Anticoagulant and antithrombotic activity

Anticoagulants are substances that prevent coagulation; that is, they stop blood from clotting (Desai, 2004). Therefore, they are a group of pharmaceuticals that can be used in vivo as a medication for thrombotic disorders. Heparin, a highly sulfated polysaccharide present in mammalian tissues, is one of the commonly used drugs of the choice in prevention of throm-boembolic disorders (Lee et al., 2008b). However, there are some well-documented problems related to its clinical application (Alban et al., 2002). Therefore recently, alternative drugs for heparin are in high demand due to its bad and long-term side effects (Athukorala et al.,

TABLE 12.1 Biological activities of fucose-rich sulfated polysaccharides and fucoidan isolated from various brown seaweeds

Seaweed species

Biological activity

Reference

E. cava

Anticoagulant (in vitro)

Athukorala et al. (2006)

E. cava

Antithrombotic

Jung et al. (2007)

F. evanescens

Anticoagulant

Kuznetsova et al. (2003)

E. cava

Anticoagulant (in vivo)

Wijesinghe et al. (2011)

P. gymnospora

Anticoagulant

Silva et al. (2005)

A. nodosum

Anticoagulant

Chevolot et al. (1999)

Anticoagulant

Soeda et al. (1992)

S. fulvellum

Anticoagulant

De Zoisa et al. (2008)

Hizikia fusiforme

Anticoagulant

Dobashi et al. (1989)

Laminaria

Anticoagulant

Yoon et al. (2007)

cichorioides

U. pinnatifida

Antitumor

Synytsya et al. (2010)

E. cava

Antiproliferation

Athukorala et al. (2009)

Antiproliferation

Aisa et al. (2004)

F. evanescens

Antitumor and

Alekseyenko et al. (2007)

antimetastatic

L. guryanovae

Anticancer

Lee et al. (2008a)

F. vesiculosus

Immunomodulation

Kim and Joo (2008)

Immunomodulation

Choi et al. (2005)

F. vesiculosus

Immunomodulation

Do et al. (2010)

F. vesiculosus

Immunomodulation

Jintang et al. (2010)

U. pinnatifida

Immunomodulation

Yoo et al. (2007)

F. vesiculosus

Immunomodulation

Yang et al. (2008)

L. japonica

Anti-inflammation

Li et al. (2011)

E. cava

Anti-inflammation

Kang et al. (2011)

A. nodosum

Angiogenesis

Matou et al. (2002)

U. pinnatifida

Antivirus

Hemmingson et al. (2006)

2007). Over the years, isolation and purification of natural sulfated poly-saccharides responsible for anticoagulant activity from different seaweed species had been reported (De Zoisa et al., 2008). The ability of sulfated polysaccharides to interfere with biological systems has a longstanding record, as illustrated with heparin (Huynh et al., 2001). In addition, anticoagulant and antithrombotic activities are among the most widely studied properties of sulfated polysaccharides.

Athukorala et al. (2006) tested anticoagulant activity of fucose-contain-ing sulfated polysaccharide isolated from brown seaweed E. cava including activated partial thromboplastin time, thrombin time, and pro-thrombin time. According to their results, the pure compound showed almost similar anticoagulant activity to that of heparin. Further study demonstrated that fucose-containing sulfated polysaccharide isolated from E. cava strongly inhibits the activities of coagulation factors via interaction with antithrombin III in both the extrinsic and the common coagulation pathways (Jung et al., 2007). Possible anticoagulation mechanism and molecular interaction of fucoidan isolated from the brown seaweed E. cava with blood coagulation factors are shown in Fig. 12.3. Fucoidans enhance ATIII-mediated coagulation factor inhibition in coagulation pathways. This contributes to its high anticoagulant activity. Wijesinghe et al. (2011) demonstrated in vivo anticoagulant activity of isolated fucose-rich sulfated polysaccharide obtained from E. cava. Anticoagulant and antithrombin activities of over sulfated fucans having different sulfate contents were reported (Nishino and Nagumo, 1992). There results showed that heparin cofactor II-mediated antithrombin activity of the over sulfated fucans also increased significantly with increase in sulfate content. In addition, it was reported that the major antithrombin activity by fucoidan was mediated by heparin cofactor II (Qui et al., 2006). Another previous study reported the partial characterization and anticoagulant activity of a heterofucan from the brown seaweed, Padina gymnospora (Silva et al., 2005). Further, they have reported that 3-O-sulfation at C-3 of 4-a-l-fucose-1! units was responsible for the anticoagulant activity of fucoidan from the particular seaweed species.

De Zoisa et al. (2008) reported the isolation and characterization of fucose-containing sulfated polysaccharide as an anticoagulant agent from the edible brown seaweed Sargassum fulvellum by means of a simple fermentation process and chromatography technique. According to their

Intrinsic

Extrinsic

Prothrombin (II)

Anticoagulant, fucoidan

Inhibition

ATIII

Thrombin (IIa)

Inhibition | ^

Fibrinogen —

FIGURE 12.3 Possible anticoagulation mechanism of fucoidan from brown seaweed Ecklonia cava.

report, fermentation could offer a tool to increase the bioactive potentials. Therefore, the report facilitates further screening and large-scale production of the bioactive molecules from fermented marine seaweed in the future.

With the evidence from previous studies, brown algal sulfated poly-saccharide, fucoidan attracted extensive interest in anticoagulative drug discovery.

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