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绿藻来源的具有独特结构特征的硫酸多糖的抗凝血性质。

Anticoagulant Property of a Sulfated Polysaccharide with Unique Structural Characteristics from the Green Alga .

机构信息

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.

Laboratory for Marine Drugs and Bioproducts, National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China.

出版信息

Mar Drugs. 2023 Jan 26;21(2):88. doi: 10.3390/md21020088.

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 is one of the largest genera in green algae and has a worldwide distribution. In the present study, a homogeneous polysaccharide from , 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-Ara-(1→ unit, partially sulfated at C-3 of →4)-β-l-Ara-(1→ and C-4 of →6)-α-d-Gal-(1→. The side chains consisting of →6)-α-d-Gal-(1→ and →5)-α-l-Ara-(1→ residues were in C-2 of →4)-β-l-Ara-(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.

摘要

海洋藻类中的硫酸多糖因其独特的结构特征而引起了人们对海洋药物开发的极大关注,它们是天然抗凝剂的潜在来源。 属是绿藻中最大的属之一,分布于世界各地。在本研究中,从 属中获得了一种均一的多糖,命名为 PCA,通过碱提取、阴离子交换和凝胶渗透色谱分离得到。基于化学和光谱分析的结果,PCA 是一种硫酸半乳阿拉伯聚糖,主要由 →4)-β-l-Ara-(1→ 单元组成,部分在 →4)-β-l-Ara-(1→的 C-3 和 →6)-α-d-Gal-(1→的 C-4 上硫酸化。侧链由 →6)-α-d-Gal-(1→和 →5)-α-l-Ara-(1→残基组成,位于 →4)-β-l-Ara-(1→单元的 C-2 上。PCA 具有很强的体外抗凝活性,通过激活部分凝血活酶时间、凝血酶时间和纤维蛋白原水平的测定来评估。还发现 PCA 具有明显的体内抗凝活性。PCA 显著抑制内源性凝血因子 XII、XI、IX 和 VIII 的活性,对常见凝血因子 II 和 X 表现出较弱的抑制作用。PCA 的抗凝机制归因于肝素辅因子 II 或抗凝血酶 III 增强的强烈凝血酶抑制作用,它还对抗凝血酶 III 介导的凝血因子 Xa 具有明显的抑制作用。研究表明,PCA 可能是一种有前途的抗凝剂,可用于促进健康和治疗血栓性疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf5/9962809/d5bffeefb653/marinedrugs-21-00088-g001a.jpg

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