Extraction, characterization, and antithrombotic activity of polysaccharides from three low-value sea cucumbers

Thrombosis, a critical complication of cardiovascular diseases, leads to fatal outcomes like myocardial infarction and stroke. Marine-derived polysaccharides show promising anticoagulant activity. This study characterized sulfated polysaccharides from three low-value sea cucumbers (Holothuria nobilis, Cucumaria frondosa Gunnerus, Thelenota ananas) to explore structure-activity relationships. Enzyme-assisted extraction, Sevag deproteinization, and DEAE-52 purification yielded fractions HOP-2, CFP-1, and TAP-1. SEM, NMR, and FT-IR analyses revealed distinct profiles: HOP-2 and CFP-1 exhibited triple-helical conformations, while TAP-1 displayed a non-helical structure that possessed the highest sulfate content among the three fractions, contained fucose residues and exhibited a lamellar morphology. In a phenylhydrazine-induced zebrafish thrombosis model, TAP-1 showed superior efficacy by reducing oxidative stress and downregulating coagulation (f2, fga, fgb) and platelet activation genes (tbxas1, ptgs2b), while preserving hemostatic genes (ptgs1, vwf, antithrombinIII). TAP-1 demonstrates potential as a selective antithrombotic agent with heparin-like characteristics.