Protective Mechanisms of Guanosine from Solanum lycopersicum on Agonist-Induced Platelet Activation: Role of sCD40L
Open Access
- 10 July 2013
- Vol. 18 (7), 8120-8135
- https://doi.org/10.3390/molecules18078120
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
This publication has 39 references indexed in Scilit:
- Role of platelets as mediators that link inflammation and thrombosis in atherosclerosisPlatelets, 2012
- Enfermedad cardiovascular en el ancianoRevista Espanola de Cardiologia, 2011
- Heart Disease and Stroke Statistics—2011 UpdateCirculation, 2011
- CD40L induces inflammation and adipogenesis in adipose cells – a potential link between metabolic and cardiovascular diseaseThrombosis and Haemostasis, 2010
- The role of platelets in the pathophysiology of atherosclerosis (Review).Molecular Medicine Reports, 2008
- Platelet Activation and AtherothrombosisThe New England Journal of Medicine, 2007
- Platelets in Inflammation and ThrombosisArteriosclerosis, Thrombosis, and Vascular Biology, 2003
- From Vulnerable Plaque to Vulnerable PatientCirculation, 2003
- Emerging Epidemic of Cardiovascular Disease in Developing CountriesCirculation, 1998
- Genetic Susceptibility to Death from Coronary Heart Disease in a Study of TwinsThe New England Journal of Medicine, 1994