Glycobiology Advance Access published online on February 12, 2007
Glycobiology, doi:10.1093/glycob/cwm014
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A comparative study of the antiinflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds
1 Department of Oncology and Neurosciences, University G. D'Annunzio Medical School & Foundation, 66013 Chieti, Italy
2 V.N. Orekhovich Research Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya str. 10, 119121 Moscow, Russian Federation
3 Consorzio Mario Negri Sud, Laboratory of Vascular Biology and Pharmacology, Santa Maria Imbaro, Chieti, 66030, Italy
4 Laboratory of plant polysaccharides
5 Laboratory of glycoconjugate chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prospect, 119991, Moscow, Russian Federation
6 Scottish Association for Marine Sciences, Oban, Argyll, Scotland, PA37 1QA, UK
7 Division of Immunogenetics, Hospital de Clínicas "José de San Martín", Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina
8 To whom correspondence should be addressed: Professor Nikolay E. Nifantiev, Laboratory of glycoconjugate chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prospect, 119991, Moscow, Russian Federation. Tel&Fax +7-495-1358784; e-mail: nen{at}ioc.ac.ru
Received on May 24, 2006; revised on January 14, 2007; accepted on February 2, 2007
The antiinflammatory, antiangiogenic, anticoagulant and antiadhesive properties of fucoidans obtained from nine species of brown algae were studied in order to examine the influence of fucoidan origin and composition onto their biological activities. All fucoidans inhibited leucocyte recruitment in an inflammation model in rats, and neither the content of fucose and sulfate, nor other structural features of their polysaccharide backbones significantly affected the efficacy of fucoidans in this model. In vitroevaluation of P-selectin-mediated neutrophil adhesion to platelets under flow conditions revealed that only polysaccharides from Laminaria saccharina, L. digitata, Fucus evanescens, F. serratus, F. distichus, F. spiralis and Ascophyllum nodosum could serve as P-selectin inhibitors. All fucoidans, except that from Cladosiphon okamuranuscarrying substantial levels of 2-O-
-D-glucuronopyranosyl branches in the linear (1
3)-linked poly--fucopyranoside chain, exhibited anticoagulant activity as measured by activated partial thromboplastin time while only fucoidans from L. saccharina, L. digitata, F. serratus, F. distichusand F. evanescensdisplayed strong antithrombin activity in a platelet aggregation test. The last fucoidans potently inhibited HUVEC tubulogenesis in vitroand this property correlated with decreased levels of PAI-1 in HUVEC supernatants, suggesting a possible mechanism of fucoidan-induced inhibition of tubulogenesis. Finally, fucoidans from L. saccharina, L. digitata, F. serratus, F. distichus and F. vesiculosusstrongly blocked MDA-MB-231 breast carcinoma cell adhesion to platelets, an effect which might have critical implications in tumour metastasis. The data presented herein provide a new rationale for the development of potential drugs for thrombosis, inflammation and tumour progression.
Key words: fucoidan / brown algae / blood coagulation / inflammation / angiogenesis
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