Nutritional and Medical Applications of Spirulina Microalgae

Abstract

Spirulina spp. and its processing products are employed in agriculture, food industry, pharmaceutics, perfumery and medicine. Spirulina has several pharmacological activities such as antimicrobial (including antiviral and antibacterial), anticancer, metalloprotective (prevention of heavy-metal poisoning against Cd, Pb, Fe, Hg), as well as immunostimulant and antioxidant effects due to its rich content of protein, polysaccharide, lipid, essential amino and fatty acids, dietary minerals and vitamins. This article serves as an overview, introducing the basic biochemical composition of this algae and moves to its medical applications. For each application the basic description of disease, mechanism of damage, particular content of Spirulina spp. for treatment, in vivo and/or in vitro usage, factors associated with therapeutic role, problems encountered and advantages are given.

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Nutritional and Medical Applications of Spirulina Microalgae
S.M. Hoseini1, K. Khosravi-Darani2* and M.R. Mozafari3
1Department of Food Science and Technology, National Nutrition and Food Technology Research Institute, Faculty of
Nutrition Sciences and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, P.O. Box:
19395-4741, Tehran, Iran; 2Department of Food Technology Research, National Nutrition and Food Technology
Research Institute, Faculty of Nutrition Sciences and Food Technology Research Institute, Shahid Beheshti University of
Medical Sciences, P.O. Box: 19395-4741, Tehran, Iran; 3Australasian Nanoscience and Nanotechnology Initiative,
Monash University LPO, P.O. Box 8052, Wellington Road, Clayton, Victoria 3800, Australia
Abstract: Spirulina spp. and its processing products are employed in agriculture, food industry, pharmaceutics,
perfumery and medicine. Spirulina has several pharmacological activities such as antimicrobial (including antiviral and
antibacterial), anticancer, metalloprotective (prevention of heavy-metal poisoning against Cd, Pb, Fe, Hg), as well as
immunostimulant and antioxidant effects due to its rich content of protein, polysaccharide, lipid, essential amino and fatty
acids, dietary minerals and vitamins. This article serves as an overview, introducing the basic biochemical composition of
this algae and moves to its medical applications. For each application the basic description of disease, mechanism of
damage, particular content of Spirulina spp. for treatment, in vivo and/or in vitro usage, factors associated with therapeutic
role, problems encountered and advantages are given.
Keywords: anticancer, antimicrobial, antioxidant, chemical composition, immunostimulant, metalloprotective, Spirulina.
INTRODUCTION
Spirulina is the general name of filamentous,
multicellular, blue-green microalgae belonging to two
genera, namely Spirulina and Arthrospira, which consist of
15 species. Spirulina platensis is the most commonly
available and widely used genus, which has been extensively
studied in different fields specially food industry and
medicine [1]. Chemical analysis of microalgae Spirulina
indicates that it is an excellent source of some macro and
micronutrients. This rich content of protein, vitamins,
essential amino acids, dietary minerals, and essential
fatty acids provide Spirulina with several health beneficial
properties. Potential health effects include
immunomodulation, anticancer, antioxidant, antiviral and
antibacterial activities, as well as positive effects against
malnutrition, hyperlipidemia, obesity, diabetes, heavy metal/
chemical-induced toxicity, inflammatory allergic reactions,
radiation damage and anemia [2-5]. A coherent collection of
medical benefits of some algae and micro algae classes has
been presented elsewhere [6].
This entry focuses on some biological properties
of Spirulina including anticancer, antimicrobial,
metalloprotective, antioxidant and immunostimulant effects.
The biochemical composition of this microalga has been
reviewed. Recent data concerning clinical potential of
Spirulina, not covered previously in the literature, as well as
*Address correspondence to this author at the Department of Food
Technology Research, National Nutrition and Food Technology Research
Institute, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-
4741, Tehran, Iran; Tel: +98-21-22376473; Fax: +98-21-22376473;
E-mail: kiankh@yahoo.com
information related to the safety and side effects of Spirulina
are also provided.
CHEMICAL COMPOSITION OF SPIRULINA
Basically, Spirulina consists of 55-70% protein and 5-6%
lipid (w/w dried cell). Polyunsaturated fatty acids (PUFAs)
constitute 1.5-2% of the total lipid content of this alga. In
fact, Spirulina spp. is rich in -linolenic acid (36% of the
total PUFAs), vitamins (B1, B2, B3, B6, B9, B12, vitamin C, D
and E), minerals (K, Ca, Cr, Cu, Fe, Mg, Mn, P, Se, Na and
Zn), pigments (chlorophyll a, xanthophyll, betacarotene,
echinenone, myxoxanthophyll, zeaxanthin, canthaxanthin,
diatoxanthin, 3-hydroxyechinenone, beta-cryptoxanthin,
oscillaxanthin, phycobiliproteins, C-phycocyanin, and
allophycocyanin) and enzymes (e.g. lipase) [7-9]. Therefore,
the biomass of this rich source of elements is employed as
feed and food additives in many industries (e.g. agriculture,
food, pharmaceutics, and perfumery). In general, the
chemical characteristics of two species belonging to the
same microalgal category differ according to specific source,
culture condition, harvest time and extraction method, even
if their appearance is similar. General composition can be
summarized as follows (% of dry weight): Proteins: 50-70%;
carbohydrates: 15-25%; lipids: 6-13%; nucleic acids: 4.2-6%
and minerals: 2.2-4.8% [2,3,10,11].
CARBOHYDRATES
The major polymeric component in S. platensis is a
branched polysaccharide, structurally similar to glycogen.
High molecular weight anionic polysaccharides with antiviral
and immunomodulating activities have been isolated from
Spirulina [12]. The antiviral and immunomodulating

1232 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 8 Hoseini et al.
activities of polysaccharides of Spirulina will be discussed in
the related sections. A sulphated polysaccharide fraction
with antiviral property (calcium spirulan) has been
extensively purified and shown to be composed of rhamnose,
3-O-methylrhamnose (acofriose), 2,3-di-O-methylrhamnose,
3-O-methylxylose, uronic acids and sulfate [4,13].
PROTEINS
Protein content of Spirulina (50-70% of dried weight),
which exceeds that of meat, eggs, dried milk, grains and
soybeans, contains all the essential amino acids specially
leucine, valine and isoleucine. However, it somewhat seems
deficient in methionine, cysteine, and lysine in comparison
to standard alimentary proteins (meat, eggs or milk), while it
is superior to all plant proteins including proteins from
legumes [2,14]. As alternative protein source, two important
nutritional values are estimated for Spirulina, the protein
efficiency ratio (PER) (weight gain of an experimental
animal, divided by the weight of proteins ingested using
reference proteins) and net protein utilization (NPU)
(percentage of nitrogen retained, when the source of proteins
is the only limiting nutritional factor). Protein contents of
Spirulina show very high digestibility (83-90% as compared
to 95.1% for pure casein) due to lack of cellulose walls.
Hence, cooking is not necessary for increasing the proteins
availability. The NPU and PER values of Spirulina are
calculated to be between 53-92% and 1.8-2.6, respectively.
This is while the PER values of pure casein, maize, rice and
wheat are 2.5, 1.23, 2.2 and 1.15 respectively [2, 3]. The
major protein constituents with significant beneficial health
effects are the phycobiliproteins phycocyanin C and
allophycocyanin (at approximately 10:1 ratio), which have
linear tetrapyrrole prosthetic groups (phycocyanobilin)
covalently linked to specific cysteine residues of the
proteins. Phycocyanins constitute about 15-25% of the dry
weight of the microalgae [15,16]. Phycocyanins can be
considered as a safe natural food colorant in non-acidic
foodstuffs such as chewing gum, confectionaries and dairy
products [16,17].
The chromophore phycocyanobilin (PCB) of Spirulina,
which represents about 4.7% of the dried mass of
phycocyanin significantly decreases Nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase activity by being
reduced to phycocyanorubin. This close homolog of bilirubin
inhibits the activity of th e enzyme complex. PCB
supplementation may be employed for the prevention and
therapy of various diseases mediated by NADPH oxidase
hyperactivity e.g. cardiovascular diseases, diabetic
complications, metabolic syndrome, allergic reactions,
rheumatoid arthritis, cancer, Parkinson's and Alzheimer's
disease. Oral uptake is possible via whole Spirulina,
phycocyanin protein or isolated tetrapyrrole chromophore
[18].
