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Protective Mechanisms of Guanosine from Solanum lycopersicum on Agonist-Induced Platelet Activation: Role of sCD40L
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
Centro de Estudios en Alimentos Procesados (CEAP), CONICYT-Regional, Gore Maule, R09I2001, Talca 3460000, Chile
Synthesis Laboratory, Chemical Institute of Natural Resources, Universidad de Talca, Talca 3460000, Chile
Institute of Plant Biology and Biotechnology, Universidad de Talca, Talca 3460000, Chile
* Author to whom correspondence should be addressed.
Received: 9 May 2013; in revised form: 8 June 2013 / Accepted: 3 July 2013 / Published: 10 July 2013
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.
Keywords: guanosine; antiplatelet; sCD40L; Solanum lycopersicum; functional foods
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Fuentes, E.; Alarcón, M.; Astudillo, L.; Valenzuela, C.; Gutiérrez, M.; Palomo, I. Protective Mechanisms of Guanosine from Solanum lycopersicum on Agonist-Induced Platelet Activation: Role of sCD40L. Molecules 2013, 18, 8120-8135.
Fuentes E, Alarcón M, Astudillo L, Valenzuela C, Gutiérrez M, Palomo I. Protective Mechanisms of Guanosine from Solanum lycopersicum on Agonist-Induced Platelet Activation: Role of sCD40L. Molecules. 2013; 18(7):8120-8135.
Fuentes, Eduardo; Alarcón, Marcelo; Astudillo, Luis; Valenzuela, Claudio; Gutiérrez, Margarita; Palomo, Iván. 2013. "Protective Mechanisms of Guanosine from Solanum lycopersicum on Agonist-Induced Platelet Activation: Role of sCD40L." Molecules 18, no. 7: 8120-8135.