Abstract
Through the perspective of the current glycomics age, fucanomics and galactanomics denote the international projects concerned with the studies of the biomedically active marine sulfated fucose- or galactose-composed polysaccharides, named sulfated fucans (SFs), and sulfated galactans (SGs), respectively. SFs and SGs are isolated from algae or marine invertebrates. The range of therapeutic actions of SFs and SGs is impressively broad. When certain structural requirements are found, some SFs and SGs may exhibit beneficial properties in inflammation, nociception, hemostasis (coagulation and thrombosis), vascular biology (angiogenesis), oncology, oxidative-stress, and virus infections. Although many biomedical applications for SFs and SGs have been pointed out over the past two decades, only inflammation, hemostasis, cancer, and vascular biology have their mechanisms of action satisfactorily elucidated. In addition, advanced structure-function relationships have been achieved only for the anticoagulant and antithrombotic activities, in which glycans of well-defined structures have been assayed. Because of this, the activities of SFs and SGs in stopping the clot and thrombus formation represent the closest therapeutic areas of having these glycans truly explored for drug development. Here, through an analytical viewpoint, we present the common methods and protocols employed to achieve such advanced structure-function relationships of SFs and SGs in anticoagulation and antithrombosis.
Similar content being viewed by others
Abbreviations
- ADP:
-
adenosine diphosphate
- aPTT:
-
activated partial thromboplastin time
- AT:
-
antithrombin
- bFGF:
-
basic fibroblast growth factor
- HCII:
-
heparin cofactor II
- HMWK:
-
high-molecular-weight kininogen
- IU:
-
international unit
- KccT:
-
kaolin cephalin clotting time
- PBS:
-
phosphate-buffered saline
- PPP:
-
platelet-poor plasma
- PRP:
-
platelet-rich plasma
- PT:
-
prothrombin time
- PTT:
-
partial thromboplastin time
- SFs:
-
sulfated fucans
- SGs:
-
sulfated galactans
- TCT:
-
thrombin clotting time
- TF:
-
tissue factor
- TT:
-
thrombin time
- UFH:
-
unfractionated heparin
- VEGF:
-
vascular endothelial growth factor
References
Pomin, V.H.: Fucanomics and galactanomics: marine distribution, medicinal impact, conceptions, and challenges. Mar Drugs 10, 793–811 (2012)
Pomin, V.H.: Fucanomics and galactanomics: current status in drug discovery, mechanisms of action and role of the well-defined structures. Bioch Biophys Acta – Gen Subj 1820, 1971–1979 (2012)
Pomin, V.H., Mourão, P.A.: Structure, biology, evolution and medical importance of sulfated fucans and galactans. Glycobiol 18, 1016–1027 (2008)
Pomin, V.H.: Review: An overview about the structure-function relationship of marine sulfated homopolysaccharides with regular chemical structures. Biopol 91, 601–609 (2009)
Berteau, O., Mulloy, B.: Sulfated fucans, fresh perspectives: Structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharide. Glycobiol 13, 29R–40R (2003)
Mourão, P.A.: Use of sulfated fucans as anticoagulant and antithrombotic agents: future perspectives. Curr Pharm Des 10, 967–981 (2004)
Cumashi, A., Ushakova, N.A., Preobrazhenskaya, M.E., Piccoli, A., Totani, L., Ustyuzhanina, N.E., Bilan, M.I., Usov, A.I., Grachev, A.A., Morozevich, G.E., et al.: A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiol 17, 541–552 (2007)
Rodrigues, J.A., Vanderlei, E.S., Silva, L.M., Araújo, I.W., Queiroz, I.N., Paula, G.A., Abreu, T.M., Ribeiro, N.A., Bezerra, M.M., Chaves, H.V., Lima, V., Jorge, R.J., Monteiro, H.S., Leite, E.L., Benevides, N.M.: Antinociceptive and anti-inflammatory activities of a sulfated polysaccharide isolated from the green seaweed Caulerpa cupressoides. Pharmacol Rep 64, 282–292 (2012)
Dore, C.M., das C Faustino Alves, M.G., Will, L.S., Costa, T.G., Sabry, D.A., de Souza Rêgo, L.A., Accardo, C.M., Rocha, H.A., Filgueira, L.G., Leite, E.L.: A sulfated polysaccharide, fucans, isolated from brown algae Sargassum vulgare with anticoagulant, antithrombotic, antioxidant and anti-inflammatory effects. Carbohydr Polym 91, 467–475 (2013)
Romanos, M.T., Andrada-Serpa, M.J., Mourão, P.A., Yoneshigue-Valentin, Y., Costa, S.S., Pereira, M.S., Miranda, M.M., Gonçalves, J.L., Wigg, M.D.: A sulphated fucan from the Laminaria abyssalis inhibits the human T cell lymphotropic virus type 1-induced syncytium formation in HeLa cells. Antivir Chem Chemother 13, 219–221 (2002)
Croci DO, Cumashi A, Ushakova NA, Preobrazhenskaya ME, Piccoli A, et al.: Fucans, but not fucomannoglucuronaans, determine the biological activities of sulfated polysaccharides from Laminaria saccharina brown seaweed. Plos One 6, e17283
Koyanagi, S., Tanigawa, N., Nakagawa, H., Soeda, S., Shimeno, H.: Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. Bioch Pharmacol 65, 173–179 (2003)
Pallister CJ, Watson MS: Haematology 2010; Scion Publishing. 2nd edition. pp. 336–347.
