Helicobacter ISSN 1523-5378

doi: 10.1111/hel.12177

REVIEW ARTICLE
Review: Prospects for the Use of Extracts and Polysaccharides
from Marine Algae to Prevent and Treat the Diseases Caused
by Helicobacter Pylori
Natalya N. Besednova, Tatyana S. Zaporozhets, Larisa M. Somova and Tatyana A. Kuznetsova
G.P. Somov Research Institute of Epidemiology and Microbiology, Siberian Branch of the Russian Academy of Medical Sciences, Vladivostok,
Russia

Keywords
Helicobacter pylori infection, fucoidan, marine
algae.
Reprint requests to: Tatyana A. Kuznetsova, G.P.
Somov Research Institute of Epidemiology and
Microbiology, Siberian Branch of the Russian
Academy of Medical Sciences, 1 Selskya St.,
Vladivostok 690087, Russia.
E-mail: niiem_vl@mail.ru
Abstract
Helicobacter pylori possesses a broad spectrum of pathogenic factors that allow
it to survive and colonize the gastric mucosa, and thus, the pathogenetic tar-
gets, which have the same diversity, require search for and the development
of alternative, effective, and innocuous means for the eradication of
H. pylori. In recent years, fucoidans have been extensively studied due to
the numerous interesting biological activities, including the anti-adhesive,
anti-oxidative, antitoxic, immunomodulatory, anticoagulant, and anti-infec-
tion effects. This review summarizes the data on the effects of extracts and
sulfated polysaccharides of marine algae, mainly fucoidans, on pathogenic
targets in Helicobacter infection. The pathogenetic targets for therapeutic
agents after H. pylori infection, such as flagellas, urease, and other enzymes,
including adhesins, cytotoxin A (VacA), phospholipase, and L-8, are charac-
terized here. The main target for the sulfated polysaccharides of seaweed is
cell receptors of the gastric mucosa. This review presents the published data
about the pleiotropic anti-inflammatory effects of polysaccharides on the
gastric mucosa. It is known that fucoidan and other sulfated polysaccharides
from algae have anti-ulcer effects, prevent the adhesion of H. pylori to, and
reduce the formation of biofilm. The authors speculate that the effect of sul-
fated polysaccharides on the infectious process caused by H. pylori is related
to their action on innate and adaptive immunity cells, and also anti-oxidant
and antitoxic potential. Presented in the review are materials indicated for
the study of extracts and sulfated polysaccharides from seaweed during
H. pylori infection, as these compounds are characterized by multimodality
actions. Based on the analysis of literary materials in recent years, the
authors concluded that fucoidan can be attributed to the generation of new
candidates to create drugs intended for the inclusion in the scheme of eradi-
cation therapy of H. pylori infection.

The discovery by Robin Warren and Barry Marshall
regarding the role of Helicobacter pylori in the develop-
ment of gastric and duodenal ulcer and gastritis proved
to be an important event in medicine, which became a
powerful incentive for further studies in pathomorphol-
ogy, gastroenterology, microbiology, immunology,
genetics, epidemiology, and pharmacology [1]. The
study of the pathogenic properties of H. pylori led
researchers to revise their views on the pathogenesis
and principles of treatment for chronic gastritis and
peptic ulcer disease (PUD). The direct dependence of
the clinical manifestation, the recurrence rate of
chronic gastritis, PUD, and the development of precan-
cerous states on the degree of colonization of the gastric
mucosa by H. pylori has been established [2–4]. The
probability of gastric cancer in individuals infected by
H. pylori is much higher than that in uninfected ones
[5]. The rate of H. pylori infection reaches 74% of the
population in developing countries and 58% in devel-
oped ones [6,7]. In Eastern Europe, the rate of H. pylori

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Polysaccharides from Marine Algae
infection is 40–70%; in Russia, this level is 50–92%
[2]. The main natural reservoir for this microorganism
is humans. Owing to its resistance to a number of anti-
bacterial drugs, administered for eradication of the
causative agent, H. pylori poses a serious problem to
medical science [8,9]. Despite the use of current treat-
ment regimens, eradication of the pathogen is achieved
in practice in no more than 70–85.5% of patients [10].
Pathogenetic Target for Therapeutic
Agents at the Helicobacter Infection
Helicobacter pylori possesses a broad enough spectrum of
pathogenic factors to survive in the acid environment
of the stomach and to colonize the gastric mucosa
[11,12]. For this reason, the agent has a spiral-like
shape and flagella, which enable it to move actively in
the gastric acid and mucus. H. pylori can attach to the
plasma membrane of epithelial cells in the stomach and
destroy the cytoskeleton components of these cells.
Colonization of the mucosa by the causative agent
would be impossible without urease, protecting the bac-
teria from hydrochloric acid [13]. Microbial cells con-
tain large amounts of urease (up to 10% of the total
protein content), which is the cytoplasmic enzyme act-
ing inside the cell and having affinity to gastric mucin.
This enzyme amplifies inflammation reactions by acti-
vating monocytes and neutrophils, stimulating the
secretion of pro-inflammatory cytokines and the forma-
tion of oxygen radicals and nitric oxide.
Helicobacter pylori forms catalase, mucinase, oxidase,
hemolysin, alkaline phosphatase, protein inhibiting the
hydrochloric acid, glutamyl transferase, and a number
of other enzymes, participating in the pathogenesis of
Helicobacter infection [11]. The excretion of catalase and
superoxide dismutase enables the agent to suppress the
immune response of the host organism. These enzymes
catalyze the reaction, which turns the bactericidal oxy-
gen compounds, released by neutrophils as a result of
infection, into innocuous substances such as water and
oxygen.
By producing the adhesion factors, bacteria pene-
trate through the mucus layer to the epithelial cells of
the stomach, attach to them, and colonize them. Adhe-
sins impede phagocytosis of the causative agent with
polymorphonuclear leukocytes.
The genome of H. pylori has recently been decoded.
Strains of this agent may differ in specific DNA regions.
In the H. pylori genome, cytotoxicity genes (CagA,
VacA, IceA, Bab A) are located within so-called “patho-
genicity islands” [14]. Cytotoxin-associated gene A
(CagA) encodes the production of highly immunogenic
vacuolizing cytotoxin A, causing inflammation, the
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increased production of interleukin-8 (IL-8), the inhibi-
tion of apoptosis, and the excessive growth of certain
types of cells [15].
Approximately, half of H. pylori strains secrete vacu-
olizing cytotoxin A (VacA), a highly immunogenic pro-
tein, causing the vacuolization of cells and forming
pores in the membrane of epitheliocytes that result in
the release of urea and anions from the cell and trigger-
ing the pro-inflammatory signaling cascade. VacA
exerts a powerful pro-inflammatory effect in the gastric
mucosa, followed by the expression of chemokines,
particularly IL-8 and RANTES (CCl5) [11,16,17], as well
as pro-apoptotic and necrotic effects on gastric cells
[12,18–20].
Phospholipases A and C, produced by H. pylori, play
a significant role in the pathogenesis of infection by
destroying the integrity of membranes of the epithelial
cells and inhibiting their resistance to damaging factors.
Moreover, these enzymes breach the protective func-
tion of the gastric mucus [21].
The induction of IL-8 production, inhibition of the
growth of host cells and apoptosis, the remodeling of
actin, the secretion system (flagellum-like structures to
introduce effectors (CagA) into host cells), as well as
lipopolysaccharides (LPS) and superficial proteins,
should also be considered pathogenicity factors [22].
