title: Isogentisin--a novel compound for the prevention of smoking-caused endothelial injury.
abstract: The best strategy in the fight against tobacco-induced diseases is prevention. However, more than one billion people around the world are smokers. Most of these people will develop or already suffer from tobacco-induced diseases. In this project, we screened 22 natural alpine plant extracts for their potential to protect human vascular endothelial cells from cigarette smoke-induced cell damage. Extracts from Gentiana lutea (Yellow Gentian) proved to be effective, and were therefore subjected to bio-guided fractionation. Although our analyses suggest that G. lutea contains several active principles, fractions containing isogentisin (1,3-dihydroxy-7-methoxyxanthone), and pure isogentisin, were most effective. In experiments addressing the nature of the mechanism of protection, we were able to show that isogentisin does not directly interfere with cigarette smoke chemicals. Addition of isogentisin to the cells as long as 4.5h after exposure to cigarette smoke chemicals protected endothelial cells from cell death. Finally, detailed analyses of intracellular oxidative stress and protein oxidation suggest that isogentisin promotes cell survival by activating cellular repair functions.
authors.affiliation: Vascular Biology Group, Division Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Fritz-Pregl-Str. 3/4 OG, 6020 Innsbruck, Austria.
authors.forename: Astrid
authors.initials: A
authors.lastname: Schmieder
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwaiger
authors.forename: Adam
authors.initials: A
authors.lastname: Csordas
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Backovic
authors.forename: Barbara
authors.initials: B
authors.lastname: Messner
authors.forename: Georg
authors.initials: G
authors.lastname: Wick
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.forename: David
authors.initials: D
authors.lastname: Bernhard
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D030012:Gentiana / Q000737:chemistry; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D012907:Smoking / Q000503:physiopathology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D044004:Xanthones; C018087:isogentisin