title: Gentiolactone, a secoiridoid dilactone from Gentiana triflora, inhibits TNF-α, iNOS and Cox-2 mRNA expression and blocks NF-κB promoter activity in murine macrophages.
abstract: BACKGROUND
  Gentian roots have been used as a herbal medicine because of their anti-inflammatory activities. However, the molecular mechanisms of these anti-inflammatory effects remain to be completely explained.
  
  
  RESULTS
  Here, we investigated anti-inflammatory effects of gentian roots and showed that root extracts from Gentiana triflora inhibited lipopolysaccharide (LPS)-induced expression of TNF-α in RAW264.7 cells. The extracts also contained swertiamarin and gentiopicroside, which are the major active compounds of gentian roots; however, neither compound had any effect on LPS-induced TNF-α production in our test system. We isolated gentiolactone as an inhibitor of TNF-α production from the extracts. Gentiolactone also inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) expression at the mRNA level. Moreover, gentiolactone suppressed NF-κB transcriptional activity without inhibition of IκB degradation or NF-κB nuclear transport.
  
  
  CONCLUSIONS
  Our results indicate that inhibition of TNF-α, iNOS and Cox-2 expression by gentiolactone is one of the mechanisms of the anti-inflammatory properties of gentian roots.
authors.affiliation: Department of Bioresource Sciences, Iwate Biotechnology Research Center, Kitakami, Iwate, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Bioresource Sciences, Iwate Biotechnology Research Center, Kitakami, Iwate, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kikuchi
authors.affiliation: Graduate School of Agriculture, Iwate University, Morioka, Iwate, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Inui
authors.affiliation: Department of Bioresource Sciences, Iwate Biotechnology Research Center, Kitakami, Iwate, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Graduate School of Agriculture, Iwate University, Morioka, Iwate, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics*; D030012:Gentiana / Q000737:chemistry*; D039823:Iridoids / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D039823:Iridoids; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C000604129:gentiolactone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2