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Antithrombotic Activity of Heparinoid G2 and Its Derivatives from the Clam Coelomactra antiquata
- Source :
- Marine Drugs, Marine Drugs; Volume 20; Issue 1; Pages: 50, Marine Drugs, Vol 20, Iss 50, p 50 (2022)
- Publication Year :
- 2022
- Publisher :
- MDPI, 2022.
-
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.
- Subjects :
- Male
Aquatic Organisms
Platelet Aggregation
QH301-705.5
Pharmaceutical Science
Administration, Oral
clam heparinoid
molecular weight
antithrombotic
oral administration
gut microbiota
Carrageenan
Article
Mice
Fibrinolytic Agents
Drug Discovery
Animals, Outbred Strains
Animals
Biology (General)
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Venous Thrombosis
Sheep
Bivalvia
Disease Models, Animal
Heparinoids
Subjects
Details
- Language :
- English
- ISSN :
- 16603397
- Volume :
- 20
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Marine Drugs
- Accession number :
- edsair.doi.dedup.....6de9d8f0bc9e8a19ec64ad2cf0da6503