Antithrombotic activities of pellitorine in vitro and in vivo

Pellitorine (PLT), an active amide compound, is well known to possess insecticidal, antibacterial and anticancer properties. However, the anti-coagulant functions of PLT are not studied yet. Here, the anticoagulant activities of PLT were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). Furthermore, the effects of PLT on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor (TNF)-α activated human umbilical vein endothelial cells (HUVECs). Treatment with PLT resulted in prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and PLT inhibited production of thrombin and FXa in HUVECs. And PLT inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these anticoagulant activities, PLT elicited anticoagulant effects in mouse. In addition, treatment with PLT resulted in the inhibition of TNF-α-induced production of PAI-1 and in the significant reduction of the PAI-1 to t-PA ratio. Collectively, PLT possesses antithrombotic activities and offers bases for development of a novel anticoagulant.