Structural characterization and antagonistic effect against P-selectin-mediated function of SFF-32, a fucoidan fraction from Sargassum fusiforme.
Structural characterization and antagonistic effect against P-selectin-mediated function of SFF-32, a fucoidan fraction from Sargassum fusiforme.
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DOI：
10.1016/j.jep.2022.115408
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发表时间：
2022-06
影响因子：
5.4
通讯作者：
Siya Wu;Jian Liu;Ya Zhang;Jianxi Song;Zhong-Shan Zhang;Yue Yang;Mingjiang Wu;Haibin Tong
中科院分区：
文献类型：
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作者：
Siya Wu;Jian Liu;Ya Zhang;Jianxi Song;Zhong-Shan Zhang;Yue Yang;Mingjiang Wu;Haibin Tong
民族药理相关性羊栖菜，或称海枣，至少从公元8世纪起就被用于传统中医，是几个中国方剂的基本成分，包括用于治疗甲状腺肿的海藻玉湖汤和用于治疗汗疹皮肤病的内消雷丽丸。其药理作用。目的确定从岩藻糖胶中分离得到的岩藻糖胶组分SFF-32的结构特征。材料与方法采用甲基化/气相色谱-质谱法和核磁共振技术确定了SFF-32的一级结构。采用扫描电子显微镜(SEM)、刚果红测试法和圆二色谱(CD)对SFF-32的表面形态和溶液构象进行了表征。采用流式细胞术、静态黏附实验和平行板流室实验检测SFF-32对P-选择素与HL-60细胞结合的抑制作用。此外，通过体外蛋白结合实验评价sF32对P-选择素与sGL1相互作用的阻断作用。结果证实sF32的主要连锁类型为→[3)-α-l-Fucp-(1→3，4)-α-l-Fucp-(1]2→[4)-β-d-Manp-(1→3)-d-GlcAp-(1]2→4)-β-d-Manp-(1→3)-β-d-Glcp-(1→4)-β-d-Manp-(1→2，3)-β-d-Galp-(1→4)-β-d-Manp-(1→[4)-α-l-Rhap-(1]3→.硫化单元或末端木糖残基通过某些岩藻糖残基的C-3连接到骨架上，而末端木糖残基通过半乳糖残基的C-3连接到主链上。结论阻断P-选择素与PSGL-1的结合可能是SFF-32抑制P-选择素介导的细胞功能的可能机制，提示SFF-32可能是一种潜在的抗炎先导化合物。
Ethnopharmacological relevanceSargassumfusiforme(Harvey) Setchell, or Haizao, has been used in traditional Chinese medicine (TCM) since at least the eighth century a.d.S. fusiformeis an essential component of several Chinese formulas, including Haizao Yuhu Decoction, used to treat goiter, and Neixiao Lei Li Wan used to treat scrofuloderma. The pharmacological efficacy ofS. fusiformemay be related to its anti-inflammatory effect.Aim of the studyTo determine the structural characteristics of SFF-32, a fucoidan fraction fromS. fusiforme,and its antagonistic effect against P-selectin mediated function.Materials and methodsThe primary structure of SFF-32 was determined using methylation/GC–MS and NMR analysis. Surface morphology and solution conformation of SFF-32 were determined by scanning electron microscopy (SEM), Congo red test, and circular dichroic (CD) chromatography, respectively. The inhibitory effects of SFF-32 against the binding of P-selectin to HL-60 cells were evaluated using flow cytometry, static adhesion assay, and parallel-plate flow chamber assay. Furthermore, the blocking effect of SFF-32 on the interaction between P-selectin and PSGL-1 was evaluated using anin vitroprotein binding assay.ResultsThe main linkage types of SFF-32 were proven to →[3)-α-l-Fucp-(1→3,4)-α-l-Fucp-(1]2→[4)-β-d-Manp-(1→3)-d-GlcAp-(1]2→4)-β-d-Manp-(1→3)-β-d-Glcp-(1→4)-β-d-Manp-(1→2,3)-β-d-Galp-(1→4)-β-d-Manp-(1→[4)-α-l-Rhap-(1]3→. The sulfated unit or terminal xylose residues were attached to the backbone through the C-3 of some fucose residues and terminal xylose residues were attached to C-3 of galactose residues. Moreover, SFF-32 disrupted P-selectin-mediated cell adhesion and rolling as well as blocked the interaction between P-selectin and its physiological ligand PSGL-1 in a dose-dependent manner.ConclusionsBlocking the binding between P-selectin and PSGL-1 is the possible underlying mechanism by which SFF-32 inhibits P-selectin-mediated function, which demonstrated that SFF-32 may be a potential anti-inflammatory lead compound.