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Microalgae and Immune Potential

  • Sree Balaji Medical College and Hospital (SBMCH)-BIHER

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Immunopotentiating activities have been found in whole cells such as bacteria, mushrooms, algae, lichens, and higher plants. Microalgae with its long history of food use, easy cultivation, and high nutritional content make it a valuable source for immunomodulating studies. One of the main components that possesses the immunomodulating activity is the polysaccharides of the cell. The basic mechanism of the immunostimulatory activity is through the stimulation of the macrophages and modulation of the complement system.
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27 Microalgae and Immune Potential
Rathinam Raja and
Shanmugam Hemaiswarya
Key Points
Immunopotentiating activities have been found in whole cells such as bacteria, mush-•
rooms, algae, lichens, and higher plants.
Microalgae with its long history of food use, easy cultivation, and high nutritional •
content make it a valuable source for immunomodulating studies.
One of the main components that possesses the immunomodulating activity is the •
polysaccharides of the cell.
The basic mechanism of the immunostimulatory activity is through the stimulation •
of the macrophages and modulation of the complement system.
Key Words: Microalgae, immunomodulators, spirulina, immunoglobulin, allergy,
metabolic diseases.
One of the most promising recent alternatives to classical antibiotic treatment is the
use of immunomodulators for enhancing host defense response (1). Several types of
immunomodulators have been identified including mammalian proteins such as inter-
feron gamma (IFN-g) (2), granulocyte colony-stimulating factor (3), and granulocyte
macrophage colony-stimulating factor (GM-CSF) (4), as well as substances isolated and
purified from microorganisms (1). Immunopotentiating activities have also been found
in whole cells like bacteria, mushrooms, algae, lichens, and higher plants. Microalgae
with its added advantages such as a long history of its food use, easy cultivation, and
high nutritional content make it a valuable source for immunomodulating studies.
Scientists are increasingly turning their attention to algae as ingredient factories, par-
ticularly the nutritional components. The omega-3 fatty acid DHA extracted from
marine algae is already in market, while several companies are offering the carotenoid
and astaxanthin (AX) from other algal sources. Spirulina, Chlorella, and Aphanizomenon
From: Dietary Components and Immune Function
Edited by: R.R. Watson et al., DOI 10.1007/978-1-60761-061-8_27
© Springer Science+Business Media, LLC 2010
Raja and Hemaiswarya
Fig. 27.1. (a–d) Morphological structures of some microalgae. (a) Spirulina sp. ×100. (b) Spirulina
sp. ×45. (c) Chlorella sp. ×100. (d) Haematococcus sp. ×100.
flos-aquae provide cellular protection with exceptional amounts of b-carotene (provita-
min A) and chlorophyll, whereas Dunaliella is the highest known natural source of
b-carotene (5–7). Some microalgae have favorable nutritional profiles for cancer and
immune therapies. Chlorella, the alga to emphasize stimulates immunity in the treat-
ment of all degenerative diseases by means of Chlorella Growth Factor (CGF).
The blue green alga (Cyanobacterium), Spirulina (Arthrospira) platensis Geitler
(Fig. 27.1a, b) has a soft cell wall made up of complex sugars and protein which is eas-
ily digestible. It has 62% amino acid which is a richest natural source of pseudo-vitamin
with (Vitamins B
and B
) and a whole spectrum of carotenoids and xanthophyll
phytopigments (8). Hence, a considerable attention has been paid for the cultivation of
Spirulina. Current world production of Spirulina for human consumption is more than
1,000 metric tons annually (9). The USA leads the world for Spirulina products in the
form of pills and spray-dried powder followed by China, India, Israel, Japan, Mexico,
Taiwan, and Thailand in the healthy food market (10). Phycocyanin (PC) extracted from
Spirulina, which is commercially known as lima blue, is used as a blue colorant for food
and cosmetics. The phycobiliproteins (phycoerythrins and phycocyanin) extracted from
Spirulina is used as fluorescence tag in connection with the detection of particular bio-
logical molecules viz., a fluorescent color marker coupled to antibiotics.
this figure will be printed in b/w
Chapter 27 / Microalgae and Immune Potential
Spirulina inhibits viral replication and strengthens cellular and humoral immune
system causing regression and inhibition of cancers (11). Several reports revealed that
the extract unique to Spirulina named as Calcium-Spirulan (a polymerized sugar mol-
ecule) inhibits replication of HIV-1, herpes simplex, human cytomegalovirus, influenza
A virus, mumps virus, and measles virus under in vitro conditions and are very safe to
human cells (12). Hamsters treated with this water soluble extract had better recovery
rates when infected with lethal herpes virus. A recent in vitro study showed in vitro that
an aqueous extract of S. platensis inhibited HIV-1 replication in human T-cells, periph-
eral blood mononuclear cells, and Langerhan cells (11). The advantage of using algal
products with proven antiviral properties in fighting certain viruses is that they can
immunomodulate even when an infection is developed. Studies on mice, hamsters,
chickens, turkeys, cats, and fish reveal that Spirulina consistently improves their
immune system functions. The rich brilliant blue polypeptide, Phycocyanin from
Spirulina, stimulates hematopoiesis and emulates the effect of hormone erythropoetin
(EPO). Phycocyanin also regulates the production of white blood cells, even when bone
marrow stem cells are damaged. Although early interest in commercial production of
Spirulina was focused mainly on its nutrient content, recent attention has been given to
its therapeutic properties such as antioxidant effects, immunomodulation, anticancer
potency, antiviral, and cholesterol regulatory properties.
Monocytes and macrophages are phagocytes, acting in both nonspecific defense (and
innate immunity) or help to initiate specific defense mechanisms (or adaptive immunity)
in vertebrate animals. Their role is to phagocytose (engulf and then digest) cellular debris
and pathogens either as stationary or as mobile cells, and to stimulate lymphocytes and
other immune cells to respond to the pathogen. In response to antigen, macrophages
secrete mediators such as nitric oxide and cytokines. Cytokines play an important role in
the inflammatory cascade and include proinflammatory cytokines such as TNF, IL-1,
IL-8, and anti-inflammatory cytokines like IL-10 (13). The proinflammatory cytokines
are responsible for initiating an effect against exogenous pathogens and anti-inflamma-
tory cytokines are crucial for downregulating the incremented inflammatory process and
maintaining homeostasis for the correct functioning of vital organs.
Mice fed with microalgal diet showed an increase in the number of splenic antibody
producing cells in response to sheep red blood cells (SRBC). Spirulina enhanced the
macrophage functions and IL-1 production, but there was no change in the IgG-antibody
production (9). IL-1 is a proinflammatory cytokine that has numerous biological effects,
including activation of many inflammatory processes, induction of expression of acute-
phase proteins, an important function in neuroimmune response, and direct effects on
the brain itself (14). Similarly, in chickens fed with the Spirulina diet had macrophages
which exhibited enhanced phagocytic activity and increased nitric oxide synthase activ-
ity (13). The enhanced macrophage phagocytic function has also been shown in cats
(15), dogs (16) as well as in humans (17, 18) fed with Spirulina platensis extract. The
immunomodulatory action has been suggested by some researchers to be mediated
through the innate immune system. All the above studies used Spirulina as powder or
hot water extract and the active components considered were phycocyanin and water
Raja and Hemaiswarya
Table 27.1
Microalgal polysaccharides with immunomodulating activity
Microalgae Polysaccharides Effect References
Aphanizomenon flos-
Increase NF-kB activa-
tion and IL-1b and
TNF-a signaling
(19, 22)
Chlorella pyrenoidosa Immurella (22, 23)
Spirulina platensis Immulina (22)
Chlorella stigmatophora Hydrosoluble
Anti-inflammatory, anal-
gesic and free radical
scavenging activities
Phaeodactylum tricor-
soluble polysaccharides. These components have been known to cause immuno-
modulation via increased proliferation of erythrocytes, granulocyte-monocyte, and
fibroblast lineage cells derived from bone marrow cells of mice (18).
A high molecular weight polysaccharide fraction (Immulina) from Spirulina was a
potent activator of NF-kB and induced both IL-1b and TNF-a mRNAs in THP-1 human
monocytes (19). Immulina dose-dependently increased the expression of chemokines,
namely, interleukin (IL)-8, MCP-1, MIP-1a, MIP-1b, IL-10 as well as the expression of
TNF-a, IL-1b, and COX-2. Thymidine uptake experiments verified that Immulina did
not affect the viability and growth rate of THP-1 cells. The activity in vitro was more
potent than the in vivo effects after oral administration (20). NF-κB activation by
Immulina is suppressed by antibodies to CD14 and TLR2 but not by antibodies to TLR4.
Similarly, NF-κB directed luciferase expression was enhanced by Immulina treatment
when cells were cotransfected with vectors expressing proteins supporting TLR2- (CD14
and TLR2) but not TLR4-(CD14, TLR4, and MD-2) dependent activation (21). In addi-
tion to Immulina, there are several other microalgae which produce polysaccharides with
immunomodulating activities especially on the macrophages (Table 27.1).
In mice, S. fusiformis (400 or 800 mg/kg body wt.) administration significantly inhib-
ited the humoral immune response, cell-mediated immune response delayed-type
hypersensitivity reaction (DTH) and TNF-alpha in a dose dependent manner (Fig. 27.2).
In vitro, S. fusiformis (50 or 100 mg/mL) decreased the mitogen (phytohemagglutinin)
induced T-lymphocyte proliferation in a concentration dependent manner when
compared with control cells. These observations clearly suggest that S. fusiformis has a
remarkable immunosuppressive effect which provides a scientific validation for the
popular use of this drug (25).
The number of hemagglutinating antibodies in serum was reduced after S. fusiformis
(400 or 800 mg/kg body wt.) dose-related treatment. During the cell-mediated immune
response, the sensitized T-lymphocytes, on being challenged with the antigen, secrete a
number of lymphokines. These lymphokines attract scavenger cells to the site of the
reaction, where they are then immobilized to promote defensive (inflammatory) reaction
(26). Therefore, the inhibition of inflammation observed in our present study indicates
that there might be an inhibition of release of lymphokines on S. fusiformis
Chapter 27 / Microalgae and Immune Potential
Fig 27.2. Hypothesized mechanism of immunomodulation.
administration. A moderate level of inflammatory mediators is essential for host sur-
vival from infection, whereas overproduction has deleterious effects. As a result, syn-
thesis of inflammatory mediators must be tightly governed. The cytokine TNF-a
induces the production of proinflammatory cytokines, active oxygen species, nitric
oxide and matrix metalloproteinases, thereby implicating TNF-a as a therapeutic target
for treating the pain, swelling, and progressive joint destruction caused by rheumatoid
arthritis (27). In the present study, the abundance of TNF-a in arthritic mice joints pro-
vides evidence of its involvement in the disease pathology, which is supported by stud-
ies demonstrating that neutralization of TNF-a leads to decreased production of other
inflammatory cytokines (28). The S. fusiformis significantly decreased the production
of TNF-a in adjuvant-induced arthritic mice in dose dependent manner.
IFN-g is a macrophage activating cytokine that promotes Th1 biased responses asso-
ciated with cell mediated immunity (29). The Th1/Th2 balance is critical in determining
whether an immune response is to be dominated by macrophage activation or by anti-
body production. An increased spleen cell production of IFN-g in mice fed with
Spirulina extract, suggests a shift toward Th1 type cell mediated immunity. It was also
indicated a Th1 bias (increased production of IFN-g) in mice fed with when Spirulina
(30) or when added to cultures of human peripheral blood mononuclear cells (increased
production of IFN-g). In addition, consumption of a hot water extract of Spirulina for
two months by human volunteers resulted in greatly enhanced production of IFN-g by
NK cells in response to IL-12 and IL-18 (17).
Raja and Hemaiswarya
Spirulina is known to immunomodulate by activating the IgA secretion. IgA
secreted at mucosal surfaces function to protect against various viral and bacterial
pathogens by its unique nature of agglutination of microorganisms, neutralization of
bacterial enzymes, toxins and inhibition of antigens (31). Several investigators have
observed an increased mucosal IgA response by long-term treatment with Spirulina
or its components or after antigen stimulation. Mice that consumed a chemically
defined chow mixed with an extract containing Immulina exhibited changes in sev-
eral immune parameters. The ex vivo production of IgA and IL-6 from Peyer’s patch
cells was enhanced two fold and (IFN-g) production from spleen cells was increased
four fold in immulina treated mice. Oral consumption of this polysaccharide can
enhance components within both the mucosal and systemic immune systems (21).
Ingestion of S. platensis by men for more than a year enhanced salivary S-IgA levels
while treatment for less than a year had no effect. Mice that ingested this extract
exhibited enhanced spleen cell IFN-g production ex vivo. Interestingly, the enhanced
production of IFN-g by spleen cells followed a time course similar to that exhibited
for production of IL-6 and IgA by Peyer’s patch cells. The similar time course may
indicate that a common cell type is initially targeted by the extract and is mediating
both the effects locally on Peyer’s patches as well as systemically on spleen cells.
The influence of Spirulina on IgA levels in human saliva and demonstrated that it
enhances IgA production, indicating an important role of microalga in mucosal
immunity (32).
It has been well documented that Spirulina exhibits anti-inflammatory properties by
inhibiting the release of histamine from mast cells (33, 34). In a recent randomized
double blind placebo-controlled trial (35), individuals with allergic rhinitis was fed
daily, either with placebo or Spirulina for 3 months. Peripheral blood mononuclear
cells were isolated before and after the Spirulina feeding and levels of cytokines [IL-4,
IFN- and IL-2] which are important in regulating immunoglobulin (Ig)E-mediated
allergy were measured. The study showed that high dose of Spirulina significantly
reduced IL-4 levels by 32%, demonstrating the protective effects of this microalgae
toward allergic rhinitis.
A Japanese team identified the molecular mechanism of the human immune capac-
ity of Spirulina by analyzing blood cells of volunteers with pre- and post-oral admin-
istration of hot water extract of Spirulina platensis. IFN-g production and Natural
Killer (NK) cell damage were increased after administration of the microalgal extracts
to male volunteers (17). In a recent double blind, placebo controlled study from
Turkey evaluating the effectiveness and tolerability of Spirulina for treating patients
with allergic rhinitis, Spirulina consumption significantly improved the symptoms
and physical findings compared with placebo, including nasal discharge, sneezing,
nasal congestion, and itching (36). It is well understood that deficiency of nutrients is
responsible for changes in immunity which manifests as changes in production of
T-cells, secretory IgA antibody response, cytokines, and NK-cell activity. The above
Chapter 27 / Microalgae and Immune Potential
studies suggest that Spirulina may modulate the immune system by its role in cover-
ing nutritional deficiencies.
Phycocyanin (PC), a water soluble protein pigment, is one of the major constitutes
of Spirulina platensis. It is in association with the outer face of the photosynthetic II
light harvesting apparatus. Some characteristics of PC make it well suitable for fluores-
cence analyses in flow cytometry, histochemistry, immunoassay, and detection of reac-
tive oxygen species (37). PC can be used as natural dyes and its medicinal and
pharmaceutical properties especially antioxidant (38), antitumor, and immunity boost-
ing effects are the focus of research (39) for a long time. Recent studies suggested that
PC inhibited cancer cell growth via the induction of apoptosis (40). It has been known
already that S. platensis is a good candidate for selenium (Se) enrichment and also
serves as a promi sing source of dietary Se supplementation (41, 42). However, very
limited information on the antiproliferative activity of selenium containing phycocyanin
(Se-PC) and the underlying mechanism is available. An influence of selenium enriched
phycocyanin on anaphylactic reaction severity and circulating antibody response against
model allergen hen’s egg white ovalbumin was studied in rats. Rats receiving Se-PC
demonstrated significantly increased specific IgG response (43). Phycocyanin can pro-
mote the expression of CD59 protein, reduce the reproduction of Hela cells. With an
ascendance of phycocyanin concentration, the expression quantities of CD59 protein
and apoptosis inducing Fas protein increased and the multiplication activity of Hela
cells declined (44).
