Fucans, but not fucomannoglucuronans, determine the biological activities of sulfated polysaccharides from Laminaria saccharina brown seaweed.
Fucans, but not fucomannoglucuronans, determine the biological activities of sulfated polysaccharides from Laminaria saccharina brown seaweed.
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DOI：
10.1371/journal.pone.0017283
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发表时间：
2011-02-28
期刊：
影响因子：
3.7
通讯作者：
Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO), Italy
中科院分区：
文献类型：
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作者：
Croci DO;Cumashi A;Ushakova NA;Preobrazhenskaya ME;Piccoli A;Totani L;Ustyuzhanina NE;Bilan MI;Usov AI;Grachev AA;Morozevich GE;Berman AE;Sanderson CJ;Kelly M;Di Gregorio P;Rossi C;Tinari N;Iacobelli S;Rabinovich GA;Nifantiev NE;Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO), Italy
从褐藻saccharina（新名称：saccharina latissima）中提取的硫酸酸化多糖显示出治疗炎症、血栓形成和癌症的良好活性；然而，这些特性背后的分子机制仍然知之甚少。本研究的目的是通过体外和体内实验，表征从糖精中提取的两个主要硫酸酸化多糖组分的抗炎、抗凝血、抗血管生成和抗肿瘤活性：a)主要由o -硫酸化甘露葡聚糖组成的L.s.-1.0组分和b)主要由硫酸酸化岩藻聚糖组成的L.s.-1.25组分。在大鼠炎症模型中，这两种成分都抑制了白细胞的募集，尽管L.s.-1.25似乎比L.s.-1.0更活跃。此外，这些组分抑制中性粒细胞与血小板的粘附。通过活化的部分凝血活素时间测量，只有ls -1.25，而ls -1.0没有显示抗凝活性。在血管生成环境下的研究表明，只有L.s.-1.25能强烈抑制胎牛血清（FBS）诱导的体外血管生成。这种效果与ls -1.25处理的内皮细胞中纤溶酶原激活物抑制剂-1 （PAI-1）水平的降低有关。此外，只有L. saccharina （L.s.-P）的亲本硫酸酸化多糖及其组分L.s.-1.25对碱性成纤维细胞生长因子（bFGF）诱导通路具有较强的抑制作用。一致地，L.s.-1.25和L.s.-P成功地干扰了成纤维细胞与人bFGF的结合。将ls - p或ls -1.25，而不是ls -1.0掺入含有黑色素瘤细胞的Matrigel塞中，可显著降低血红蛋白含量以及肿瘤相关血管的频率。此外，L.s.-1.25和L.s.-P （L.s.-1.0）可显著降低同基因小鼠的肿瘤生长。最后，L.s.-1.25显著抑制乳腺癌细胞对人血小板包被表面的粘附。因此，硫酸化岩藻聚糖主要与l.s charina褐藻多糖的抗炎、抗凝血、抗血管生成和抗肿瘤活性有关。
Sulfated polysaccharides from Laminaria saccharina (new name: Saccharina latissima) brown seaweed show promising activity for the treatment of inflammation, thrombosis, and cancer; yet the molecular mechanisms underlying these properties remain poorly understood. The aim of this work was to characterize, using in vitro and in vivo strategies, the anti-inflammatory, anti-coagulant, anti-angiogenic, and anti-tumor activities of two main sulfated polysaccharide fractions obtained from L. saccharina: a) L.s.-1.0 fraction mainly consisting of O-sulfated mannoglucuronofucans and b) L.s.-1.25 fraction mainly composed of sulfated fucans. Both fractions inhibited leukocyte recruitment in a model of inflammation in rats, although L.s.-1.25 appeared to be more active than L.s.-1.0. Also, these fractions inhibited neutrophil adhesion to platelets under flow. Only fraction L.s.-1.25, but not L.s.-1.0, displayed anticoagulant activity as measured by the activated partial thromboplastin time. Investigation of these fractions in angiogenesis settings revealed that only L.s.-1.25 strongly inhibited fetal bovine serum (FBS) induced in vitro tubulogenesis. This effect correlated with a reduction in plasminogen activator inhibitor-1 (PAI-1) levels in L.s.-1.25-treated endothelial cells. Furthermore, only parent sulfated polysaccharides from L. saccharina (L.s.-P) and its fraction L.s.-1.25 were powerful inhibitors of basic fibroblast growth factor (bFGF) induced pathways. Consistently, the L.s.-1.25 fraction as well as L.s.-P successfully interfered with fibroblast binding to human bFGF. The incorporation of L.s.-P or L.s.-1.25, but not L.s.-1.0 into Matrigel plugs containing melanoma cells induced a significant reduction in hemoglobin content as well in the frequency of tumor-associated blood vessels. Moreover, i.p. administrations of L.s.-1.25, as well as L.s.-P, but not L.s.-1.0, resulted in a significant reduction of tumor growth when inoculated into syngeneic mice. Finally, L.s.-1.25 markedly inhibited breast cancer cell adhesion to human platelet-coated surfaces. Thus, sulfated fucans are mainly responsible for the anti-inflammatory, anticoagulant, antiangiogenic, and antitumor activities of sulfated polysaccharides from L. saccharina brown seaweed.
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影响因子：
4.7
作者：
Kusaykin, Mikhail;Bakunina, Irina;Zvyagintseva, Tatyana
通讯作者：
Zvyagintseva, Tatyana
影响因子：
4.8
作者：
Lake, Andrew C.;Vassy, Roger;Letourneur, Didier
通讯作者：
Letourneur, Didier
影响因子：
4.5
作者：
Kim, Kui-Jin;Lee, Ok-Hwan;Lee, Boo-Yong
通讯作者：
Lee, Boo-Yong
影响因子：
4
作者：
BROWN, KJ;HENDRY, IA;PARISH, CR
通讯作者：
PARISH, CR
DOI：
10.3390/molecules13081671
发表时间：
2008-08-12
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Li B;Lu F;Wei X;Zhao R
通讯作者：
Zhao R