It has been proven that H. pylori are able to form a
biofilm on the surface of gastric mucosa [23–25]. The
formation of biofilm communities is known to be one
of the main strategies for the survival of bacteria in eco-
logical niches that are occupied by them [25]. Coticchia
et al. [26] found no biofilms in patients with a negative
biopsy urease test (BUT), while 97.3% of mucosa biop-
sies with positive BUT had an evident biofilm, that is,
its formation is apparently associated with a more
severe infectious process.
As follows, from the brief description of the causa-
tive agent, factors of its effect on macroorganism are
highly diverse, and thus, the pathogenetic targets,
which are as diverse, require the search for and devel-
opment of alternative, effective, and innocuous means
for the eradication of H. pylori.
The present report is a review of the latest literature,
dedicated to the effects exerted by extracts and sulfated
polysaccharides of marine algae, mainly fucoidans, on
the pathogenetic targets of H. pylori. In recent decades,
the anti-adhesive, anti-oxidative, antitoxic, immuno-
modulatory, anticoagulant, and anti-infection effects of
these compounds have drawn scientists’ attention in
many countries [27–30]. Thanks to their multipoint
influence on organism, these polysaccharides produce
numerous beneficial actions in organs and tissues at
various pathological processes.
© 2015 John Wiley & Sons Ltd, Helicobacter 20: 89–97
Besednova et al.
Receptors of Gastric Mucosa Cells are the
Main Target for Polysaccharides Derived
from Marine Algae
Adhesion is a process that all microorganisms need to
penetrate into a receptive organism. In most cases,
adhesion of the causative agent takes place when lec-
tins on the surface of microorganisms interact with the
carbohydrate determinants of host cells. The search for
anti-adhesive drugs is based on the creation of effective
barriers with diverse mechanisms of action, which
establish interactions between ligands and receptors.
The study of the molecular nature of ligand–receptor
complexes, formed during the interactions of microor-
ganisms with their corresponding target cells, as well as
the investigation into factors influencing the adhesion
process in vitro and ex vivo, enables researchers to
develop preventive measures aimed at the inhibition of
earlier phases of an infection process [9,31–33]. Appli-
cation of natural and synthetic analogues of cell recep-
tors and components of the tissue fluid may
substantially decrease and sometimes completely pre-
vent the attachment of microorganisms to host cells.
The triggering factor of the infection process, caused
by H. pylori, is adhesion of the causative agent to
mucoid cells of the gastric epithelium; it is determined
by the ability of this agent to attach to oligosaccharide
components of specific phospholipids on the mem-
branes of gastric cells. Other possible binding sites for
H. pylori are extracellular matrix components such as
laminin and fibronectin, as well as various types of
collagen.
Adhesins of H. pylori are associated with the mem-
brane that provides the agent an opportunity for closer
contact with host cells [34]. Moreover, adhesion is nec-
essary for microorganisms, as it enables mechanical
removal to be avoided and the creation of conditions
for invasion, persistence, and replication.
Anti-adhesive properties are typical for almost all
polysaccharides, including fucoidans, derived from both
terrestrial and marine objects. These compounds and
their synthetic molecular fragments inhibit contact
between pathogens from various taxonomic groups and
eukaryotic cells.
Various biologically active substances, and even
polysaccharides of berries (cranberry and cowberry),
green tea, etc., were studied in various years to find
protection against pathogens in vitro and ex vivo
[33,35]. Among polysaccharides of marine origin,
anti-adhesive biopolymers such as chitosan [36],
polysaccharides from marine bacteria of the genus
Pseudoalteromonas [37], and sulfated polysaccharides of
marine algae [38] are worth mentioning.
© 2015 John Wiley & Sons Ltd, Helicobacter 20: 89–97
Polysaccharides from Marine Algae
In the literature, the issue of the eradication of
H. pylori and minimization of the inflammation process
caused by this agent in the stomach, by means of sul-
fated polysaccharides from various algal species, has
been discussed frequently and for a long time, as these
compounds manifest the anti-adhesive effect and
decrease intensity of the inflammation process by inhib-
iting the production of pro-inflammatory cytokines pro-
duced by epithelial cells of the mucosa [39–41].
