Fucoidan from sea cucumber Holothuria polii: Structural elucidation and stimulation of hematopoietic activity

Fucoidan from sea cucumber Holothuria polii: Structural elucidation and stimulation of hematopoietic activity
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DOI:
10.1016/j.ijbiomac.2019.11.036
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发表时间:
2020-07-01
影响因子:
8.2
通讯作者:
Yu, Guangli
Yu, Guangli
中科院分区:
化学1区
文献类型:
--
作者:
Li, Chao;Niu, Qingfeng;Yu, Guangli

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多糖的结构解析对于理解其结构-生物活性关系和相关药物开发至关重要。本研究从海参海参中提取并纯化了岩藻依聚糖(Fuc(hp))。其硫酸盐含量为39.5 +/- 1.4%,“重均”分子量为103.1 +/- 2.8 kDa。通过结合酸降解、串联质谱和核磁共振波谱分析,阐明了 Fuc(hp) 的一级结构。结果发现,Fuc(hp)由四岩藻糖重复单元[-> 3-alpha-L-Fucp-1 -> 3-alpha-L-Fucp2(OSO3-)-1 -> 3-alpha-L-Fucp2(OSO3-)-1 -> 3-alpha-L-Fucp2,4 (OSO3-)-1 ->]组成。在环磷酰胺诱导的小鼠模型中进一步评估了刺激造血作用。基于这些发现,腹腔注射Fuc(hp)可以加速白细胞和中性粒细胞的恢复,其活性超过重组人粒细胞集落刺激因子(rhG-CSF)。同时,在环磷酰胺引起的免疫抑制背景下,Fuc(hp)治疗可减少CTX引起的血小板聚集,因此可能具有降低血栓形成风险的作用。因此,Fuc(hp)可以作为未来有潜力的造血刺激剂来开发。 (C) 2019 Elsevier B.V. 保留所有权利。
The structural elucidation of polysaccharides is essential for understanding their structure-bioactivity relationship and related drug development. In this study, fucoidan (Fuc(hp)) was extracted and purified from sea cucumber Holothuria polii. Its sulfate content was 39.5 +/- 1.4%, and the "weight-average" molecular mass was 103.1 +/- 2.8 kDa. The primary structure of Fuc(hp) was clarified using a combination of acid degradation, tandem mass spectrometry, and nuclear magnetic resonance spectroscopy analysis. As a result, Fuc(hp) was found to be composed of a tetrafucose repeating unit [-> 3-alpha-L-Fucp-1 -> 3-alpha-L-Fucp2(OSO3-)-1 -> 3-alpha-L-Fucp2(OSO3-)-1 -> 3-alpha-L-Fucp2,4 (OSO3-)-1 ->]. The stimulating hematopoiesis was further evaluated in a mouse model induced by cyclophosphamide. Based on these findings, intraperitoneally administered Fuc(hp) may accelerate the recovery of white blood cells and neutrophils, in which its activity exceeded that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Meanwhile, in the background of cyclophosphamide-induced immunosuppression, treatment with Fuc(hp) reduces platelet aggregation caused by CTX, so it might have the effect of reducing the risk of thrombosis. Therefore, Fuc(hp) can be exploited as potentially promising stimulator of hematopoiesis in the future. (C) 2019 Elsevier B.V. All rights reserved.