Phlorotannin from Turbinaria ornata exhibits anticoagulant and antiplatelet activity: A promising natural resource for thrombotic disorder management

Abstract

Phlorotannins derived from the brown macroalga Turbinaria ornata exhibit anticoagulant and antiplatelet activity, making them a promising natural resource for functional foods targeting thrombotic disorders. The phlorotannin extract (TOC), identified as a mixture of eckols, fuhalols, and carmalol derivatives, exhibited a total phenolic content of 141.3 mg GAE/g and a phlorotannin content of 21.1 mg PGE/g (p < 0.05). Further purification of TOC with Amberlite XAD-16 resin produced a phlorotannin-rich fraction (TOP), exhibiting an elevated total phenolic content (171.2 mg GAE/g) and phlorotannin content (38.2 mg PGE/g). Bioactivity assessment revealed that TOP exhibited potent antioxidant activity (IC₅₀ ⁓ 0.2 mg/mL) and significant anticoagulant properties. TOP (25 μg/mL) significantly prolonged coagulation times by increasing activated partial thromboplastin time (aPTT) from 22.95 s to 131.35 s and prothrombin time (PT) from 23.90 s to 86.02 s. In thrombin-induced human umbilical vein endothelial cells (HUVECs), TOP (6.25–25 μg/mL) reduced intracellular calcium mobilization by 22.8–50 % and fibrin polymerization by 36.7–59.4 % in plasma. Additionally, TOP (6.25–25 μg/mL) decreased the fluorescent intensities of phosphorylated MARCKS (p-MARCKS) and factor Xa (FXa) by 18.2–74.9 % and 43.1–85.2 %, respectively (p < 0.05). In a dose-dependent manner, TOP (6.25–25 μg/mL) inhibited total thrombin production by 20.5–60.3 %. Furthermore, TOP (6.25–25 μg/mL) reduced adenosine diphosphate (ADP)-induced platelet aggregation by 18.14–63.97 % and induced structural changes in platelets, promoting a less aggregated state. The ability of phlorotannins to modulate both intrinsic and extrinsic coagulation cascades highlights the therapeutic potential of TOP in regulating clot formation and preventing vascular damage, thereby warranting further molecular and clinical investigations.