Thus, in ex vivo experiments using mice with gastri-
tis caused by H. pylori, the introduction of fucoidans
from brown algae Cladosiphon ocamuranus, F. evanescens,
and F. vesiculosus in drinking water resulted in the relief
of symptoms of this disease. Fucoidans significantly
suppressed the process of H. pylori adhesion to the gas-
tric mucosa [39]. Fucoidan from the brown alga C. oca-
muranus inhibited the attachment of H. pylori to the
gastric mucosa in pigs at both pH 2.0 and pH 4.0, while
the other two fucoidans used in these experiments
inhibited agent’s attachment only at pH 2.0. Nonsulfat-
ed (dextran and mannan) and also carboxylated poly-
saccharides did not possess the ability to suppress the
adhesion of H. pylori to mucin [39].
By their in vivo experiments over Mongolian ger-
bils, Shibata et al. [39] showed that all of the animals
infected intragastrally with H. pylori ATCC43504 devel-
oped evident edema and hemorrhages in the pyloric
portion of the stomach. Under the microscope, erosions
with infiltration by large quantities of neutrophils and
lymphocytes were observed. This was shown by the fact
that the weight of the stomachs infected with H. pylori
was twice as large as that in uninfected animals.
In cases where fucoidan had been applied 3 days
before inoculation, the symptoms of gastritis completely
vanished in six of 10 gerbils. When animals had drunk
water with 0.05% fucoidan, the number of gerbils with
gastric mucosal edema decreased to 40%, and hemor-
rhages with mucosal edema were registered only in half
of them. In 100% of the control group animals (which
had not been given fucoidan) infected with H. pylori,
mucosal edema, hemorrhages, and a pronounced infec-
tion process were observed. When fucoidan was added
to the drinking water at a concentration of 0.5%, colo-
nization of the gastric mucosa was registered in only
20% of animals.
The authors also infected gerbils with a large dose of
H. pylori to obtain a rapid and pronounced infection
process. The pronounced infection process developed in
80% of the animals which had received a dose of 106
cells of H. pylori per individual. To determine the effec-
tiveness of fucoidan from the alga C. ocamuranus under
these conditions, the polysaccharide was added to
the water for 3 weeks prior to inoculation. As a result,
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Polysaccharides from Marine Algae
fucoidan was found in the stomachs simultaneously
with H. pylori and preventing adhesion of the causative
agent. Application of fucoidan for 3 weeks after the
infection of gerbils yielded no results, as the agent
could have attached to the gastric mucin.
Other authors [40], when studying fucoidan from
the same algal species, C. ocamuranus, showed that the
causative agent specifically recognizes glycosphingoli-
pids, which are present on epithelial host cells. Fucoi-
dan, as a polymer with a sulfate group, inhibits the
adhesion of H. pylori to a carbohydrate chain. The
authors assume that fucoidan is fixed on the surface of
H. pylori bacteria; as a result, the agent loses the ability
to adhere to the mucosa, and symptoms of gastritis
recede. As it has been revealed that polysaccharide is
bound to the protein surface of the microorganism, the
authors note that medicines with anti-adhesive activity,
particularly fucoidans, should be introduced per os to
achieve the desired effect.
When the ability to prevent the adhesion of H. hepa-
ticus and H. pullorum to mouse macrophages of the
strain J774A.1 was studied among various sulfated
polysaccharides (heparin, heparansulfate and fucoidan),
fucoidan was proven to be the most effective substance,
as it reduced the growth of these microorganisms by
60–90%, as compared to heparin (30–60%) [41].
H. pylori served as the control in these experiments.
A direct correlative relationship between the hydropho-
bicity of the surface of bacteria and the degree of adhe-
sion has been found. With regard to the vaccine against
this infection, the authors suggest supplementing it
with compounds which prevent adhesion of the agent
to the mucosa, particularly fucoidan. The ability to
block the adhesion of H. pylori was also described for
polysaccharides of unicellular marine algae [42,43].
