Eutigoside C inhibits the production of inflammatory mediators (NO, PGE(2), IL-6) by down-regulating NF-kappaB and MAP kinase activity in LPS-stimulated RAW 264.7 cells.
Eutigoside C, a compound isolated from the leaves of Eurya emarginata, is thought to be an active anti-inflammatory compound which operates through an unknown mechanism. In the present study we investigated the molecular mechanisms of eutigoside C activity in lipopolysacchardide (LPS)-stimulated murine macrophage RAW 264.7 cells. Treatment with eutigoside C inhibited LPS-stimulated production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and interleukin-6 (IL-6). To further elucidate the mechanism of this inhibitory effect of eutigoside C, we studied LPS-induced nuclear factor (NF)-kappaB activation and mitogen-activated protein (MAP) kinase phosphorylation. Eutigoside C suppressed NF-kappaB DNA binding activity, interfering with nuclear translocation of NF-kappaB. Eutigoside C suppressed the phosphorylation of three MAP kinases (ERK1/2, JNK and p38). These results suggest that eutigoside C inhibits the production of inflammatory mediators (NO, PGE(2) and interleukin-6) by suppressing the activation and translocation of NF-kappaB and the phosphorylation of MAP kinases (ERK1/2, JNK and p38) in LPS-stimulated murine macrophage RAW 264.7 cells.
Department of Pharmacology, College of Medicine, Cheju National University, Jeju 690-756, South Korea.
Hye-Ja
HJ
Lee
Tae-Heon
TH
Oh
Weon-Jong
WJ
Yoon
Gyeoung-Jin
GJ
Kang
Eun-Jin
EJ
Yang
Sun-Soon
SS
Park
Nam-Ho
NH
Lee
Hee-Kyoung
HK
Kang
Eun-Sook
ES
Yoo
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis*; D015536:Down-Regulation; D005960:Glucosides / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation
D000893:Anti-Inflammatory Agents; D005960:Glucosides; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010636:Phenols; C505499:eutigoside C; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone