title: Vasodilator effect of Phlomis bracteosa constituents is mediated through dual endothelium-dependent and endothelium-independent pathways.
abstract: 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 μM)-induced contractions at the concentration range of 1.0-1000 μg/mL. Marrubiin, phlomeoic acid, RA, and RB concentration dependently (3.0-10 μg/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 N(ω)-nitro-L-arginine methyl ester in endothelium-intact 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 endothelium-dependent N(ω)-nitro-L-arginine methyl ester-sensitive nitric oxide-modulating mechanism.
authors.affiliation: Center for Natural Products Research and Drug Discovery, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. arifullahkhan979asia@yahoo.com
authors.forename: Arif-Ullah
authors.initials: AU
authors.lastname: Khan
authors.forename: Riaz
authors.initials: R
authors.lastname: Ullah
authors.forename: Asifullah
authors.initials: A
authors.lastname: Khan
authors.forename: Mohamad Rais
authors.initials: MR
authors.lastname: Mustafa
authors.forename: Javid
authors.initials: J
authors.lastname: Hussain
authors.forename: Dharmani Devi
authors.initials: DD
authors.lastname: Murugan
authors.forename: A Hamid Bin A
authors.initials: AH
authors.lastname: Hadi
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D031345:Phlomis / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D004224:Diterpenes; D014665:Vasodilator Agents; C557438:phlomeoic acid; C105731:marrubiin; D019331:NG-Nitroarginine Methyl Ester