A Review on Antioxidant Properties of Spirulina

Abstract

Spirulina is free-floating filamentous microalgae growing in alkaline water bodies. As early as over 400 years ago, Spirulina was eaten as food by the Mayas, Toltec’s and Kanembu in Mexico during the Aztec civilization. Spirulina is a well-known source of valuable food supplements, such as proteins, vitamins, amino acids, minerals, fatty acids, etc. It is widely used in human and animal nutrition, as well as in the cosmetic industry. Both in vivo and in vitro trials have shown effective and promising results in the treatment of certain cancers and allergies, anemia, hepato-toxicity, viral infection, vascular diseases, radiation protection, and obesity. The antioxidant activities of Spirulina were demonstrated in a large number of preclini-cal studies. Antioxidants in preventing many human diseases. Findings of this study showed Spirulina can be used as a source of antioxidants.

Full text

Journal of Applied Biotechnology Reports
Review Article
Journal of Applied Biotechnology Reports, Volume 3, Issue 1, Winter 2016; 345-351
All rights reserved for official publication of Baqiyatallah university of medical sciences
©
A Review on Antioxidant Properties of Spirulina
Asieh Asghari1, Mohammad Fazilati1*, Ali Mohammad Latifi2*, Hossain Salavati1,
Ali Choopani1,2
Abstract
Introduction
Cancer is now a major cause of mortality throughout the
World [1]. In the developed world, it is generally exceeded
only by Cardiovascular disease but developing countries
are responsible for the globally increasing trend. Over 10
million new cases and over 7 million deaths from cancer
occurred worldwide in 2000. The contribution of develop-
ing countries was 53% for incidence and 56% for deaths.
From 1990 to 2000, the incidence and deaths increased by
2.4% per annum by 2020, it is predicted that these diseases
will be causing seven out of every 10 deaths in developing
countries (Fig. 1) [2-5].
Figure 1. Static of cancer incidence and deaths in 2012.
Based on high costs cancer treatment strategies (Fig. 2)
[6], in recent years antioxidants therapy has been devel-
oped to prevent cancer. Studies showed that free radicals
can lead to degenerative disease like cancer, aging, age
related macular degeneration etc [7].
Figure 2. Cost of cancer care by phase of care, in 2010.
Antioxidants help to protect the body against free radicals;
these are substances that neutralize free radicals or their
actions. Antioxidants include carotenoids, flavonoids and
related polyphenols, α-lipoic acid, glutathione etc. The
main source of antioxidants for the body is vegetables and
fruits. Unavailable of fruit and vegetables in many aria of
world, scientists rethought to provide antioxidants from
other sources [8, 9]. Starting at middle 1980’s, great efforts
and extensive investigations have been turned to the
development of nutraceuticals or functional food for
preventing or managing various diseases [10-13]. The first
Spirulina is free-floating filamentous microalgae growing in alkaline water bodies.
As early as over 400 years ago, Spirulina was eaten as food by the Mayas, Toltec’s
and Kanembu in Mexico during the Aztec civilization. Spirulina is a well-known
source of valuable food supplements, such as proteins, vitamins, amino acids, min-
erals, fatty acids, etc. It is widely used in human and animal nutrition, as well as in
the cosmetic industry. Both in vivo and in vitro trials have shown effective and
promising results in the treatment of certain cancers and allergies, anemia, hepato-
toxicity, viral infection, vascular diseases, radiation protection, and obesity. The
antioxidant activities of Spirulina were demonstrated in a large number of preclini-
cal studies. Antioxidants in preventing many human diseases. Findings of this study
showed Spirulina can be used as a source of antioxidants.
Keywords: Spirulina, Microalgae, Antioxidant, Anticancer
1. Department of Biochemistry, Faculty of
Biologic Science, payame noor University, Tehran,
Iran
2. Applied Biotechnology Research Center,
Bqiyatallah University of Medical Sciences, Teh-
ran, Iran
*Corresponding Authors
Mohammad Fazilati
Department of Biochemistry, Faculty of Biologic
Science, payame noor University, Tehran, Iran
E-mail: Mfazilati@yahoo.com
Ali Mohammad Latifi
E-mail: amlatifi290@gmail.com
Submission Date: 12/18/2015
Accepted Date: 3/29/2016

Asieh Asghari, et al. Antioxidant Properties of Spirulina
178 Journal of Applied Biotechnology Reports, Volume 3, Issue 1, Winter 2016
reports on antioxidants employed for food lipids were
about using natural sources; in 1852, Wright reported that
elm bark was effective in preserving butterfat and lard [8,
9, 13].
Spirulina was initially classified in the plant kingdom
because of its richness in plant pigments as well as its
ability of photosynthesis. It was later placed in the bacteria
kingdom based on new understanding on its genetics,
physiology and biochemical properties [14]. Spirulina
naturally grows in high-salt alkaline water reservoirs in
subtropical and tropical areas including America, Mexico,
Asian and Central Africa [14, 15]. The nutritional value of
Spirulina is well recognized with its unusual high protein
content (60–70% by dry weight) and its richness in
vitamins, minerals, essential fatty acids and other
nutrients [15-17]. Recent studies suggest that Spirulina, a
unicellular blue-greenalga (Fig. 3), may have a variety of
health benefits and therapeutic properties and is also
capable of acting as an antioxidant and anti-inflammatory
agent [18]. Spirulina is also used for health food, feed and
forthe biochemical products since 1980s. In fact, Spirulina
is the most concentrated and nutritious whole food known
to science, Moreover Spirulina has got no side effects and
is non-toxic in nature [9, 14, 16].
Figure 3. Microscopic view of Spirulina.
Spirulina have well-documented protective effects against
viral and bacterial infections, cancer, allergies, diabetes,
inflammation, and hyper lipidemia in addition, due to its
concentrated nutrition, Spirulina was recommended by
both National Aeronautics and Space Administration
(NASA) and the European Space Agency (ESA) as one of
the primary foods during long-term space missions.
Spirulina has been orally administered to patients as an
anti-cancer and anti-viral agent although the molecular
mechanism by which Spirulina acts on the immune system
remains largely undefined. Recent study showed that when
the Spirulina was enriched with Selenium and combined
with theanticancer drugs, a significant decrease of the
proliferation rate and an increase of apoptosis rate were
observed [9, 13, 17, 19, 20]. Spirulina is a complete food
resource of Chlorophyll, Phycocyanin, & Carotenoids. It is
also has an application as a natural dye in food industry,
cosmetic and pharmaceutical industry [21].
Figure 4. Amount of pigment in one gram Spirulina powder.
Chlorophyll
Chlorophyll is an essential compound in many everyday
products. It is used not only as an additive in pharmaceuti-
cal and cosmetic products but also as a natural food
coloring agent. Additionally, it has antioxidant and
antimutagenic properties (Fig. 5) [22, 23].
Figuer 5. Structure of chlorophyll.
Chlorophyll has been found to accelerate wound healing
by more than 25% in some studies. Since chlorophyll
stimulates tissue growth; it prevents the advancement of
bacteria and speeds up the wound healing process. Chloro-
phyll is similar in chemical structure to hemoglobin and, as
such, is predicted to stimulate tissue growth in a similar
fashion through the facilitation of a rapid carbon dioxide
and oxygen interchange. Because of this property,
chlorophyll is used not only in the treatment of ulcers and
oral sepsis but also in proctology [23-25].
Chlorophyll derivatives such as pheophorbide b and pheo-
phytin b have always been known as strong antioxidants.
However, these derivatives exist in very low concentra-
tions in fruits and vegetables. The most significant activity
of chlorophyll derivatives in the prevention of cancer is the
trapping of mutagens in the gastrointestinal tract. Further-
more, the ability of both natural and commercial
chlorophyll derivatives to act as photosensitizers have en-
abled their utilization as effective agents in photodynamic-
therapy of cancer. in vitro and in vivo consistent with the
346

Asieh Asghari, et al. Antioxidant Properties of Spirulina
Journal of Applied Biotechnology Reports, Volume 3, Issue 1, Winter 2016 177
prevention of cancer including antioxidant activity, anti-
mutagenic activity, modulation of xenobiotic metabolizing
enzymes, and induction of apoptotic events in
cancer cell lines [23, 25].
Carotenoids
Spirulina extracts containing carotenes and various carote-
noids (Fig. 6) are frequently used as natural coloring
materials [19]. Carotenoids are vitally important antioxi-
dants. Numerous studies have indicated that people whose
diets contain a lot of foods rich in carotenoids lower their
risk of developing various types of cancer [10].
Figure 6. Molecular structure of nature’s two forms of beta-
carotene.
They possess antioxidant activity, especially in the pres-
ence of light. Carotenoids also have important metabolic
functions in animals and man, including conversion to Vit
A, enhancement of the immune response and protection
against diseases such as cancer by way of scavenging free
radicals, β-carotene, as a major carotenoid of Spirulina is a
potential antioxidant having anti-carcinogenic and
radio-protective effects. Spirulina contains up to 2,000
IU/g dry weight of β-carotene [26-28]. Eating foods rich in
antioxidants such as carotenoids, phycocyanin, superoxide
dismutase and vitamins C and E is another great way to
help prevent cancer. [7, 29]. Numerous studies have
indicated that people whose diets contain a lot of foods
rich in carotenoids lower their risk of developing various
types of cancer [30], most people get only 25-30% of the
daily dietary carotenoid intake recommended in a cancer-
preventive diet; and many people are unwilling to make
radical dietary changes[19]. Spirulina is a whole food with
its beta-carotene in a naturally chelated food matrix. And
Spirulina is not only rich in beta-carotene, it contains other
very important carotenoids like zeaxanthin and beta-
cryptoxanthin as well as lesser known carotenoids such as
myxoxanthophyll and echinenone. Spirulina extracts are
capable in inhibiting carcinogenesis [31]. In one study
found that Spirulina stabilized the liver disease and
prevented the disease from progressing to cirrhosis. An-
other mouse study showed that Spirulina reduced both skin
and stomach tumors significantly. Spirulina was shown to
reduce both the size of the tumors and to reduce the inci-
dence of tumors. They concluded that diets
containing carotenoid-rich fruits and vegetables may be
protective against prostate cancer [19]. Many earlier
studies have found similar relationships between carote-
noid intake and other forms of cancer. Beta-carotene may
also help to protect the skin against the damaging effects
of sunlight and help to prevent skin cancers [26]. The
results of the trial were surprising in that contrary to the
hypothesis, the beta-carotene supplemented group had a
small (statistically insignificant) increase in the incidence
of lung cancer. Interestingly, the group in the study with
the highest blood levels of beta carotene from dietary
sources had the lowest incidence of lung cancer [26].
