Curcumin Protects against White Matter Injury through NF-κB and Nrf2 Cross Talk

Amita Daverey, Sandeep K. Agrawal

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Inflammation and oxidative stress play a central role in the pathogenesis of white matter injury (WMI). Curcumin (Cur), a polyphenolic compound, exhibits anti-inflammatory and anti-oxidant effects on several conditions. The objective of this study was to investigate neuroprotective effects of Cur on WMI and explore its underlying mechanisms of action. Sprague-Dawley rats were subjected to the removal of white matter from the dorsal column of the spinal cord. Dorsal columns were randomly divided into three groups: Sham (Ringer's solution bubbled with 95% O2 and 5% CO2), hypoxia (Hyp; Ringer's solution bubbled with 95% N2 and 5% CO2 for 1 h), and Cur-treated (Hyp+Cur; Ringer's solution bubbled with 95% N2 and 5% CO2 for 1 h in the presence of 50 μM Cur). For NF-κB inhibition experiments, dorsal columns were incubated with 50 μM BAY 11-7082 (BAY) for 30 min in 95% O2 and 5% CO2 prior to 1-h incubation with 50 μM Cur in 95% N2 and 5% CO2. Our data show that Cur inhibited hypoxia-induced HIF1-α expression and tissue damage by demonstrating the improved morphology of astrocytes and remarkable reduction in vacuolation. Cur also inhibited the hypoxia-induced upregulation of glial fibrillary acidic protein (GFAP) and neurofilament-H (NF-H) after hypoxia and downregulated the expression of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin 1 (IL-1). Terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-assay analysis showed that Cur effectively attenuated apoptosis in white matter. In addition, we demonstrated that Cur exerted its neuroprotective effect through cross talk between nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. In conclusion, our results indicate that treatment with Cur inhibited the hypoxia, inflammation and apoptosis associated with WMI. Further, the Nrf-2 pathway inhibits NF-κB activation by preventing IkB degradation and increasing HO-1 expression, which in turn reduces reactive oxygen species (ROS) and as a result NF-κB activation is suppressed. Similarly, NF-κB-mediated transcription reduces Nrf2 activation by reducing anti-oxidant response element (ARE) gene and free CREB binding protein by competing with Nrf2 for CBP thus inhibiting the Nrf-2 activation.

Original languageEnglish (US)
Pages (from-to)1255-1265
Number of pages11
JournalJournal of Neurotrauma
Volume37
Issue number10
DOIs
StatePublished - May 15 2020

Keywords

  • curcumin
  • hypoxia
  • oxidative stress
  • polyphenolic compounds
  • spinal cord injury
  • white matter

ASJC Scopus subject areas

  • Clinical Neurology

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