Inhibitory effect of obovatol on nitric oxide production and activation of NF-kappaB/MAP kinases in lipopolysaccharide-treated RAW 264.7cells.
The components of Magnolia obovata are known to have many pharmacological activities. In this study, we investigated the effects of obovatol, a neolignan compound isolated from the leaves of M. obovata, on nitric oxide (NO) production and NF-kappaB activity in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The results show that obovatol (1-5 microM) significantly inhibited LPS-induced NO production in a concentration-dependent manner (IC(50): 0.91 microM). Consistent with the inhibitory effect on NO production, obovatol inhibits the expression of inducible nitric oxide synthase and cyclooxygenase-2 expression. Furthermore, obovatol suppressed NF-kappaB (p50 and p65) translocation to the nucleus as well as IkappaB release resulting in the inhibition of the DNA binding activity of the NF-kappaB. Obovatol also inhibited c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signal, which are the most significantly involved signal in NO production and NF-kappaB activation. When the cells were treated with the combination of obovatol with U0126 (an ERK inhibitor) or SP600125 (a JNK inhibitor) as well as with SC-514 (an IKK2 inhibitor), much more inhibition of NO production was observed than that by obovatol alone. The present results suggest that obovatol has an inhibitory effect on NO production through the inhibition of NF-kappaB/MAPK activity, and thus can be used as an anti-inflammatory agent.
Choi
Myoung Suk
MS
College of Pharmacy, Chungbuk National University, 48, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea.
Lee
Seung Ho
SH
Cho
Ho Seong
HS
Kim
Youngsoo
Y
Yun
Yeo Pyo
YP
Jung
Hai Young
HY
Jung
Jae Kyoung
JK
Lee
Bum Chun
BC
Pyo
Hyeong Bae
HB
Hong
Jin Tae
JT
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D031566:Magnolia / Q000737:chemistry; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010647:Phenyl Ethers / Q000494:pharmacology*
D000873:Anthracenes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D002070:Butadienes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D010647:Phenyl Ethers; C113580:U 0126; C432165:pyrazolanthrone; D009569:Nitric Oxide; C036795:obovatol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4