Spirulina is the richest beta carotene food known, having
over ten times more beta carotene than any other food,
including carrots. Beta carotene is one of the most
effective substances for deactivating free radicals, which
damage cells, leading to cancer. Free radicals are molecu-
lar fragments from environmental pollution, toxic
chemicals, drugs, and physical and emotional stress [32].
Beta carotene prevents free radicals from reacting, and
decreases incidence of lung cancer, prevents chemically
induced tumors in animals, prevents precancerous pre-
chromosome damage and enhances immunological re-
sistance. Evidence linking natural beta carotene and cancer
prevention is impressive [7, 26]. For those who do not eat
4-9 servings of fruits and vegetables daily, Spirulina will
add natural carotene insurance[19]. According to the find-
ings of the National Cancer Institute, United States of
America, an intake of 6.0 mg ß-carotene daily may be ef-
fective in minimizing the risk of cancer. If anybody takes
4.0 g Spirulina daily, that is sufficient to get 6 mg ß-
carotene [28].
Beta carotene was found to significantly inhibit the for-
mation of squamous cell carcinoma of hamster buccal
pouch when a solution was applied topically three times
weekly for 22 weeks in an experiment with 40 hamsters. In
a second experiment with 80 hamsters, beta carotene was
found to inhibit oral carcinogenesis in an initiation-
promotion hamster buccal pouch system. Beta carotene in
hibited both initiation and promotion [33]. Studies among
preschool children in India have demonstrated Spirulina
fusiform is to be an effective source of dietary vitamin A.
Supplementation with Spirulina did not increase serum
concentrations of retinal or beta carotene, nor was it asso-
ciated with toxicity [32, 34].
Another study showed that beta-carotene reduces the size
of tumors that were already present in hamsters and
slowed new tumor growth, extending the hamsters' surviv-
al time [10, 33]. Numerous studies have shown that people
whose diets are high in beta-carotene have a lower
incidence of various cancers. Smokers, who are especially
vulnerable, should maintain their beta-carotene levels.
Low beta-carotene levels in the blood of smokers have
been connected with the later appearance of lung cancer.
Researchers at Albert Einstein College of Medicine have
shown that beta-carotene exerts a protective effect against
the development and progression of cervical cancer. Beta-
carotene may also help to protect the skin against the
damaging effects of sunlight and help to prevent skin
cancers. In the early 1980’s a landmark study by the US
National Science Foundation entitled Diet, Nutrition
and cancer, concluded on the basis of epidemiological
347

Asieh Asghari, et al. Antioxidant Properties of Spirulina
178 Journal of Applied Biotechnology Reports, Volume 3, Issue 1, Winter 2016
evidence that diets rich in beta carotene were correlated
with a reduction in the incidence of cancer. In fact, over
200 studies of dietary consumption of beta-carotene
indicated a reduction of a range of cancers [19, 26].
Phycocyanin
Phycocyanin is one of the key ingredients that make
Spirulina such a wonderful Super food, and a vital
difference between Spirulina and other green foods like
chlorella, wheat grass and barley [35]. The Japanese have
found that phycocyanin protects the liver and the kidneys
during detoxification, as well as activating the immune
system. Researchers at the Osaka Medical Center for
cancer and Cardiovascular Diseases said “Spirulina is
surmised to potentiate the immune system leading to sup-
pression of cancer development and viral infection [36].
Spirulina selectively inhibited development of some
tumoral cell lines, showing potential anticancer activity
against human stomach cancer cells (AGS), human liver
cancer cells (Hep3B), human lung cancer cells (A549), and
breast cancer cells (MCF-7) [16]. Phycocyanin is a power-
ful water soluble antioxidant [27, 37]. A great deal of
research has been done in Japan on phycocyanin. The
Japanese have found that phycocyanin protects the liver
and the kidneys during detoxification, as well as activating
the immune system. Researchers at the Osaka Medical
Center for Cancer and Cardiovascular Diseases said
“Spirulina is surmised to potentiate the immune system
leading to suppression of cancer development and viral
infection [19]. C-phycocyanin (C-PC) is one of the major
Bili proteins of Spirulina with antioxidant and radical
scavenging properties (Fig. 7) [38].
Figure 7. Chemical structure of C-phycocyanin.
