Anticoagulant Activity Of Marine Algae

After the investigation of blood anticoagulant properties from marine brown algae, it has been reported that SPs derived from marine algae are alternative sources for manufacture of novel anticoagulant drugs (Church et al., 1989; Matsubara, 2004; Nishino et al., 2000). Anticoagulant activity is among the most widely studied properties of SPs and anticoagulants from marine algae have previously been reviewed (McLellan and Jurd, 1992; Mestechkina and Shcherbukhin, 2010). Various anticoagulant SPs from marine algae have been isolated and characterized (Table 18.1). Two types of SPs are identified with high anticoagulant activity including sulfated galactans, also known as carrageenan, from marine red algae (Carlucci et al., 1997; Kolender et al., 1997; Sen et al., 1994) and sulfated fucoidans from marine brown algae (Chevolot et al., 1999; Colliec et al., 1991; Dobashi et al., 1989). However, there are fewer reports of anticoagulant SPs reported from marine green algae compared to brown and red algae (Mao et al., 2009). Jurd et al. (1995) found that

TABLE 18.1 Some marine algae with anticoagulant sulfated polysaccharides (SPs)

Marine algae with anticoagulant SPs

Ref.

Chlorophyta

Monostroma latissimum Monostroma nitidum Ulva conglobata Codium fragile Codium pugniformis Codium cylindricum Phaeophyta Ecklonia cava Ecklonia kurom Laminaria japonica Ascophyllum nodosum Lessonia vadosa

Rhodophyta Lomentaria catenata Gigartina skottsbergii Schizymenia binderi Grateloupia indica Porphyra haitanensis Nothogenia fastigiata

Mao et al. (2009) Maeda et al. (1991) Mao et al. (2006) Hayakawa et al. (2000) Matsubara et al. (2000) Matsubara et al. (2001)

Athukorala et al. (2006) Nishino et al. (1991) Wang et al. (2010) Nardella et al. (1996) Chandia and Matsuhiro (2008)

Pushpamali et al. (2008) Carlucci et al. (1997) Zuniga et al. (2006) Sen et al. (1994) Zhang et al. (2010) Kolender et al. (1997)

the anticoagulant-active SPs from Codium fragile subspecies atlanticum (Chlorophyta) contain xyloarabinogalactans. A sulfated galactan with anticoagulant activity has also been reported from Codium cylindricum (Matsubara et al., 2001). In addition, Maeda et al. (1991) have revealed that the anticoagulant SPs from Monostroma nitidum (Chlorophyceae) yielded a sixfold higher activity than that of heparin. In comparison, marine brown algae extracts exhibit higher anticoagulant activity than red and green algae extracts (Chevolot et al., 1999; Patankar et al., 1993).

Since a few studies reported the prolongation of PT by marine SPs, it suggests that marine SPs interfered a little or may not inhibit the extrinsic pathway of coagulation. The relationship between structure and anticoagulant activity of some SPs has been reported (Colliec et al., 1991; Hayakawa et al., 2000). The presence of sulfate groups in SPs can increase both their specific and nonspecific binding to a wide range of biologically active proteins. Anticoagulant activity of sulfated galactans depends on the nature of the sugar residue, the sulfation position of the structure, and the sulfate content in the SPs (Melo et al., 2004; Silva et al., 2010). Moreover, the O-sulfated 3-linked a-galactans enhanced the inhibition of thrombin and factor Xa by antithrombin and/or heparin cofactor II in the intrinsic pathway of blood coagulation (Pereira et al., 2002). Further, high molecular weight carrageenans with high sulfate content have shown higher anticoagulant activity than low molecular weight and low sulfate content SPs (Shanmugam and Mody, 2000).

Unfractionated heparins and low molecular weight heparins are the only sulfated polysaccharides currently used as anticoagulant drugs. Seaweed-derived SPs have been described to possess anticoagulant activity similar to or higher than heparin (Costa et al., 2010). Collectively, these evidences suggest that SPs derived from seaweeds have a promising potential to be used as anticoagulant agents in the pharmaceutical industry.

Phlorotannins from S. thunbergii have been analyzed for their potential anticoagulant activity and suggested that phlorotannins are potential anticoagulants in vitro and in vivo. According to their results, phlorotan-nins from S. thunbergii had a significant effect on the prolongation of APTT, PT, and TT especially at the concentration of 1 mg/ml. In addition, phloroglucinol can be developed as a novel anticoagulant in the pharmaceutical industry (Bae, 2011).

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