Anti-Thrombotic Activities of Veratramine via Inhibiting Platelet Aggregation and FIIa/FXa

There is growing interest in plant-derived compounds for managing vascular diseases. Veratramine (VRT), a steroidal alkaloid isolated from plants of the Veratrum genus, exhibits diverse biological effects such as antihypertensive, analgesic, and antitumor activities, yet its influence on hemostasis and thrombus formation has not been characterized. This investigation sought to determine whether VRT exerts anticoagulant effects using integrated in vitro and murine models.

VRT's anticoagulant profile was comprehensively evaluated using integrated biochemical, cellular, and murine models, including clotting time assays (aPTT/PT), chromogenic enzymatic assays, fibrin polymerization analysis, platelet aggregometry, and endothelial modulation of PAI-1/t-PA under inflammatory conditions.

VRT treatment significantly prolonged both intrinsic and extrinsic coagulation times, directly inhibited enzymatic activities of thrombin and FXa, and attenuated their generation by endothelial cells. Additionally, VRT interfered with fibrin clot formation and diminished agonist-induced platelet aggregation. Ex vivo coagulation analyses confirmed its anticoagulant action, while endothelial studies revealed a reduced PAI-1/t-PA ratio following VRT exposure.

These data establish VRT as possessing novel direct dual inhibition of thrombin and FXa alongside suppression of fibrin polymerization, platelet reactivity, and PAI-1 expression-positioning it as a promising multifunctional anticoagulant agent. While preclinical murine models preclude direct clinical translation absent pharmacokinetic data, these findings warrant further mechanistic and translational investigation.