title: Effects of Artemetin on Nitric Oxide Release and Protection against Peroxidative Injuries in Porcine Coronary Artery Endothelial Cells.
abstract: Artemetin is one of the main components of Achillea millefolium L. and Artemisia absinthium, which have long been used for the treatment of various diseases. To date, however, available information about protective effects of their extracts on the cardiovascular system is scarce. Therefore, we planned to analyze the effects of artemetin on nitric oxide (NO) release and the protection exerted against oxidation in porcine aortic endothelial (PAE) cells. In PAE, we examined the modulation of NO release caused by artemetin and the involvement of muscarinic receptors, β2-adrenoreceptors, estrogenic receptors (ER), protein-kinase A, phospholipase-C, endothelial-NO-synthase (eNOS), Akt, extracellular-signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen activated protein kinase (p38 MAPK). Moreover, in cells treated with hydrogen peroxide, the effects of artemetin were examined on cell survival, glutathione (GSH) levels, apoptosis, mitochondrial membrane potential and transition pore opening. Artemetin increased eNOS-dependent NO production by the involvement of muscarinic receptors, β2-adrenoreceptors, ER and all the aforementioned kinases. Furthermore, artemetin improved cell viability in PAE that were subjected to peroxidation by counteracting GSH depletion and apoptosis and through the modulation of mitochondrial function. In conclusion, artemetin protected endothelial function by acting as antioxidant and antiapoptotic agent and through the activation of ERK1/2 and Akt. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Laboratory of Physiology and Experimental Surgery, Department of Translational Medicine, University of Eastern Piedmont 'A. Avogadro', Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Grossini
authors.affiliation: Laboratory of Physiology and Experimental Surgery, Department of Translational Medicine, University of Eastern Piedmont 'A. Avogadro', Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Marotta
authors.affiliation: Laboratory of Physiology and Experimental Surgery, Department of Translational Medicine, University of Eastern Piedmont 'A. Avogadro', Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Farruggio
authors.affiliation: Laboratory of Physiology and Experimental Surgery, Department of Translational Medicine, University of Eastern Piedmont 'A. Avogadro', Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Sigaudo
authors.affiliation: Laboratory of Physiology and Experimental Surgery, Department of Translational Medicine, University of Eastern Piedmont 'A. Avogadro', Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors.forename: Fatima
authors.initials: F
authors.lastname: Qoqaiche
authors.affiliation: Laboratory of Physiology and Experimental Surgery, Department of Translational Medicine, University of Eastern Piedmont 'A. Avogadro', Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Raina
authors.affiliation: Laboratory of Physiology and Experimental Surgery, Department of Translational Medicine, University of Eastern Piedmont 'A. Avogadro', Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: de Giuli
authors.affiliation: Laboratory of Physiology and Experimental Surgery, Department of Translational Medicine, University of Eastern Piedmont 'A. Avogadro', Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Mary
authors.affiliation: Laboratory of Physiology and Experimental Surgery, Department of Translational Medicine, University of Eastern Piedmont 'A. Avogadro', Via Solaroli 17, Azienda Ospedaliera Universitaria Maggiore della Carità, corso Mazzini 36, Novara, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vacca
authors.affiliation: Dept. Drug Sciences, University East Piedmont 'A. Avogadro', Largo Donegani 2, Novara, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pollastro
keywords: apoptosis; artemetin; cell survival; endothelium; mitochondria; nitric oxide