Moracin attenuates LPS-induced inflammation in nucleus pulposus cells via Nrf2/HO-1 and NF-κB/TGF-β pathway

Biosci Rep. 2019 Dec 20;39(12):BSR20191673. doi: 10.1042/BSR20191673.

Abstract

The present study was designed to investigate the protective effect of moracin on primary culture of nucleus pulposus cells in intervertebral disc and explore the underlying mechanism. Moracin treatment significantly inhibited the LPS-induced inflammatory cytokine accumulation (IL-1β, IL-6 and TNF-α) in nucleus pulposus cells. And moracin also dramatically decreased MDA activity, and increased the levels of SOD and CAT induced by LPS challenge. Moreover, the expressions of Nrf-2 and HO-1 were decreased and the protein levels of p-NF-κBp65, p-IκBα, p-smad-3 and TGF-β were increased by LPS challenge, which were significantly reversed after moracin treatments. Moracin treatments also decreased the levels of matrix degradation enzymes (MMP-3, MMP-13) as indicated by RT-PCR analysis. However, Nrf-2 knockdown abolished these protective effects of moracin. Together, our results demonstrated the ability of moracin to antagonize LPS-mediated inflammation in primary culture of nucleus pulposus in intervertebral disc by partly regulating the Nrf2/HO-1 and NF-κB/TGF-β pathway in nucleus pulposus cells.

Keywords: LPS; Moracin; Nrf-2; inflammation; intervertebral disc degeneration.

MeSH terms

  • Benzofurans / pharmacology*
  • Heme Oxygenase (Decyclizing) / genetics*
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Lipopolysaccharides / toxicity
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 3 / genetics
  • NF-E2-Related Factor 2 / genetics*
  • NF-kappa B / genetics
  • Nucleus Pulposus / drug effects
  • Nucleus Pulposus / metabolism
  • Stilbenes / pharmacology*
  • Transforming Growth Factor beta / genetics*

Substances

  • Benzofurans
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • Stilbenes
  • Transforming Growth Factor beta
  • moracin C
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3