Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao 266003, China.
Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China.
Int J Biol Macromol. 2020 Jul 1;154:1123-1131. doi: 10.1016/j.ijbiomac.2019.11.036. Epub 2019 Nov 18.
The structural elucidation of polysaccharides is essential for understanding their structure-bioactivity relationship and related drug development. In this study, fucoidan (Fuc) 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 was clarified using a combination of acid degradation, tandem mass spectrometry, and nuclear magnetic resonance spectroscopy analysis. As a result, Fuc was found to be composed of a tetrafucose repeating unit [→3-α-l-Fucp-1 → 3-α-l-Fucp2(OSO)-1 → 3-α-l-Fucp2(OSO)-1 → 3-α-l-Fucp2,4(OSO)-1→]. The stimulating hematopoiesis was further evaluated in a mouse model induced by cyclophosphamide. Based on these findings, intraperitoneally administered Fuc 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 reduces platelet aggregation caused by CTX, so it might have the effect of reducing the risk of thrombosis. Therefore, Fuc can be exploited as potentially promising stimulator of hematopoiesis in the future.
多糖的结构阐明对于理解其结构-生物活性关系以及相关药物开发至关重要。在本研究中，我们从海参 Holothuria polii 中提取并纯化了褐藻糖胶（Fuc）。其硫酸基含量为 39.5±1.4%，重均分子量为 103.1±2.8 kDa。通过酸降解、串联质谱和核磁共振波谱分析相结合的方法阐明了 Fuc 的一级结构。结果表明，Fuc 由四糖重复单元组成[→3-α-l-Fucp-1→3-α-l-Fucp2(OSO)-1→3-α-l-Fucp2(OSO)-1→3-α-l-Fucp2,4(OSO)-1→]。进一步在环磷酰胺诱导的小鼠模型中评估了其刺激造血的作用。基于这些发现，腹腔内给予 Fuc 可能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，在环磷酰胺诱导的免疫抑制背景下，Fuc 处理可减少 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 有望成为未来具有潜力的造血刺激剂。
