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 language | English (US) |
---|---|
Pages (from-to) | 175-181 |
Number of pages | 7 |
Journal | Biochemical Pharmacology |
Volume | 67 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2004 |
Externally published | Yes |
Bibliographical note
Funding Information:This work was partially supported by both Korea Research Institute of Bioscience and Biotechnology and a grant R05-2002-000-01323-0 from Korea Science & Engineering Foundation.
Keywords
- Cyclooxygenase-2
- Interleukin-1β
- NF-κB/Rel
- Prostaglandin E2
- Sepsis
- Silymarin