Anti-neuroinflammatory effect of curcumin on Pam3CSK4-stimulated microglial cells

Int J Mol Med. 2018 Jan;41(1):521-530. doi: 10.3892/ijmm.2017.3217. Epub 2017 Oct 27.


Curcumin is the main curcuminoid present in Curcuma longa and it has been previously reported to exhibit a wide range of pharmacological activities. In the present study, the inhibitory effects of curcumin on the inflammatory mediators released by Pam3CSK4-stimulated BV-2 microglial cells were investigated. The production of pro-inflammatory mediators and cytokines, including tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2), were measured by enzyme‑linked immunosorbent assay (ELISA). The expression of inflammatory genes, including inducible nitric oxide synthase and cyclooxygenase-2, were further investigated using reverse transcription-quantitative polymerase chain reaction. The effects of curcumin on heme oxygenase-1 (HO-1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways were analyzed by western blotting. The results revealed that curcumin dose-dependently inhibited Pam3CSK4-induced nitric oxide, PGE2, and TNF-α secretion. Curcumin suppressed the secretion of inflammatory mediators through an increase in the expression of HO-1. Curcumin induced HO-1 transcription and translation through the Nrf2/antioxidant response element signaling pathway. Inhibitory experiments revealed that HO-1 was required for the anti-inflammatory effects of curcumin. Further mechanistic studies demonstrated that curcumin inhibited neuroinflammation by suppressing NF-κB and MAPK signaling pathways in Pam3CSK4-activated microglial cells. The results of the present study suggest that curcumin may be a novel treatment for neuroinflammation-mediated neurodegenerative disorders.

MeSH terms

  • Antioxidant Response Elements / genetics
  • Cell Line
  • Curcumin / administration & dosage*
  • Dinoprostone / genetics
  • Gene Expression Regulation / drug effects
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / genetics
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Lipopeptides / administration & dosage
  • Lipopeptides / genetics*
  • MAP Kinase Kinase 1 / antagonists & inhibitors
  • MAP Kinase Kinase 1 / genetics
  • Microglia / drug effects
  • Microglia / pathology
  • NF-E2-Related Factor 2 / antagonists & inhibitors
  • NF-E2-Related Factor 2 / genetics
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / pathology
  • Nitric Oxide / genetics
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / genetics


  • Lipopeptides
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Pam(3)CSK(4) peptide
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • MAP Kinase Kinase 1
  • Curcumin
  • Dinoprostone