Carabrol suppresses LPS-induced nitric oxide synthase expression by inactivation of p38 and JNK via inhibition of I-kappaBalpha degradation in RAW 264.7 cells.
Carabrol, isolated from Carpesium macrocephalum, showed anti-inflammatory potential in LPS-induced RAW 264.7 murine macrophages. In present study, carabrol demonstrated the inhibitory activity on pro-inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. In addition, mRNA and protein levels of iNOS and COX-2 were reduced by carabrol. Molecular analysis revealed that these suppressive effects were correlated with the inactivation of p38 and JNK via inhibition of NF-kappaB activation. Immunoblotting showed that carabrol suppressed LPS-induced degradation of I-kappaBalpha and decreased nuclear translocation of p65. Taken together, these results suggest that carabrol can be a modulator of pro-inflammatory signal transduction pathway in RAW 264.7 cells.
Lee
Hwa Jin
HJ
Department of Life Science, Research Center for Women's Diseases, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Lim
Hyo Jin
HJ
Lee
Da Yeon
DY
Jung
Hyeyoun
H
Kim
Mi-Ran
MR
Moon
Dong-Cheul
DC
Kim
Keun Il
KI
Lee
Myeong-Sok
MS
Ryu
Jae-Ha
JH
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects*; D051550:I-kappa B Kinase / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D053583:Interleukin-1beta; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C547206:carabrol; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse