Korean J Hematol.  2010 Mar;45(1):51-57. 10.5045/kjh.2010.45.1.51.

Biological effects of fucoidan isolated from Fucus vesiculosus on thrombosis and vascular cells

Affiliations
  • 1Thrombosis and Vascular Biochemistry Lab., Department of Biochemistry, College of Medicine, CHA University, Seongnam, Korea. hoe@cha.ac.kr
  • 2R&D Center, CHA-BioMed Co. Ltd., Seongnam, Korea.

Abstract

BACKGROUND
Fucoidan is a highly sulfated glycosaminoglycan, which has a molecular structure similar to that of heparin. The antithrombotic effects of fucoidan in vitro have been widely reported, but its antithrombotic effects in vivo as well as its other biological properties in vitro have not been well investigated.
METHODS
This study investigated the effects and mechanism of fucoidan from Fucus vesiculosus on thrombosis both in vitro and in vivo. A ferric chloride-induced mouse carotid artery thrombosis model was used to determine the antithrombotic effects of fucoidan in vivo. Additionally, changes in the levels of proinflammatory cytokines and chemokines were examined in vascular cells treated with fucoidan.
RESULTS
In vivo studies employing a ferric chloride-induced mouse carotid artery thrombosis model indicated that fucoidan had a stronger antithrombotic activity than heparin. Further, vascular cells treated with fucoidan demonstrated a decrease in proinflammatory cytokine and chemokine production as well as inhibition of proliferation.
CONCLUSION
The major findings of this study showed that fucoidan has a stronger antithrombotic effect than heparin in vivo and that fucoidan has an inhibitory effect on proinflammatory cytokine production and proliferation of vascular cells.

Keyword

Fucoidan; Fucus vesiculosus; Antithrombotic effect; Proinflammatory cytokines; Vascular cell proliferation

MeSH Terms

Animals
Carotid Artery Thrombosis
Chemokines
Cytokines
Fucus
Glycosaminoglycans
Heparin
Mice
Molecular Structure
Polysaccharides
Thrombosis
Chemokines
Cytokines
Glycosaminoglycans
Heparin
Polysaccharides

Figure

  • Fig. 1 Ferric chloride-induced mouse carotid artery thrombosis model. (A) Expose of left common carotid artery, (B) Induction of total occlusion by applying a filter paper saturated with 25% ferric chloride solution, (C) Monitoring of carotid blood flow with micro-optical probe, (D) Photoplethysmography of carotid blood flow until time to occlusion.

  • Fig. 2 The inhibitory effect of fucoidan in an in vivo mouse thrombosis model. The antithrombotic effect of fucoidan was 2.3 times stronger than heparin in a ferric chloride-induced mouse carotid artery occlusion model. The time to delay occlusion twice was represented as the ED50 value.

  • Fig. 3 The inhibitory effect of fucoidan on platelet aggregation (n=3). The inhibitory effect of fucoidan on platelet aggregation was approximately 2.8 times stronger than that of heparin (Error bar is not shown).

  • Fig. 4 The inhibitory effect of fucoidan and heparin on thrombin (A) and factor Xa (B) by antithrombin. The enzyme activities were determined by chromogenic assay methods.

  • Fig. 5 The inhibitory effect of fucoidan on SMC proliferation. The antiproliferative effect of fucoidan on SMC was stronger than that of heparin. Cell proliferation was inhibited at 50 µg/mL of both fucoidan and heparin. Above a concentration of 500 µg/mL, fucoidan showed a stronger antiproliferative effect on SMCs than heparin. *P<0.01

  • Fig. 6 Change in the levels of inflammatory cytokines in HUVECs after treatment with fucoidan. HUVECs were pre-incubated with fucoidan for 8 h and then further incubated for 16 h in the presence of 10 ng/mL TNF-alpha.


Reference

1. Pereira MS, Mulloy B, Mourão PA. 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. 1999; 274:7656–7667. PMID: 10075653.
2. Cumashi A, Ushakova NA, Preobrazhenskaya ME, et al. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology. 2007; 17:541–552. PMID: 17296677.
Article
3. Pereira MS, Melo FR, Mourão PA. Is there a correlation between structure and anticoagulant action of sulfated galactans and sulfated fucans? Glycobiology. 2002; 12:573–580. PMID: 12244069.
Article
4. Smorenburg SM, Van Noordan CJ. The complex effects of heparins on cancer progression and metastasis in experimental studies. Pharmacol Rev. 2001; 53:93–105. PMID: 11171940.
5. San Antonio JD, Verrecchio A, Pukac LA. Heparin sensitive and resistant vascular smooth muscle cells: biology and role in restenosis. Connect Tissue Res. 1998; 37:87–103. PMID: 9643650.
Article
6. Matsunaga M, Ohtaki H, Takaki A, et al. Nucleoprotamine diet derived from salmon soft roe protects mouse hippocampal neurons from delayed cell death after transient forebrain ischemia. Neurosci Res. 2003; 47:269–276. PMID: 14568108.
Article
7. Lange RA, Hillis LD. Antiplatelet therapy for ischemic heart disease. N Engl J Med. 2004; 350:277–280. PMID: 14724308.
Article
8. Hirsh J. Hyperactive platelets and complications of coronary artery disease. N Engl J Med. 1987; 316:1543–1544. PMID: 3587283.
9. Casscells W. Migration of smooth muscle and endothelial cells: Critical events in restenosis. Circulation. 1992; 86:723–729. PMID: 1516183.
Article
10. Post MJ, Borst C, Kuntz RE. The relative importance of arterial remodeling compared with intimal hyperplasia in lumen renarrowing after balloon angioplasty. A study in the normal rabbit and the hypercholesterolemic Yucatan micropig. Circulation. 1994; 89:2816–2821. PMID: 8205696.
Article
11. Farrehi PM, Ozaki CK, Carmeliet P, Fay WP. Regulation of arterial thrombolysis by plasminogen activator inhibitor-1 in mice. Circulation. 1998; 97:1002–1008. PMID: 9529269.
Article
12. Mourão PA. Use of sulfated fucans as anticoagulant and antithrombotic agents: future perspectives. Curr Pharm Des. 2004; 10:967–981. PMID: 15078127.
13. Cumashi A, Ushakova NA, Preobrazhenskaya ME, et al. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology. 2007; 17:541–552. PMID: 17296677.
Article
14. Dürig J, Bruhn T, Zurborn KH, Gutensohn K, Bruhn HD, Béress L. Anticoagulant fucoidan fractions from Fucus vesiculosus induce platelet activation in vitro. Thromb Res. 1997; 85:479–491. PMID: 9101640.
Article
15. Alwayn IP, Appel JZ, Goepfert C, Buhler L, Cooper DK, Robson SC. Inhibition of platelet aggregation in baboons: therapeutic implications for xenotransplantation. Xenotransplantation. 2000; 7:247–257. PMID: 11081759.
Article
16. Church FC, Meade JB, Treanor RE, Whinna HC. Antithrombin activity of fucoidan. The interaction of fucoidan with heparin cofactor II, antithrombin III, and thrombin. J Biol Chem. 1989; 264:3618–3623. PMID: 2914965.
17. Nishino T, Nagumo T. Anticoagulant and antithrombin activities of oversulfated fucans. Carbohydr Res. 1992; 229:355–362. PMID: 1394292.
Article
18. Patel MK, Mulloy B, Gallagher KL, O'Brien L, Hughes AD. The antimitogenic action of the sulphated polysaccharide fucoidan differs from heparin in human vascular smooth muscle cells. Thromb Haemost. 2002; 87:149–154. PMID: 11848445.
Article
19. Religa P, Kazi M, Thyberg J, Gaciong Z, Swedenborg J, Hedin U. Fucoidan inhibits smooth muscle cell proliferation and reduces mitogen-activated protein kinase activity. Eur J Vasc Endovasc Surg. 2000; 20:419–426. PMID: 11112459.
Article
20. duPont NC, Wang K, Wadhwa PD, Culhane JF, Nelson EL. Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: determinations of a panel of nine cytokines in clinical sample culture supernatants. J Reprod Immunol. 2005; 66:175–191. PMID: 16029895.
Article
21. Ramsden L, Rider CC. Selective and differential binding of interleukin (IL)-1 alpha, IL-1 beta, IL-2 and IL-6 to glycosaminoglycans. Eur J Immunol. 1992; 22:3027–3031. PMID: 1425926.
Full Text Links
  • KJH
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr