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Y Alamgeer

University of Sargodha, Pakistan

Title: Endothelium-independent vasorelaxant effect of a Berberis orthobotrys root extract via inhibition of phosphodiesterases in the porcine coronary artery

Biography

Biography: Y Alamgeer

Abstract

This study was aimed to evaluate the vasoactive properties of Berberis orthobotrys root extract and its fractions. An aqueous methanolic extract of Berberis orthobotrys roots was prepared and submitted to a multi-step liquid-liquid fractionation with solvents of increasing polarity. Vascular reactivity of the different fractions was assessed using porcine coronary artery rings with and without endothelium. The ability of Berberis orthobotrys extracts to affect phosphodiesterase (PDE) activity was evaluated using a radioenzymatic method and purified phosphodiesterases. The aqueous methanol extract induced similar relaxations in coronary artery rings with and without endothelium, and, amongst all three derived preparations, the butanol fraction (BFBO) was slightly but significantly more effective. BFBO significantly potentiated the relaxations induced by cyclic GMP- and cyclic AMP-dependent relaxing agonists, and inhibited contractions to KCl, CaCl2, and U46619 in endothelium denuded rings. BFBO concentration-dependently inhibited the cyclic GMP-.hydrolyzing activity of basal PDE1, calmodulin-activated PDE1 and PDE5, and of cyclic AMP-hydrolyzing activity of PDE3 and PDE4 with IC50 values ranging from 40 to 130 μg/ml. Analysis of the butanol fraction (BFBO) by LC-MS indicated the presence of four major isoquinoline alkaloids including berbamine and berberine. In conclusion, the butanol fraction of the aqueous methanol extract from Berberis orthobotrys roots induced pronounced endothelium-independent relaxations and inhibited contractile responses by acting directly at the vascular smooth muscle in the coronary artery. Moreover, BFBO potentiated relaxations induced by both cyclic GMP- and cyclic AMP-dependent vasodilators most likely due to its ability to inhibit several vascular PDEs, and in particular PDE4 and PDE5.