Carbohydrate Polymers 91 (2013) 467–475 Contents lists available at SciVerse ScienceDirect Carbohydrate Polymers jo u rn al hom epa ge: www.elsevier.com/locate/carbpol A sulfated polysaccharide, fucans, isolated from brown algae Sargassum vulgare with anticoagulant, antithrombotic, antioxidant and anti-inflammatory effects Celina Maria P. Guerra Dore a , Monique Gabriela das C. Faustino Alves a , Luiza Sheyla E. Pofírio Will a , Thiago G. Costa a , Diego A. Sabry b , Leonardo Augusto R. de Souza Rêgo a , Camila M. Accardo b , Hugo Alexandre O. Rocha a , Luciana Guimarães A. Filgueira a , Edda Lisboa Leite a,∗ a Laboratory of Glycobiology, Department of Biochemistry, Federal University of Rio Grande do Norte (UFRN), Av. Sen Salgado Filho, No. 3000, Natal, RN, Brazil b Departament of Biochemistry, Federal University of São Paulo, UNIFESP, São Paulo, SP, Brazil a r t i c l e i n f o Article history: Received 1 May 2012 Received in revised form 19 July 2012 Accepted 29 July 2012 Available online 3 August 2012 Keywords: Marine algae Fucans Anticoagulant Antioxidant Anti-inflamatory Sargassum vulgare a b s t r a c t Fucan (SV1) sulfated polysaccharides from the brown algae Sargassum vulgare were extracted, fraction- ated in acetone and examined with respect to chemical composition, anticoagulant, anti-inflammatory, antithrombotic effects and cellular proliferation. These polysaccharides contain low levels of protein, high level of carbohydrate and sulfate. Monosaccharides analysis revealed that SV1 was composed of fucose, galactose, xylose, glucuronic acid and mannose. SV1 polysaccharide prolonged activated partial throm- boplastin time (aPTT) and exhibited high antithrombotic action in vivo, with a concentration ten times higher than heparin activity. PSV1, a purified form in gel filtration showed very low biological activities. SV1 stimulated the enzymatic activity of FXa. Its action on DPPH radical scavenging activity was 22%. This polymer has no cytotoxic action (hemolytic) on ABO and Rh blood types in different erythrocyte groups. It displays strong anti-inflammatory action at all concentrations tested in the carrageenan-induced paw edema model, demonstrated by reduced edema and cellular infiltration. © 2012 Elsevier Ltd. All rights reserved. 1. Introduction Seaweeds have been the focus of growing interest in the biomedical area, mainly due to their bioactive substances, which show great potential for anti-inflammatory, antimicrobial, antivi- ral, and anti-tumoral drugs (Bluden, 1993). Sulfated fucans, polysaccharides that contain neutral sugars, substantial percent- ages of l-fucose and sulfated ester groups, are constituents of brown algae and some marine invertebrates (Berteau & Mulloy, 2003). Their structure varies according to algal species and extraction procedure. Although several studies have attempted to determine the fine structure of fucans, only a few examples of regularity were found. The linkages, branching, sulfate positions and compo- sition of monosaccharides differ significantly, and the relationship between structure and biological activity has yet to be established (Holtkamp, Kelly, Ulber, & Lang, 2009). Sargassum (Phaeophyceae) is an algal genus with an exten- sive geographical range (Duarte, Cardoso, Noseda, & Cerezo, 2001). Early studies of fucans from the Sargassum genus indicate they are generally composed of glucuronic acid, mannose, and galactose residues, with partially sulfated side-chains consisting of galactose, ∗ Corresponding author. Tel.: +55 084 3215 3416; fax: +55 084 3215 3415. E-mail address: eddaleite@cb.ufrn.br (E.L. Leite). xylose, and fucose. Fucans from Sargassum are widely studied owing to their broad therapeutic applications (Zhang, Hu, Liu, & Shuai, 2011). Most thromboembolic processes require anticoagulant therapy. This explains current efforts to develop specific and potent anti- coagulant and antithrombotic agents (Cumashi et al., 2007). Since the 1940s, heparin, sulfated polysaccharides, has been the pre- dominant drug for treatment and prevention of venous thrombosis and thromboembolism. However, an obvious side effect of heparin administration is hemorrhagic. It is well-documented that marine brown algae are an abundant source of anticoagulant polysaccha- rides containing a variety of sulfated l-fucans with anticoagulant activity (Olson & Björk, 1993; Zhu et al., 2009). The proposed mech- anism of anticoagulant action for fucoidan was predominantly related to in vitro potential ion of natural inhibitors of activated factor II (thrombin) and activated factor X (Ananthi et al., 2010). Oxidative stress has been defined as a disturbance in the equi- librium between pro-oxidant and antioxidant systems in favor of pro-oxidation, due to intracellular signaling and defense against microorganisms (Ananthi et al., 2010). Other symptoms may result from ROS production associated with activation of the immune sys- tem. Cell membrane lipids and proteins are also sites of free radical reactions. Several investigations have been conducted to verify and to demonstrate the antioxidant properties in algae (Yuan et al., 2005). 0144-8617/$ – see front matter © 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.carbpol.2012.07.075