title: Impact of trans-resveratrol-sulfates and -glucuronides on endothelial nitric oxide synthase activity, nitric oxide release and intracellular reactive oxygen species.
abstract: Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels. Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol. In this study, we compare side by side different physiologically relevant resveratrol metabolites (resveratrol sulfates- and -glucuronides) and their parent compound in their influence on eNOS enzyme activity, endothelial NO release, and intracellular ROS levels. In contrast to resveratrol, none of the tested resveratrol metabolites elevated eNOS enzyme activity and endothelial NO release or affected intracellular ROS levels, leaving the possibility that not tested metabolites are active and able to explain in vivo findings.
authors.affiliation: Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. angela.ladurner@univie.ac.at.
authors.forename: Angela
authors.initials: A
authors.lastname: Ladurner
authors.affiliation: Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. daniel.schachner@univie.ac.at.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schachner
authors.affiliation: Department of Nutritional and Physiological Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. katharina.schueller@univie.ac.at.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schueller
authors.affiliation: Department of Nutritional and Physiological Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. marc.pignitter@univie.ac.at.
authors.forename: Marc
authors.initials: M
authors.lastname: Pignitter
authors.affiliation: Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. elke.heiss@univie.ac.at.
authors.forename: Elke H
authors.initials: EH
authors.lastname: Heiss
authors.affiliation: Department of Nutritional and Physiological Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. veronika.somoza@univie.ac.at.
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
authors.affiliation: Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. verena.dirsch@univie.ac.at.
authors.forename: Verena M
authors.initials: VM
authors.lastname: Dirsch
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020719:Glucuronides / Q000494:pharmacology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013431:Sulfates / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D020719:Glucuronides; D017382:Reactive Oxygen Species; D013267:Stilbenes; D013431:Sulfates; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D000077185:Resveratrol