Fruitflow inhibits platelet function by suppressing Akt/GSK3β, Syk/PLCγ2 and p38 MAPK phosphorylation in collagen-stimulated platelets

Abstract

Background Platelets play an important role in the progression of atherosclerosis and cardiovascular events. The inhibition of platelet function is a main strategy to reduce risk of cardiovascular events. Some studies have shown that tomato extracts inhibit platelet function, but the molecular mechanisms remain unclear. Fruitflow is a water-solute tomato extract and the main ingredients including flavonoids, adenosine, chlorogenic acid, phytosterols, naringenin, and carotenoids. The present study investigated the effects of fruitflow on adenosine diphosphate (ADP)- and collagen- stimulated platelet aggregation, platelet adhesion, and levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (PGF1α), and platelet factor 4 (PF4) and explored the underlying molecular mechanisms. Methods Platelet-rich plasma (PRP) was used for measurement of platelet aggregation, TXB2, 6-keto- PGF1α, and PF4 levels. Platelet aggregation was analyzed using a Chrono-Log aggregometer. TXB2, 6-keto- PGF1α, and PF4 levels were determined using enzyme-linked immunosorbent assay kits. Immunoblotting was used to detect protein expression and phosphorylation on washed platelets. Platelet adhesion and spreading were determined by immunofluorescence. Results Fruitflow (1, 3, 10 and 100 μg/ml) dose-dependently inhibited platelet aggregation that was induced by ADP and collagen. Fruitflow (100 μg/ml) treatment completely suppressed ADP- and collagen-stimulated platelet aggregation. Fruitflow (100 μg/ml) significantly decreased TXB2 and 6-keto-PGF1α generation and PF4 release in ADP- and collagen-stimulated platelets. Treatment with fruitflow effectively blocked collagen-induced platelet spreading. To determine the potential molecule mechanism of action of fruitflow, we investigated the protein expression and phosphorylation of several signaling molecules in collagen-activated platelets. Fruitflow dose-dependently suppressed Akt, Glycogen synthase kinase-3β (GSK-3β), spleen tyrosine kinase (Syk) and phospholipase Cγ2 (PLCγ2) and p38 MAPK phosphorylation that was induced by collagen. Conclusion Fruitflow inhibited platelet aggregation and reduced TXB2, 6-keto-PGF1α, and PF4 levels in ADP- and collagen-stimulated platelets. The mechanism of action of fruitflow may be associated with the suppression of Akt/GSK3β, Syk/PLCγ2, and p38 MAPK phosphorylation in collagen-activated platelets. Fruitflow is a natural product derived from tomato and can be used as a health food for decreasing platelet activity.

The role of platelets in central hubs of inflammation: A literature review

“…[ 16 ] Huilian Chen showed that fruit flow could inhibit platelet function by suppressing Akt/GSK3β, Syk/PLCγ2 and p38 MAPK phosphorylation in collagen-stimulated platelets. [ 17 ] Min Li reanalyzed the GSE45111 dataset of a spectrum of asthma, and they showed that platelet activation could enhance the Th2 immune response and induce lung inflammation through δ, α, λ granule released by platelets. [ 18 ] Maximilian Mauler used two murine models of acute inflammation, and they showed that LPS challenge in Tph1-/- mice prevented leukocyte recruitment and reduced platelet neutrophil complex formation.…”

Hydroxyls on the B ring and gallic acyl are essential for catechins to restrain ADP-induced thrombosis

“…46 P38 MAPK phosphorylation could also induce platelet aggregation. 47 C had a limited effect on the phosphorylation of Akt308, while the other five catechins could significantly restrain it (Fig. 4a and b).…”

Potential Drug–Nutrient Interactions of 45 Vitamins, Minerals, Trace Elements, and Associated Dietary Compounds with Acetylsalicylic Acid and Warfarin—A Review of the Literature

“…Unclear additive antiplatelet effect. Lycopene has an antithrombotic and antiplatelet effect [263][264][265]. One study compared platelet aggregation in vitro between ASA and concentrated lycopene and found a synergistic effect at 4 µmol/L of lycopene supplementation daily but not at higher concentrations [266].…”