C-PC, a selective cyclooxygenase-2 inhibitor, induces
apoptosis in lipopolysaccharide-stimulated RAW 264.7
macrophages. It is also known to exhibit anti-
inflammatory and anticancer properties. Phycocyanin has
the ability to scavenge free radicals, including alkoxyl,
hydroxyl and peroxyl radicals. It also decreases nitrite
production, suppresses inducible nitric oxide synthase
(iNOS) expression, and inhibits liver microsomal lipidpe-
roxidation. Phycocyanin of Spirulina inhibits the growth of
human leukemia K562 cells [35].
Serum glutamate oxaloacetate and serum glutamate py-
ruvate transaminase activity along with increase in liver
GSH level. The activities of antioxidants enzymes
superoxide dismutase, catalase and Glutathione-S-
transferase were also concomitantly restored to near
normal level by Spirulina supplementation to mercuric
chloride intoxicated mice. The results clearly demonstrate
that Spirulina treatment augments the antioxidants defense
mechanism in mercuric chloride induced toxicity and
provides evidence that it may have a therapeutic role in
free radical mediated diseases [39, 40]. phycocyanin is a
potent peroxyl radical scavenger with an IC(50) of 5.0 μM
and the rate constant ratios obtained for phycocyanin and
uric acid (a known peroxyl radical scavenger) were 1.54
and 3.5, respectively. These studies clearly suggest that the
covalently linked chromophore, phycocyanobilin, is
involved in the antioxidant and radical scavenging activity
of phycocyanin [7, 41].
Other studiesof Spirulina application in cancers
Liver fibrosis is a chronic liver disease that will further
develop to cirrhosis if severe damage continues to form. A
potential treatment for liver fibrosis is to inhibit activated
hepatic stellate cell (HSC) proliferation and, subsequently,
to induce HSC apoptosis. It has been reported that antioxi-
dants are able to inhibit the proliferation of HSCs. In this
study, the aqueous extract of Spirulina was chosen as the
source of antioxidant to investigate the inhibitory effect on
the proliferation of HSC [42].
The growth inhibitory effects of aqueous Spirulina and
chlorella extract on human liver cancer cells, HepG2, were
also studied and compared in pairs. Results indicated that
the total phenol content of Spirulina was almost five times
greater than that of chlorella (6.86 +/- 0.58 vs 1.44 +/- 0.04
mg tannic acid equivalent/g of algae powder, respectively).
The aqueous extracts of these two algae both showed anti-
proliferative effects on HSC and HepG2, but Spirulina was
a stronger inhibitor than chlorella [42].
Water-soluble polysaccharides of Spirulina appear to dis-
play antioxidant, anticancer, and antiviral effects [36]. In
addition, Spirulina does not have secondary undesirable
effects, not being described episodes of occasional human
or animal death as occurred with other microalgae, mainly
due to the presence in those microalgae of hepato and neu-
rotoxins. In parallel with those initial antiviral and anti-
cancer studies, Spirulina extracts were tested for their
immunomodulatory capacities. Since then, enhancement of
the immune system by Spirulina has turned into a key
research line for future uses of this organism. Recently, the
Food and Drug Administration of the United States of
America has included Spirulina in the group of Generally
Recognized as Safe (GRAS) products [16, 20].
It is well established that exercise promotes the production
of reactive oxygen and nitrogen species, which contribute
to skeletal muscle fatigue and damage. Two clinical trials
were conducted to investigate the effects of Spirulina on
preventing excise induced skeletal muscle fatigue and
damage through its antioxidant property. In one study with
16 student volunteers, intake of a diet containing 5%
Spirulina for 3 weeks resulted in a significant reduction of
plasma oxidative marker malondialdehyde (MDA) with a
concurrent increase in the blood superoxide dismutase
(SOD) activity [11, 29, 43].
In a study from the Department of Microbiology and
Immunology at Hokkaido University in Japan, Spirulina
extract was found to excite antitumor natural killer cell
348

Asieh Asghari, et al. Antioxidant Properties of Spirulina
Journal of Applied Biotechnology Reports, Volume 3, Issue 1, Winter 2016 177
response. For their study, the researchers transplanted tu-
mors into a specific species of mice. After orally adminis-
tering hot water extracts of Spirulina to the mice, they
watched for molecular signals in the major histocompati-
bility complex of the micecells. At first, a sub cell line
showed slight expressions of NT response, but as the study
furthered, they noticed natural killer cell activation signals
going off through expressions of Rae-1, a ligand for NK
activation. With natural killer cells now arriving onto the
scene of the tumor-ridden cells, the implanted melanoma
slowly regressed, until the natural killer cell defense effec-
tively eliminated the entire tumor [36, 37].
In China, the influence of water soluble polysaccharide
from Spirulina platensis on excision repair of DNA was
investigated by means of endonuclease assay and radio
autography. The results showed that the presence of the
polysaccharide enhanced significantly both the repair
activity of radiation damaged DNA excision and the
unscheduled DNA synthesis (UDS). During the examina-
tion of the time course of the excision process, it was
found that the presence of polysaccharide of Spirulina not
only increased the initial rates of the damaged DNA
excision and the UDS, but also postponed the saturations
of both important reactions of excision and repair DNA
synthesis [44, 45].