LIPIDS
Lipids, contents of Spirulina, are separated into a
saponifiable fraction (83%) and a non-saponifiable fraction
(17%), containing essential pigments, paraffin, sterols and
terpene alcohol. Half of the total lipids are fatty acids
(mostly -6 [12,14]) and Cholesterol (< 0.1 mg/100 g of
Spirulina dry mass) [14], which is a component of Spirulina
sterol fraction [19]. S. maxima and S. platensis contain -
linolenic acid (GLA) , which comprise 10-20% and 49% of
their fatty acids, respectively. Therefore, after human milk
and some vegetable oils such as evening primrose, borage,
blackcurrant seed and hemp oil, Spirulina can be considered
as a good source of GLA S. maxima also contains
unsaturated oleic and linoleic acids as well as saturated
palmitic acid, which constitute more than 60% of its lipids.
Monogalactosyl- and sulfoquinovosyl-diacylglycerol as well
as phosphatidylglycerol are the major Spirulina lipids (20-
25% each) [20].
MINERALS AND VITAMINS
Spirulina is claimed to be the richest whole-food source
of vitamin B12 (and even its corrinoid forms, analogs and
pseudovitamin B12) and provitamin A ( carotene). Only 20g
of this microalgae fulfils body requirements of vitamins B1
(thiamine), B2 (riboflavin) and B3 (niacin) [2,3,14,21].
Although Spirulina does not fulfill the specific functional
roles of vitamin B12 for humans [22] but its intake does not
interfere with mammalian B12 metabolism [23]. A very
sensitive microbiological test shows that 36% of vitamin B12
molecules present in Spirulina spp. are active in humans [5].
S. platensis consists of biologically active form of vitamin
B12, methylcobalamin, at concentration of 35-38 μg/100 g of
dry Spirulina biomass [24].
The high levels of several micronutrients - especially
minerals (iron 0.58-1.8, calcium 1.3-14, phosphorus 6.7-9.0
and potassium 6.4-15.4 g/kg) - in Spirulina, which have
made it suitable nutritional supplement for vegetarians, are
due to absorption of these elements while growing.
Consequently, mineral content of Spirulina depends on
source and culture conditions. Calcium, phosphorus and
magnesium are present in quantities comparable to those
found in milk. Spirulina is considered to be an iron rich food,
with an iron content of ten times higher than common iron
rich foods. Absorption of Spirulina iron is 60% more than
ferrous sulphate (present in iron supplements) [2,3].
There is no risk for the consumer in taking in of
excessive iodine by Spirulina consumption (3 μg in 10g of
dried biomass) [25,26], since the upper safe levels for total
daily intake of iodine established by European Food Safety
Authority (EFSA) and Scientific Committee on Food (SCF)
is reported to be 600μg for a 60kg bodyweight adult.
ANTICANCER EFFECT OF SPIRULINA
The potential cancer chemopreventive effect of Spirulina
has been reported [27, 28]. Carcinogenic steps can be
inhibited or reversed by some specific agents (natural or
synthetic) before the onset of cancer [27]. Grawish reported
a tumor suppressive effect in hamster cheek pouch mucosa
by Spirulina extract due to repair of the damaged DNA.
Repair of DNA damage is due to endonuclease activity,
which can be stimulated by the unique polysaccharide
contents of Spirulina [28].
Studies suggest a relation between cancer and high level
of prostaglandins (PGs) [29]. Cyclooxygenase (Cox, PGs H
synthase) is a bifunctional enzyme, which catalyzes

Nutritional and Medical Applications of Spirulina Microalgae Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 8 1233
biosynthesis of PGs from arachidonic acid as a substrate.
Cyclooxygenase-1 (Cox-1) and cyclooxygenase-2 (Cox-2)
are the two observed forms of this bifunctional enzyme.
