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Anticoagulant and Antithrombotic Properties in Vitro and in Vivo of a Novel Sulfated Polysaccharide from Marine Green Alga Monostroma nitidum

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 of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(4), 247; https://doi.org/10.3390/md17040247
Received: 3 April 2019 / Revised: 21 April 2019 / Accepted: 23 April 2019 / Published: 25 April 2019
(This article belongs to the Special Issue Discovery and Application of Macroalgae-Derived Natural Products)
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Abstract

Sulfated polysaccharides from marine algae have high potential as promising candidates for marine drug development. In this study, a homogeneous sulfated polysaccharide from the marine green alga Monostroma nitidum, designated MS-1, was isolated using water extraction and anion-exchange and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that MS-1 mainly consisted of →3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→ residues, with additional branches consisting of 4-linked β-d-xylose, 4-/6-linked d-glucose, terminal β-d-glucuronic acid, and 3-/2-linked α-l-rhamnose. Sulfate ester groups substituted mainly at C-2/C-4 of →3)-α-l-Rhap-(1→ and C-4 of →2)-α-l-Rhap-(1→ residues, slightly at C-2 of terminal β-d-glucuronic residues. MS-1 exhibited strong anticoagulant activity in vitro and in vivo as evaluated by the activated partial thromboplastin time and thrombin time assays, and significantly decreased platelet aggregation. The anticoagulant activity mechanism of MS-1 was mainly attributed to strong potentiation thrombin by heparin cofactor-II, and it also hastened thrombin and coagulation factor Xa inhibitions by potentiating antithrombin-III. MS-1 possessed markedly thrombolytic activity evaluated by plasminogen activator inhibitior-1, fibrin degradation products, and D-dimer levels using rats plasma, and recanalization rate by FeCl3-induced carotid artery thrombosis in mice. MS-1 exhibited strong antithrombotic activity in vitro and in vivo evaluated by the wet weighs and lengths of thrombus, and thrombus occlusion time by electrically-induced carotid artery thrombosis in rats. These results suggested that MS-1 could be a promising marine drug for prevention and therapy of thromboembolic disease. View Full-Text
Keywords: marine green algae; sulfated polysaccharide; structural characteristics; anticoagulant property; antithrombotic activity marine green algae; sulfated polysaccharide; structural characteristics; anticoagulant property; antithrombotic activity
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Cao, S.; He, X.; Qin, L.; He, M.; Yang, Y.; Liu, Z.; Mao, W. Anticoagulant and Antithrombotic Properties in Vitro and in Vivo of a Novel Sulfated Polysaccharide from Marine Green Alga Monostroma nitidum. Mar. Drugs 2019, 17, 247.

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