Abstract
Myocardial infarction and cerebral ischemic stroke during the process of arterial thrombosis are prominently causes of death worldwide. Platelets are anucleated cells and play a critical factor in these diseases. Columbianadin (CBN), a coumarin derivative from plants, inhibits effective platelet activation. In this study, platelet function analysis revealed that the closure time of the platelet plug in human whole blood significantly prolonged by CBN, whereas CBN did not pointedly prolong the bleeding time in mice. BAY11-7082 (an inhibitor of IκB kinase) and MG-132 (an inhibitor of proteasome) inhibited collagen-stimulated platelet aggregation and ATP-release in human platelets, BAY11-7082 exhibited a higher potency than MG-132. Moreover, CBN markedly reduced NF-κB activation (e.g., IκBα and p65 phosphorylation) and reversed IκBα degradation in activated platelets. We investigated intercellular signaling events between mitogen-activated protein kinases and NF-κB, and found that BAY11-7082 abolished JNK1/2 and ERK1/2 phosphorylation. Interestingly, SP600125 (an inhibitor of JNK) but not PD98059 (an inhibitor of ERK) had no effect in NF-κB activation in activated platelets. Moreover, CBN but not BAY11-7082 significantly reduced hydroxyl radical (HO●) formation in platelets. Therefore, we propose that CBN inhibits NF-κB activation in human platelets and could present a potent clinical treatment for thromboembolic diseases.
Highlights
The world major causes of death considered are arterial thrombotic events, such as myocardial infarction, ischemic stroke, and venous thromboembolisms [1]
The closure time (CT) of the CADP membrane in whole blood treated with solvent control (0.1% Dimethyl sulfoxide (DMSO)) was 81.5 ± 5.1 s (n = 8); CBN (90 μM) significantly prolonged CT (45 μM, 99.8 ± 5.6 s, n = 8; p > 0.05; 90 μM, 114.0 ± 9.8 s, n = 8; p < 0.05) compared with the solvent control (Figure 1A)
Platelet adhere to collagen depended on flow conditions, and inactive platelets were unable to adhere to the CADP membrane under flow conditions
Summary
The world major causes of death considered are arterial thrombotic events, such as myocardial infarction, ischemic stroke, and venous thromboembolisms [1]. Sci. 2020, 10, 7323 which are small and discoid in shape and have a lifespan of 7–10 days [2]. Over activation of platelets is associated with atherothrombotic process and profoundly contribute to the pathology of venous thrombosis [3]. Platelets are adaptable fragments of cytoplasm that have the primary function of arresting bleeding. Understanding the causes of platelet activation and aggregation is imperative
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call