitogen-Activated Protein Kinases / genetics

Substances

  • Chemokine CCL3
  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • p38 Mitogen-Activated Protein Kinases
  • Curcumin
  • Glucose
  • Oxygen