When discussing the issue of the anti-adhesive prop-
erties of algal polysaccharides, we cannot help mention-
ing the study by Loke et al. [9], which was conducted
in vitro and in vivo with polysaccharides from a micro-
alga Arthrospira. In the in vitro experiments, the
researchers used a commercial (“Sigma-Aldrich”,
Missouri, USA.) mucin from pig stomach and H. pylori,
adapted to the mouse organism. The feeding of mice
with the polysaccharide and a powder of alga during
4 weeks prior to inoculation resulted in a decrease in
bacterial load by 94 and 87%, respectively. The produc-
tion of urease also declined. The authors believe that
the polysaccharide prevents the binding of H. pylori to
mucin as well as being due to agglutination of microor-
ganisms by this polymer; this has also been proven
through experiments. The presumable adhesins were
attributed by the authors to a large family of proteins
in the outer membrane of bacteria. Superficial antigens
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Besednova et al.
AhpC and UreA play a major role in the binding of
H. pylori to mucin and colonization of the mucosa. The
authors find the carbohydrate components to be the
best candidates for anti-adhesins, as they are effective
and do not cause habituation, as seen for antibiotics.
The anti-ulcer effect of fucoidans (Sigma) from vari-
ous algal species has been established at the manifesta-
tion of peptic ulcer in rats, infected with H. pylori [44].
The rate of recovery constituted from 21.1 to 49.1% in
various experiments. The same authors confirmed the
anti-adhesive potential of polysaccharides. Similar
results were obtained by Sinurat and Marraskurante
[45], who studied the anti-adhesive and anti-ulcer
effects of fucoidan from the alga C. ocamuranus.
The anti-ulcer effect of fucoidan was recorded at
PUDs, caused by other factors [46]. The mechanism of
anti-ulcer action of an aqueous extract from the brown
alga P. minor and a sulfated polysaccharide derived
from this seaweed was studied by Amornlerdpison et al.
[47]. Earlier, researchers [48,49] reported this extract to
also possess hypotensive and anti-oxidative effects. The
authors found that the extract exerts regenerative
effects in the case of ulcers, which emerges as a result
of histamine impact. Histamine causes ulcers to form
under more active acid secretion, stimulated by the his-
tamine receptor H2. Antagonists of the receptor H2 sup-
press acid secretion in the stomach through
competition with histamine for the H2 receptor. At the
dose of 200 mg/kg, extract from the brown alga
P. minor led to 99% inhibition of ulcers, while the rate
of recovery after the application of cimetidine at a dose
of 100 mg/kg was only 93%. Like cimetidine, which is
a H2 antagonist, P. minor extract decreases the acidity of
the gastric juice and raises the pH value in an isolated
rat stomach, that is, the mechanism of action of the
algal extract is similar to that of cimetidine, and
the extract is actually an antagonist of the H2 receptor.
The authors believe that the unpurified polysaccharide,
the proportion of which in the extract is 18.6%, may
contribute to the anti-ulcer effect of the extract.
Amaro et al. [50] showed that the effectiveness of
the application of algal extracts at an infection with
H. pylori is determined by the presence of sulfated poly-
saccharides and carotenoids in them. The former com-
pounds block the agent adhesion, while carotenoids
exert a direct bactericidal effect on it.
Long synthesized fragments of fucoidan molecules,
which are potential inhibitors of microorganism adhe-
sion, have been recently obtained [51]. The first series of
compounds consisted of di-, tetra-, hexa-, octa-, dodeca-,
and hexadecasaccharides, comprised of (1?3)-linked
a-L-fucopyranose residuals, which corresponded to the
structure of polysaccharides isolated from the algae
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Besednova et al.
