title: Inhibition of COX-2 and NF-κB1 Gene Expression, NO Production, 5-LOX, and COX-1 and COX-2 Enzymes by Extracts and Constituents of Onopordum acanthium.
abstract: The present study focused on the investigation of the inhibition of cyclooxygenase-2 and nuclear factor kappa B1 gene expression, nitric oxide production, leukotriene biosynthesis (5-lipoxygenase), and cyclooxygenase-1 and cyclooxygenase-2 enzymes of Onopordum acanthium, and the isolation and identification of its active compounds. From the chloroform soluble part of the MeOH extract prepared from aerial parts, lignans [pinoresinol (1), syringaresinol (2), and medioresinol (3)] and flavonoids [hispidulin (4), nepetin (5), apigenin (6), and luteolin (7)] were isolated by a combination of different chromatographic methods. The structures of the compounds were determined by means of mass spectrometry and 1D- and 2D-nuclear magnetic resonance spectroscopy, and by comparison of the spectral data with literature values. Extracts of different polarity and the isolated compounds obtained from the aerial parts, together with those previously isolated from the roots of the plant [4β,15-dihydro-3-dehydrozaluzanin C (8), zaluzanin C (9), 4β,15,11β,13-tetrahydrozaluzanin C (10), nitidanin diisovalerianate (11), 24-methylenecholesterol (12), and 13-oxo-9Z,11E-octadecadienoic acid (13)], were evaluated for their inhibitory effects on cyclooxygenase-2 and nuclear factor kappa B1 gene expression, inducible nitric oxide synthase, 5-lipoxygenase, and cyclooxygenase-1 and cyclooxygenase-2 enzymes in in vitro assays. It was found that O. acanthium extracts exert strong inhibitory activities in vitro and some lignans, flavonoids, and sesquiterpenes may play a role in these activities. 4β,15-Dihydro-3-dehydrozaluzanin C and zaluzanin C at 20 µM were the most active constituents tested against lipopolysaccharide/interferon-γ-induced nitric oxide production (100.4 ± 0.5 % and 99.4 ± 0.8 %) in the inhibition of cyclooxygenase-2 (98.6 ± 0.2 % and 97.0 ± 1.1 %) and nuclear factor kappa B1 gene expression (76.7 ± 7.3 % and 69.9 ± 3.4 %). Furthermore, it was shown that these inhibitory effects are not due to cytotoxicity of the compounds.
authors.affiliation: Department of Pharmacognosy, University of Szeged, Szeged, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Lajter
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens University Graz, Graz, Austria.
authors.forename: San-Po
authors.initials: SP
authors.lastname: Pan
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens University Graz, Graz, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nikles
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens University Graz, Graz, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ortmann
authors.affiliation: Department of Pharmacognosy, University of Szeged, Szeged, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vasas
authors.affiliation: Department of Pharmacognosy, University of Szeged, Szeged, Hungary.
authors.forename: Boglárka
authors.initials: B
authors.lastname: Csupor-Löffler
authors.affiliation: Department of Pharmacognosy, University of Szeged, Szeged, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Forgó
authors.affiliation: Department of Pharmacognosy, University of Szeged, Szeged, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Hohmann
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens University Graz, Graz, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D031183:Onopordum / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D010936:Plant Extracts; D009569:Nitric Oxide; D001094:Arachidonate 5-Lipoxygenase; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; C583212:ALOX5 protein, human