Astaxanthin inhibits platelet-mediated thrombosis via suppression of bidirectional αIIbβ3 signaling.

Platelets are central mediators of hemostasis and thrombosis, and dysregulated platelet activation substantially contributes to the pathogenesis of cardiovascular diseases. Astaxanthin (AZ), a xanthophyll carotenoid and a bioactive compound derived from Haematococcus lacustris, possesses potent antioxidant and anti-inflammatory properties. Nevertheless, its regulatory effects on platelet function remain insufficiently elucidated. This study investigated the impact of AZ on platelet function and thrombosis. In vitro experiments demonstrated that AZ significantly inhibited agonist-induced platelet aggregation, secretion of dense and α-granules, intracellular calcium mobilization, αIIbβ3 integrin activation, platelet spreading, and clot retraction. In addition, AZ reduced intracellular reactive oxygen species (ROS) generation under collagen-related peptide (CRP)-stimulated platelet activation in a concentration-dependent manner. Mechanistic analyses revealed that AZ suppressed the phosphorylation of key kinases involved in the bidirectional signaling of αIIbβ3 integrin, including spleen tyrosine kinase (Syk), phospholipase C (PLC), phosphoinositide 3-kinase (PI3K), Akt, proline-rich tyrosine kinase 2 (Pyk2), and focal adhesion kinase (FAK). In vivo, oral administration of AZ significantly prolonged FeCl3-induced carotid artery occlusion time and tail bleeding time. Collectively, these findings suggest that AZ modulates platelet activation and thrombosis through coordinated effects on integrin-associated signaling, intracellular kinase phosphorylation, and redox-related regulatory mechanisms.