Silibinin Suppresses Mediators of Inflammation through the Inhibition of TLR4-TAK1 Pathway in LPS-induced RAW264.7 Cells

Ji-Hyeon Song¹, Kui-Jin Kim¹ and Boo-Yong Lee^1,

¹Department of Food Science and Biotechnology, CHA University, Kyonggi 463-400, South Korea

Cite this paper:
Ji-Hyeon Song, Kui-Jin Kim and Boo-Yong Lee. Silibinin Suppresses Mediators of Inflammation through the Inhibition of TLR4-TAK1 Pathway in LPS-induced RAW264.7 Cells. Journal of Food and Nutrition Research. 2016; 4(8):515-521. doi: 10.12691/jfnr-4-8-5

Abstract

Silibinin is the major bioactive compound of silymarin which is the mixture of flavonolignans extracted from milk thistle. Silibinin has been shown to possess anti-inflammatory activity. However, the underlying mechanisms still remain unclear. The aims of this study were to determine the effect of silibinin on molecular mechanism in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. Here, we observed that silibinin attenuated the production of nitric oxide (NO) and its regulatory protein inducible nitric oxide synthase (iNOS) expression. The pro-inflammatory cytokine interleukin (IL)-1β was inhibited by silibinin in a time dependent manner. Moreover, silibinin decreased the expression of toll-like receptor (TLR)-4, TAK1, and IRF3. TLR- associated MAPK signaling pathway was also dramatically down-regulated in LPS-induced RAW 264.7 cells with presence of silibinin. Silibinin repressed oxidative stress-associated proteins including NOX4, G6PDH, and CuZnSOD, while silibinin increased the expression of GR and catalase in LPS-induced RAW264.7 cells. In the current study, silibinin suppresses the LPS-induced inflammation via modulation of TLR4-TAK1 signaling and subsequently attenuated the production of inflammation mediators in RAW264.7 cells. Therefore, we suggest that silibinin has a potential bioactivity for prevention and intervention of endotoxin-mediated inflammation and TLR4-TAK1-associated chronic diseases.

Keywords:
silibinin TLR4 TAK1 MAPK Inflammation LPS RAW264.7

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