Abstract
Pimpinellin is a coumarin-like compound extracted from the root of Toddalia asiatica. Its effects on platelet function has not been investigated. This study found that pimpinellin pretreatment effectively inhibited collagen-induced platelet aggregation, but did not alter ADP- and thrombin-induced aggregation. Platelets pretreated with pimpinellin showed reduced α granule (CD62) level and secretion of dense granule (ATP release). Pimpinellin-treated platelets also exhibited decreased clot reaction and TxB2 production. Pimpinellin pretreatment suppressed adhesion and spreading of human platelets on the fibrinogen coated surface. Analysis of tail bleeding time of mice administered with pimpinellin (40 mg/kg) revealed that pimpinellin did not change tail bleeding time significantly, number of blood cells, and APTT and PT levels. Pimpinellin inhibited collagen-induced ex vivo aggregation of mice platelets. Immunoblotting results showed that pimpinellin suppressed collagen-induced phosphorylation of PI3K-Akt-Gsk3β and PKC/MAPK in platelets.
Highlights
Platelets play a central role in thrombosis and hemostasis
Pimpinellin Inhibits Platelet Aggregation and adenosine triphosphate (ATP) Secretion Induced by Collagen
We examined the effect of pimpinellin on platelet aggregation induced by different agonists
Summary
Platelets play a central role in thrombosis and hemostasis. They are the smallest biologically active blood cells and are the core regulators of the important balance between thrombosis and bleeding in the blood circulation (Koupenova et al, 2017a). Platelet activation is initiated by the binding of various ligands to their surface receptors, which triggers an intracellular signaling cascade. This leads to platelets’ change in shape, the release of particle content, synthesis and release of thromboxane A2, and thrombus formation (Gibbins, 2004). An important pathological basis of thromboembolic diseases is the abnormal activation of platelets (Koupenova et al, 2017b), and antiplatelet therapy is an important way to prevent and treat thrombotic diseases
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