Studies on the anti-inflammatory effect of silymarin = Silymarin의 항염증작용에 관한 연구

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Silymarin, a polyphenolic flavonoid antioxidant, is known to have anti-inflammatory, hepatoprotective, and anticarcinogenic effects. In the present study, we report anti-septic and anti-atherogenic activity of silymarin. This study showed that silymarin protected mice against LPS-induced sepsis. In this model of sepsis, silymarin improved the rate of survival of LPS-treated mice from 6% to 38%. To investigate the mechanism responsible for anti-septic effect of silymarin, we examined the effect of silymarin on the production of inflammatory mediators, including nitric oxide (NO), Interleukin-1β(IL-1β), prostaglandin $E_2 (PGE_2)$, and tumor necrosis factor-α(TNF-α). Silymarin dose dependently suppressed the LPS-induced production of NO in isolated peritoneal macrophages and RAW 264.7 cells, a murine macrophage-like cell line. Also, LPS-induced production of IL-1β and $PGE_2$ in isolated mouse peritoneal macrophages and RAW 264.7 cells. However, TNF-α production was not affected in LPS-stimulated macrophages. Consistent with these results, mRNA expression of iNOS, IL-1β, and COX-2 was significantly abrogated by silymarin in LPS-stimulated RAW 264.7 cells and TNF-α mRNA level was not affected by silymarin treatment. To further investigate the mechanism responsible for the inhibition of gene expression of inflammatory mediators by silymarin, we examined the effect of silymarin on LPS-induced nuclear factor-κB (NF-κB)/Rel$ activation, which regulates various genes involved in immune and inflammatory response. In RAW 264.7 cells, the LPS-induced DNA binding activity of NF-κB/Rel was significantly inhibited by silymarin, and this effect was mediated through the inhibition of the degradation of inhibitory factor-κB-α (IκB-α)$. NF-κB/Rel -dependent reporter gene expression was also suppressed by silymarin in LPS-stimulated RAW 264.7 cells. Further study showed that silymarin suppressed the production of reactive oxygen species generated by $H_2O_2$ in RAW 264.7 cells. C...
Yang, Kyu-Hwan양규환
한국과학기술원 : 생물과학과,
Issue Date
180981/325007 / 000985007

학위논문(박사) - 한국과학기술원 : 생물과학과, 2003.2, [ xi, 79 p. ]


silymarin; 항염증작용; inflammation

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