Cox-1 (as a constitutive enzyme) is responsible for
maintaining normal physiologic function and the produced
PGs play a protective role. Cox-2 (as an inducible form
whose stimulators are mitogens, oncogenes, tumor
promoters, and growth factors) is responsible for the
production of PGs at inflammation sites [30]. It was shown
that activity of Cox-2 (and not Cox-1) increases in malignant
tissues of the colorectal cancer as well as human gastric and
breast tumors [31]. S.platensis produces C-phycocyanin as a
selective inhibitor of Cox-2. This inhibition is due to the
conformation and big structure of phycocyanin (Fig. 1),
which facilitates the proper binding to the active site of Cox-
2 [29]. It has recently been shown that selenium enriched S.
platensis inhibited the growth of MCF-7 human breast
cancer cells [32].
Fig. (1). Chemical structure of C-phycocyanin.
ANTIVIRAL ACTIVITY OF SPIRULINA
The major polymer in S. platensis is a branched
polysaccharide, with a structure similar to glycogen. High
molecular weight anionic polysaccharides isolated from
Spirulin a [33] possess antiviral and immunomodulating
activities. A sulphated polysaccharide fraction with antiviral
action (calcium spirulan) has extensively been purified and
shown to be composed of rhamnose, 3-O-methylrhamnose
(acofriose), 3-O-methylxylose, 2,3-di-O-methylrhamnose,
uronic acids and sulphate [34]. An acidic polysaccharide
fraction isolated from S. platensis has also been reported
which induces the synthesis of Tumor Necrosis Factor-alpha
(TNF-) in macrophages [33].
The most promising active constituents of Spirulin a are
the protein phycocyanin [13], sulfated polysaccharide
fractions [33], GLA [25] and certain sulfolipids [26].
Sulfated polysaccharide of Spirulina exerts its antiviral effect
by inhibiting the replication of herpes simplex, human
cytomegalovirus, influenza A, measles, mumps, human
immunodeficiency and white spot syndrome viruses [2]. The
effective concentration of calcium spirulan that can reduce
viral replication by 50% is 11.4-2600 μg/ml [35]. It is known
that Spirulina contains 2–5% of sulfolipids, which are
effective against human immunodeficiency virus by
selectively acting against DNA polymerase. For 50%
inhibition of the virus, a minimum concentration of 24nM is
required. Both the sulfonic acid moiety and the fatty acid
ester side chain have a significant effect in potentiating the
extent of inhibition [36]. A protein-bound pigment (i.e.
allophycocyanin) purified from S. platensis, has shown an
antiviral activity against enterovirus 71 [14]. This pigment
inhibits 50% of enterovirus 71-induced cytopathic effect,
viral plaque formation and viral-induced apoptosis at
concentrations of 0.056–0.101 μM. Kaushik et al. [37]
showed that addition of allophycocyanin to the cells before
viral infection has a great impact on preventing enterovirus
infection due to interfering with adsorption and penetration
of the virus.
ANTIBACTERIAL ACTIVITY OF SPIRULINA
Antimicrobial activity of Spirulina extracts obtained
using different solvents has been studied. Demule et al. [38]
reported that the antimicrobial activity of the methano lic
extract of S. platensis is due to the presence of -linolenic
acid, an antibiotically-active fatty acid present in a high
concentration in this alga. Mendiola et al. [39] studied
the antimicrobial activities of Spirulina extract against
Staphylococcus aureus (gram positive bacterium),
Escherichia coli (gram negative bacterium), Candida
albicans (yeast) and Aspergillus niger (fungus). Results
showed that C. albicans were the most sensitive
microorganism to all Spirulina fractions, which were
obtained by the supercritical fluid extraction. This
antimicrobial activity could be related to a synergic effect of
fatty acids. Mala et al. [40] studied the antibacterial activities
of various organic and aqueous extracts of S. platensis
against different species of human pathogenic bacteria by the
agar-solid diffusion method. Maximum and minimum
antimicrobial activity of water extract was observed against
Klebsiella pneumoniae and Proteus vulgaris, respectively.
Acetone extract also showed the highest biological activity
against Klebsiella pneumonia [40].
