Chelidonine inhibits TNF-α-induced inflammation by suppressing the NF-κB pathways in HCT116 cells

Phytother Res. 2018 Jan;32(1):65-75. doi: 10.1002/ptr.5948. Epub 2017 Oct 17.

Abstract

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a complex that regulates several hundreds of genes, including those involved in immunity and inflammation, survival, proliferation, and the negative feedback of NF-κB signaling. Chelidonine, a major bioactive, isoquinoline alkaloid ingredient in Chelidonium majus, exhibits antiinflammatory pharmacological properties. However, its antiinflammatory molecular mechanisms remain unclear. In this work, we explored the effect of chelidonine on TNF-induced NF-κB activation in HCT116 cells. We found chelidonine inhibited the phosphorylation and degradation of the inhibitor of NF-κB alpha and nuclear translocation of RELA. Furthermore, by inhibiting the activation of NF-κB, chelidonine downregulated target genes involved in inflammation, proliferation, and apoptosis. Chelidonine also inhibited mitogen-activated protein kinase pathway activation by blocking c-Jun N-terminal kinase and p38 phosphorylation. These results suggest that chelidonine may be a potential therapeutic agent against inflammatory diseases in which inhibition of NF-κB activity plays an important role.

Keywords: IκBα; NF-κB; apoptosis; chelidonine; inflammation.

MeSH terms

  • Apoptosis
  • Benzophenanthridines / administration & dosage
  • Benzophenanthridines / pharmacology
  • Benzophenanthridines / therapeutic use*
  • Berberine Alkaloids / administration & dosage
  • Berberine Alkaloids / pharmacology
  • Berberine Alkaloids / therapeutic use*
  • HCT116 Cells / metabolism*
  • Humans
  • NF-kappa B / metabolism*
  • Signal Transduction
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Benzophenanthridines
  • Berberine Alkaloids
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • chelidonine