title: Protective mechanisms of guanosine from Solanum lycopersicum on agonist-induced platelet activation: role of sCD40L.
abstract: In the past 30 years, only three natural products have been sources of new drugs with antiplatelet activity. In this study, we have demonstrated for the first time that guanosine from Solanum lycopersicum possesses antiplatelet (secretion, spreading, adhesion and aggregation) activity in vitro and inhibition of platelet inflammatory mediator of atherosclerosis (sCD40L). According to ADP-induced platelet aggregation inhibiting, the total extract residue was fractionated by liquid chromatography/phase separation, affording an aqueous fraction. This fraction was subjected to repeated permeation over Sephadex LH-20 and semi-preparative TLC. The isolated compound finally obtained was identified as guanosine on the basis of its UV-spectra, HPLC and 1H-NMR data. Guanosine concentration dose-dependently (1 to 4 mmol/L) inhibited platelet secretion and aggregation induced by ADP and collagen. Spread of human platelets on collagen in the presence of guanosine was fully inhibited. After incubation of whole blood with guanosine, the platelet adhesion and aggregation under flow conditions was inhibited concentration dependently (0.2 to 2 mmol/L). At the same concentrations that guanosine inhibits platelet aggregation, levels of sCD40L were significantly decreased. Guanosine is thus likely to exert significant protective effects in thromboembolic-related disorders by inhibiting platelet aggregation.
authors.affiliation: Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Universidad de Talca, Talca 3460000, Chile.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fuentes
authors.forename: Marcelo
authors.initials: M
authors.lastname: Alarcón
authors.forename: Luis
authors.initials: L
authors.lastname: Astudillo
authors.forename: Claudio
authors.initials: C
authors.lastname: Valenzuela
authors.forename: Margarita
authors.initials: M
authors.lastname: Gutiérrez
authors.forename: Iván
authors.initials: I
authors.lastname: Palomo
mesh_terms: D001792:Blood Platelets / Q000187:drug effects; D023201:CD40 Ligand / Q000037:antagonists & inhibitors* / Q000187:drug effects; D006151:Guanosine / Q000494:pharmacology*; D006801:Humans; D018551:Solanum lycopersicum / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D006151:Guanosine; D023201:CD40 Ligand