HEAVY-METAL POISONING ACTIVITY OF
SPIRULINA
Different metals damage certain tissues by causing
oxidative stress. Aerobic organisms can be protected against
free radicals by antioxidants, which are endogenously
synthesized compounds such as reduced glutathione (GSH),
superoxide dismutase (SOD) and nitric oxide (NO) [41].
Some examples of the protection effects of Spirulina against
metal poisoning are given in the following sections.
CADMIUM INDUCED POISONING
Cadmium induces cellular thiol depletion that may cause
an imbalance between the pro-oxidant and antioxidant
systems. Cadmium increases the production of reactive
oxygen species (ROS) in tissues and inhibits the activity of
some enzymes of the antioxidative defense system. ROS
(e.g. H2O2, O2
- and OH radical), which are formed and
degraded by all aerobic organisms, can readily react with
some biomolecules including lipids, proteins, lipoproteins
and DNA. The protective effect of S. platensis against
cadmium-induced oxidative stress could be either indirect
through the enhancement of the activity of GSH peroxidase
and superoxide dismutase (free radical scavengers) or direct
by inhibiting peroxidation of lipid and scavenging of free
radicals. These characteristics are due to the high
concentration of antioxidant components of S. platensis [41].

1234 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 8 Hoseini et al.
LEAD INDUCED POISONING
Lead poisoning causes morphological changes in bone
marrow cells, pathophysiological changes in tissues and
necrosis in proximal tubular cells. Furthermore, it causes
dysfunction in kidney, alters glomerular filtration rate,
decreases sperm count and causes changes in the
composition of proteins and lipids of the red blood cell
membrane. The later inhibits hemoglobin (Hb) synthesis and
leads to insufficient erythrocyte production and reduced red
cell survival. Spirulina showed a protective effect against
cadmium and lead induced alteration in the counts of T
lymphocyte, reticulocyte, red and white blood cells in rats
[19]. Spirulina may improve the metabolism of iron and Hb
in rats with Pb, Cd, Zn, and Hg induced poisoning [41, 42].
This phenomenon is attributed to the metal-binding
capacities of the blue-green algae [21].
IRON INDUCED TOXICITY
One of the most important agents that cause oxidative
stress and decline of neuronal functions is iron. Oxidative
stress and formation of the reactive oxygen species (ROS)
are caused by iron interactions with many cellular processes.
Iron toxicity also induces a significant elevation in lactate
dehydrogenase (LDH) release due to cellular necrosis.
Spirulina extract (especially phycocyanin) increases the
cellular antioxidant enzymes (glutathione reductase and
glutathione peroxidase), which are known to protect the
body against the deleterious effects of ROS [20].
MERCURIC CHOLORIDE INDUCED POISONING
Mercury causes many adverse health effects (renal,
neurological, respiratory, dermatologic, immune, reproductive
and developmental sequel). Mercuric chloride causes
significant increase in lipid peroxidation level, serum
glutamic oxloacetic transminase (SGOT) and serum glutamic
pyruvic transminase (SGPT) activity and significant decrease
in the activity of reduced glutathione, superoxide dismutase,
catalase and glutathione-S-transferase activity in liver.
Spirulina significantly increases liver glutathione (GSH)
level, superoxide dismutase (SOD), catalase (CAT) and
glutathione S- transferase (GST) activity as antioxidant
potential and thereby decreases the level of lipid peroxidation,
which in turn reduces the transaminases (SGOT & SGPT)
activity in serum [43]. The metalloprotective role of
Spirulina may be related to its contents of vitamins E and C,
beta-carotene, as well as enzyme superoxide dismutase,
selenium and brilliant blue polypeptide pigment phycocyanin
[43, 44].
ANTIOXIDANT ACTIVITY OF SPIRULINA
Spirulina has antioxidant properties as indicated by the in
vitro and in vivo studies [38, 45-47]. The protective effects
of Spirulina against CCl4-induced liver toxicity are due to
free radical scavenging. This observation is attributed to its
high contents of proteins, lipids, minerals (zinc, manganese,
magnesium and selenium), and some vitamins (beta
carotene, riboflavin, cyanocobalamin, alfa-tocopherol, and
alfa-lipoic acid).
