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

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) is a complex that regulates several hundreds of genes, including those involved in immunity and inflammation, survival, proliferation, and the negative feedback of NF-B 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-B activation in HCT116 cells. We found chelidonine inhibited the phosphorylation and degradation of the inhibitor of NF-B alpha and nuclear translocation of RELA. Furthermore, by inhibiting the activation of NF-B, 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-B activity plays an important role.