Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1beta and prostaglandin E2 synthesis by silymarin.
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-1beta (IL-1beta) and prostaglandin E2 (PGE2) production in macrophages. Silymarin dose-dependently suppressed the LPS-induced production of IL-1beta and PGE2 in isolated mouse peritoneal macrophages and RAW 264.7 cells. Consistent with these results, the mRNA expression of IL-1beta 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-kappaB/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-1beta and PGE2.
Kang
Jong Soon
JS
Korea Research Institute of Bioscience and Biotechnology, Taejon, South Korea.
Jeon
Young Jin
YJ
Park
Song-Kyu
SK
Yang
Kyu-Hwan
KH
Kim
Hwan Mook
HM
D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use*; D018805:Sepsis / Q000139:chemically induced / Q000517:prevention & control*; D012838:Silymarin / Q000627:therapeutic use*
D007375:Interleukin-1; D007527:Isoenzymes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020011:Protective Agents; D012838:Silymarin; D004247:DNA; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone