机构地区:[1]Centerfor Biomechanopharmacology,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing [2]Science and Technology Center,ByHeaIth Co.,Ltd.,Guangzhou [3]Department of Cardiovascular,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing,China
出 处:《World Journal of Traditional Chinese Medicine》2019年第4期260-268,共9页世界中医药杂志(英文)
基 金:financially supported by the China Academy of Chinese Medical Sciences(ZZ11-044)
摘 要:Objective:To investigate the antiplatelet aggregation effect of water-soluble tomato concentrate(WSTC)and explore the underlying molecular mechanisms.Materials and Methods:Platelet aggregometry was used to quantify rat platelet aggregation with the maximum aggregation rate in vitro and ex vivo.Then,the fibrinogen(FIB)binding assay was employed to detect the effect of WSTC on the activation of platelet integrinαIIβ3(GP IIb/IIIa).Furthermore,Western blot was performed to assess the platelet protein levels of phosphoinositide 3-kinase 110β(PI3 K110β),protein disulfide isomerase(PDI),platelet endothelial cell adhesion molecule 1(PECAM-1),andβ1-Tubulin.Results:WSTC inhibited adenosine diphosphate(ADP)and collagen-induced platelet aggregation in a concentration-dependent manner in vitro,at IC50 values of 3.05 g/L and 8.03 g/L,respectively.Significantly reduced ex vivo ADP induced platelet aggregation was observed after oral consumption of WSTC for 4 weeks in rats;average inhibition rates were 24.42%,21.48%,and 20.87%for 25 mg/Kg,75 mg/Kg,and 150 mg/Kg WSTC,respectively.It appeared that WSTC had no influence on coagulation function in rats.Incubation with WSTC decreased FIB binding to GP IIb/IIIa by 17.47%and 32.29%at the concentrations of 0.6 and 6 g/L,respectively.WSTC at 0.6 and 6 g/L markedly downregulated PI3 K110β,PDI,and PECAM-1 in platelets,and upregulatedβ1-Tubulin,in a concentration-dependent manner.Conclusion:WSTC inhibits platelet activation through modulation of platelet skeletal stability and suppresses GP IIb/IIIa receptor-mediated platelet aggregation,likely via the PI3 K signaling pathway and PDI inhibition.Objective: To investigate the antiplatelet aggregation effect of water-soluble tomato concentrate(WSTC) and explore the underlying molecular mechanisms. Materials and Methods: Platelet aggregometry was used to quantify rat platelet aggregation with the maximum aggregation rate in vitro and ex vivo. Then, the fibrinogen(FIB) binding assay was employed to detect the effect of WSTC on the activation of platelet integrin αIIβ3(GP IIb/IIIa). Furthermore, Western blot was performed to assess the platelet protein levels of phosphoinositide 3-kinase 110 β(PI3 K110 β), protein disulfide isomerase(PDI), platelet endothelial cell adhesion molecule 1(PECAM-1), and β1-Tubulin. Results: WSTC inhibited adenosine diphosphate(ADP) and collagen-induced platelet aggregation in a concentration-dependent manner in vitro, at IC50 values of 3.05 g/L and 8.03 g/L, respectively. Significantly reduced ex vivo ADP induced platelet aggregation was observed after oral consumption of WSTC for 4 weeks in rats; average inhibition rates were 24.42%, 21.48%, and 20.87% for 25 mg/Kg, 75 mg/Kg, and 150 mg/Kg WSTC, respectively. It appeared that WSTC had no influence on coagulation function in rats. Incubation with WSTC decreased FIB binding to GP IIb/IIIa by 17.47% and 32.29% at the concentrations of 0.6 and 6 g/L, respectively. WSTC at 0.6 and 6 g/L markedly downregulated PI3 K110 β, PDI, and PECAM-1 in platelets, and upregulated β1-Tubulin, in a concentration-dependent manner. Conclusion: WSTC inhibits platelet activation through modulation of platelet skeletal stability and suppresses GP IIb/IIIa receptor-mediated platelet aggregation, likely via the PI3 K signaling pathway and PDI inhibition.
关 键 词:GP IIb/IIIa platelet aggregation PDI PI3K PECAM-1 watersoluble tomato concentrate
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