fibrin and sesamin

Sesamin (SM) and epi-sesamin (ESM) were isolated from Asarum sieboldii and their anticoagulant activities were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). In addition, the effects of SM and ESM on the expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). Treatment with ESM, but not SM, resulted in significantly prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and ESM inhibited production of thrombin and FXa in HUVECs; and ESM inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these anticoagulant activities, ESM elicited anticoagulant effects in mice. In addition, treatment with ESM, but not SM, resulted in the inhibition of TNF-α-induced production of PAI-1, and treatment with ESM resulted in a significant reduction of the PAI-1 to t-PA ratio. Of particular interest, inhibition of the anticoagulant activity by ESM was more potent than that by SM, likely due to differences between their three-dimensional structures. Collectively, ESM possesses antithrombotic activities and offers a basis for the development of a novel anticoagulant.

Topics: Animals; Asarum; Bleeding Time; Blood Coagulation; Blood Coagulation Tests; Cysteine Endopeptidases; Dioxoles; Female; Fibrin; Fibrinolysis; Fibrinolytic Agents; Human Umbilical Vein Endothelial Cells; Humans; Lignans; Mice; Mice, Inbred ICR; Neoplasm Proteins; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Polymerization; Structure-Activity Relationship; Thrombin; Tissue Plasminogen Activator