Researchers in both Japan and China have examined the
potential of Spirulina’s polysaccharides in cancer therapy.
In a study titled “Inhibition of tumor invasion and metasta-
sis by Calcium Spirulan,” scientists at Japan’s Toyama
Medical and Pharmaceutical University found that lung
metastasis was significantly reduced by Calcium Spirulan
by inhibiting tumor invasion of the cell membranes [46].
The results of the present study clearly point to the thera-
peutic potential of Spirulina in Cadmium-induced terato-
genicity and probably through its antioxidant activity. Or-
ganic foods often contain high levels of cadmium it is a
little-known fact that the USDA organic program does not
regulate, or measure, or in any way limit the concentration
of heavy metals in "certified organic" foods. Natural News
has found that many "organic" foods contain alarming
levels of heavy metals such as cadmium, lead, mercury,
arsenic and even lighter metals like aluminum [47, 48].
The iron chelating properties of Spirulina was discovered
when human neuroblastoma cells in vitro were exposed to
toxic amounts of iron and then to Spirulina, which
revealed that the iron induced oxidative stress was
reduced. Geriatric patients administered Spirulina for 16
weeks showed a remarkable improvement in the antioxi-
dant potential, as measured by the increased levels of
antioxidant status in plasma of these individuals. A dou-
ble-blinded, placebo controlled study performed on indi-
viduals after exercise, showed decreased amount of crea-
tine kinase, (an indicator of muscular breakdown) when
they were supplemented with Spirulina. Moreover, their
exhaustiontime in the treadmill exercise increased by 52
seconds.This could be explained by the antioxidant poten-
tial of Spirulina [32].
Studies the influence of Spirulina on IgA levels in human
saliva and demonstrated that it enhances IgA production,
suggesting a pivotal role of micro alga in mucosal immuni-
ty. A Japanese team identified the molecular mechanism of
the human immune capacity of Spirulina by analyzing
blood cells of volunteers with pre- and post-oral admin-
istration of hot water extract of Spirulina platensis. IFN-γ
production and Natural Killer (NK) cell damage were
increased after administration of the micro alga extracts to
male volunteers. In a recent double-blind, placebo con-
trolled [49].
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 (P
< .001), including nasal discharge, sneezing, nasal conges-
tion and itching [49].
Spirulina can also be exploited for the production of
various enzymes especially antioxidant enzymes. It has a
very high amount of the superoxide dismutase enzyme,
which is an important free radical scavenging enzyme.
This enzyme can be used therapeutically for the treatment
of various diseases related to oxidative stress or as a com-
ponent in anti-wrinkle skin lotions and face masks as aging
is believed to a consequence of oxidative stress [9, 50].
Reactive oxygen species (ROS) can be generated in a
biological system by processes such as irradiation. These
affect various systems like digestive, hematopoietic,
immune etc. Defense mechanisms include antioxidant
enzymes such as super oxide dismutase (SOD), glutathione
peroxidase (GPx) and catalase, as well as the non-
enzymatic antioxidants like beta-carotene, glutathione,
vitamin E etc. Radiation protection offered by Spirulina
may be due to the phytopigments (carotenoids, chloro-
phyll, phycocyanin) as well as polysaccharides [51].
Another mouse study showed that Spirulina reduced both
skin and stomach tumors significantly. Spirulina was
shown to reduce both the size of the tumors and to reduce
the incidence of tumors [39]. The study determined the
histopathologic and hematologic effects of Spirulina
platensis and Moringa oleifera Lam., and their synergism
on tumor-induced Sprague-Dawley rats. Induction of tu-
mors was done through intraperitoneal administration of
1,2-dimethylhydrazine and 7,12-dimethylbenzanthracene
for four weeks. Readily available capsules and tablets of
Spirulina and malunggay mixed with water were used to
achieve the desired 50% and 75% concentration. Intraper-
itoneal administration of the extracts and intravenous
administration of 5-fluorouracil as the positive control
treatment were done for two weeks post tumor induction.
After treatment, representatives of each treatment groups
were drawn blood and dissected for hematologic and his-
topathologic examination, respectively. Results show anti-
tumor activity of all extracts in the liver in contrast to their
ineffectiveness in the lungs. Furthermore, all but the 75%
Spirulina extract were effective against gastric tumor
development while both concentrations of Spirulina and its
75% concentration successfully countered development of
tumors of the small intestine and large intestine, respec-
tively. All of the extracts caused a general negative effect
on the complete blood count. In conclusion, S. platensis
proved to be the more effective against tumor
development [52].
349

Asieh Asghari, et al. Antioxidant Properties of Spirulina
178 Journal of Applied Biotechnology Reports, Volume 3, Issue 1, Winter 2016
Thus Selenium-enriched Spirulina as a vector for anti-
cancer drug delivery enables to associate any anticancer
drug with Se. This process allows high drug delivery and
produce significant anti-proliferative effect the functionali-
zation of selenium nanoparticles (SeNPs) with Spirulina
polysaccharides (SPS) that has been developed in a study.