For evaluating the antioxidant activity of different
natural products, metal-chelating activity is widely used.
Bermejo et al. [4] demonstrated that S. platensis protein
extract possessed an excellent antioxidant activity. Results
showed that the protein extract of S. platensis scavenged
hydroxyl and peroxyl radicals and also had inhibitory
activity against lipid peroxidation. Scavenging of these free
radicals by S. platensis can be an effective prevention for a
living organism against oxidative stress. An antioxidant can
function either by inhibiting the processes that activate free
radical formation (by intercepting the formation of the
reactive radical species), or inhibiting free radical action (by
scavenging the radical) or suppressing amplification of the
radical damage (by further intercepting the attack of
secondary-derived radicals on their biological components)
or reducing iron ions which are known to catalyze many
processes leading to the appearance of free radicals (by iron-
chelating properties) [45]. Gad et al. [46] reported that the
chelating activity of Spirulina exhibited a strong inhibition of
errozine–Fe2+ complex formation due to its antioxidant
compounds as electron donors.
IMMUNOSTIMULANT EFFECTS OF SPIRULINA
Spirulina facilitates production of antibody, increases
activated peritoneal macrophages, and induces growth of
spleen cells in response to Concavalin A (Con A).
Production of IL-1 and antibody was enhanced by the
addition of the Spirulina extract to the cultured spleen cells
[48]. The initial target cells for Spirulina are macrophages. In
myeloid cells, Spirulina exhibits an additive effect on Toll-
like receptor (TLR)-mediated cytokine production pathways.
Spirulina glycolipids serve as Toll ligands for stimulation of
TLR2 & 4 together with bacillus calmette-guerin (BCG) cell
wall skeleton [49].
Watanuki et al. [50] studied the immunostimulant effects
of the dietary S. plantensis in carp, Cyprinus carpio. Fish
were fed with Spirulina and the parameters of non-specific
defense mechanisms (phagocytosis and superoxide anion
production) were performed on the 1st, 3rd and 5th day.
Spirulina enhances responses of phagocytic activity and
superoxide anion production in kidney phagocytic cells (for
at least 5 days). The expression of interleukin (IL)-1 and
tumor necrosis factor (TNF)- genes also increased in fish
treated with Spirulina. The expression of IL-10 gene was
decreased. Furthermore, the numbers of Aeromonas
hydrophila were decreased in the liver and kidney of
Spirulina-treated fish [50]. Antimicrobial (including antiviral
and antibacterial), metalloprotective and immunostimulant
effects as well as antitumor and antioxidant activities of
Spirulina are summarized in Table 1.
In general, Spirulina is considered a generally recognized
as safe (GRAS) nontoxic dietary supplement [14] at normal
levels of consumption. However, information on the possible
interactions with pharmaceutical compounds or other dietary
supplements is lacking. Few side effects have been reported
from the ingestion of Spirulina including headache, stomach
ache, flushing of the face and muscle pain [51]. A few cases
of severe side-effects of hepatotoxicity [52] and rabdomyolysis
[51] are also reported. Spirulina spp. should be avoided by
phenylketonuria patients [51] and patients with autoimmune
diseases [53,54] (due to its immunomodulatory activity). It
has been reported that Spirulina caused diarrhea and

Nutritional and Medical Applications of Spirulina Microalgae Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 8 1235
erythema after consumption of amounts corresponding to
four Spirulina tablets over a 3-h period, in a 14-year old
individual [55]. A study in a mouse model of Amytrophic
Lateral Sclerosis (ALS) has revealed a neuroprotective effect
of Spirulina consumption which is believed to be due to
slowing down or stopping of motor neuron degeneration
[55]. Until better efficacy and safety studies are published,
the ALSUntangled Group does not support the use of
Spirulina in patients with ALS [56].