Human CD59 is a plasma membrane anchored glycoprotein containing a 4 kDa
N-linked carbohydrate chain that functions as an inhibitor of the CD5b-9 membrane
attack complex (MAC) of human complement (45, 46). Thereby, it restricts the cytolytic
activity of the CD5b-9 complex to protect human blood and vascular cells from autolo-
gous complement attack (47, 48). CD59 plays a pivotal role in regulating immunity and
suppressing the hyperacute rejection (HAR) in xenograft transplantation (49). It was
reported that CD59 has close relationship with the occurrence of hurt, inflammation,
and tumor (50, 51). PC has an antitumor activity, and probably it acts as a kind of mito-
sis depressor able to combine with the receptor of mitosis depressor on the surface of
tumor cells. Through the linkage of receptor and the activation of cell death promoting
protein kinases by complicated pathway, the transcription and expression of CD59 gene
was promoted. Meanwhile excessively expressed CD59 protein can induce Fas protein
expression on the surface of Hela cells and then combine with Fas antigen which can
activate death domain and activate the conduction of proapoptosis signal in tumor cells.
In the end, the proliferation of tumor cells is held back and cells go to die. The studies
provide us a new idea about the molecular mechanism of the antitumor activity of PC
(44). In another study, after two weeks the white blood cells (lymphocyte activity) of a
PC group were higher than the control group and higher than or equal to a normal group
without cancer. This suggests that PC raises lymphocyte activity (21). These results
imply that phycocyanin has anticancer activity and also strengthens the body’s resist-
ance through increasing general immunity. Experts deem that taking a small dosage of
PC daily can prevent generation of malignant cancer or can inhibit its recurrence (29).
Raja and Hemaiswarya
27.8 Chlorella
One of the most powerful algae against cancer is Chlorella (Fig. 27.1c) – an unicel-
lular, green algae containing the highest chlorophyll level per ounce of any plant, as
well as protein (nearly 58%), carbohydrates, all of the vitamins B, C, and E, amino
acids, enzymes, and rare trace minerals (9). In a study, lab mice were supplemented with
Chlorella for ten days, and injected the mice with three types of cancer. According to
Moss, over 70% of the Chlorella strengthened mice did not develop cancer while all of
the untreated mice died within twenty days. Research regarding Chlorellas immune
boosting effect is not limited to animal studies. According to another study, 15 glioblas-
toma patients were treated with powdered and liquid Chlorella along with standard
chemotherapy or radiation therapy. Although glioblastoma patients normally display a
2 year survival rate of 10%, the 15 Chlorella treated patients exhibited a survival rate of
40%. This is only one of the many successful studies linking Chlorella to strengthened
immune response thus making Chlorella a necessary component of effective and well-
rounded cancer treatment. It acts as both a powerful nutrient and a detoxifying food.
An experimental study was designed to assess the effects of oral administration of
Chlorella protein hydrolysate (Cv-PH) on the recovery of both innate and specific
immune responses of undernourished mice (52). The facts in support of the hypothesis
are as follows: the treatment of starved mice with Cv-PH provided benefits in terms of
(a) hemopoiesis (recovery of bone marrow cellularity and the lymphocyte pool), (b)
macrophage activation and phagocytosing capacity, and (c) stimulation of both humoral
and cell immune functions such as antibody response and the reconstitution of delayed-
type hypersensitivity response. Different immune cell populations might be induced
after activation in the gut-associated lymphoid tissue. Chlorella and its hydrophilic
extracts have been shown to possess many physiological functions, including immune
system improvement, hypoglycemic effects, lowering hyperlipidemic state in high fat
fed animals, etc. However, lipophilic extract of Chlorella (LEC) is less appreciated in
terms of its physiological actions. In the concentration ranges that were devoid of cyto-
toxicty, LEC produced a dose dependent (between 0.25 and 0.0315 mg/mL) inhibition
on LPS-induced nitric oxide production. The study shows LEC effectively block LPS-
induced nitric oxide production, is through blockage of expression of iNOS mRNA.
Chlorella powder was tested in 118 in vitro enzyme assay systems. The powder
showed potent inhibitions of peptidase cathepsin S, thromboxane A (2) synthase, and
cyclooxygenase-2 in a dose concentration manner. Other activities observed were inhi-
bitions of tumor necrosis factor alpha converting enzyme, protein tyrosine phosphatase
(SHP-2), calpain, protein kinases, and protein tyrosine phosphatases. Chlorella powder
had no significant effect on cyclooxygenase-1 (53). These actions to inhibit cyclooxy-
genase-2 and thromboxane synthase could contribute to the purported anti-inflamma-
tory and antithrombotic effects of Chlorella.
27.9 haematoCoCCuS
The green alga, Haematococcus pluvialis (Fig. 27.1d) accumulates high amounts
of AX under adverse environmental conditions, and it is the world’s richest source
of astaxanthin (54). AX plays an important role in protecting the alga against UV
Chapter 27 / Microalgae and Immune Potential
light damage and photo-oxidation of the polyunsaturated AX. It exhibits strong free
radical scavenging activity, protects against lipid peroxidation and oxidative damage
of LDL-cholesterol, cell membranes, cells, and tissues. Several studies have clearly
shown the effectiveness of astaxanthin as a cancer preventive agent in rats and mice.
The effect of AX on colon cancer in male rats is well executed (55). A recent study
with rats indicated that astaxanthin is effective at ameliorating retinal injury, and it
is effective in protecting photoreceptors from degeneration. AX was also found to
easily cross the blood–brain barrier (unlike b-carotene) and did not form any crystals
in the eye (56).
