title: Inhibitory effect of obovatol on nitric oxide production and activation of NF-kappaB/MAP kinases in lipopolysaccharide-treated RAW 264.7cells.
abstract: 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.
authors.affiliation: College of Pharmacy, Chungbuk National University, 48, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Myoung Suk
authors.initials: MS
authors.lastname: Choi
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Ho Seong
authors.initials: HS
authors.lastname: Cho
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Yeo Pyo
authors.initials: YP
authors.lastname: Yun
authors.forename: Hai Young
authors.initials: HY
authors.lastname: Jung
authors.forename: Jae Kyoung
authors.initials: JK
authors.lastname: Jung
authors.forename: Bum Chun
authors.initials: BC
authors.lastname: Lee
authors.forename: Hyeong Bae
authors.initials: HB
authors.lastname: Pyo
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: 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*
chemical_list: 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