Department of Biomedical Sciences, University of Sassari, Viale San Pietro, 43b, 07100 Sassari, Italy.
MERLN Institute for Technology-Inspired Regenerative Medicine, Complex Tissue Regeneration Department, Maastricht University, 6200 MD Maastricht, The Netherlands.
Mar Drugs. 2024 Mar 21;22(3):139. doi: 10.3390/md22030139.
Thromboembolic conditions are the most common cause of death in developed countries. Anticoagulant therapy is the treatment of choice, and heparinoids and warfarin are the most adopted drugs. Sulphated polysaccharides extracted from marine organisms have been demonstrated to be effective alternatives, blocking thrombus formation by inhibiting some factors involved in the coagulation cascade. In this study, four acidic glycan fractions from the marine sponge were purified by anion-exchange chromatography, and their anticoagulant properties were investigated through APTT and PT assays and compared with both standard glycosaminoglycans and holothurian sulphated polysaccharides. Moreover, their topographic localization was assessed through histological analysis, and their cytocompatibility was tested on a human fibroblast cell line. A positive correlation between the amount of acid glycans and the inhibitory effect towards both the intrinsic and extrinsic coagulation pathways was observed. The most effective anticoagulant activity was shown by a highly charged fraction, which accounted for almost half (about 40%) of the total hexuronate-containing polysaccharides. Its preliminary structural characterization, performed through infrared spectroscopy and nuclear magnetic resonance, suggested that it may consist of a fucosylated chondroitin sulphate, whose unique structure may be responsible for the anticoagulant activity reported herein for the first time.
血栓栓塞性疾病是发达国家最常见的死亡原因。抗凝治疗是首选治疗方法,肝素类药物和华法林是最常采用的药物。从海洋生物中提取的硫酸多糖已被证明是有效的替代品,通过抑制凝血级联反应中的一些因子来阻止血栓形成。在这项研究中,从海洋海绵中分离出的四种酸性糖胺聚糖通过阴离子交换色谱进行了纯化,并通过 APTT 和 PT 测定法研究了它们的抗凝特性,并与标准糖胺聚糖和海参硫酸多糖进行了比较。此外,通过组织学分析评估了它们的拓扑定位,并在人成纤维细胞系上测试了它们的细胞相容性。观察到酸性糖含量与对内源性和外源性凝血途径的抑制作用之间存在正相关。带高电荷的部分表现出最强的抗凝活性,它占总含己糖醛酸多糖的近一半(约 40%)。通过红外光谱和核磁共振对其进行的初步结构表征表明,它可能由岩藻糖基硫酸软骨素组成,其独特的结构可能是其首次报道的抗凝活性的原因。