Results suggest that the strategy to use SPS as a surface
decorator could be an effective way to enhance the cellular
uptake and anticancer efficacy of nanomaterials. SPS-
SeNPs may be a potential candidate for further evaluation
as a chemo preventive and chemotherapeutic agent against
human cancers [53].
Also study of antimicrobial activities of Spirulina extract
against Staphylococcus aureus (Gram positive bacterium),
Escherichia coli (Gram negative bacterium), Candida
albicans (yeast) and Aspergillus niger (fungus) showed
that C. albicans is the most sensitive microorganism to all
Spirulina fractions, which were obtained by the supercriti-
cal fluid extraction. This antimicrobial activity could be
related to a synergic effect of fatty acids.
Conclusion
Spirulina is a potent mixture of antioxidants and most of
Spirulina’s health benefits are associated with its antioxi-
dant pigments. These are carotenoids (mixture of carotenes
and xanthophylls), chlorophyll and the unique blue
pigment phycocyanin. A little of its usage in medicine has
been established by numerous studies still more of its
hidden properties are yet to be explored. Some of its
properties such as Anti oxidant, Anti inflammatory, Anti
cancer, Anti aging (prevents cell death), Drug delivery
system., etc. Along with these actions in Humans has been
described briefly in this Review. Hope this review will
serve the purpose of aiding in future Research work to
unleash the further components present in Spirulina.
Acknowledgements
This study is extracted from MSc’s thesis which approved
and supported by Applied Biotechnology Research Center,
Baqiyatallah University of Medical Sciences, Tehran, Iran.
The authors would like to thanks the staff of this research
center for their kind help.
References
1. Bisen, P., Marine Microbes: Unexplored Therapeutic Bio-
mine. J Cancer Sci Ther, 2012, Vol. 4, pp. 14121-14127.
2. Boutayeb, A., Boutayeb, S., The double burden of
communicable and non-communicable diseases in developing
countries. Int J Equity Health, 2005, Vol. 4, pp. 2-8
3. Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C.,
Rebelo, M., Parkin, D.M., Forman, D., Bray, F., Cancer
incidence and mortality worldwide: sources, methods and
major patterns in globocan 2012. Int J Cancer, 2015, Vol. 136,
pp. E359-E386.
4. Agnihotri, A., Aruoma, O., Bahorun, T., Cancer: Global
Health Perspectives. Arch Med Biomed Res, 2014, Vol. 1, pp.
1-9.
5. Males, S., Pancreatic cancer. Cancer, 2014, Vol. pp. 2-10
6. Mariotto, A.B., Yabroff, K.R., Shao, Y., Feuer, E.J., Brown,
M.L., Projections of the cost of cancer care in the United
States: 2010–2020. J Nati Cancer Inst, 2011, Vol. pp. 21-26.
7. Devasagayam, T., Tilak, J., Boloor, K., Sane, K.S., Ghaskadbi,
S.S., Lele, R., Free radicals and antioxidants in human health:
current status and future prospects. J Assoc Physician India,
2004, Vol. 52, pp. 4-10.
8. Wanasundara, P., Shahidi, F., Antioxidants: science,
technology, and applications. Bailey's Industrial Oil and Fat
Products, 6th Edition, Wiley, 2005, Vol. 6.
9. Desai, K., Sivakami, S., Spirulina: the womder food of the
21th century. Asia Pac Biotech News, 2004, Vol. 8, pp. 1298-
1302.
10. Khan, Z., Bhadouria, P., Bisen, P., Nutritional and therapeutic
potential of Spirulina. Curr pharm biotechnol, 2005, Vol. 6,
pp. 373-379.
11. Deng, R., Chow, T.J., Hypolipidemic, antioxidant, and
antiinflammatory activities of microalgae Spirulina.
Cardiovasc Ther, 2010, Vol. 28, pp. 33-45.
12. Belay, A., Kato, T., Ota, Y., Spirulina (Arthrospira): potential
application as an animal feed supplement. J Appl Phycol,
1996, Vol. 8, pp. 303-311.
13. Ghaeni, M., Roomiani, L., Masomozadeh, Z., Review for
uses and therapeutic effects of spirulina, Spirulina platensis
microalgae. Global J Adv Pure Appl Sci, 2014, Vol. 4, pp.7-
11.
14. Vonshak, A., Spirulina platensis arthrospira: physiology,
cell-biology and biotechnology. 1997: CRC Press.
15. Ismail, M., Hossain, M.F., Tanu, A.R., Shekhar, H.U., Effect
of spirulina intervention on oxidative stress, antioxidant
status, and lipid profile in chronic obstructive pulmonary
disease patients. BioMed Res Int, 2015, Vol. 2015, pp.7-15.
16. Parages, M.L., Rico, R.M., Abdala-Díaz, R.T., Chabrillón,
M., Sotiroudis, T.G., Jiménez, C., Acidic polysaccharides of
Arthrospira (Spirulina) platensis induce the synthesis of TNF-
α in RAW macrophages. J Appl Phycol, 2012, vol. 24, pp.