CONCLUSION
Limited consumption of natural food stuff in the 21st
century leads to deficiency of vitamins and main minerals in
the human population. Production of blue green microalgae
S. platensis, serves as an alternative approach as feed and
food additives due to their rich contents of protein, poly-
unsaturated fatty acids (-linolenic acid), vitamins as well as
minerals, pigments and enzymes. Spirulina has several
pharmacological activities such as anticancer, antiviral,
antibacterial, metalloprotective, antioxidant and
immunostimulant effects. Mechanisms of anticancer,
antiviral and antimicrobial effects of Spirulina are due to its
content of endonuclease (which repair damaged DNA),
calcium sulfated polysaccharide (which inhibits in vitro
replication of viruses) and fatty acids (specially high content
of -linolenic acid), respectively. In addition, the
metalloprotective role of Spirulina may be attributed to the
presence of beta-carotene, vitamins C and E, enzyme
superoxide dismutase, selenium and brilliant blue
polypeptide pigment phycocyanin. Research has also
focused on the immunostimulant effects of Spirulina. Some
experimental observations indicate that phycocyanin,
sulfated polysaccharide fractions, GLA and certain
sulfolipids are the most promising active constituents of
Spirulina. Nevertheless, more research is needed to rate the
effectiveness of Spirulina as a source of potential
pharmaceuticals and nutraceuticals.
Different chemical composition and various
pharmacological activities have been reported for the
microalgae. These contradictory results may be related to
differences in the geographical origin, harvesting period,
aqueous medium characteristics as well as genetic variations,
post-harvest processing conditions, the method of extraction
and type of solvents used. Furthermore, interaction of
microalgae with intrinsic or extrinsic properties of the
consumed food e.g. pH, fat, protein, water content,
antioxidants, oxygen concentration and preservative, needs
more investigation.
CONFLICT OF INTEREST
The authors confirm that this article content has no
conflicts of interest.
ACKNOWLEDGEMENTS
Declared none.
ABBREVIATIONS
PER = Protein efficiency ratio:
NPU = Net protein utilization
PCB = Chromophore phycocyanobilin
NADPH = Nicotinamide adenine dinucleotide phosphate
GLA = -linolenic acid
EFSA = European Food Safety Authority
SCF = Scientific Committee on Food
Table 1. Summary of some Studied Biological Effects of Spirulina Microalgae.
Biological Properties Specific Effects Bioactive Component References
Repairing of damaged DNA Polysaccharides [5]
Selective Inhibition of Cyclooxygenase-2 C-phycocyanin [6]
Anticancer
Induction of G1 cell cycle arrest, mitochondria mediated apoptosis in MCF-7
human breast carcinoma Se-enriched Spirulina [9]
Blocking virus adsorption and penetration into vero cells Calcium spirulan
(sulfated polysaccharide) [10-12]
I Inhibition of the DNA polymerase activity Sulfolipids [13]
Antiviral
Inhibition of enterovirus 71-induced cytophtic effect, viral plaque formation,
and viral-induced apoptosis
Protein-bound pigment
allophycocyanin [14]
Antibacterial Fatty acids e.g. GLA [15-19]
Metalloprotective Inhibiting lipid peroxidation, scavenging free radicals, enhancement of the
activity of GSH peroxidase and superoxide dismutase Antioxidant components [20-24]
Antioxidant Metal-chelating activity, free radical scavenging activity Carotenoids, vitamin E,
Phycocyanin, and chlorophyll [25-27]
Immunostimulant [28-30]

1236 Mini-Reviews in Medicinal Chemistry, 2013, Vol. 13, No. 8 Hoseini et al.
PGs = Prostaglandins
Cox = Cyclooxygenase
TNF- = Tumor necrosis factor-alpha
GSH = Glutathione
SOD = Superoxide dismutase
NO = Nitric oxide
ROS = Reactive oxygen species
Hb = Hemoglobin
LDH = lactate dehydrogenase
SGOT = Glutamic oxloacetic transminase
SGPT = Serum glutamic pyruvic transminase
GSH = Glutathione
SOD = Superoxide dismutase
CAT = Catalase
GST = Glutathione S- transferase:
TNF = Tumor necrosis factor
TLR = Toll-like receptor
BCG = Bacillus calmette-guerin
GRAS = Generally recognized as safe:
ALS = Amytrophic Lateral Sclerosis
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Received: July 08, 2012 Revised: December 21, 2012 Accepted: March 18, 2013