Anticoagulant Effects of Albiflorin via Factor Xa Inhibition

Abstract

Albiflorin (AF), a primary bioactive compound from the roots of Paeonia lactiflora Pall. (Peony), demonstrates anti-inflammatory, antioxidant, and cytoprotective effects. This study aims to investigate the antithrombotic potential of AF and clarify its mechanisms of action. Its anticoagulant effects were assessed via activated partial thromboplastin time, prothrombin time, thrombin, and factor Xa (FXa) activities, as well as fibrin formation and platelet aggregation. Additionally, the effect of plasminogen activator inhibitor type 1 and tissue-type plasminogen activator was evaluated in tumor necrosis factor-α-stimulated human umbilical vein endothelial cells (HUVECs). Our experiments revealed that AF exhibited antithrombotic activity comparable to that of rivaroxaban, a well-established direct FXa inhibitor, particularly in suppressing FXa activity and platelet aggregation induced by adenosine diphosphate (ADP) and U46619, a synthetic thromboxane A2 analog. AF also reduced the surface expression of P-selectin, inhibited phosphorylation of myristoylated alanine-rich C kinase substrate, and decreased PAC-1 activation following ADP or U46619 stimulation. Furthermore, AF enhanced nitric oxide production while preventing excess endothelin-1 release in HUVECs exposed to these agonists. In vivo experiments in mouse models of arterial and pulmonary thrombosis demonstrated that AF is a potent anticoagulant and antithrombotic agent. These findings indicate that AF could serve as a promising lead compound for developing innovative anti-FXa and antiplatelet therapeutics.