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

Abstract

BACKGROUND:

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.

METHODS:

Cell growth inhibition induced by silibinin was measured by MTS assay. Histamine release was measured by enzyme immunoassay. The tumor necrosis factor-α (TNF-α), 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-κB promoter activity was examined by a luciferase assay.

RESULTS:

Silibinin suppressed the growth of HMC-1 cells and also reduced the production and mRNA expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8. Moreover, silibinin inhibited the nuclear translocation of nuclear factor (NF)-κB through inhibition of the phosphorylation of IκBα and suppressed NF-κB transcriptional activity in stimulated HMC-1 cells.

CONCLUSIONS:

Taken together, these results indicate that silibinin inhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast cells, suggesting that silibinin could be used for the treatment of mast cell-derived allergic inflammatory diseases.

• Authors: Beom-Rak Kim, Hye-Sook Seo, Jin-Mo Ku, Gyung-Jun Kim, Chan Yong Jeon, Jong Hyeong Park, Bo-Hyoung Jang, Sun-Ju Park, Yong-Cheol Shin, Seong-Gyu Ko
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 62 Issue 11 Pg. 941-50 (Nov 2013) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 24045679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Allergic Agents
• Cytokines
• NF-kappa B
• RNA, Messenger
• Silymarin
• Silybin
• I-kappa B Kinase

Topics

• Animals
• Anti-Allergic Agents (pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Cytokines (antagonists & inhibitors, genetics, metabolism)
• Humans
• I-kappa B Kinase (metabolism)
• Mast Cells (drug effects, metabolism)
• Mice
• NF-kappa B (antagonists & inhibitors)
• RNA, Messenger (metabolism)
• Silybin
• Silymarin (pharmacology)