Anticoagulant and antithrombotic activities of low-molecular-weight propylene glycol alginate sodium sulfate (PSS)

Eur J Med Chem. 2016 May 23:114:33-40. doi: 10.1016/j.ejmech.2016.02.063. Epub 2016 Mar 2.

Abstract

Propylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide derivative, has been used as a heparinoid drug to prevent and treat hyperlipidemia and ischemic cardio-cerebrovascular diseases in China for nearly 30 years. To extend the applications of PSS, a series of low-molecular-weight PSSs (named FPs) were prepared by oxidative-reductive depolymerization, and the antithrombotic activities were investigated thoroughly in vitro and in vivo. The bioactivity evaluation demonstrated a positive correlation between the molecular weight and the anticoagulant and antithrombotic activities of FPs. FPs could prolong the APTT and clotting time and reduce platelet aggregation significantly. FPs could also effectively inhibit factor IIa in the presence of AT-III and HC-II. FPs decreased the wet weights and lengths of the thrombus and increased occlusion times in vivo. FP-6k, a PSS fragment with a molecular weight of 6 kDa, is an optimal antithrombotic candidate for further study and showed little chance for hemorrhagic action.

Keywords: Anticoagulant; Antithrombotic; Molecular weight; Oxidative reduction; Propylene glycol alginate sodium sulfate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemical synthesis
  • Alginates / chemistry
  • Alginates / pharmacology*
  • Animals
  • Anticoagulants / chemical synthesis
  • Anticoagulants / chemistry
  • Anticoagulants / pharmacology*
  • Blood Coagulation Tests
  • Dose-Response Relationship, Drug
  • Fibrinolytic Agents / chemical synthesis
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / pharmacology*
  • Hemorrhage / prevention & control*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Molecular Structure
  • Molecular Weight
  • Platelet Aggregation / drug effects
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship
  • Sulfates / chemical synthesis
  • Sulfates / chemistry
  • Sulfates / pharmacology*
  • Thrombosis / drug therapy*

Substances

  • Alginates
  • Anticoagulants
  • Fibrinolytic Agents
  • Sulfates
  • sodium sulfate
  • propylene glycol alginate ester