title: Inhibition of leukocyte eicosanoid generation and radical scavenging activity by gnaphalin, a lipophilic flavonol isolated from Helichrysum picardii.
abstract: The lipophilic aglycone 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphalin) isolated from the aerial flowering parts of Helichrysum picardii Boiss. & Reuter (Asteraceae) was tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in stimulated rat peritoneal leukocytes, and for its effects on leukocyte granular enzyme release, cell viability and interactions with reactive oxygen species. Gnaphalin dose-dependently inhibited generation of the cyclo-oxygenase metabolite thromboxane B2 (IC50 = 39.9 +/- 3.9 microM), and of the 5-lipoxygenase metabolite leukotriene B4, although the potency was two-fold less (IC50 = 81.8 +/- 12.9 microM). At concentrations of 6 to 320 microM, gnaphalin did not affect secretion of the pro-inflammatory enzymes lysozyme, myeloperoxidase and beta-glucuronidase from the neutrophil secretory granules, and did not scavenge hydrogen peroxide or hypochlorous acid. However, gnaphalin effectively scavenged superoxide radicals generated in the hypoxanthine/xanthine oxidase system (IC50 = 40 microM) and by PMA-stimulated leukocytes (> 60% at 500 microM), directly inhibited xanthine oxidase (85% at 395 microM) and inhibited Fe(3+)-ascorbate-induced liposomal peroxidation (IC50 = 215 microM). Thus, like some other flavonoids found in medicinal herbs, gnaphalin possesses an array of potentially beneficial anti-eicosanoid and free-radical scavenging properties which may alongside other constituents contribute to the claimed medicinal properties of the plant from which it is derived.
authors.affiliation: Pharmacology Department, Faculty of Pharmacy, University of Seville, Spain.
authors.forename: R
authors.initials: R
authors.lastname: de la Puerta
authors.forename: R A
authors.initials: RA
authors.lastname: Forder
authors.forename: J R
authors.initials: JR
authors.lastname: Hoult
mesh_terms: D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000201:enzymology; D015777:Eicosanoids / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009113:Muramidase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010946:Plants, Medicinal; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D005419:Flavonoids; D016166:Free Radical Scavengers; D016859:Lipoxygenase Inhibitors; C121845:gnaphalin; D009195:Peroxidase; D014969:Xanthine Oxidase; D009113:Muramidase; D005966:Glucuronidase; D013755:Tetradecanoylphorbol Acetate