Cell Wall Polysaccharides of Marine Algae 22.5 Biological Activities and Medicinal Applications 567
Part D | 22.5
particles onto the host cell surface and/or direct inhibition of viral replication, or (ii) activation of immune
pathways. Many viruses are able to bind to cell surface
proteoglycans (heparan sulfates), which is important for
the entrance of viral particles into the cell. Because they
have a strong affinity to viruses, algal sulfated polysaccharides may inhibit the adhesion of viral particles onto
the cell surface and thus put obstacles into the viral
life circle [22.170]. If the antiviral effect of polysaccharides is significant only at the early stage of the viral
replication cycle, viral adsorption is proved. By contrast, antiviral activity after infection confirms that the
polysaccharide directly inhibits the viral replication and
transition of virions between uninfected and infected
cells (virucidal effect). For example, sulfated galactans from red algae Sphaerococcus coronopifolius and
Boergeseniella thuyoides inhibit in vitro replication of
both HIV and HSV-1. However, in the case of the HSV1 cycle, these polysaccharides block the adsorption
step, while a direct virucidal effect was observed for
HIV-1 replication [22.341]. Antimicrobial and antiprotozoal activities of algal sulfated polysaccharides may
be caused by direct interaction with microorganisms,
blocking of microorganism-binding cell receptors, or
by modulation of the immune response. For example,
fucoidan (sulfated galactofucan) from Undaria pinnatifida sporophyll might inhibit cryptosporidiosis by
direct binding to the Cryptosporidium parvum-derived
functional mediators in the intestinal epithelial cells of
neonatal mice [22.385]. This polysaccharide also exhibits anti-malarial activity against cultured Plasmodium falciparum parasites in vitro and on Plasmodium
berghei-infected mice in vivo [22.414].
22.5.5 Anticoagulant
and Antithrombotic Activities
The anticoagulant activity of sulfated polysaccharides,
including those from algal sources is based on the
interactions with plasma cofactors, which are natural inhibitors of coagulation proteases [22.415]. These
interactions are complex and depend on the monosaccharide composition, the molecular weight, and the
structure and distribution of sulfate groups. Sulfation
is always important for both anticoagulant and antithrombotic activities, but the charge density is not
always critical. Commonly anticoagulant activity of algal hydrocolloids, i. e., sulfated galactans, mannans,
rhamnans, fucans, or more complex polysaccharides,
is described as activated partial thromboplastin time
(aPTT), thrombin time (TT), prothrombin time (PT),
and antithrombin to anticoagulation factor Xa activities in comparison with corresponding values of heparin
obtained at the same in vitro and/or in vivo experimental conditions [22.416]. The anticoagulant activity of
algal sulfated polysaccharides is mainly attributed to
thrombin inhibition mediated by antithrombin and/or
heparin cofactor II, while other mechanisms have also
been proposed. For example, several different fucoidan
preparations from various algal species, including Fucus versiculosus [22.417, 418], Laminaria brasiliensis [22.417], Ecklonia kurome [22.418], Ascophyllum
nodosum [22.419], Pelvetia caniculata [22.420], and
the sporophyll of Undaria pinnatifida [22.384], have
been reported for their anticoagulant activity. Fucoidans
have potent anticoagulant activity mediated by antithrombin and/or heparin cofactor II [22.421]. The
differences in anticoagulation mechanisms could be explained by the structural diversity of these polysaccharides and the interaction with several target proteases.
The driving force for the formation of the sulfated
polysaccharide/protein complex is the nonspecific electrostatic interaction between these macromolecules;
then the complex is stabilized by other (polar or nonpolar) short-range interactions [22.422]. Anticoagulant
polysaccharide should undergo appropriate conformational transitions to possess distorted ordered conformation suitable for protein binding. Model invertebrate
sulfated ˛-L-fucans and sulfated ˛-L-galactans of regular linear structure show in vitro anticoagulant activity;
some of them also express antithrombotic activity on
in vivo models [22.421]. More complex algal sulfated
polysaccharides having similar structural patterns may
exhibit similar activities, which are not determined by
charge density, but rather depend on monosaccharide
composition and sulfation pattern. Partially, disulfated
internal monosaccharide residues probably have the
highest potential for anticoagulant activity due to their
ability to place sulfate groups in spatial positions adequate for interaction with proteins. Slight differences in
the proportions and/or distribution of sulfated residues
may be critical for the interaction between proteases,
inhibitors, and activators of the coagulation system, resulting in a distinct pattern in anti and pro-coagulant
activities and in the antithrombotic action of algal sulfated galactans [22.337]. Sulfated galactans need much
longer chains for the anticoagulant effect than heparin. Macromolecules of 1545 kDa are able to bind
antithrombin but are too short to link the plasma inhibitor and thrombin. Binding to different sites on
antithrombin, sulfated galactans are less effective than
heparin at promoting antithrombin conformational ac-
Part D | 22.5
particles onto the host cell surface and/or direct inhibition of viral replication, or (ii) activation of immune
pathways. Many viruses are able to bind to cell surface
proteoglycans (heparan sulfates), which is important for
the entrance of viral particles into the cell. Because they
have a strong affinity to viruses, algal sulfated polysaccharides may inhibit the adhesion of viral particles onto
the cell surface and thus put obstacles into the viral
life circle [22.170]. If the antiviral effect of polysaccharides is significant only at the early stage of the viral
replication cycle, viral adsorption is proved. By contrast, antiviral activity after infection confirms that the
polysaccharide directly inhibits the viral replication and
transition of virions between uninfected and infected
cells (virucidal effect). For example, sulfated galactans from red algae Sphaerococcus coronopifolius and
Boergeseniella thuyoides inhibit in vitro replication of
both HIV and HSV-1. However, in the case of the HSV1 cycle, these polysaccharides block the adsorption
step, while a direct virucidal effect was observed for
HIV-1 replication [22.341]. Antimicrobial and antiprotozoal activities of algal sulfated polysaccharides may
be caused by direct interaction with microorganisms,
blocking of microorganism-binding cell receptors, or
by modulation of the immune response. For example,
fucoidan (sulfated galactofucan) from Undaria pinnatifida sporophyll might inhibit cryptosporidiosis by
direct binding to the Cryptosporidium parvum-derived
functional mediators in the intestinal epithelial cells of
neonatal mice [22.385]. This polysaccharide also exhibits anti-malarial activity against cultured Plasmodium falciparum parasites in vitro and on Plasmodium
berghei-infected mice in vivo [22.414].
22.5.5 Anticoagulant
and Antithrombotic Activities
The anticoagulant activity of sulfated polysaccharides,
including those from algal sources is based on the
interactions with plasma cofactors, which are natural inhibitors of coagulation proteases [22.415]. These
interactions are complex and depend on the monosaccharide composition, the molecular weight, and the
structure and distribution of sulfate groups. Sulfation
is always important for both anticoagulant and antithrombotic activities, but the charge density is not
always critical. Commonly anticoagulant activity of algal hydrocolloids, i. e., sulfated galactans, mannans,
rhamnans, fucans, or more complex polysaccharides,
is described as activated partial thromboplastin time
(aPTT), thrombin time (TT), prothrombin time (PT),
and antithrombin to anticoagulation factor Xa activities in comparison with corresponding values of heparin
obtained at the same in vitro and/or in vivo experimental conditions [22.416]. The anticoagulant activity of
algal sulfated polysaccharides is mainly attributed to
thrombin inhibition mediated by antithrombin and/or
heparin cofactor II, while other mechanisms have also
been proposed. For example, several different fucoidan
preparations from various algal species, including Fucus versiculosus [22.417, 418], Laminaria brasiliensis [22.417], Ecklonia kurome [22.418], Ascophyllum
nodosum [22.419], Pelvetia caniculata [22.420], and
the sporophyll of Undaria pinnatifida [22.384], have
been reported for their anticoagulant activity. Fucoidans
have potent anticoagulant activity mediated by antithrombin and/or heparin cofactor II [22.421]. The
differences in anticoagulation mechanisms could be explained by the structural diversity of these polysaccharides and the interaction with several target proteases.
The driving force for the formation of the sulfated
polysaccharide/protein complex is the nonspecific electrostatic interaction between these macromolecules;
then the complex is stabilized by other (polar or nonpolar) short-range interactions [22.422]. Anticoagulant
polysaccharide should undergo appropriate conformational transitions to possess distorted ordered conformation suitable for protein binding. Model invertebrate
sulfated ˛-L-fucans and sulfated ˛-L-galactans of regular linear structure show in vitro anticoagulant activity;
some of them also express antithrombotic activity on
in vivo models [22.421]. More complex algal sulfated
polysaccharides having similar structural patterns may
exhibit similar activities, which are not determined by
charge density, but rather depend on monosaccharide
composition and sulfation pattern. Partially, disulfated
internal monosaccharide residues probably have the
highest potential for anticoagulant activity due to their
ability to place sulfate groups in spatial positions adequate for interaction with proteins. Slight differences in
the proportions and/or distribution of sulfated residues
may be critical for the interaction between proteases,
inhibitors, and activators of the coagulation system, resulting in a distinct pattern in anti and pro-coagulant
activities and in the antithrombotic action of algal sulfated galactans [22.337]. Sulfated galactans need much
longer chains for the anticoagulant effect than heparin. Macromolecules of 1545 kDa are able to bind
antithrombin but are too short to link the plasma inhibitor and thrombin. Binding to different sites on
antithrombin, sulfated galactans are less effective than
heparin at promoting antithrombin conformational ac-