Lifestyle-related diseases have complex pathological processes consist of several different steps. Pathogenesis of lifestyle-related diseases is attributed to unhealthy lifestyles in dietary habits and in physical activity. The unhealthy lifestyles induce risk factors such as hypertension, dyslipidemia, obesity, and hyperglycemia. These risk factors promote arteriosclerosis leading to serious vascular complications such as myocardial infarction and cerebral infarction. Our major research interest is in prevention of thrombotic diseases by food factors. Garlic (Allium sativum L.) has some potent pharmacological functions. We have been studying anti-cancer, anti-inflammatory, anti-obesity, and anti-thrombotic property of flavor component derived from garlic. Blood coagulation and fibrinolysis system are responsible for homeostasis of bloodstream. Tissue factor (TF, coagulation factor III) is an initiator of extrinsic coagulation pathway that is upregulated at inflamed arteriosclerotic plaque. Platelets are involved in thrombus formation at initial stage of hemostasis. ADP receptor P2Y12 on platelet is an important target in development of anti-platelet drug. This study was aimed at clarifying the effect of diallyl trisulfide (DATS), a flavor component derived from garlic, on platelet aggregation and its inhibitory mechanisms in the formation of thrombus by focusing on P2Y12. DATS inhibited platelet aggregation induced by ADP. Stimulation of platelet with ADP caused phosphorylation of Akt (Ser473) as well as Gsk3β and p38 MAPK which are downstream signaling molecules of Akt. DATS attenuated the phosphorylation of both Akt (Ser473) and Gsk3β. We further examined phosphorylation of vasodilator-stimulated phosphoprotein (VASP) that is regulated by the cAMP pathway. ADP decreased the phosphorylation of VASP and DATS canceled the decrease in phosphorylation of VASP induced by ADP. DATS also prolonged plasma clotting time initiated by TF in vitro and suppressed TF mRNA expression induced by TNFα in human umbilical vein endothelial cells in culture. Taken together, it was suggested that DATS suppresses platelet aggregation by inhibiting both PI3K/Akt and cAMP pathways and the following blood coagulation by inhibiting extrinsic pathway. We also overview the anti-lifestyle-related disease function of phytochemicals derived from spice and edible vegetables such as pepper, cinnamon, ginger or onion at molecular basis.

Anti-thrombotic effect of garlic attributes inhibition of platelet function and coagulation pathway by allyl sulfide

256th National Meeting (2018)

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