Therapeutic importance of sulfated polysaccharides from seaweeds: updating
the recent findings
Seema Patelcorresponding author
Abstract
Seaweeds, being prolific sources of bioactive components have garnered unprecedented
interest in recent times. The complex polysaccharides from the brown, red and
green seaweeds possess broad spectrum therapeutic properties. Especially, the
sulfated polysaccharides, viz. fucans, carrageenans and ulvans have exhibited
strong antioxidant, antitumor, immunostimulatory, anti-inflammatory, pulmonary
fibrosis anticoagulant/antithrombotic, lipid lowering, antiviral, antibacterial,
antiprotozoan, hyperplasia prevention, gastrointestinal, regenerative and nano
medicine applications. Considering the immense biomedical prospects of sulfated
polysaccharides, the profound and emerging functional properties published in
recent times will be discussed here with experimental evidences. The limitations
of the seaweed-derived sulfated polysaccharides in healthcare will be summarized.
Strategies to maximize extraction and bioavailability will be pondered.
Introduction
In recent years, much attention has been focused on polysaccharides isolated
from natural sources. During the last decade, numerous bioactive polysaccharides
with interesting functional properties have been discovered from seaweeds (Fig.
1). Several algal species belonging to phaeophyta, rhodophyta and chlorophyta
divisions have been recognized as crucial sources of sulfated polysaccharides
(SP). These SP constitute an important ingredient of cell walls and get harvested
by suitable extraction or precipitation method, followed by purification, characterization
and biological studies (Fig. 2). The biological features of the SP reported
till now are antioxidant, antitumor, immunomodulatory, inflammation, anticoagulant,
antiviral, antiprotozoan, antibacterial, antilipemic. Currently, the regenerative
medicine and tissue engineering application of the SP has become a hot research
area. Jiménez-Escrig et al. (2011) have reviewed the vital role of SP from seaweeds
in human health.
Bioactive SP extracted from seaweeds can be classified into three
types. The major fucan yielding brown seaweeds genera are Fucus, Sargassum,
Laminaria, Undaria, Lessonia, Dictyota, Dictyopteris,Ascophyllum, Eclonia, Canistrocarpus,
Lobophota, Turbinaria, Padina, Adenocystis, Sphacelaria, Cystoseira, etc. Fucan
represents a family of water soluble, SP rich in sulfated l-fucose, extracted
from extracellular matrix of these weeds (Li et al. 2008; Costa et al. 2011a).
Fucoidan, the sulfated alpha-l-fucan (term often interchangeably used with fucans)
has demonstrated a wide range of pharmacological activities. Carrageenans are
a family of linear SP, extracted from red seaweeds, viz. Gracialaria, Gigartina,
Gelidium, Lomentaria, Corallina, Champia, Solieria, Gyrodinium, Nemalion,Sphaerococcus,
Boergeseniella, Sebdenia, Scinaia, etc. This group of polysaccharides has a
backbone of alternating 3-linked β-d-galactose and 4-linked α-d-galactose residues
(Tuvikene et al. 2006). Three categories of carrageenans, kappa (κ), iota (ι),
and lambda (λ) have been identified till now based on their sulfation degree,
solubility and gelling properties (Leibbrandt et al. 2010). Ulvan is the major
water soluble, sulfated polysaccharide, extracted from the cell wall of green
algae, viz.Ulva, Enteromorpha, Monostroma, Caulerpa, Codium, Gayralia. Ulvans
are composed of disaccharide repetition moieties made up of sulfated rhamnose
linked to either glucuronic acid, iduronic acid, or xylose and represent about
8–29 % of the algal dry weight (Lahaye and Robic 2007). The above-described
SP have been illustrated in Fig. 3.
The therapeutic mechanisms of these SP vary, hence it is yet to be studied precisely.
For anticoagulation potency, the formation of the SP/protease protein complex
and the associated non-specific polar interaction between the negatively and
positively charged groups in the polysaccharide and protein is responsible for
anticoagulant activity. The anticoagulant activity is mainly attributed to thrombin
inhibition mediated by heparin cofactor II, with different effectiveness depending
on the compound. Similarly, selectin blockade, inhibition of enzyme and complement
cascade seem to be the triggers leading to anti-inflammation. Combating viral
infection has been shown by adsorption and internalization steps (Kim et al.
2011, 2012).
Ion exchange, gel filtration, FTIR, NMR analyses are employed to elucidate the composition and structure of SP. Cutting edge technologies, viz. MTT assay, flow cytometry, western blot analysis, BCA protein assay, SDS-PAGE and gelatin zymography has been employed for analysis of their functional properties (Jiang and Guan 2009). Although the use of the seaweed-derived polysaccharides in food industry as thickening, gelling agents, and stable excipients for control release tablets are well established, the clinical use is still to gain ground. Manifold increase in the published findings on this aspect in recent time is evidence enough for the craze over this highly promising domain. Recently, Senni et al. (2011) have reviewed the advancement in therapeutic potential of marine polysaccharides. However, this report was not confined to seaweeds and dealt only with the tissue engineering applications. Also, Wijesekara et al. (2011) have published an overview of clinically crucial SP extracted from marine algae. Keeping with the hot trend and in an attempt to present a new perspective, the present review summarizes the up-to-date literature data and discusses the pharmaceutical potential of different SP extracted from brown, red and green seaweeds.
Researchers across the globe are waking up to the discovery that seaweed-derived bioactive products are a storehouse of healthy attributes. Recent times have seen a surge in interest to tap these unexploited marine sources to develop novel therapeutics. The SP of algal origin have exhibited miraculous biological properties. The common seaweeds, their SP and observed bioactivity spectra have been presented in Table 1.
Table 1
The studied seaweeds, their bioactive sulfated polysaccharides and therapeutic
properties
Biological properties Seaweed Sulfated polysaccharide References
Antioxidant
Gracilaria birdiae (red) Fucoidan Souza et al. (2012)
Fucus vesiculosus (brown) Galactan Veena et al. (2007)
Gigartina skottsbergii (red) Carrageenan Barahona et al. (2011)
Schizymenia binderi (red) Rhamnan Magalhaes et al. (2011)
Lessonia vadosa (brown) Costa et al. (2011a, b)
Dictyopteris delicatula (brown) Wang et al. (2008)
Sargassum filipendula (brown) Devaki et al. (2009)
Laminaria japonica (brown) Camara et al. (2011)
Ulva lactuca (green) Hu et al. (2010)
Canistrocarpus cervicornis (brown) Yang et al. (2011)
Undaria pinnitafida (brown) Costa et al. (2010)
Corallina officinalis (red)
Corallinasertularioide (red)
Dictyotacervicornis (brown)
Sargassumfilipendula (brown)
Dictyopterisdelicatula (brown)
Antitumor
Saccharina japonica (brown) Galactofucan Vishchuk et al. (2011)
Undaria pinnatifida (brown) Mannoglucuronofucan Costa et al. (2010)
Sargassumfilipendula (brown) Charles et al. (2007)
Dictyopterisdelicatula (brown) Ye et al. (2008)
Caulerpaprolifera (green) Croci et al. (2011)
Dictyotamenstrualis (brown) Ermakova et al. (2011)
Monostroma nitidum (green) Costa et al. (2011a, b)
Sargassum pallidum (brown) Magalhaes et al. (2011)
Laminaria saccharina (brown) Jin et al. (2010)
Ecklonia cava (brown) Lins et al. (2009)
Sargassum hornery (brown) Foley et al. (2011)
Costaria costata (brown) Haneji et al. (2005)
Sargassum filipendula (brown)
Dictyopteris delicatula (brown)
Champia feldmannii (red)
Ascophyllum nodosum (brown)
Cladosiphon okamuranus Tokida
Immunostimulatory
Enteromorpha prolifera (green) Fucoidan Kim et al. (2011, 2012)
Champia feldmannii (red) κ-carrageenan Lins et al. (2009)
Fucus vesiculosus (brown) Oligosaccharides Kawashima et al. (2011)
Kappaphycus striatum (red) Kima and Joo (2008)
Antiinflammation and antinociceptive Solieria filiformis (red) Galactan de Araújo
et al. (2011)
Gelidium crinale (red) Mannoglucuronofucans Farias et al. (2011)
Sargassum hemiphyllum (brown) κ-carrageenan de Sousa et al. (2011a)
Gracilaria cornea (red) Oligosaccharides Hwang et al. (2011)
Gracilaria birdiae (red) Coura et al. (2011)
Laminaria saccharina (brown) Croci et al. (2011)
Lobophora variegate (brown) Medeiros et al. (2008)
Turbinaria ornata (brown) Ananthi et al. (2009)
Padina gymnospora (brown) Marques et al. (2012)
Jiang and Guan (2009)
Anticoagulation and antithrombosis
Ecklonia cava (brown) Arabinogalactans Wijesinghe et al. (2011)
Dictyota cervicornis (brown) Rhamnan Costa et al. (2010)
Caulerpa cupresoides (green) Galactan Ciancia et al. (2007)
Codium fragile (green) Li et al. (2011)
Codium vermilara (green) Mao et al. (2008)
Monostroma latissimum (green) Camara et al. (2011)
Monostroma nitidum (green) Albuquerque et al. (2004)
Canistrocarpus cervicornis (brown) Pushpamali et al. (2008)
Dictyota menstrualis (brown) Croci et al. (2011)
Lomentaria catenata (red)
Laminaria saccharina (brown)
Lipid lowering Ulva lactuca (green) Fucoidan Kim et al. (2010)
Sargassum polycystum (brown) Sathivel et al. (2008)
Sargassum wightii (brown) Raghavendran et al. (2005)
Laminaria japonica (brown) Huang et al. (2010)
Antiviral (Influenza, herpes, HIV)
Gyrodinium impudium (red) Galactan Ghosh et al. (2009)
Nemalion helminthoides (red) Mannans Kim et al. (2011, 2012)
Gayralia oxysperma (green) Heterorhamnan Recalde et al. (2009)
Sphaerococcus coronopifolius (red) Xylomannan sulfate Cassolato et al. (2008)
Boergeseniella thuyoides (red) Xylogalactofucan Bouhlal et al. (2011)
Sebdenia polydactyla (red) Xylomannan Bandyopadhyay et al. (2011)
Sphacelaria indica (brown) Mandal et al. (2007)
Cystoseira indica (brown)
Grateloupia indica (red) Chattopadhyay et al. (2007)
Laminaria angustata (brown) Trinchero et al. (2009)
Adenocystis utricularis (brown) Mandal et al. (2008)
Scinaia hatei (red)
Antibacterial (ampicillin resistant E. coli) Antiprotozoan
(cryptosporidiosis, malaria)
Kappaphycus alvarezii (red) Fucoidan Kumaran et al. (2010)
Padina boergessenii (brown) Maruyama et al. (2007)
Undaria pinnatifida (brown) Chen et al. (2009)
Prevent hyperplasia Brown seaweeds Fucoidan Hlawaty et al. (2011)
Freguin-Bouilland et al. (2007)
Cause gastrointestinal contraction Halymenia floresia (red) Galactan Graça et
al. (2011)
Cladosiphon okamuranus Tokida (brown) Fucoidan Matsumoto et al. (2004)
Regenerative and nano medicine Brown seaweeds Fucoidan Sezer et al. (2008)
Ulva rigida (green) Ulvan Murakami et al. (2010)
Nakamura et al. (2008)
Fukuta and Nakamura (2008)
Toskas et al. 2011)
Antioxidant
Souza et al. (2012) isolated a SP by aqueous extraction from the red seaweed
Gracilaria birdiae and observed that the slimy substance exhibits moderate antioxidant
properties as measured by DPPH free-radical scavenging effect. Veena et al.
(2007) evaluated the efficacy of fucoidan from edible seaweed Fucus vesiculosus
in Wistar rats (5 mg/kg body wt.). Advocation of the SP enhanced the antioxidant
status, thereby preventing membrane injury and averting stone formation. Barahona
et al. (2011) evaluated the antioxidant capacity of sulfated galactans from
red seaweed Gigartina skottsbergii and Schizymenia binderi, commercial carrageenans,
and fucoidan from brown seaweed Lessonia vadosa by the oxygen radical absorbance
capacity (ORAC) method. Fucoidan from L. vadosa and the sulfated galactan from
S. binderi exhibited the highest antioxidant capacity. The antioxidant capacity
was also evaluated by ABTS and hydroxyl radical scavenging assays. Corallinasertularioide,
Dictyotacervicornis, Sargassumfilipendula and Dictyopterisdelicatula were studied
and found to have SP having immense antioxidant potential in the form of total
antioxidant, reducing power and ferrous ion chelating activities (Costa et al.
2010). Two SP fractions rich in galactose and xylose from Corallina officinalis
demonstrated considerable antioxidant properties (Yang et al. 2011). Hu et al.
(2010) isolated two sulfated rhamnose-rich polysaccharide fractions from Undaria
pinnatifida and evaluated their antioxidant abilities in vitro. It was revealed
that the SP possessed strong antioxidant properties. Ye et al. (2008) evaluated
the antioxidant activities of SP from Sargassum pallidum by DPPH (2,2-diphenyl-1-picrylhydrazyl)-free-radical
scavenging assay and reported activity, though low at the tested concentration.