Pereira, M.S., Mulloy, B., Mourão, P.A.: Structure and anticoagulant activity of sulfated fucans. Comparison between the regular, repetitive, and linear fucans from echinoderms with the more heterogeneous and branched polymers from brown algae. J Biol Chem 274, 7656–7667 (1999)
Andersson, L.O., Barrowcliffe, T.W., Holmer, E., Johnson, E.A., Sims, G.E.: Anticoagulant properties of heparin fractionated by affinity chromatography on matrix-bound antithrombin iii and by gel filtration. Thromb Res 9, 575–583 (1976)
Matsubara, K., Matsuura, Y., Bacic, A., Liao, M., Hori, K., Miyazawa, K.: Anticoagulant properties of a sulfated galactan preparation from a marine green alga, Codium cylindricum. Int J Biol Macromol 28, 395–399 (2001)
Matsubara, K., Matsuura, Y., Hori, K., Miyazawa, K.: An anticoagulant proteoglycan from the marine green alga, Codium pugniformis. J Appl Phycol 12, 9–14 (2000)
Maraganore, J.M., Chao, B., Joseph, M.L., Jablonski, J., Ramachandran, K.L.: Anticoagulant activity of synthetic hirudin peptides. J Biol Chem 264, 8692–8698 (1989)
Pereira, M.S., Melo, F.R., Mourão, P.A.: Is there a correlation between structure and anticoagulant action of sulfated galatans and sulfated fucans? Glycobiol 12, 573–580 (2002)
Fonseca, R.J., Oliveira, S.N., Melo, F.R., Pereira, M.G., Benevides, N.M., Mourão, P.A.: Slight differences in sulfation of algal galactans account for differences in their anticoagulant and venous antithrombotic activities. Thromb Haemost 99, 539–545 (2008)
Fonseca, R.J., Oliveira, S.N., Pomin, V.H., Mecawi, A.S., Araujo, I.G., Mourão, P.A.: Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides. Thromb Haemost 103, 994–1004 (2010)
Glauser, B.F., Vairo, B.C., Oliveira, S.N., Cinelli, L.P., Pereira, M.S., Mourão, P.A.: Structure and haemostatic effects of generic versions of enoxaparin available for clinical use in Brazil: similarity to the original drug. Thromb Haemost 107, 302–14 (2012)
Eitzman, D.T., Westrick, R.J., Nabel, E.G., et al.: Plasminogen activator inhibitor-1 and vitronectin promote vascular thrombosis in mice. Blood 95, 577–580 (2000)
Wessler, S., Reimer, S.M., Sheps, M.C.: Biological assay of a thrombosis inducing activity in human serum. J Appl Physiol 14, 943–946 (1959)
Herbert, J.M., Bernat, A., Maffrand, J.P.: Importance of platelets in experimental venous thrombosis in rats. Blood 80, 2281–2286 (1992)
Mourão, P.A., Pereira, M.S.: Searching for alternatives to heparin: sulfated fucans from marine invertebrates. Trends Cardiovasc Med 9, 225–32 (1999)
Conflict of interest
Although this document comprises a review in which most of the information sources are coming from already published materials, the use of the current information was totally done under legal procedures regarding the law of copyrights, reprints and permission. The authors state that he is not aware of any authorship, affiliations, memberships, funding, or financial holdings that might be perceived as damaged or as affecting the objectivity of the content of this material. The author declares no conflict of interest by any part.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pomin, V.H. How to analyze the anticoagulant and antithrombotic mechanisms of action in fucanome and galactanome?. Glycoconj J 31, 89–99 (2014). https://doi.org/10.1007/s10719-013-9509-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10719-013-9509-3