Fruitflow，a Water-soluble Tomato Concentrate，Inhibits Platelet Activation，Aggregation and Thrombosis by Regulating the Signaling Pathway of PI3K/Akt and MAPKs / 中山大学学报(医学科学版)

ABSTRACT

@#【Objective】Platelet hyper- reactivity plays an important role in thrombosis and cardiovascular diseases. As a dietary supplement，Fruitflow，a water-soluble tomato concentrate，plays an important role in preventing cardiovascular diseases，but the mechanisms have been poorly understood，and there is no direct evidence about the effect of Fruitflow on thrombosis. This study intends to explore the effects of Fruitflow on platelet aggregation，activation and thrombosis in healthy people，and explore its possible mechanism.【Methods】Platelets from healthy men and women were incubated with different concentrations（0，20，40，80 mg/L）of Fruitflow，and the platelet aggregation was measured by platelet aggregometer. Platelet αIIbβ3 activation and fibrinogen binding to the activated platelets was measured by flow cytometry. The thrombosis in FeCl3- induced mesenteric artery thrombosis model in mice was observed by stereoscopic fluorescence microscope. The bleeding time was measured by tail clipping in mice. The total and phosphorylation levels of platelet Akt， Erk1/2 and JNK were determined by Western blotting.【Results】After the stimulation of ADP，Fruitflow could significantly attenuate platelet aggregation in the dose of 20，40，80 mg/L. Compared with that in the control group（43.75±5.91）%， platelet aggregation in the 80 mg/L group decreased to（8.25 ± 4.57）%（P < 0.000 1）. Fruitflow also inhibited the activation of platelet αIIbβ3. Compared with that in the control group（79.36±6.26），the platelet αIIbβ3 in the 80 mg/L group decreased to（65.79±5.73，P < 0.01）. Fruitflow reduced the platelet fibrinogen binding to the activated platelets. Compared with that in the control group（69.34 ± 6.63），platelet fibrinogen binding to the activated platelets in the 80 mg/L group decreased to（56.70±8.86，P < 0.05）. Fruitflow attenuated the thrombosis in FeCl3-induced mesenteric artery thrombosis model. Compared with that in the control group（22.50±4.86），the vessel occlusion in the 80 mg/L group was extended to（39.20 ± 4.61，P < 0.01）. There was no statistical difference between the control group （5.95 ± 0.69） and the 80 mg/L group（5.74 ± 0.76）in bleeding time（P > 0.05）. Fruitflow down- regulated the phosphorylation levels of platelet Akt， Erk1/2 and JNK proteins. Compared with the control group，P- Akt/Akt decreased from 0.97 ± 0.07 to 0.33 ± 0.13（P <0.001），P-Erk1/2/Erk1/2 decreased from 0.89±0.09 to 0.24±0.02（P < 0.01），and P-JNK/JNK decreased from 0.97±0.12 to 0.45±0.04（P < 0.01）in the 80 mg/L group.【Conclusion】Inhibition of platelet PI3K/Akt and MAPKs signaling pathway may be one of the mechanisms that Fruitflow inhibits platelet aggregation ，activation and thrombosis.