Immune response cells are particularly sensitive to oxidative stress and membrane
damage by free radicals because they rely heavily on cell to cell communications via
cell membrane receptors. Furthermore, the phagocytic action of some of these cells
releases free radicals that can rapidly damage these cells if they are not neutralized by
antioxidants (57). AX significantly influences immune function in several in vitro and
in vivo assays using animal models. Other evidences also pointout to the immunomodu-
lating activity of astaxanthin on the proliferation and functions of murine immuno
competent cells (58). Finally, studies on human blood cells in vitro have demonstrated
enhancement by AX of immunoglobulin production in response to T-dependent stimuli.
AX increases the production of T-helper cell antibody and increases the number of
antibody secretory cells from primed spleen cells (59). The above study discovered the
effect of AX in the production of immunoglobulins in vitro by human blood cells and
found that it increases the production of IgA, IgG, and IgM in response to T-dependent
stimuli (60). Other studies performed in vivo using mice have shown the immunomodu-
lating action of AX and other carotenoids for humoral responses to T-dependent anti-
gens and suggested that the supplementation with carotenoids may be useful to restore
immune responses (61). In agreement with the above results, various foods and drinks
with added AX have been prepared to increase the immune response mediated by
T-lymphocytes and NK cells to alleviate or prevent the decrease of immunological func-
tions caused by stress (62). Due to its immunomodulating action, AX has also been
utilized as a medication for the treatment of autoimmune diseases such as multiple
sclerosis, rheumatoid arthritis, and Crohn’s disease (63).
Malnutrition induced by dietary restriction produces a series of metabolic changes
that lead to depression of immunocompetence and several studies have assessed the
effects of nutritional support on immunity (64). Algal protein hydrolysates possess
various biological activities and have been administered to patients with different
protein metabolic diseases (65), but there are no reports on its immunomodulating
properties. Immunomodulation by using natural products can provide an alternative
to conventional therapy for a variety of diseases, especially when the host defense
mechanism has to be activated under the conditions of impaired immune response or
when a selective immunosuppression is desired in situations like autoimmune disor-
ders. Though enhancement of immune function has been claimed by various natural
products, very few have been subjected to randomized clinical trails. Recently, novel
vaccine delivery system has been developed using single-celled alga, Chlamydomonas
reinhardtii. Microalgae in particular, Chlamydomonas have many features that are
desirable for vaccine delivery systems, including its ease for genetic manipulation,
Raja and Hemaiswarya
inexpensive to produce and nontoxic. The first antigen to be tested was the p57
antigen, the causing agent of bacterial kidney disease. It is caused by Renibacterium
salmoninarum and infects all wild and farmed salmonids. The vaccine was well
expressed in the algae and effects in the immune functions were noted in the immu-
nized animals such as fish and rabbits. Issues that remain to be addressed include
expression of the antigen, posttranslational modifications, antigen immunogenicity,
and effective means of production.
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Author Query
Chapter No.: 27
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AU1 Please provide text for “Conclusions and Perspectives.
... The most promising alternative to conventional antibiotic treatment is the use of immunostimulants for enhancing immune responses (Raja & Hemaiswarya 2010). Most microalgae are rich in antibacterial compounds such as linolenic acids, capable of rescinding methicillin-resistant Staphylococcus aureus. ...
... The enzyme regulates both the baseline mucus production in the gut, thus mitigating the damage to the intestinal mucosal lining due to inflammatory diseases (Schreiber et al. 2013). Raja and Hemaiswarya (2010) have reported negative physiological activity of a lipophilic extract of Chlorella (LEC) at a dose of between 0.0315 and 0.25 mg mL À1 , which inhibits lipopolysaccharide-induced nitric oxide production by blocking the expression of iNOS mRNA. On the other hand, dietary supplementation of C. vulgaris at 5-10% reverses the nitric oxide production that was suddenly stopped by arsenic-induced liver and gills immunotoxicity in Nile tilapia O. niloticus (Zahran & Risha 2014). ...
Microalgae biomass is used in aquaculture as feed, growth enhancers and immunostimulants. Chlorella vulgaris is an important species with a good biomolecular composition. Commercially, it is one of the most commonly used microalga in aquaculture. Several studies confirmed its ability to improve nutrition, immunity, aquatic bioremediation, amelioration of stress, disease resistance of fish and inhibits bacterial quorum sensing when used appropriately. Despite claims of its benefits, C. vulgaris is reported to have unfavourable effects when incorporated in diets at higher inclusion levels. In addition, its rigid cell wall might restrict the access of digestive enzymes to the intracellular components for proper digestion and assimilation. Thus, this review discusses the role of C. vulgaris and its importance in aquaculture with emphasis on its environmental requirements, morphology, pigments, digestibility, dynamics on growth performance, antibacterial activity, bacterial quorum sensing, immunomodulatory effect, anti‐stress effect, gut microbiome, aquatic bioremediation and its safety as food or feed.
... It also increases the immune response by NK cells and decreases stress related inflammation. Yakoot and Salem, 2012;Liu et al., 2020;Raja and Hemaiswarya, 2010;Sansone et al., 2020 Vitamin E improved antibody responses after injection with hepatitis-B virus surface antigen, pneumococcal polysaccharides or tetanus toxoid (Goldrosen and Straus, 2004). ...
... Hydrophilic extracts of Chlorella have been exhibited many physiological functions such as hypoglycemic effects, lessen hyperlipidemic condition, and eventually improved the immunity system. The green micro alga, Haematococcus lacustris (formerly Haematococcus pluvialis) contains high amount of astaxanthin which increase the production of immunoglobulins (IgA, IgG, and IgM) by stimulating T-helper (Th) cells (Raja and Hemaiswarya, 2010). It also increases the immune response by NK cells and decreases stress related inflammation. ...
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Aquafoods are diverse and rich in containing various health functional compounds which boost natural immunity. In this manuscript, the contents of biofunctional compounds such as vitamins, minerals, protein and amino acids, ω-3 polyunsaturated fatty acids, and pigments, etc. in various aquafoods like fishes, molluscs, crustaceans, seaweeds etc. are reported. The functional roles of those compounds are also depicted which enhance the immunecompetence and immunomodulation of the consumers. This paper provides an account of the recommended daily dietary intake level of those compounds for human. Those compounds available in aquafoods are recommended as they fight against various infectious diseases by enhancing immunity. Available reports on the bioactive compounds in aquafoods reveal the immunity boosting performances which may offer a new insight into controlling infectious diseases.
... contain large amounts of highly unsaturated fatty acids and are high in vitamins and rich in pigments such as carotenoids, chlorophylls and mycosporine-like amino acids (Ishaq, Matias-Peralta, & Basri, 2016). The observed immunological effect of this microalgae in Nile tilapia juveniles might be related to the presence of these bioactive compounds, which have been reported to modulate immune responses (Raja & Hemaiswarya, 2010;Xu et al., 2020). ...
... contain large amounts of highly unsaturated fatty acids and are high in vitamins and rich in pigments such as carotenoids, chlorophylls and mycosporine-like amino acids (Ishaq, Matias-Peralta, & Basri, 2016). The observed immunological effect of this microalgae in Nile tilapia juveniles might be related to the presence of these bioactive compounds, which have been reported to modulate immune responses (Raja & Hemaiswarya, 2010;Xu et al., 2020). ...
... contain large amounts of highly unsaturated fatty acids and are high in vitamins and rich in pigments such as carotenoids, chlorophylls and mycosporine-like amino acids (Ishaq, Matias-Peralta, & Basri, 2016). The observed immunological effect of this microalgae in Nile tilapia juveniles might be related to the presence of these bioactive compounds, which have been reported to modulate immune responses (Raja & Hemaiswarya, 2010;Xu et al., 2020). ...
Considering algae as novel dietary ingredient for aquafeeds, this study evaluates the effects of three algae, Ulva rigida, Crassiphycus corneus (formerly Hydropuntia cornea) and Scenedesmus almeriensis, on non‐specific immune response and fatty acid profile in juvenile Nile tilapia (Oreochromis niloticus) after a short dietary administration period (30 days). U. rigida, C. corneus and S. almeriensis diets (UL‐25, CC‐25 and SC‐25 respectively) included 25% dry algae biomass, whereas an algae‐free diet was used as control. Biological samples were taken at 7, 15 and 30 days. Diet SC‐25 significantly improved respiratory burst, alternative complement (ACH50) and lysozyme activity (p < .05). Regarding tissue fatty acid composition, SC‐25 diet reduced the levels of saturated fatty acid in liver and muscle, while increased levels of C20:3n6 and eicosapentaenoic acid (EPA) in liver, and total n‐3 content, arachidonic acid (ARA), EPA and docosahexaenoic acid (DHA) in muscle (p < .05). UL‐25 and CC‐25 groups showed the lowest levels of ARA in liver but increased levels of monounsaturated fatty acids. In conclusion, the results obtained lead us to consider the use of a short pulse of dietary algae is suited for improving the immune response and modulating the tissue fatty acid composition in this fish species.
... The Oscillatoriophycideae algae Arthrospira platensis is considered an immune-enhancing antioxidant that controls infectious agents and toxicants (Ragap et al., 2012;Kim et al., 2013;Al-Homaidan et al., 2015;Kwak et al., 2015;Markou et al., 2015). The immune-enhancing properties of A. platensis are attributed to its high content of vitamins, minerals, phycocyanin, βcarotene and algal polysaccharides (Khan et al., 2005;Raja and Hemaiswarya, 2010). As fish are usually exposed to low concentration of pollutants during the fattening period and to improve the cultivation of O. niloticus, this study was designed to investigate the potential therapeutic effects of A. platensis on the fish exposed to long-term low concentrations of PbNO 3 . ...
In this study, the impacts of lead toxicity on Oreochromisniloticus were investigated. Additionally, the potential ameliorative effects of the Spirulina algae Arthrospira platensis were evaluated. The median lethal concentration (LC50) of PbNO3 was determined to be 143.3 mg/l for O. niloticus weighing 42 ± 2.5 g. O. niloticus were exposed to 10 % of the estimated PbNO3LC50 for 12 weeks. The cumulative mortality rate (CMR) increased with exposure time. The results of assays for red blood cells (RBCs), haemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration (MCHC) indicated that the exposed O. niloticussuffered from anaemia. The levels of liver enzymes, namely, aspartate transaminase (AST) and alanine transaminase (ALT), as well as metallothionein)MT(revealed deterioration of hepatic tissue. The activity of the antioxidant enzymes glutathione peroxidase (GPx) as well as catalase (CAT) was stimulated in the hepatic tissue of O. niloticusexposed to PbNO3 and in those treated with A. platensis. Based on the results of serum bactericidal activity (SBA) and oxidative burst activity (OBA) assays as well as challenge tests with Aeromonas hydrophila, it was clear that supplementation with 5 or 10 g/kg A. platensis significantly enhanced the fish immune status and decreased the mortality rate (MR). However, these effects were reduced by PbNO3 exposure with no differences in MR percentage. Therefore, it was clear that O. niloticus reared in lead nitrate-polluted water were immunosuppressed, while diet supplementation with A. platensis could ameliorate such impacts.
... It has been reported that Scenedesmus obliquus could improve the immunity of tilapia [13]. These immune-enhanced effects of microalgae in fishes might be related to the presence of abundant phycocyanin, algal polysaccharides and β-carotene [14,15]. The Toll-like receptor (TLR) signaling pathway plays an essential role in the innate immune response to pathogen infection; the pathway includes the myeloid differentiation factor 88 (MyD88)-independent and MyD88dependent pathways [16]. ...
... Microalgal polysaccharides with immunomodulating activities are known to trigger the cell secretion of both pro-inflammatory and antiinflammatory cytokines [13,40,42,47,48] associated also with anticancer immune responces and perspective therapeutic intervention [49][50][51]. ...
Many microalgal species produce a wide range of highly-value products which are interesting for biotechnological applications. Cultivation of microalgal species Dictyosphaerium pulchellum and Dictyosphaerium tetrachotomum, strains Růžicka and Fott resulted yields of 0.2, 0.7 and 1.8 g/L of extracellular biopolymers (EPSs), respectively. All biopolymers were shown to be anionic proteoglycans. The sugar composition analyses of all EPSs showed high contents of hexoses and the presence of partially methylated monosaccharide residues, i.e. hexoses, and deoxy hexoses. The dominant sugar component of all EPSs was found to be galactose. Extracellular microalgal biopolymers were subjected to immunobiological and immunotoxicological evaluation using murine melanoma cancer cells B16, murine fibroblast cell line NIH-3T3, murine macrophages cell line RAW 264.7 and skin construct EpiDerm™ (EPI-200). The EPSs exerted the antiproliferative effectivity; treatment of EPS induced proinflammatory cytokines TNF-α IL-6, IL-12, IL-1β and IL-17, also engaged in anti-cancer immunity. Immunotoxicological studies revealed their non-toxic character and safe application on EpiDerm™.
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There is an immediate need to identify alternative sources of high-nutrient feedstocks for domestic livestock production and poultry, not only to support growing food demands but also to produce microalgae-source functional foods with multiple health benefits. Various species of microalgae and cyanobacteria are used to supplement existing feedstocks. In this review, microalgae have been defined as a potential feedstock for domestic animals due to their abundance of proteins, carbohydrates, lipids, minerals, vitamins, and other high-value products. Additionally, the positive physiological effects on products of animals fed with microalgal biomass have been compiled and recommendations are listed to enhance the assimilation of biomolecules in ruminant and nonruminant animals, which possess differing digestive systems. Furthermore, the role of microalgae as prebiotics is also discussed. With regards to large scale cultivation of microalgae for use as feed, many economic trade-offs must be considered such as the selection of strains with desired nutritional properties, cultivation systems, and steps for downstream processing. These factors are highlighted with further investigations needed to reduce the overall costs of cultivation. Finally, this review outlines the pros and cons of utilizing microalgae as a supplementary feedstock for poultry and cattle, existing cultivation strategies, and the economics of large-scale microalgal production.
Microalgal biomasses (MAB) is the most abundant source of various natural value-added biomolecules and bioactive compounds (BACs), therefore, considered as the best promising feedstock for the food and pharmaceutical industries. Microalgae-based BACs such as carotenoids, peptide molecules, phycocyanins, polyphenols, and polyunsaturated fatty acids (PUFAs) have significant application as functional ingredients in the pharmaceutical and nutraceutical industries. Due to the awareness of the consumers about the nutraceuticals in combating the occurrence of lifestyle and chronic diseases, the demands for the algal-based nutraceuticals have recently increased by several folds. Microalgae pigments, such as phycobiliproteins, chlorophylls, and carotenoids, have enormous possibilities for commercialization due to its therapeutic activities, which include antimicrobial, antioxidant, anti-inflammatory, antiproliferative, and anti-atherogenic activities. As per the estimates, the nutraceuticals market would cross about $278.96 billion by the end of 2021. Similarly, microalgae-based polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid, EPA, docosahexaenoic acid, arachidonic acid, etc. are also an important commercial product, and its global market is around USD 9.0 billion/Year. This chapter provides a comprehensive overview of bioactive compounds of microalgae and its pharmaceutical and nutraceutical properties. Various strategies used for the profitable production of microalgae biomass and extraction of bioactive compounds from algal biomass are discussed in detail. The commercial potential of algae BACs, associated safety, and regulatory issues are also discussed.
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Phycobiliproteins are brilliantly colored, highly fluorescent components of the photosynthetic light-harvesting antenna complexes of cyanobacteria (blue-green algae), red algae and cryptomonads. These proteins carry covalently attached linear tetrapyrrole pigments related structurally to biliverdin. Phycobiliproteins, purified from certain organisms, are isolated as either trimers, ()3, of approximatelyM r 110–120103 (e.g., allophycocyanins), or hexamers, ()6, of aboutM r 250103 (certain phycoerythrins). Three phycobiliproteins R-phycoerythrin, B-phycoerythrin, and allophycocyanin serve as valuable fluorescent tags with numerous applications in flow cytometry, fluorescence activated cell sorting, histochemistry and, to a limited degree, in immunoassay and detection of reactive oxygen species. These applications exploit the unique physical and spectroscopic properties of phycobiliproteins.
The extraction of unicellular green algae Chlorella and Scenedesmus with organic solvents was studied as a possible pre-treatment of algal biomass prior to enzymatic hydrolysis of cell proteins. The digestion of extracted algae by subtilisin afforded protein hydrolysates in yields of 60–70%. No significant differences were observed in processing Chlorella and Scenedesmus algae. The influence of different reaction parameters was investigated to improve the efficiency of the enzymatic hydrolysis. During the first 2 h the degree of hydrolysis gradually went up to 20–22% and remained constant throughout the process, although the yield of hydrolysed protein kept increasing until hydrolysis was over. Pilot plant experiments with batches of 100 kg algae Scenedesmus were carried out and several protein products were prepared. The amino acid composition of the obtained protein hydrolysates practically met the requirements of FAO for a balanced protein product for human nutrition. The hydrophobicity of the algae protein hydrolysates, or so-called Q-value, was estimated at 1040 cal mole −1, corresponding to a low bitterness. The application of the obtained algae protein hydrolysates as food additives is discussed.
The complement system is an important branch of the innate immune response, constituting a first line of defence against invading microorganisms which activate complement via both antibody-dependent and-independent mechanisms. Activation of complement leads to (a) a direct attack upon the activating cell surface by assembly of the pore-forming membrane attack complex (MAC), and (b) the generation of inflammatory mediators which target and recruit other branches of the immune system. However, uncontrolled complement activation can lead to widespread tissue damage in the host, since certain of the activation products, notably the fragment C3b and the C5b-7 complex, can bind nonspecifically to any nearby cell membranes. Therefore it is important that complement activation is tightly regulated. Our own cells express a number of membrane-bound control proteins which limit complement activation at the cell surface and prevent accidental complement-mediated damage. These include decay-accelerating factor, complement receptor 1 and membrane cofactor protein, all of which are active at the level of C3/C5 convertase formation. Until recently, cell surface control of MAC assembly had been attributed to a single 65-kD membrane protein called homologous restriction factor (alternatively named C8-binding protein and MAC-inhibiting protein). However a second MAC-inhibiting protein has since been discovered and it is now clear that this protein plays a major role in the control of membrane attack. This review charts the rapid progress made in elucidating the protein and gene structure, and the mechanism of action of this most recently discovered complement inhibitor, CD59.
The feasibility of mixotrophic culture of high selenium-enriched Spirulina platensis was investigated in this study. The results indicated that supplementation of acetate to the mixotrophic culture of S. platensis led to a significant enhancement in biomass concentration, chlorophyll a, lutein, β-carotene, phycocyanin and allophycocyanin production when compared to the photoautotrophic culture. Stepwise addition of selenium (Se) source during the exponential growth phase of S. platensis can avoid the inhibitory effect of high Se concentration on cell growth. At an accumulative Se concentration of 450 mg L−1 under mixotrophic culture conditions, the highest Se yield was obtained; while significant enhancement in Se accumulation capability, algal biomass concentration and photosynthetic pigment yield was also observed. These results indicated that the application of mixotrophic culture with stepwise addition of Se to culture of S. platensis offers a more effective and economical way for the production of high Se-enriched biological compounds.
This study examined the effects of oral administration of an enzymatic protein hydrolysate from green microalga Chlorella vulgaris (Cv-PH) on the recovery of both innate and specific immune responses of undernourished Balb/c mice after a 3-day fasting period. Cv-PH was prepared by hydrolysis of ethanol-extracted cell biomass with pancreatin (20 AU/g) at pH 7.5 and 45 °C for 4 h. The treatment with Cv-PH (500 mg/kg) for 8 days provided benefits in terms of haemopoiesis, as judged by the recovery of bone marrow cellularity and the leukocyte counts in peripheral blood, particularly the lymphocyte pool, which increased up to 128% compared to control animals. Starved mice treated with Cv-PH showed a higher number of peritoneal exudate cells and the macrophage activation was demonstrated by the enhancement in glucose consumption and acid phosphatase activities relative to non-supplemented mice. The increased carbon clearance in peripheral blood suggested the stimulation of mononuclear phagocytic system. Cv-PH also stimulated both humoral and cell mediated immune functions positively, such as T-dependent antibody response and the reconstitution of delayed-type hypersensitivity response (DTH). These findings indicate that Chlorella protein hydrolysate can be used for developing physiologically functional foods with immunopotentiating activity.
ABSTRACT The purpose of this study was to evaluate the immunomodulatory activity of Spirulina, a bluegreen alga used as a food supplement. The effects of Spirulina on the secretion of three cytokines from unstimulated and stimulated human peripheral blood mononuclear cells (PBMC) were examined. In resting PBMC, Spirulina stimulated secretion of interleukin (IL)-1beta, IL-4, and interferon (IFN)-gamma to nearly 2.0, 3.3, and 13.6 times basal levels, respectively. Spirulina induced levels of IFN-gamma (229 +/- 104 pg/ml) that were comparable to those seen after phytohemagglutinin (PHA) stimulation (476 +/- 121 pg/ml). However, it was much less mitogenic than PHA (13.1 +/- 6.9 pg/ml) with respect to the induction of IL-4 secretion (0.34 +/- 0.1 pg/ml). In PHA-stimulated cells, Spirulina enhanced secretion of IL-1beta, IL-4, and IFN-beta by 2.9, 4.0., and 1.6 times, respectively. Although Spirulina stimulates several cytokines, it is clearly more effective in the generation of a Thl-type response. This in vitro study offers additional data for consideration of the potential therapeutic benefits of Spirulina.