title: Deconvoluting the Dual Antiplatelet Activity of a Plant Extract.
abstract: A thorough evaluation of the antiplatelet activity profile of hexane olive leaf extract in human platelets indicated a potent activity accomplished through a two axis inhibition of platelet activation triggered both by ADP and thrombin. To delineate the extract components responsible for this dual activity, an NMR based method was established to determine and quantify the triterpenoid content leading to the characterization of uvaol, erythrodiol, and oleanolic acid. The antiplatelet profile of the total extract and of the 3 determined triterpenoids was evaluated against in vitro platelet aggregation induced by several platelet agonists as also on PAC-1 binding and P-selectin membrane expression both in healthy volunteers and in platelets from patients with an acute coronary syndrome receiving dual antiplatelet therapy with aspirin and ticagrelor. The extract was identified to inhibit ADP-induced platelet activation due to its erythrodiol content and TRAP-induced platelet activation due to the activity of uvaol and oleanolic acid.
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, University of Ioannina , 45110 Ioannina, Greece.
authors.forename: Vassiliki G
authors.initials: VG
authors.lastname: Kontogianni
authors.affiliation: Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of Chemistry, University of Ioannina , 45110 Ioannina, Greece.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Tsoumani
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, University of Ioannina , 45110 Ioannina, Greece.|Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens , Athens, Greece.
authors.forename: Tahsin F
authors.initials: TF
authors.lastname: Kellici
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens , Athens, Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, University of Ioannina , 45110 Ioannina, Greece.
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Gerothanassis
authors.affiliation: Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of Chemistry, University of Ioannina , 45110 Ioannina, Greece.
authors.forename: Alexandros D
authors.initials: AD
authors.lastname: Tselepis
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, University of Ioannina , 45110 Ioannina, Greece.
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakos
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D054641:Dual Specificity Phosphatase 2 / Q000378:metabolism; D006801:Humans; D031658:Olea / Q000737:chemistry*; D019007:P-Selectin / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019007:P-Selectin; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; C517032:DUSP2 protein, human; D054641:Dual Specificity Phosphatase 2
keywords: antiplatelet activity; cardiovascular disease; human platelets; olive leaf extract; triterpenes