Camara et al. (2011) extracted heterofucans from Canistrocarpus cervicornis
by proteolytic digestion followed by sequential acetone precipitation. The SP
exhibited total antioxidant capacity, low hydroxyl radical scavenging activity,
good superoxide radical scavenging efficiency and excellent ferrous chelating
ability. Devaki et al. (2009) studied the liver mitochondrial and microsomal
fraction from rats to evaluate the antioxidative effect of oral gavaging with
Ulva lactuca polysaccharide extract (200 mg/kg body weight, daily for 21 days).
Electron microscopy of rat liver tissue intoxicated with d-galactosamine revealed
the swelling and loss of mitochondrial cristae. However, the rats pre-treated
with the SP overcame the d-galactosamine challenge without significant abnormality
of TCA, microsomal enzymes and mitochondria structural aberrations. These results
suggested that the SP play crucial role in stabilizing the functional status
of mitochondrial and microsomal membrane by prevention of the oxidative stress
induced by d-galactosamine. Fucoidan was extracted from Laminaria japonica through
anion-exchange column chromatography and their antioxidant activities were investigated.
Superoxide and hydroxyl radical scavenging activity, chelating ability and reducing
power analysis showed that all fractions possessed considerable antioxidant
activity (Wang et al. 2008). Gao et al. (2011) investigated the effects of fucoidan
on improving learning and memory impairment in rats induced by infusion of beta-amyloid
peptide, Aβ (1–40) and its possible mechanisms. The results indicated that fucoidan
could ameliorate Aβ-induced cognitive disorders in neural maladies like Alzheimer’s.
The mechanisms appeared to regulate the cholinergic system (increasing the activity
of choline acetyl transferase), reduce the oxidative stress (reduced malondialdehyde
content in hippocampal tissue of brain) and inhibit the cell apoptosis (increase
of Bcl-2/Bax ratio and a decrease of caspase-3 activity). Hong et al. (2011)
investigated the protective effect of fucoidan on dimethylnitrosamine-induced
liver fibrogenesis in rats. When administered (100 mg/kg, 3 times per week),
fucoidan improved liver fibrosis by inhibiting the expression of transforming
growth factor beta 1 [TGF-β (1)]/Smad3 and the tissue inhibitor of metalloproteinase
1 (TIMP-1), and increasing the expression of metalloproteinase-9 (MMP-9). Fucoidan
also significantly decreased the accumulation of the extracellular matrix and
collagen, confirming its anti-fibrotic effect. Costa et al. (2011b) obtained
five sulfated heterofucans from S. filipendula by proteolytic digestion followed
by sequential acetone precipitation, which displayed considerable antioxidant
potential. Magalhaes et al. (2011) obtained six families of SP from seaweed
D. delicatula employing above-mentioned protocols, followed by molecular sieving
on Sephadex G-100. Some fractions of the heterofucans showed high ferrous ion
chelating activity and some fractions showed reasonable reducing power, about
53.2 % of the activity of vitamin C. These results clearly indicate the beneficial
effects of SP from seaweeds in antioxidant status of consumers.
Antitumor
Vishchuk et al. (2011) isolated fucoidans from brown seaweeds Saccharina japonica
and U. pinnatifida and tested their antitumor activity against human breast
cancer T-47D and melanoma SK-MEL-28 cell lines. The highly branched partially
acetylated sulfated galactofucan, built up of (1 → 3)-α-l-fucose residues from
S. japonica and U. pinnatifida distinctly inhibited proliferation and colony
formation in both breast cancer and melanoma cell lines in a dose-dependent
manner. These results indicated that the fucoidan from the studied seaweeds
may be a potential approach toward cancer treatment. After 72-h incubation of
HeLa cell with SP (0.01–2 mg/ml), the proliferation was inhibited between 33.0
and 67.5 % by S. filipendula; 31.4 and 65.7 % by D.delicatula; 36.3 and 58.4
% by Caulerpaprolifera, and 40.2 and 61.0 % by Dictyotamenstrualis. Costa et
al. (2010) inferred that the antiproliferative efficacy of SP positively correlated
with the sulfate content. In Sprague–Dawley rats fed with Monostroma nitidum
diet, significant increase in UGT1A1 and UGT1A6 mRNA levels was found, indicating
potential application in chemoprevention medicine (Charles et al. 2007). Ye
et al. (2008) evaluated the antitumor activities of SP from S. pallidum by MTT
[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, which
showed a significantly high antitumor activity against the human hepatocellular
carcinoma (HepG2), human lung adenocarcinoma epithelial (A549) and human gastric
carcinoma (MGC-803) cells. Croci et al. (2011) explored the possible antitumor
activities of SP from the brown seaweed Laminaria saccharina. The incorporation
of the parent SP and the sulfated fucans into Matrigel plugs containing melanoma
cells induced a significant reduction in hemoglobin content as well as the frequency
of tumor-associated blood vessels. Also, these two SP administrations resulted
in a significant reduction of tumor growth when inoculated into mice. The sulfated
fucan fraction markedly inhibited breast cancer cell adhesion to human platelet-coated
surfaces. Ermakova et al. (2011) showed that fucoidans from brown algae Eclonia
cava, Sargassum hornery and Costaria costata play an inhibitory role in colony
formation in human melanoma and colon cancer cells. Costa et al. (2011b) observed
antiproliferative activity of fucan from S. filipendula against HeLa cells by
MTT test. The heterofucan was extracted from the brown seaweed by proteolytic
digestion followed by sequential acetone precipitation. This SP showed antiproliferative
activity on Hela cells and induced apoptosis by mitochondrial release of apoptosis-inducing
factor (AIF) into cytosol. In addition, it decreased the expression of anti-apoptotic
protein Bcl-2 and increased expression of apoptogenic protein Bax. Magalhaes
et al. (2011) obtained six families of SP from seaweed D. delicatula by proteolytic
digestion, followed by acetone fractionation and molecular sieving on Sephadex
G-100. A fraction of the heterofucan showed high antiproliferative activity
inhibiting almost 100 % of HeLa cell proliferation. Jin et al. (2010) investigated
the effects of fucoidan on the apoptosis of human promyeloid leukemic cells
and fucoidan-mediated signaling pathways. Fucoidan induced apoptosis of human
promyelocytic leukemia (HL-60), human promyelocytic (NB4) and THP-1 (human acute
monocytic leukemia) cell line. Fucoidan treatment of HL-60 cells induced activation
of caspases 8, 9, and 3, the cleavage of Bid, and altered mitochondrial membrane
permeability. Buthionine-[R,S]-sulfoximine rendered HL-60 cells more sensitive
to fucoidan. It was concluded that the activation of MEKK1, MEK1, ERK1/2 and
JNK, depletion of glutathione and production of NO are important mediators in
fucoidan-induced apoptosis of human leukemic cells. Lins et al. (2009) investigated
the in vitro and in vivo antitumor properties of a SP isolated from the seaweed
C. feldmannii. The SP did not show any significant in vitro cytotoxicity at
the experimental dose, but showed in vivo antitumor effect. The inhibition rates
of sarcoma 180 tumor development were 48.62 and 48.16 % at the doses of 10 and
25 mg/kg, respectively. It also increased the response elicited by anti-cancer
drug, 5-fluorouracil (5-FU) from 48.66 to 68.32 %. Though liver and kidney were
moderately affected, the enzymatic activity of alanine aminotransferase or urea/creatinine
levels was not disturbed. Leucopenia associated with 5-fluorouracil treatment
was prevented when the chemotherapeutic was administered along with SP. An unfractionated
fucoidan was extracted from the brown alga Ascophyllum nodosum and its effect
on the apoptosis of human HCT116 colon carcinoma cells was studied and the signaling
pathways involved were investigated. Fucoidan decreased cell viability and induced
apoptosis of the carcinoma cells, through activation of caspases 9 and 3 and
the cleavage of PARP (Foley et al. 2011). Haneji et al. (2005) examined the
effect of fucoidan from the brown seaweed Cladosiphon okamuranus Tokida against
an incurable form of cancer, the adult T-cell leukemia (ATL). It was observed
that fucoidan inhibited the growth of peripheral blood mononuclear cells of
ATL patients and caused apoptosis of HTLV-1-infected T-cell lines through a
cascade of down regulations. In vivo treatment of the cancer transplanted in
mice also showed partial inhibition of the tumors. Now that, cancer has assumed
an epidemic proportion and the treatment scenario is still bleak, the SP from
the marine weeds hold the promise for novel anticancer formulae.
