Identification of a novel compound that inhibits iNOS and COX-2 expression in LPS-stimulated macrophages from Schisandra chinensis.
A novel alpha-iso-cubebenol, which has anti-inflammatory effects in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, was isolated from the fruits of Schisandra chinensis. alpha-iso-cubebenolinhibited LPS-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production. Consistent with these findings, alpha-iso-cubebenol also reduced the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at the protein and mRNA levels in a concentration-dependent manner. alpha-iso-cubebenol also inhibited LPS-induced nuclear translocation of the NF-kappaB p65 subunit. Furthermore, alpha-iso-cubebenol suppressed the phosphorylation of ERK, JNK, and p38 kinase induced by LPS. Since the novel alpha-iso-cubebenol blocked the production of several pro-inflammatory mediators induced by LPS in macrophages, the molecule can be useful material for the development of anti-inflammatory agents against bacterial infections or endotoxin.
Lee
You Jin
YJ
Department of Horticultural Bioscience, Pusan National University, Miryang 627-706, Republic of Korea.
Park
Sun Young
SY
Kim
Sun Gun
SG
Park
Da Jung
DJ
Kang
Jum Soon
JS
Lee
Sang Joon
SJ
Yoon
Sik
S
Kim
Young Hun
YH
Bae
Yoe-Sik
YS
Choi
Young-Whan
YW
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D032141:Schisandra / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013729:Terpenes
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; D013729:Terpenes; C571662:alpha-iso-cubebenol; C547468:alpha-iso-cubenol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020929:Mitogen-Activated Protein Kinase Kinases