Vasodilator effect of phlomis bracteosa constituents is mediated through dual Endothelium-Dependent and Endothelium-Independent pathways

This study describes the vasorelaxant potential of some pure compounds isolated from Phlomis bracteosa L.: marrubiin, phlomeoic acid, and two new constituents labeled as RA and RB. In rat thoracic aortic rings denuded of endothelium, marrubiin, phlomeoic acid, RA, and RB caused relaxation of high K+ (80 mM) and phenylephrine (1 ìM)-induced contractions at the concentration range of 1.0�1000 ìg/mL. Marrubiin, phlomeoic acid, RA, and RB concentration dependently (3.0�10 ìg/mL) shifted the Ca++ curves to the right obtained in Ca++-free medium. The vasodilator effect of marrubiin, phlomeoic acid, RA, and RB was partially blocked by Nù-nitro-L-arginine methyl ester in endotheliumintact aorta preparations. These results reveal that P. bracteosa constituents: marrubiin, phlomeoic acid, RA, and RB exhibit vasodilator action occurred via a combination of endothelium-independent Ca++ antagonism and endotheliumdependent Nù-nitro-L-arginine methyl ester-sensitive nitric oxide-modulating mechanism