Immunostimulatory
Water-soluble SP extracted from Enteromorpha prolifera and fractionated using
ion-exchange chromatography was investigated to determine their in vitro and
in vivo immunomodulatory activities. Some fractions stimulated a macrophage
cell line Raw 264.7 inducing considerable nitric oxide (NO) and various cytokine
production via up-regulated mRNA expression. The in vivo experiment results
showed increase in IFN-γ and IL-2 secretions, suggesting that the SP is a strong
immunostimulator. It is implied that the SP can activate T cells by up-regulating
Th-1 response (Kim et al. 2011). Lins et al. (2009) demonstrated that SP extracted
from C. feldmannii is an immunomodulatory agent, evident from the increase in
the production of specific antibodies. Kawashima et al. (2011) demonstrated
that fucoidan enhances the probiotic effects of lactic acid bacteria on immune
functions. In vitro test results showed that fucoidan amplified interferon (IFN)-γ
production mediated by IL-12 production from Peyer’s patch and spleen cells
in response to a strain of LAB, Tetragenococcus halophilus KK221. In vivo study
showed that Th1/Th2 immunobalance was significantly improved by oral administration
of both fucoidan and KK221 to ovalbumin-immunized mice. Kima and Joo (2008)
observed that fucoidan from F. vesiculosus shows immunostimulating and maturing
effects on dendritic cells (DCs) via a pathway involving nuclear factor-κB (NF-κB).
κ-Carrageenan oligosaccharides from red algae Kappaphycus striatum have immunomodulation
effects on S180 tumor-bearing mice. The sulfated derivative (200 μg/g/day) showed
an increase in natural killer cells (NK cells) up to 76.1 %. It suggested that
chemical modification (especially sulfation) of carrageenan oligosaccharides
can enhance their antitumor effect and boost their antitumor immunity. Yuan
et al. (2011) reported not only the capacity of SP to elicit cellular immunity
but also the importance of chemical modification of the parent polysaccharide.
Anti-inflammation/antinociception/inhibition of pulmonary fibrosis
de Araújo et al. (2011) studied the antiinflammatory and antinociception (less
sensitivity to painful stimulus) properties of seaweed Solieria filiformis in
vivo. Male Swiss mice pre-treated with the SP, on receiving an injection of
0.8 % acetic acid, 1 % formalin or 30 min prior to a thermal stimulus, showed
significantly reduced number of writhes. It showed antinociceptive action through
a peripheral mechanism; however, did not show any significant anti-inflammatory
effect. The SP from the brown seaweed Spatoglossum schroederi was assayed for
the antinociceptive effect on Swiss mice. The SP purified by anion-exchange
chromatography inhibited both phases of the formalin test. In the first phase
the maximum 45 % reduction in paw licking was observed. This inhibitory effect
suggested a mixed mechanism similar to morphine, which was not confirmed in
the hot-plate test. It was concluded that the pronounced antinociceptive effect
of SP could be developed as a new source of analgesic drugs (Farias et al. 2011).
The SP galactan extracted from the red marine alga Gelidium crinale was purified
by ion-exchange chromatography and tested by intravenous route in rodent experimental
models of inflammation and nociception. The anti-inflammatory activity was evaluated
in the model of rat paw edema induced by different inflammatory stimuli. Antinociceptive
effect was assessed in models of nociception/hyperalgesia elicited by chemical
(formalin test), thermal (hot plate), and mechanical (von Frey) stimuli in mice.
It was observed that SP inhibited the time course of dextran-induced paw edema
and showed a maximal effect at 1 mg/kg (42 %). At the highest dose, the SP also
inhibited the paw edema induced by histamine (49 %) and phospholipase A(2) (44
%). The galactan inhibited both neurogenic and inflammatory phases of the formalin
test and the treatment was well tolerated by the test animals (de Sousa et al.
