Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1β and prostaglandin E2 synthesis by silymarin

Jong Soon Kang, Young J Jeon, Song Kyu Park, Kyu Hwan Yang, Hwan Mook Kim

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

Silymarin is known to have hepatoprotective and anticarcinogenic effects. Recently, anti-inflammatory effect of silymarin is attracting an increasing attention, but the mechanism of this effect is not fully understood. Here, we report that silymarin protected mice against lipopolysaccharide (LPS)-induced sepsis. In this model of sepsis, silymarin improved the rate of survival of LPS-treated mice from 6 to 38%. To further investigate the mechanism responsible for anti-septic effect of silymarin, we examined the inhibitory effect of silymarin on interleukin-1β (IL-1β) and prostaglandin E2 (PGE2) production in macrophages. Silymarin dose-dependently suppressed the LPS-induced production of IL-1β and PGE2 in isolated mouse peritoneal macrophages and RAW 264.7 cells. Consistent with these results, the mRNA expression of IL-1β and cyclooxygenase-2 was also completely blocked by silymarin in LPS-stimulated RAW 264.7 cells. Moreover, the LPS-induced DNA binding activity of nuclear factor-κB/Rel was also inhibited by silymarin in RAW 264.7 cells. Taken together, these results demonstrate that silymarin has a protective effect against endotoxin-induced sepsis, and suggest that this is mediated, at least in part, by the inhibitory effect of silymarin on the production of IL-1β and PGE2.

Original languageEnglish (US)
Pages (from-to)175-181
Number of pages7
JournalBiochemical Pharmacology
Volume67
Issue number1
DOIs
StatePublished - Jan 1 2004

Keywords

  • Cyclooxygenase-2
  • Interleukin-1β
  • NF-κB/Rel
  • Prostaglandin E2
  • Sepsis
  • Silymarin

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