Saccharina latissima and Chorda filum. The second series of
components represented di-, tetra-, and hexasaccha-
rides, comprised of (1?3)- and (1?4)-linked a-L-fuco-
pyranose residuals, resembling the fucoidan fragments
from the brown algae Fucus evanescens, F. distihus, etc.
A clinical study has been conducted to ascertain the
effectiveness of fucoidan following Helicobacter infection
in humans [52]. The study lasted for 4 weeks under
the conditions of a randomized, double-blind, placebo-
controlled experiment. A total of 60 patients were
examined. The results showed that the number of indi-
viduals infected after the application of fucoidan
declined to a greater extent compared to the group that
consumed placebo. For this reason, the authors suggest
using the polysaccharide as an ingredient of products of
functional and dietetic nutrition for patients with
Helicobacter infection.
Thus, the inhibition of adhesion of H. pylori to gas-
tric mucin is the leading but not the only mechanism
behind the effect exerted by algal polysaccharide on the
infection process caused by this agent.
The Effect of Sulfated Polysaccharides on
the Biofilm, Formed by H. pylori on the
Gastric Mucosa
Biofilms of H. pylori are another target toward which
sulfated polysaccharides and algal extracts may be
aimed. The therapeutic effect on biofilms can be ori-
ented against the mechanism of primary adhesion of
bacteria to the surface (the process is described above),
blocking the synthesis or destruction of the polymer
matrix, and against disturbances in extracellular
exchanges of information. Moreover, it may be com-
bined with bactericidal agents (such as antibiotics). As
is already known, polysaccharides from algae can mani-
fest an antifilm effect [53]. The anti-adhesion and anti-
film properties of polysaccharides make them promising
compounds for the creation of new effective medicines.
The Direct Bactericidal Effect of Sulfated
Polysaccharides
Polysaccharides from natural sources, including fucoi-
dans, may have a direct bactericidal influence on vari-
ous microorganisms. Thus, the bactericidal action of
citrus pectin, which is a branched, high molecular
weight polysaccharide found in the cell walls of higher
plants, against H. pylori has been described in the litera-
ture [54]. The bactericidal effect of pectin was estab-
lished for 16 clinical and two reference strains of the
causative agent. The results of the experiments, con-
firming in vitro the bactericidal effect of fucoidan on
© 2015 John Wiley & Sons Ltd, Helicobacter 20: 89–97
Polysaccharides from Marine Algae
H. pylori, are provided in the description of the patent
[55]. The author highlighted the importance of further
searches for alternative methods of treatment of the
Helicobacter infection, including new antibacterial com-
pounds, which would serve a basis for standardized
pharmaceutical substances to be created in the future.
The Influence of Sulfated Polysaccharides
on Inflammatory Process in the Gastric
Mucosa
Inflammation of the gastric mucosa is an inevitable
result of the interaction between H. pylori and cells of
the gastric epithelium. Sulfated polysaccharides of algae
are able to exert an anti-inflammatory effect on the gas-
trointestinal tract at PUD, colitides, etc., by decreasing
the intensity of inflammatory response through the sup-
pression of synthesis of a number of inflammatory medi-
ators produced by epithelial cells of the intestine, the
excess of which is registered at Helicobacter infection
[45,56]. The anti-inflammatory property has been estab-
lished for almost all algae, their extracts, and most bio-
logically active substances derived from them [57–61].
The pleiotropic anti-inflammatory action of fucoidan
includes the inhibition of selectins [62], complement
[63], and enzymes, such as heparanase, elastase and
metalloprotease, participating in the destruction of tis-
sues during inflammation [64]. The anti-inflammatory
effects of fucoidan are determined by inhibition of the
key signaling pathways of NF-kB (the universal nuclear
transcription factor) activation [65].
Inhibitors of COX-2, iNOS, PGE2, IL-6, TNFa, and
IL-1b have been found in extracts of brown algae [66].
Sulfated polysaccharides from these aquatic organisms
also possess the ability to inhibit a high level of COX-2
and NO [67]. The inhibitory effect is followed by a
dose-dependent decline in the expression of iNOS and
COX-2 genes. The fraction obtained from a brown alga
inhibited the expression of COX-2 and iNOS genes and
decreased the levels of cytokines TNFa, IL-1b, and IL-6
in the macrophage culture RAW264.7. The expression
of genes encoding these interleukins also decreased.
Other authors [68] showed, through in vitro tests based
on a culture of mouse epithelial CMT-93 cells, that fu-
coidans from the algae C. ocamuranus and Kjelmaniella
crassifolia inhibited the increased production of IL-6. In
Balb/c mice with experimental colitis, which had con-
sumed fucoidan, the levels of IL-6, TGFb, and myelop-
eroxidase lowered, which was not observed in animals
from the control group.
Fucoidan from the alga Polyopes affinis suppressed
the formation of PGE2 and NO through inhibition of
the expression of corresponding genes in microglial
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BV2 cells, stimulated by LPS [69], and also inhibited
IFNa in glial cells [70,71].
Helicobacter pylori activates the complement system,
thus causing complement-related inflammation [13].
For this reason, fucoidans, manifesting the effect of
inhibition of the alternative and classical ways of com-
plement activation [63], can also be applied to ease
inflammation in the stomach wall.
Thus, as the contribution of inflammatory process
into pathogenesis of the Helicobacter infection is signifi-
cant, sulfated polysaccharides with an anti-inflammatory
effect may find a use in the therapy of this disease.
The Antitoxic Potential of Sulfated
Polysaccharides and the Probability of its
Manifestation During Helicobacter
Infection
The capability of the adhesion and invasion of a causa-
tive agent in the host organism is not always sufficient
for the infection process to develop. In many cases,
microorganisms use such pathogenicity factors as tox-
ins. H. pylori can influence organisms with potent toxic
substances. These are cytotoxin A (Vac A), causing vac-
uolization of epithelial cells by forming pores in the
cytoplasmic membrane, as well as CagA, LPS, heat
shock proteins, and hemolysin. We could not find data
on the antitoxic effect of sulfated polysaccharides at
Helicobacter infection in the literature. However, this
property of marine compounds may contribute to pro-
tection against infection, as fucoidans from brown algae
of various species have been shown to possess a high
antitoxic potential [28].
Oxidative Stress Following Helicobacter
Infection and the Possibility for Sulfated
Polysaccharide to Influence It
Helicobacter pylori is known to induce local oxidative
stress [72]. Activation of lipid peroxidation in the epi-
thelial layer results in the release of a broad spectrum
of free-radical genotoxic and carcinogenic compounds,
including superoxide anion (O2 ), nitric oxide (NO),
hydroxyl radicals, peroxinitrite, and nitrosonium ions.
Free radicals of NO may have a direct damaging effect
on the DNA structure of epitheliocytes [73]. Hence,
oxidative stress, provoked by H. pylori, poses a serious
threat in the form of genetic mutations and the initia-
tion of carcinogenesis in the early stages of chronic
gastritis.
As numerous studies have showed, extracts and sul-
fated polysaccharides of algae are potent anti-oxidants
[74,75], capable of preventing the development of
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Besednova et al.
oxidative stress in living organisms [43,76], and thus,
they can serve a basis for creating medicines with anti-
oxidative effects.
The materials above indicate that sulfated poly-
saccharides can be applied as anti-oxidants at the
Helicobacter infection.
Immunomodulatory Effects of Fucoidans
and Prospects for the Use of These
Compounds to Correct Disturbances of
Helicobacter Infection
The immunomodulatory effect of fucoidans is com-
monly known [27–29,61,77,78]. The negative influ-
ences exerted by H. pylori on inborn and acquired
immunity have been discussed above [56,79,80]. Poly-
saccharides from marine algae, while possessing a broad
spectrum of biological activities, are also antagonists of
functions of both inborn and acquired immunity; this
finding enables researchers to recommend them as cor-
rectors of disturbances caused by humoral and cellular
factors of the organisms defense against the H. pylori
infection.
As they are different in structure, fucoidans from
brown algae specifically interact with TLRs in vitro and
are ligands for TLR2, TLR4/TLR6, causing the activation
of NF-kB via the MyD88 signaling pathway or via the
adapter pair TRIF/TRAM [81]. Fucoidans from brown
algae, manifesting the pronounced immunotropic activ-
ity in an ex vivo system, are capable of inducing geneti-
cally determined biochemical processes, which initiate
the activation of genes responsible for cytokine synthe-
sis, and promoting defense against pathogens of various
taxonomic groups.
Sulfated polysaccharides of marine algae are induc-
ers of dendritic cell maturation with their activity being
at least as high as that of the classic inducer, TNFa
[78]. These compounds enhance the functional activity
of neutrophils, macrophages, and NK cells [27], and
also increase the level of humoral and cellular immune
response. Sulfated polysaccharides act at the membrane
level by modulating the activity of key signal transduc-
tion systems; also, they alter early phases of activation
of immune competent cells, which determine the fol-
lowing phases of the development of cell functional
responses. We could not find any reports on how sul-
fated polysaccharides influence immune systems during
H. pylori infection, although information on the effec-
tiveness of immunomodulators of other origins (deri-
nat, immunal, ribomunyl, and lycopid) is available
[82,83]. Nevertheless, convincing materials, characteriz-
ing these compounds as antagonists of inborn and
acquired immunity functions, as well as numerous
© 2015 John Wiley & Sons Ltd, Helicobacter 20: 89–97
Besednova et al.
reports on their anti-infection potential, enable us to
assume that the introduction of extracts or polysaccha-
rides from brown algae in the treatment of Helicobacter
infection would reduce the disturbances caused by the
immune system.
Conclusion
Overcoming the drug resistance of H. pylori is an
extremely important issue in the healthcare service, as
eradication of the causative agent becomes impossible
in 15–20% of cases. The fact that most of the success-
fully treated patients are re-infected by H. pylori within
the following 3–5 years should also be taken into
account. The consequences of a long-term infection of
this organism have been discussed above. For this rea-
son, searching for new ways to fight this disease is an
urgent problem.
The present materials indicate that studies related
to the use of polysaccharides from marine algae for
treating the Helicobacter infection are promising, as
these compounds are characterized by multimodal
action and possess anti-adhesive, antitoxic, immuno-
modulatory, anti-oxidative, and anti-inflammatory
properties. Algae-derived polysaccharides also exert a
direct bactericidal effect and are able to destroy bio-
films formed by microorganisms. The materials that
are currently available in the literature are mostly
experimental ones, considering effectiveness of alga-
derived polysaccharides at infections caused by
H. pylori. There are no official medicines based on
these compounds, because obtaining specimens with a
standard structure remains a challenge, even to date.
In foreign countries, extracts and polysaccharides from
seaweeds are actively used. Most authors recommend
the introduction of alga-derived sulfated polysaccha-
rides into functional nutrition products for patients
with Helicobacter infection.
Polysaccharides, including sulfated ones, have a
number of advantages: the availability of raw materials,
the lower complexity of technological processes of isola-
tion and purification, the pronounced pharmacological
activity, and, as a rule, the lower toxicity are the main
ones. Sulfated polysaccharides from brown algae fucoi-
dans can be referred to as a generation of new drugs
with associated activity, showing sufficient promise
when introduced in therapeutic schemes for the eradi-
cation of Helicobacter infection.
Acknowledgements and Disclosures
Competing interests: The authors have no competing
interests.
© 2015 John Wiley & Sons Ltd, Helicobacter 20: 89–97
Polysaccharides from Marine Algae
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