2011a). Hwang et al. (2011) explored SP from brown seaweed Sargassum hemiphyllum
for possible anti-inflammatory effect. The SP was administered against the mouse
macrophage cell line (RAW 264.7) activated by lipopolysaccharide (LPS). The
secretion profiles of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α,
and NO, were found significantly to be reduced in 1–5 mg/ml dose ranges of SP
treatments. RT-PCR analysis suggested that the SP inhibits the LPS-triggered
mRNA expressions of IL-β, iNOS and COX-2 in a dose-dependent manner. It was
concluded that the anti-inflammatory properties of SP may be attributed to the
down-regulation of NF-κB in nucleus. Coura et al. (2011) evaluated the effects
of SP from the red seaweed Gracilaria cornea in nociceptive and inflammatory
mice models. At all tested doses, the SP significantly reduced nociceptive responses,
as measured by the number of writhes. In a formalin test, the SP significantly
reduced licking time in both phases of the test at a dose of 27 mg/kg. In a
hot-plate test, the antinociceptive effect was observed only in animals treated
with 27 mg/kg of SP, suggesting that the analgesic effect occurs through a central
action mechanism at the highest dose. The lower doses of SP (3 and 9 mg/kg)
caused only a slight reduction in neutrophil migration in the rat peritoneal
cavity but significantly inhibited paw edema induced by carrageenan, especially
at 3 h after treatment. Reduction in edema was confirmed by myeloperoxidase
activity in the affected paw tissue. After 14 consecutive days of intraperitoneal
administration of the SP (9 mg/kg), the biochemical, hematological and histopathological
evaluations of the internal organs are performed and no systemic damage was
found. de Sousa et al. (2011b) investigated the involvement of the hemoxygenase-1
(HO-1) pathway in the anti-inflammatory action of a SP from the red seaweed
G. birdiae. The SP was administered at various concentrations to Wistar rats
and observed that at 10 mg/kg concentration, it exerted an anti-inflammatory
effect. A remarkable decrease in leukocytes in the peritoneal cavity was also
observed. The SP also reduced the paw edema induced by carrageenan and inhibited
the paw edema induced by dextran in the first half-hour. The O-sulfated mannoglucuronofucans
and sulfated fucan fractions from the brown seaweed L. saccharina were evaluated
for possible treatment of inflammation in vivo. Both types of SP exhibited inhibition
of leukocyte rush into the sites of inflammation in the murine models (Croci
et al. 2011). Medeiros et al. (2008) extracted a sulfated heterofucan from the
brown seaweed Lobophora variegata by proteolytic digestion, followed by acetone
fractionation, molecular sieving, and ion-exchange chromatography. The fucoidan
revealed that it inhibits leukocyte migration to the inflammation site. Ear
swelling caused by croton oil was also inhibited when sulfated polysaccharides
from F. vesiculosus and L. variegata were used. Ananthi et al. (2009) investigated
the anti-inflammatory effect of crude SP from brown alga Turbinaria ornata against
carrageenan-induced paw edema in rats and vascular permeability in mice. Oral
administration of SP reduced the paw edema and showed inhibitory effect on vascular
permeability considerably, in a dose-dependent manner. SP extracted from brown
algae Padina gymnospora showed efficacy in reducing leukocyte influx into the
peritoneal cavity in mice at 10 mg/kg body weight, causing a decrease of 60
%, without any cytotoxicity (Marques et al. 2012). Idiopathic pulmonary fibrosis
is a pathological condition characterized by accumulation of excess fibroblasts,
deposition of collagen and inflammation in lungs. The pro-fibrogenic cytokine
transforming growth factor-beta 1 (TGF-beta1) has attracted much attention for
its potential role in the etiology of this serious lung injury. MS80, a new
kind of sulfated oligosaccharide extracted from seaweed, inhibits TGF-beta1-induced
pulmonary fibrosis in vitro and bleomycin-induced pulmonary fibrosis in vivo.
The oligosaccharide competitively inhibited heparin/HS-TGF-beta1 interaction
through its high binding affinity for TGF-beta1, also arrested human embryo
pulmonary fibroblast (HEPF) cell proliferation and collagen deposition. MS80
proved to be a potent suppressor of bleomycin-induced rat pulmonary fibrosis
in vivo (Jiang and Guan 2009). Du et al. (2010) reported that efficacy of MS80
lies in targeting the CD40 signal pathway by blocking RIP2. The precise mechanism
of functionality is not clear; nevertheless, the sulfated polysaccharides studied
above promise therapeutic potential in inflammatory disorders.
Anticoagulation
Batteries of assays for assessment of anticoagulation properties of SP from
seaweeds have been conducted in recent times. Tests ranging from activated partial
thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), antithrombin
to anticoagulation factor Xa activities have been performed and compared with
heparin. Wijesinghe et al. (2011) purified a SP from brown seaweed Ecklonia
cava and investigated its anticoagulant activity in vitro and in vivo. It extended
the coagulation time in Wistar rats in a dose- and time-dependent manner. Costa
et al. (2010) evaluated in vitro anticoagulant activities of marine algae SP
by APTT test. D. cervicornis SP prolonged the coagulation time, only 1.4-fold
lesser than Clexane®, a low molecular weight commercial heparin. In the prothrombin
time (PT) test, which evaluates the extrinsic coagulation pathway, Caulerpa
cupresoides showed aggression. Codium fragile and Codium vermilara water-soluble
sulfated arabinogalactans prevented coagulation, but they induced platelet aggregation.
It was observed that anticoagulant activity was higher in SP samples with higher
sulfate content. In this regard, C. vermilara proved to be superior with a higher
degree of sulfation and arabinose content (Ciancia et al. 2007). The hot water
extract of green alga Monostroma latissimum gives a sulfated rhamnan polysaccharide
with an anticoagulant activity. The anticoagulant activity as evaluated by assays
of the APTT and thrombin time promises that it can be a potential source of
anticoagulant (Li et al. 2011). Mao et al. (2008) isolated two sulfated, rhamnose-containing
polysaccharides from marine green algae M. nitidum and evaluated their anticoagulant
activities. The results showed that both the SP possess high anticoagulant activities,
and were potent thrombin inhibitors mediated by heparin cofactor II. They also
hastened thrombin and coagulation factor Xa inhibition by potentiating antithrombin
III. Camara et al. (2011) extracted sulfated heterofucans from C. cervicornis
which prolonged APTT. Four sulfated polysaccharides doubled APTT with only 0.1
mg/ml of plasma, only 1.25-fold less than Clexane®. Albuquerque et al. (2004)
extracted heterofucans from the brown seaweed D. menstrualis by proteolytic
digestion, followed by sequential acetone precipitation. The anticoagulant activities
of these heterofucans were determined by APTT test. A fucan fraction (20 g/ml)
demonstrated significant anticoagulant activity, about 4.88-fold lesser than
Clexane® (4.1 g/ml). Pushpamali et al. (2008) isolated a highly sulfated (21.76
%), 100–500 kDa molecular weight galactan anticoagulant from microbial-fermented
freeze-dried red algae Lomentaria catenata. It demonstrated that the anticoagulant
compound showed better efficacy than heparin and prolonged activity toward APTT
and PT assays. Croci et al. (2011) studied that the SP from the brown seaweed
L. saccharina shows promising activity on thrombosis. Fernández et al. (2012)
studied the anticoagulation efficacy of sulfated β-d-mannan extracted from green
seaweed C. vermilara and reported that higher sulfate content leads to more
pronounced effect. Fucoidan has been proposed as a potential substitute of the
anticoagulant heparin, with added merits. Unlike mammalian mucosa-derived heparin,
fucoidan is extracted from plants, so less likely to contain infectious agents,
such as viruses or prions (Boisson-Vidal et al. 1995). The current findings
promise a host of possible candidates for natural anticoagulant preparation.
Lipid lowering
Fucoidan has been reported to affect the development of adipocytes. To elucidate
the role of fucoidan in adipogenesis, its inhibitory effect on adipocyte differentiation
via mitogen-activated protein kinase (MAPK) signaling pathway in 3T3-L1 preadipocytes
was studied. Fucoidan treatment inhibited the adipocyte differentiation, evidenced
by decreased lipid accumulation and down-regulation of adipocyte markers. Also,
it inhibited the expression of adipogenic transcription factors, α (C/EBPα),
γ (PPARγ) and AP2, crucial for adipocyte development (Kim et al. 2010). Sathivel
et al. (2008) evaluated the anti-peroxidative and anti-hyperlipidemic property
of U. lactuca polysaccharide extract against d-galactosamine (500 mg/kg body
weight)-induced anomaly in rat. d-Galactosamine-intoxicated rats showed significant
liver damage with acute aberration in serum lipid profile, hepatic protein thiols,
deposits of lipid droplets and abnormal appearance of mitochondria. Rats pretreated
with ulvan (30 mg/kg body weight/day/for 21 days) showed a significant inhibition
against abnormality induced by d-galactosamine. The effect of Sargassum polycystum
crude SP extract on lipid metabolism was examined against acetaminophen-induced
hyperlipidemia in experimental rats. The prior oral administration of S. polycystum
(200 mg/kg body wt./day for a period of 15 days) crude SP extract showed considerable
prevention in the severe disturbances of lipid profile and metabolizing enzymes
(serum lecithin cholesterol acyl transferase and hepatic triglyceride lipase)
triggered by acetaminophen. Liver histology also supported their protective
nature against fatty changes induced during acetaminophen intoxication (Raghavendran
et al. 2005). Josephine et al. (2007) studied the possible capacity of SP in
normalizing hyperlipidemia induced by the immunosuppressant drug cyclosporine
A (25 mg/kg body weight, orally for 21 days) in Wistar rat kidney. As a side
effect of the drug, lipid profile showed fluctuation resulting in nephrotoxicity
manifested by the enhanced urinary excretion of urea, uric acid and creatinine.
The SP-treated groups (5 mg/kg body weight, subcutaneously) showed a normalized
lipid profile and lipid metabolizing enzymes. Moreover, this group of rats showed
a normal concentration of urinary constituents. Huang et al. (2010) investigated
the effect of fucoidan from L. japonica on hyperlipidemic rats. The SP reduced
the concentration of serum total cholesterol, triglyceride and low-density lipoprotein
cholesterol and increased the concentration of high-density lipoprotein cholesterol
of the studied rats. The activities of lipoprotein lipase, hepatic lipoprotein
and lecithin cholesterol acyltransferase were also enhanced. Above findings
corroborate that the SP from seaweeds are ideal option for effective abatement
of the lipid abnormalities.
Antiviral
Many viruses display affinity for cell surface heparan sulfate proteoglycans
playing crucial role in virus entry. This raises the possibility of the application
of SP in antiviral therapy (Ghosh et al. 2009). Kim et al. (2012) purified a
SP, p-KG03, from the red marine microalga, Gyrodinium impudium. The galactan
conjugated to uronic acid and sulfated groups had showed inhibition of encephalomyocarditis
virus. The inhibitory activity of the SP against influenza virus was examined.
The results of a cytopathic effect reduction assay using MDCK cells demonstrated
that p-KG03 exhibited the 50 % effective concentration (EC50) values of 0.19–0.48
μg/ml against influenza type A virus infection. The antiviral activity of p-KG03
was deduced to be directly associated with its interaction with viral particles,
interfering with its adsorption and internalization into host cell. It was expected
to be a candidate for antiviral drug development. The soluble fractions of a
sulfated, (1 → 3)-linked α-d-mannans obtained by hot water extraction from Nemalion
helminthoides showed appreciable antiherpetic activity (Recalde et al. 2009).
A homogeneous branched sulfated heterorhamnan was obtained by aqueous extraction,
followed by ultrafiltration from the green seaweed Gayralia oxysperma which
exerted high specific activity against herpes simplex virus (HSV-1) (Cassolato
et al. 2008). Treatment of human immunodeficiency virus type 1 (HIV-1), the
dreaded etiological agent of AIDS poses tough challenges. The limitations encountered
in therapeutic strategy are toxicity, resistance and high costs. Water-soluble
sulfated galactans isolated from two red algae Sphaerococcus coronopifolius
(Gigartinales, Sphaerococcaceae) and Boergeseniella thuyoides (Ceramiales, Rhodomelaceae)
inhibited in vitro replication of the human immunodeficiency virus (HIV) at
12.5 μg/ml. In addition, the studied polysaccharides were capable of inhibiting
the in vitro replication of HSV-1 on Vero cells. The adsorption step of HSV-1
to the host cell seemed to be the specific target for the SP action. While for
HIV-1, these results suggest a direct inhibitory effect on HIV-1 replication
by controlling the appearance of the new generations of virus and potential
virucidal effect (Bouhlal et al. 2011). Ghosh et al. (2009) studied that xylomannan
sulfate and its sulfated derivatives purified from Sebdenia polydactyla showed
strong activity against HSV-1. The IC50 values were in the range 0.35–2.8 μg/ml
and they did not exert cytotoxicity at concentrations up to 1,000 μg/ml. Many
xylogalactofucan- and alginic acid-containing fractions from marine alga Sphacelaria
indica showed antiherpetic activity. The IC50 values of their chemically sulfated
derivatives against HSV-1 were in the range of 0.6–10 μg/ml and they lacked
cytotoxicity at concentrations up to 200 μg/ml (Bandyopadhyay et al. 2011).
Sulfated fucan-containing fractions isolated from the brown seaweed Cystoseira
indica showed potent antiviral activity against HSV-1 and 2 HSV-2 without cytotoxicity
for Vero cell cultures. Chemical, chromatographic and spectroscopic methods
showed that the anti-herpetic activity of the SP is by inhibition of the virus
adsorption (Mandal et al. 2007). Chattopadhyay et al. (2007) analyzed the SP
fractions isolated from crude water extract of Grateloupia indica and showed
their potent anti-HSV activity. The SP, xylogalactofucan fractions extracted
from Laminaria angustata, after addition of sulfate groups showed enhanced capability
to inhibit HSV-1. The IC50 values of these fractions against HSV-1 were in the
range of 0.2–25 μg/ml and they lacked cytotoxicity at concentrations up to 1,000
μg/ml (Saha et al. 2012). SP fractions from brown seaweed Adenocystis utricularis
were analyzed for their in vitro anti-HIV-1 activity. Two of the five studied
fractions showed potent anti-HIV-1 activity both against wild type and drug-resistant
HIV-1 strains, mediated by blockade of early events of viral replication (Trinchero
et al. 2009). The antiviral activity was dependent on the sulfate contents of
the polysaccharides. Kazłowski et al. (2012) conducted both in vitro and in
vivo studies on Japanese encephalitis virus prevention property of novel SP
from Gracilaria sp. and M. nitidum. During in vitro studies performed by MTT
or plaque assays, low-degree-polymerization SP showed a remarkably high positive
effect on survivability in JEV-infected C3H/HeN mice. The in vivo antiviral
activity was assumed to be a resultant of better absorption of low-DP SP than
undigested PS. The results support the feasibility of antiviral drug development
from various SP and their derivatives.
Antibacterial and antiprotozoan
Kumaran et al. (2010) studied that SP extracted from red alga Kappaphycus alvarezii
and brown alga Padina boergessenii exert promising inhibitory response against
antimicrobial-resistant Escherichia coli strains and, in particular, the inhibitory
response of ampicillin-resistant E. coli, isolated from local fish markets and
seafood processing plants. Maruyama et al. (2007) investigated the effects of
fucoidan isolated from the sporophyll of U. pinnatifida on the Cryptosporidium
parvum adhesion to the cultured human intestinal cells and its infection in
neonatal mice. The C. parvum adhesion to human intestinal 407 cells was significantly
suppressed by a low dose (1 mg/ml) of fucoidan (1 μg/ml). The results of the
in vivo experiments revealed that C. parvum oocysts in the fucoidan-treated
mice was reduced to nearly one-fifth of the oocysts number treated with phosphate
buffered saline. It was concluded that fucoidan might inhibit cryptosporidiosis
through the direct binding of fucoidan to the C. parvum-derived functional mediators
in the intestinal epithelial cells in neonatal mice. Chen et al. (2009) investigated
the inhibitory effects of fucoidan from the edible brown seaweed U. pinnatifida,
on the growth of Plasmodium parasites. The antimalarial activity of fucoidan
was assessed against the cultured Plasmodium falciparum parasites in vitro and
on Plasmodium berghei-infected mice in vivo. Fucoidan significantly inhibited
the invasion of erythrocytes by P. falciparum merozoites. Its 50 % inhibition
concentration was similar to those for the chloroquine-sensitive P. falciparum
3D7 strain and the chloroquine-resistant K1 strain. Four-day suppressive testing
in P. berghei-infected mice with fucoidan resulted in a 37 % suppressive effect
versus the control group and a delay in death associated with anemia.
Prevent hyperplasia
Hlawaty et al. (2011) investigated the therapeutic potential of low molecular
weight fucoidan on vascular smooth muscle cell and human vascular endothelial
cell proliferation and migration in vitro and in vivo. Sprague–Dawley rats with
induced thoracic aorta injury were treated with SP (5 mg/kg/day) for 14 days.
Results showed that SP prevented intimal hyperplasia in rat thoracic aorta.
In situ zymography showed that the activity of matrix metalloproteinase (MMP)-2
in the neo-intima is significantly reduced. Fucoidans have been shown to mobilize
bone marrow-derived progenitor cells via stimulation of stromal-derived factor
(SDF)-1 release. Mobilized progenitor cells have been suggested to repair intimal
lesions after immune-mediated endothelial injury and thus prevent intimal proliferation.
Freguin-Bouilland et al. (2007) evaluated the therapeutic effect of these SP,
in Brown Norway and Lewis rat aortic allograft model of transplant arteriosclerosis.
The recipient rats were treated with SP (5 mg/kg/day) for 30 days. In contrast
to untreated aortic allografts, the SP-treated allografts showed significantly
less intimal proliferation. The SP treatment stimulated allograft reendothelialization,
as evidenced by strong intimal endothelial nitric oxide synthase antibody and
CD31 signals.
Gastrointestinal functions
Graça et al. (2011) showed that a sulfated galactan isolated from red algae
Halymenia floresia has promising effects on gastrointestinal (GI) motor functions
mediated by voltage-gated Ca2+ channels. So, it is suggested that the SP can
be useful when gastrointestinal contraction is necessary during motility-related
disorders. Inflammatory bowel disease caused by enteric pathogens is a severe
form of gastric disease characterized by excess production of proinflammatory
cytokine IL-6. Fucoidan derived from brown algae C. okamuranus Tokida imparts
LPS tolerance and prevents the expression of IL-6 mRNA as evidenced by in vitro
and in vivo tests (Matsumoto et al. 2004).
In regenerative and nano medicine
Sezer et al. (2008) prepared a fucoidan–chitosan hydrogel by swelling the polymers
in acidic solution and investigated its dermal burn treatment efficiency. Dermal
burns were inflicted on male New Zealand white rabbits and the prepared hydrogel
was applied on the wounds. Histopathological evaluation of the biopsy samples
was done at intervals. No edema was seen in tested groups after 3-day treatment
and fibroplasia and scar were fixed after 7-day treatment. The best regeneration
on dermal papillary formation and the fastest closure of the wounds were observed
in fucoidan–chitosan hydrogels after 14-day treatment. Murakami et al. (2010)
developed a hydrogel sheet by blending alginate, chitosan and fucoidan, for
rapid wound healing. The hydrogel absorbed Dulbecco’s minimal essential medium
(DMEM) and fluid absorption became constant within 18 h. On application, this
hydrogel is expected to act as tissue adhesive and heal the wound in a moist
milieu. Histological examination showed the advanced granulation tissue and
capillary formation in the healing-impaired wounds treated with the hydrogel
on day 7. Nakamura et al. (2008) reported that a chitosan/fucoidan complex-hydrogel
enhanced the half life of fibroblast growth factor (FGF-2) by shielding it against
denaturants as heat and proteolysis. Subcutaneous injection of the FGF-2-containing
complex-hydrogel into the back of mice showed controlled release of bioactive
protein. Slow diffusion of the growth factor induced neovascularization and
fibrous tissue formation near the site of injection after 1 week. The complex-hydrogel
was biodegraded after 4 weeks after supplying adequate amount of the angiogenic
agents for protection of the ischemic heart. Fukuta and Nakamura (2008) reported
that fucoidan and its oligosaccharides have the ability to stimulate production
of hepatocyte growth factor (HGF) by induction during translation. So, it is
believed that fucoidan may protect tissues and organs by mechanisms involving
HGF.
Toskas et al. (2011) evaluated the nanofiber ability of an ulvan-rich extract from the alga Ulva rigida. Ulvan-based uniform, crystalline nanofibers of diameter 84 nm were produced by blending them with poly(vinyl alcohol) (PVA). The interesting biological and physicochemical properties of the nanofibers can lead to new biomedical applications such as drug release systems. Taken together, these findings indicate that the SP can revolutionize regenerative and nanomedicine, if exploited properly.
Go to:
Bottlenecks encountered
Extraction yield differs with respect to species, period and season of seaweed
harvest (Robic et al. 2009). The SP are extracted from the seaweed biomass by
many methods which influence their amount and chemical composition. The fucans
of brown algae are highly complex and heterogeneous in structure, rendering
their study difficult. Fonseca et al. (2008) compared the galactans from two
species of red algae having same structure and size but slight variation in
sulfation. Due to the variation in sulfate content, the two SP differed in their
anticoagulant and venous antithrombotic activities. From the results it was
concluded that slight differences in the proportions of sulfated residues in
the galactan chain may be critical for the interaction between proteases, inhibitors
and activators of the coagulation system. Also, the variations pose challenges
in developing therapeutics. Furthermore, the high molecular weights of SPs pose
issue in bio-availability (Jiao et al. 2011).
Go to:
Structure–function correlation of SP
It is important to understand the biochemical and molecular mechanism of therapeutic
actions of SP, in order to develop effective drugs. The monomeric constituents,
molecular size, sulfation site, specific structural motif, degree of branching
determination are vital for reproducibility of result. Pomin (2009) has reported
that the anticoagulant action of SP lies in its ability to inhibit plasma proteases
via allosteric changes. The stereospecificities of the carbohydrate–protein
complexes hinge on the number of residues in the repeating units, sulfation
pattern, anomeric configuration, glycosidic linkage position and molecular mass.
Also, the heterogeneities, such as acetylation, methylation and pyruvilation
contribute in eliciting variations in functionality (Bilan et al. 2007). A single
structural change has been traced to result considerable qualitative difference
in results. Pomin and Mourao (2008) reported that preparation of oligosaccharides
with well-defined chemical structures from sulfated fucan helps in the studies
of carbohydrate–protein interaction. Fonseca et al. (2008) reported that algal
sulfated galactans have a procoagulant effect along with the serpin-dependent
anticoagulant activity. The procoagulant effect depends on the sulfation pattern
of the SP. Slight differences in the proportions and/or distribution of sulfated
residues along the galactan chain is critical for the interaction between proteases,
inhibitors, and activators of the coagulation system, resulting in a distinct
pattern in anti- and procoagulant activities. Identification of structural attributes
of SP vital for their biological activities has been limited by their heterogeneous
structures. Alasalvar et al. (2010) reported the strong correlation between
structure of SP and their antioxidant potency. The monomeric constitution, degree
of sulfation and their position, type of glycosidic linkage were held chief
determining factors for variation in activity. High sulfate content and low
molecular size were studied to exert stronger radical scavenging activities.
Frenette and Weiss (2000) determined that sulfation is critical for efficacy
of fucoidan in hematopoietic progenitor activity. The desulfated fucoidan failed
to promote angiogenesis in vitro or to induce immature CD34+ cell mobilization
in vivo. Fucoidan inhibits the human complement system mediated through interactions
with certain proteins belonging to the classical pathway, particularly the protein
C4. NMR spectra showed that the branched fucoidan oligosaccharides display a
better anticomplementary activity compared to linear structures. Spectroscopy
and molecular modeling of fucoidan oligosaccharides indicated that the presence
of side chains reduces the flexibility of the backbone, mimicking a conformation
recognized by the protein C4 (Clement et al. 2010). Leiro et al. (2007) observed
that immunostimulatory activity of ulvan-like SP extracted from U. rigida was
decreased significantly after desulfation of the SP, suggesting the importance
of the functional group in eliciting immune response. To tackle the problem
of heterogeneity of algal SP, a new approach has been established. The information
obtained from studies of invertebrate SP that have a regular structure can be
used to deduce the functionally of algal SP (Jiao et al. 2011).
Go to:
Maximization of the extraction and improvement in bioavailability
Aqueous (Ghosh et al. 2009) and acetone extraction (Marques et al. 2012) are
the most prevalent techniques in SP production from seaweeds. Due to the variations
in active growth parameters and extraction conditions, every new SP purified
is a unique compound with signature structural features, promising a potential
new drug. Rodriguez-Jasso et al. (2011) extracted fucoidan from brown seaweed
F. vesiculosus by microwave-assisted extraction. Extraction at 120 psi, 1 min,
using 1 g/25 ml water proved optimum condition for maximum fucoidan recovery.
It was concluded that pressure, extraction time and alga/water ratio affected
the SP yield (Rodriguez-Jasso et al. 2011). Supercritical CO2 extraction, ultrasonic-aid
extraction and membrane separation technology may be applied to harvest SP from
the seaweeds. Short extraction times, and non-corrosive solvents, cost effective
an environmentally benign technique are required for maximum yield. Acid hydrolysis
of high molecular weight fucans into low molecular weight compounds facilitates
their structural investigation. Further, the low molecular weight fucoidans
can be obtained by fucoidanase (E.C.3.2.1.44) treatment. This enzyme sourced
from hepatopancreas of invertebrates, marine bacteria and fungi has an added
advantage of hydrolyzing the SP without messing with its side substitute groups
(Qianqian et al. 2011). Endolytic enzymes, such as ulvan lyases isolated from
the flavobacteria Persicivirga ulvanivorans cleave the glycosidic bond between
the sulfated rhamnose and a glucuronic or iduronic acid in the ulvans (Collen
et al. 2011). Alkali modifications of carrageenans are suggested for improved
application potential (Campo et al. 2009). Success of commercial reproducibility
of highly diverse fucoidan lies in proper characterization with the help of
powerful analytical tools (Fitton 2011).
Go to:
Conclusion
The research on SP from seaweeds and their wide biological spectrum have skyrocketed
in recent years. Their clinical evaluation for possible noble therapeutics development
is catching momentum like never before. For above goals to materialize, the
underlying molecular mechanisms need to be understood precisely and elucidated
clearly. The relation between structure and function should be unraveled by
intensive studies. This up-to-date review on this emerging technique is expected
to contribute significantly in supplementing background knowledge, kindling
interest for future explorations. Further purification steps and investigation
on structural features as well as in vivo experiments are needed to test the
viability of their use as therapeutic agents. The SP with appreciably few side
effects and myriad benefits could potentially be exploited for complementary
medicine use and disease management.
3 Biotech. 2012 Sep; 2(3): 171–185.
Published online 2012 Apr 15. doi: 10.1007/s13205-012-0061-9
PMCID: PMC3433884