Crataegus special extract WS 1442 causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of endothelial NO synthase but not via activation of estrogen receptors.
OBJECTIVE
This study determined whether the Crataegus (Hawthorn species) special extract WS 1442 stimulates the endothelial formation of nitric oxide (NO), a vasoprotective factor, and characterized the underlying mechanism.


RESULTS
Vascular reactivity was assessed in porcine coronary artery rings, reactive oxygen species (ROS) formation in artery sections by microscopy, and phosphorylation of Akt and endothelial NO synthase (eNOS) in endothelial cells by Western blot analysis. WS 1442 caused endothelium-dependent relaxations in coronary artery rings, which were reduced by N-nitro-L-arginine (a competitive inhibitor of NO synthase) and by charybdotoxin plus apamin (two inhibitors of endothelium-derived hyperpolarizing factor-mediated responses). Relaxations to WS 1442 were inhibited by intracellular ROS scavengers and inhibitors of Src and PI3-kinase, but not by an estrogen receptor antagonist. WS 1442 stimulated the endothelial formation of ROS in artery sections, and a redox-sensitive phosphorylation of Akt and eNOS in endothelial cells.


CONCLUSIONS
WS 1442 induced endothelium-dependent NO-mediated relaxations of coronary artery rings through the redox-sensitive Src/PI3-kinase/Akt-dependent phosphorylation of eNOS.
Anselm
Eric
E
Département de Pharmacologie et Physico-Chimie, UMR 7175, Université Louis Pasteur de Strasbourg, Strasbourg, France.
Socorro
Vanesca Frota Madeira
VF
Dal-Ros
Stéphanie
S
Schott
Christa
C
Bronner
Christian
C
Schini-Kerth
Valérie B
VB
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D027825:Crataegus / Q000737:chemistry*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*; D019061:src-Family Kinases / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D005419:Flavonoids; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C421782:WS 1442; C007145:crataegus extract; D052250:Nitric Oxide Synthase Type III; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt