title: Lignan derivatives from Krameria lappacea roots inhibit acute inflammation in vivo and pro-inflammatory mediators in vitro.
abstract: The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (1-11) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID₅₀ 77 μg/cm²) as well compounds 1-11 (ID₅₀ 0.31-0.60 μmol/cm²) exhibited topical antiedematous properties comparable to those of indomethacin (ID₅₀ 0.29 μmol/cm²) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NF-κB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E₂ synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug.
authors.affiliation: Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Josef-Moeller-Haus, Innrain 52c, 6020 Innsbruck, Austria.
authors.forename: Lisa
authors.initials: L
authors.lastname: Baumgartner
authors.forename: Silvio
authors.initials: S
authors.lastname: Sosa
authors.forename: Atanas G
authors.initials: AG
authors.lastname: Atanasov
authors.forename: Antje
authors.initials: A
authors.lastname: Bodensieck
authors.forename: Nanang
authors.initials: N
authors.lastname: Fakhrudin
authors.forename: Julia
authors.initials: J
authors.lastname: Bauer
authors.forename: Giorgia Del
authors.initials: GD
authors.lastname: Favero
authors.forename: Cristina
authors.initials: C
authors.lastname: Ponti
authors.forename: Elke H
authors.initials: EH
authors.lastname: Heiss
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwaiger
authors.forename: Angela
authors.initials: A
authors.lastname: Ladurner
authors.forename: Ute
authors.initials: U
authors.lastname: Widowitz
authors.forename: Roberto Della
authors.initials: RD
authors.lastname: Loggia
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.forename: Verena M
authors.initials: VM
authors.lastname: Dirsch
authors.forename: Aurelia
authors.initials: A
authors.lastname: Tubaro
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects; D001317:Austria; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors; D031326:Krameriaceae / Q000737:chemistry*; D017705:Lignans / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry; D000071876:Prostaglandin-E Synthases
chemical_list: C562126:2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001572:Benzofurans; D017705:Lignans; D016328:NF-kappa B; C447284:conocarpan; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases