{Reference Type}: Journal Article
{Title}: 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.
{Author}: Huang WC;Liu JC;Hsia CW;Fong TH;Hsia CH;Tran OT;Velusamy M;Yang CH;Sheu JR;
{Journal}: J Agric Food Chem
{Volume}: 69
{Issue}: 16
{Year}: Apr 2021 28
{Factor}: 5.895
{DOI}: 10.1021/acs.jafc.1c00367
{Abstract}: 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.