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.
Highlights
The incidence and prevalence of cardiovascular diseases (CVD) has increased significantly in recent years, at least in part as a result of the progressive aging of the population [1,2]
As observed in figure 6, we found that guanosine significantly reduced thrombin-induced soluble CD40 ligand (sCD40L)
5'- diphosphatebis (ADP) and collagen, bovine serum albumin (BSA), acetylsalicylic acid (ASA) and prostaglandin E1 (PGE1) were obtained from Sigma-Aldrich, whereas Luciferase/ luciferin reagent was obtained in Chrono-Log corp (Havertown, PA, USA) and microfluidic chambers were from Bioflux (Fluxion, San Francisco, CA, USA)
Summary
The incidence and prevalence of cardiovascular diseases (CVD) (i.e., acute myocardial infarction, cerebrovascular disease and peripheral arterial thrombosis) has increased significantly in recent years, at least in part as a result of the progressive aging of the population [1,2]. From the point of view of public health, efforts should be directed to primary prevention, namely, to reduce the aforementioned cardiovascular risk factors [14,15] In this context, regular consumption of fruits and vegetables (F&V), part of the so called Mediterranean Diet [16], has been shown to be beneficial in terms of reducing the incidence of CVD in certain populations. In the last 30 years only three such phytochemicals have generated new drugs derived from natural products with platelet aggregation inhibition and only six with antithrombotic activity [19] In this sense, highly consumed tomato (Solanum lycopersicum) presents antiplatelet activity [20]. The purpose of this research was to isolate and identify bioactive compounds from S. lycopersicum that present antiplatelet activity and inhibition of platelet sCD40L release
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