Antithrombotic Activity of Heparinoid G2 and Its Derivatives from the Clam Coelomactra antiquata

Abstract

Clam heparinoid G2 (60.25 kDa) and its depolymerized derivatives DG1 (24.48 kDa) and DG2 (6.75 kDa) prepared from Coelomactra antiquata have been documented to have excellent fibrinolytic and anticoagulant activity. In this study, to further explore the antithrombotic activity of G2, DG1 and DG2, azure A, sheep plasma, and clot lytic rate assays were used to determine their anticoagulant and thrombolytic activity in vitro. The results indicated that the anticoagulant titer of G2 was approximately 70% that of heparin and the thrombolytic activity of DG2 was greater than G2, DG1, and heparin activities. Moreover, in a carrageenan-induced venous thrombosis model, oral administration of G2 and DG1 each at 20 mg/kg and 40 mg/kg for 7 days significantly reduced blacktail thrombus formation, increased tissue-type plasminogen activator, fibrin degradation products, and D-dimer levels, decreased von Willebrand factor and thromboxane B2 levels, and restored phylum and genus abundance changes of intestinal bacteria. DG2 had no antithrombotic effect. At 20 mg/kg, G2, DG1, and heparin had comparable antithrombotic activities, and DG1 at 40 mg/kg had more muscular antithrombotic activity than G2. Thus, DG1 could be an antithrombotic oral agent owing to its more robust antithrombotic activity and lower molecular weight.

Chitosan/Alginate Nanoparticles for the Enhanced Oral Antithrombotic Activity of Clam Heparinoid from the Clam Coelomactra antiquata

“…G2 is prepared by using the extraction of G15 as a reference, and DG1 is a low molecular weight fragment of the vitamin-catalysed free-radical depolymerisation of G2. In a previous study, in a mice blacktail model, we found that gavage of equal doses of DG1, G2, and heparin sodium had a comparable ability to reduce the blacktail ratio in mice [9].…”

“…Low molecular weight clam heparinoid DG1 with a molecular weight of 24.48 kDa are derived from vitamin catalytic free-radical depolymerisation of native clam heparinoid G2. We chose DG1 to prepare oral antithrombotic nanoparticles because of its strong oral antithrombotic activity and low molecular weight [9]. In this study, we analysed physicochemical properties that impact the preparation of DG1 nanoparticles.…”

Nutritional, functional, and ethno‐medical properties of sweet corn cob: a concurrent review

“…Heparin therapy includes a number of adverse effects, such as bleeding and thrombocytopenia in contrast to the possibility of infectious organism contamination, which restricts its use reported by Chen et al . (2022). When working with polysaccharides, anticoagulant action is constantly taken into account.…”

“…The anticoagulant medication mammalian-derived heparin, which is generated from swine intestinal and bovine lung, both protects and cures thromboembolic illness. Heparin therapy includes a number of adverse effects, such as bleeding and thrombocytopenia in contrast to the possibility of infectious organism contamination, which restricts its use reported by Chen et al (2022). When working with polysaccharides, anticoagulant action is constantly taken into account.…”