摘要

Platelets play a crucial role in cardiovascular disorders (CVDs); thus, development of a therapeutic target that prevents platelet activation reduces CVDs. Pterostilbene (PTE) has several remarkable pharmacological activities, including anticancer and neuroprotection. Herein, we examined the inhibitory mechanisms of PTE in human platelets and its role in the prevention of vascular thrombosis in mice. At very low concentrations (1-5 μmol/L), PTE strongly inhibited collagen-induced platelet aggregation, but it did not have significant effects against thrombin and 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin (U46619). PTE markedly reduced P-selectin expression on isolated α-granules by a novel microchip. Moreover, PTE inhibited adenosine triphosphate (ATP) release, intracellular ([Ca2+]i) mobilization (resting, 216.6 ± 14.0 nmol/L; collagen-activated platelets, 396.5 ± 25.7 nmol/L; 2.5 μmol/L PTE, 259.4 ± 8.8 nmol/L; 5 μmol/L PTE, 231.8 ± 9.7 nmol/L), phospholipase C (PLC)γ2/protein kinase C (PKC), Akt, and mitogen-activated protein kinase (MAPK) phosphorylation. Neither 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536) nor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reversed platelet aggregation inhibited by PTE. PTE did not affect vasodilator-stimulated phosphoprotein phosphorylation. In mice, PTE obviously reduced the mortality (from 100 to 37.5%) associated with acute pulmonary thromboembolism without increasing the bleeding time. Thus, PTE could be used to prevent CVDs.
原文英語
頁(從 - 到)4697-4707
頁數11
期刊Journal of Agricultural and Food Chemistry
69
發行號16
DOIs
出版狀態已發佈 - 4月 28 2021

指紋

深入研究「Pterostilbene, a Dimethylether Analogue of Resveratrol, Possesses High Potency in the Prevention of Platelet Activation in Humans and the Reduction of Vascular Thrombosis in Mice」主題。共同形成了獨特的指紋。

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