1537-1546.
17. Alam, M.A., Haider, N., Ahmed, S., Alam, M.T., Azeez, A.,
Perveen, A., Tahlab (Spirulina) And Few other Medicinal
Plants Having Anti-Oxidant & Immunomodulatory Properties
Described In Unani Medicine-A Review. Int J Pharm Sci
Res, 2013, Vol. 4, pp. 4158-4164.
18. Henrikson, R., Earth food spirulina. Laguna Beach, CA:
Ronore Enterprises, Inc, 1989, Vol. pp.187
19. Moorhead, K., Capelli, B., Spirulina. 1993, Vol. 5, pp. 66-78.
20. Karkos, P., Leong, S., Karkos, C., Sivaji, N.,
Assimakopoulos, D., Spirulina in clinical practice: evidence-
based human applications. Evid Based Complement Alternat
Med, 2010, Vol. 2011, pp. 4-10.
21. Hosseini, E., Mohamadamini, M., Akbari, M., Nejati, F.,
Mazdapour, M., Ghasemian, M., Bahmani, A., The
Laboratory Scale Evaluation of Multiple pH ranges on
Spirulina platensis culture in the Production of Dry Biomass,
Chlorophyll, Phycocyanin, & Carotenoids. Bull Env
Pharmacol Life Sci, 2015, Vol. 4, pp. 13-18.
22. Ferruzzi, M.G., Blakeslee, J., Digestion, absorption, and
cancer preventative activity of dietary chlorophyll
derivatives. Nutr Res, 2007, Vol. 27, pp. 1-12.
23. Hosikian, A., Lim, S., Halim, R., Danquah, M.K.,
Chlorophyll extraction from microalgae: a review on the
process engineering aspects. Int j chem Eng, 2010, Vol. 2010,
pp.11-18.
24. de Oliveira Rangel-Yagui, C., Danesi, E.D.G., de Carvalho,
J.C.M., Sato, S., Chlorophyll production from Spirulina
platensis: cultivation with urea addition by fed-batch process.
Bioresource Technol, 2004, Vol. 92, pp. 133-141.
25. Chauhan, U., Pathak, N., Effect of different conditions on the
production of chlorophyll by Spirulina platensis. J Algal
Biomass Utln, 2010, Vol. 1, pp. 89-99.
350

Asieh Asghari, et al. Antioxidant Properties of Spirulina
Journal of Applied Biotechnology Reports, Volume 3, Issue 1, Winter 2016 177
26. Krinsky, N.I., Johnson, E.J., Carotenoid actions and their
relation to health and disease. Mol Aspects Med, 2005, Vol.
26, pp. 459-516.
27. Mohan, A., Misra, N., Srivastav, D., Umapathy, D., Kumar,
S., Spirulina-The Nature’s Wonder: A Review. Lipids, Vol. 5,
pp. 7-12.
28. Ranga Rao, A., Raghunath Reddy, R., Baskaran, V., Sarada,
R., Ravishankar, G., Characterization of microalgal
carotenoids by mass spectrometry and their bioavailability
and antioxidant properties elucidated in rat model. J Agric
Food Chem, 2010, Vol. 58, pp. 8553-8559.
29. Kalafati, M., Jamurtas, A.Z., Nikolaidis, M.G., Paschalis, V.,
Theodorou, A.A., Sakellariou, G.K., Koutedakis, Y.,
Kouretas, D., Ergogenic and antioxidant effects of spirulina
supplementation in humans. Med Sci Sports Exerc, 2010,
Vol. 42, pp. 142-151.
30. Malila, N., Virtamo, J., Virtanen, M., Pietinen, P., Albanes,
D., Teppo, L., Original Communications-Dietary and serum
a-tocopherol, b-carotene and retinol, and risk for colorectal
cancer in male smokers. Eu J Clin Nutr, 2002, Vol. 56, pp.
615-621.
31. Ibañez, E., Herrero, M., Mendiola, J.A., Castro-Puyana, M.,
Extraction and characterization of bioactive compounds with
health benefits from marine resources: macro and micro
algae, cyanobacteria, and invertebrates, in Marine Bioactive
Compounds. 2012, Springer. p. 55-98.
32. Sherer, L., Anderson, T., Gibson, B., Achterhoff, J., Hope,
A., Spiritual Eating & Cooking. vol. pp.
33. Suda, D., Schwartz, J., Shklar, G., Inhibition of experimental
oral carcinogenesis by topical beta carotene. Carcinogenesis,
1986, vol. 7, pp. 711-715.
34. Bodri, B., how to help support the body’s healing after
intenese radioactive or radiation exposure, 2004, Top Shape
Publishing, LLC.
Top Shape Publishing, LLC.
35. Subhashini, J., Mahipal, S.V., Reddy, M.C., Reddy, M.M.,
Rachamallu, A., Reddanna, P., Molecular mechanisms in C-
Phycocyanin induced apoptosis in human chronic myeloid
leukemia cell line-K562. Biochem Pharmacol, 2004, Vol. 68,
pp. 453-462.
