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

Guanlan Chen, Rui Zeng, Xin Wang, Hongying Cai, Jiajia Chen, Yingxiong Zhong, Saiyi Zhong, Xuejing Jia

Marine drugs 2022 Jan 05

filter terms:

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.

Citation

Guanlan Chen, Rui Zeng, Xin Wang, Hongying Cai, Jiajia Chen, Yingxiong Zhong, Saiyi Zhong, Xuejing Jia. Antithrombotic Activity of Heparinoid G2 and Its Derivatives from the Clam Coelomactra antiquata. Marine drugs. 2022 Jan 05;20(1)