Affiliation:
1. Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
2. Laboratory for Marine Drugs and Bioproducts, National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China
Abstract
Sulfated polysaccharides from marine algae have attracted a great amount of attentions for the development of marine drugs due to their unique structural features, and they are great potential sources of naturally occurring anticoagulant agents. The genus Chaetomorpha is one of the largest genera in green algae and has a worldwide distribution. In the present study, a homogeneous polysaccharide from Chaetomorpha aerea, designated as PCA, was obtained by alkali extraction, anion-exchange and size-exclusion chromatography. Based on the results of chemical and spectroscopic analyses, PCA was a sulfated galactoarabinan which was mainly constituted of a backbone of →4)-β-l-Arap-(1→ unit, partially sulfated at C-3 of →4)-β-l-Arap-(1→ and C-4 of →6)-α-d-Galp-(1→. The side chains consisting of →6)-α-d-Galp-(1→ and →5)-α-l-Araf-(1→ residues were in C-2 of →4)-β-l-Arap-(1→ unit. PCA had a strong anticoagulant activity in vitro as evaluated by the assays of activated partial thromboplastin time, thrombin time and fibrinogen level. The obvious anticoagulant activity in vivo of PCA was also found. PCA significantly inhibited the activities of the intrinsic coagulation factors XII, XI, IX and VIII, and exhibited weak inhibition effects on the common coagulation factors II and X. The anticoagulant mechanism of PCA was attributed to strong thrombin inhibition potentiated by heparin cofactor II or antithrombin III, and it also possessed an apparent inhibition effect on coagulation factor Xa mediated by antithrombin III. The investigation demonstrated that PCA could be a promising anticoagulant agent for health promotion and the treatment of thrombotic diseases.
Funder
National Key Research and Development Program of China
Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology
Subject
Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science
Cited by
5 articles.
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