Affiliations: [a] Laboratory of Cardiovascular Research and Integrative Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, Pakistan
| [b] Faculty of Pharmacy, The University of Lahore, I-Km defence road, Lahore | [c] University College Of Pharmacy, University Of The Punjab, Lahore, India
| [d] UMR CNRS 7213, Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University of Strasbourg, Illkirch, France
| [e] Pharmacology Research Group, School of Life Sciences, University of Nottingham, Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, United Kingdom
Corresponding author: Richard E. Roberts, Pharmacology Research Group, School of Life Sciences, University of Nottingham, Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, United Kingdom. Tel.: +44 0 1158230190; E-mail: [email protected]. and Alamgeer, University College Of Pharmacy, University Of The Punjab, Lahore, India. Tel.: +923437547785; E-mail: [email protected].
Abstract: BACKGROUND:Fruits of Crataegus songarica are commonly used for the treatment of vascular insufficiency and heart problems. OBJECTIVE:Our aim was to determine the effect of C. songarica on vascular tone and to determine the mechanisms underlying the vasorelaxant properties. METHODS:Extracts of C. songarica were tested for vasodilator activity of porcine coronary artery after pre-contraction with the thromboxane mimetic U46619 in the presence or absence of inhibitors of intracellular signaling cascades. Reactive oxygen species were assessed by dihydroethidine staining and the level of eNOS and AKT phosphorylation was measured by immunohistochemical staining. RESULTS:Extracts of C. songarica berries produced endothelium dependent vasorelaxation, with most significant effect induced by aqueous fraction (AS-CS). This vasorelaxant effect of AS-CS was reduced by inhibition of nitric oxide pathways and inhibition of potassium channels. Inhibition of phosphatidylinositol 3- kinase and Src tyrosine kinase, as well as scavenging of reactive oxygen species, produced an attenuation of the relaxation response. Estrogen receptor antagonists(tamoxifen and ICI 182,782) reduced the AS-CS mediated vasorelaxation. AS-CS also stimulated the endothelial formation of ROS and phosphorylation of Akt and eNOS. CONCLUSION:The data indicated that C. songarica produces an endothelium-dependent vasorelaxation, which is partly dependent upon estrogen receptors, and sensitive to inhibition of ROS/Src/PI3K/NO pathways.