36. Hirahashi, T., Matsumoto, M., Hazeki, K., Saeki, Y., Ui, M.,
Seya, T., Activation of the human innate immune system by
Spirulina: augmentation of interferon production and NK
cytotoxicity by oral administration of hot water extract of
Spirulina platensis. Int Immunopharmacol, 2002, Vol. 2, pp.
423-434.
37. Akao, Y., Ebihara, T., Masuda, H., Saeki, Y., Akazawa, T.,
Hazeki, K., Hazeki, O., Matsumoto, M., Seya, T.,
Enhancement of antitumor natural killer cell activation by
orally administered Spirulina extract in mice. Cancer Sci,
2009, Vol. 100, pp. 1494-1501.
38. Hoseini, S., Khosravi-Darani, K., Mozafari, M., Nutritional
and medical applications of spirulina microalgae. Mini
reviews in medicinal chemistry, 2013, vol. 13, pp. 1231-1237.
39. Ravi, M., De, S.L., Azharuddin, S., Paul, S.F., The beneficial
effects of Spirulina focusing on its immunomodulatory and
antioxidant properties. Nutr Diet Suppl, 2010, Vol. 2, pp. 73-
83.
40. Farooq, S.M., Ebrahim, A.S., Subramhanya, K.H., Sakthivel,
R., Rajesh, N.G., Varalakshmi, P., Oxalate mediated
nephronal impairment and its inhibition by c-phycocyanin: a
study on urolithic rats. Mol Cell Biochem, 2006, Vol. 284, pp.
95-101.
41. Bhat, V.B., Madyastha, K., C-phycocyanin: a potent peroxyl
radical scavenger in vivo and in vitro. Biochem biophys Res
Commun, 2000, Vol. 275, pp. 20-25.
42. Wu, L.-c., Ho, J.-a.A., Shieh, M.-C., Lu, I.-W., Antioxidant
and antiproliferative activities of Spirulina and Chlorella
water extracts. J Agric Food Chem, 2005, Vol. 53, pp. 4207-
4212.
43. Hassanen, M.R., Mahfouz, M.K., Farid, A.S., Fadlullah,
A.H., Biochemical effects of spirulina platensis against
oxidative stress caused by doxorubicin. Vol. 10, pp.8-14.
44. Pang, Q., Guo, B., Ruan, J., Enhancement of endonuclease
activity and repair DNA synthesis by polysaccharide of
Spirulina platensis. Acta Genetica Sinica, 1988, Vol. 15, pp.
374-378.
45. Jihong, P.Q.G.B.R., Enhancement of Endonuclease Activity
and Repair DNA Synthesis by Polysaccharide of Spirulina
plaennsis. Acta Genetica Sinica, 1988, Vol. 5, pp. 8-15.
46. Mishima, T., Murata, J., Toyoshima, M., Fujii, H., Nakajima,
M., Hayashi, T., Kato, T., Saiki, I., Inhibition of tumor
invasion and metastasis by calciumspirulan (Ca-SP), a novel
sulfated polysaccharide derived from a blue-green alga,
Spirulina platensis. Clin Exp Metastasis, 1998, Vol. 16, pp.
541-550.
47. Paniagua-Castro, N., Escalona-Cardoso, G., Hernández-
Navarro, D., Pérez-Pastén, R., Chamorro-Cevallos, G.,
Spirulina (Arthrospira) protects against cadmium-induced
teratogenic damage in mice. J Med Food, 2011, Vol. 14, pp.
398-404.
48. Agrawal, A., Toxicity and fate of heavy metals with
particular reference to developing foetus. Adv Life Sci, 2012,
Vol. 2, pp. 29-38.
49. KUMARI, D.J., Babitha, B., Jaffar, S., PRASAD, M.G.,
Ibrahim, M., KHAN, M.S.A., Potential Health Benefits of
Spirulina platensis. Int J Adv Pharm Sci, 2011, Vol. 2, pp.
417-422.
50. Capelli, B., Cysewski, G.R., Potential health benefits of
spirulina microalgae*. Nutrafoods, 2010, vol. 9, pp. 19-26.
51. Patra, R., Rautray, A.K., Swarup, D., Oxidative stress in lead
and cadmium toxicity and its amelioration. Vet Med Int,
2011, Vol. 2011, pp. 9-14.
52. Besaa, J.J.V., Salibay, C.C., Synergistic Effects of
Arthrospira platensis (Spirulina) and Moringa oleifera
Lam.(Malunggay) on Tumor-induced Rattus norvegicus
(Sprague-Dawley Rat). J Asian Med Students' Assoc, 2013,
Vol. 2, pp. 17-20.
53. Yang, F., Tang, Q., Zhong, X., Bai, Y., Chen, T., Zhang, Y.,
Li, Y., Zheng, W., Surface decoration by Spirulina
polysaccharide enhances the cellular uptake and anticancer
efficacy of selenium nanoparticles. Int J Nanomed, 2012,
Vol. 7, pp. 835-844.
351