Silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-kappa B signaling pathway in HMC-1 human mast cells

Abstract

Silibinin is the major active molecule of silymarin, the mixture of flavonolignans extracted from Cirsium japonicum. It has been used for the treatment of hepatitis and inflammation-related diseases. In the present study, the effects of silibinin on allergic inflammation and its signaling were investigated in the induced human mast cells. Cell growth inhibition induced by silibinin was measured by MTS assay. Histamine release was measured by enzyme immunoassay. The tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8) secreted protein levels and mRNA levels were measured by the ELISA assay and RT-PCR, respectively. The NF-kappa B promoter activity was examined by a luciferase assay. Silibinin suppressed the growth of HMC-1 cells and also reduced the production and mRNA expression of pro-inflammatory cytokines such as TNF-alpha, IL-6, and IL-8. Moreover, silibinin inhibited the nuclear translocation of nuclear factor (NF)-kappa B through inhibition of the phosphorylation of I kappa B alpha and suppressed NF-kappa B transcriptional activity in stimulated HMC-1 cells. Taken together, these results indicate that silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-kappa B signaling pathway in HMC-1 human mast cells, suggesting that silibinin could be used for the treatment of mast cell-derived allergic inflammatory diseases.