title: Salvia fruticosa Induces Vasorelaxation In Rat Isolated Thoracic Aorta: Role of the PI3K/Akt/eNOS/NO/cGMP Signaling Pathway.
abstract: Salvia fruticosa (SF) Mill. is traditionally used for its antihypertensive actions. However, little is known about its pharmacologic and molecular mechanisms of action. Here we determined the effects of an ethanolic extract of SF leaves on rings of isolated thoracic aorta from Sprague-Dawley rats. Our results show that SF extract increased nitric oxide production and relaxed endothelium-intact rings in a dose-dependent (0.3 µg/ml-1 mg/ml) manner, and the maximum arterial relaxation (Rmax) was significantly reduced with endothelium denudation. Pretreatment of endothelium-intact rings with L-NAME (a non-selective inhibitor of nitric oxide synthase, 100 µM), or ODQ (an inhibitor of soluble guanylyl cyclase, 10 µM) significantly diminished SF-mediated vasorelaxation. Furthermore, SF induced Akt phosphorylation as well as increased cGMP levels in rings treated with increasing doses of SF. Prior exposure to PI3K inhibitors, wortmannin (0.1 µM) or LY294002 (10 µM), decreased cGMP accumulation and attenuated the SF-induced vasorelaxation by approximately 50% (Rmax). SF-evoked relaxation was not affected by indomethacin, verapamil, glibenclamide, tetraethylammonium, pyrilamine or atropine. Taken together, our results indicate that SF induces endothelium-dependent vasorelaxation through the PI3K/Akt/eNOS/NO/sGC/cGMP signaling pathway. Our data illustrate the health-orientated benefits of consuming SF which may act as an antihypertensive agent to reduce the burden of cardiovascular complications.
authors.affiliation: College of Arts and Sciences, Qatar University, Department of Biological and Environmental Sciences, Doha, P.O. Box 2713, Qatar.
authors.forename: M Akhtar
authors.identifier: http://orcid.org/0000-0002-5380-3195
authors.initials: MA
authors.lastname: Anwar
authors.affiliation: Lebanese International University, Department of Biomedical Sciences, Beirut, P.O. Box 146404, Lebanon.|Lebanese University, Faculty of Public Health IV, Department of Anatomy, Zahlé, Lebanon.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Samaha
authors.affiliation: Lebanese University, Faculty of Public Health IV, Department of Anatomy, Zahlé, Lebanon.
authors.forename: Samar
authors.initials: S
authors.lastname: Ballan
authors.affiliation: College of Arts and Sciences, Qatar University, Department of Biological and Environmental Sciences, Doha, P.O. Box 2713, Qatar.
authors.forename: Alaaeldin I
authors.initials: AI
authors.lastname: Saleh
authors.affiliation: College of Science, United Arab Emirates University, Department of Biology, Al Ain, P.O. Box 15551, United Arab Emirates. r_iratni@uaeu.ac.ae.
authors.forename: Rabah
authors.initials: R
authors.lastname: Iratni
authors.affiliation: College of Arts and Sciences, Qatar University, Department of Biological and Environmental Sciences, Doha, P.O. Box 2713, Qatar. ae81@aub.edu.lb.|American University of Beirut, Faculty of Medicine, Department of Pharmacology and Toxicology, Beirut, P.O. Box 11-0236, Lebanon. ae81@aub.edu.lb.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Eid
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011968:Receptors, Histamine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D027544:Salvia / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; D010936:Plant Extracts; D015221:Potassium Channels; D011968:Receptors, Histamine; D011976:Receptors, Muscarinic; D014665:Vasodilator Agents; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D006152:Cyclic GMP