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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

Anselm, Eric PhD*; Socorro, Vanesca Frota Madeira PhD*†; Dal-Ros, Stéphanie*; Schott, Christa*; Bronner, Christian PhD*; Schini-Kerth, Valérie B PhD*

Journal of Cardiovascular Pharmacology: March 2009 - Volume 53 - Issue 3 - p 253-260
doi: 10.1097/FJC.0b013e31819ccfc9
Original Article

Purpose: 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.

Methods and 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 Nω-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.

From the *Département de Pharmacologie et Physico-Chimie, UMR 7175, Université Louis Pasteur de Strasbourg, Strasbourg, France; and †Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, Brasil.

Received for publication December 3, 2008; accepted January 15, 2009.

Supported, in part, by a research grant from Dr. Willmar Schwabe Pharmaceuticals (Karlsruhe, Germany).

The authors report no conflicts of interest.

Reprints: Valérie B. Schini-Kerth, PhD, Département de Pharmacologie et Physico-Chimie, UMR CNRS 7175, Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, 74, route du Rhin, B.P. 60024, F-67401 Illkirch, France (e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.