title: Anti-inflammatory effect of 4-O-methylhonokiol, compound isolated from Magnolia officinalis through inhibition of NF-kappaB [corrected].
abstract: The bioactive constituents isolated from the bark of Magnolia officinalis such as magnolol, honokiol and obovatol have anti-inflammatory properties through the inactivation of NF-kappaB which is an important factor in the regulation of inflammatory reaction. We recently isolated neolignan compound, 4-O-methylhonokiol, from M. officinalis. In the present study, we investigated whether or not 4-O-methylhonokiol inhibits inflammatory reaction through the inhibition of NF-B activity [corrected]. The results showed that 4-O-methylhonokiol (2.5-10 microM) inhibited LPS (1 microg/ml)-induced NO generation in macrophage Raw 264.7 cells in a concentration-dependent manner with IC(50) value 9.8 microM. The inhibition of NO generation by 4-O-methylhonokiol was consistent with the inhibitory effect on the expression as well as transcriptional activity of inducible nitric oxide synthase (iNOS). In addition, 4-O-methylhonokiol inhibited the LPS-induced transcriptional and DNA binding activities of NF-kappaB as well as p50 and p65 translocation into the nucleus. Topical application of 4-O-methylhonokiol (0.1-1 mg/ear) inhibited 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory ear edema formation, NF-kappaB activity, and iNOS and COX-2 expression. The present results provided evidence that 4-O-methylhonokiol has anti-inflammatory properties through inhibition of the NF-kappaB pathway, and suggested that 4-O-methylhonokiol can be used as an anti-inflammatory agent.
authors.affiliation: College of Pharmacy, CBITRC, Chungbuk National University, 12, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Ju Hoon
authors.initials: JH
authors.lastname: Oh
authors.forename: La La
authors.initials: LL
authors.lastname: Kang
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Ban
authors.forename: Young Heui
authors.initials: YH
authors.lastname: Kim
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004427:Ear Diseases / Q000139:chemically induced / Q000188:drug therapy; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D031566:Magnolia / Q000737:chemistry*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology / Q000633:toxicity; D014158:Transcription, Genetic
chemical_list: C542058:4-O-methylhonokiol; D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate