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Abstract

C-phycocyanin (C-PC) is a biliprotein found in edible blue-green algae. Its anti-cancer, anti-inflammatory, anti-proliferative and anti-oxidant activities has been evidenced by many in vitro and in vivo studies. Anti-inflammatory activity of C-PC demonstrated by free radical scavenging, inhibition of DNA damage, and decreased ROS. Here, the effects of C-PC on cytotoxicity and cell signaling through the apoptotic and other pathways were studied. Results indicated that anti-proliferative effects of C-PC are mediated by inactivation of BCR-ABL signaling and the downstream pathway PI3K/AKT. Phycocyanin induces apoptotic death, and Bcl-2 expression inhibits it via generation of free radicals. C-PC exerted antimelanogenic mechanisms by downregulating p38 MAPK-regulated CREB pathway activation and upregulating MAPK/ERK-dependent degradation of MITF protein. C-PC-mediated PDT (photodynamic therapy) is approved as a potential therapy for cancer. Phycocyanin can be consumed as a dietary supplement or a food component to obtain health benefits against CVD (cardiovascular disease) and NAFLD (non-alcoholic fatty liver disease). These results suggest that phycocyanin which had been obtained from blue green algae are potential medicaments in the treatment of various kinds of human ailments and cancers. © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research.
Soni et al., IJPSR, 2015; Vol. 6(11): 4588-4600. E-ISSN: 0975-8232; P-ISSN: 2320-5148
International Journal of Pharmaceutical Sciences and Research 4588
IJPSR (2015), Vol. 6, Issue 11 (Review Article)
Received on 14 May, 2015; received in revised form, 21 June, 2015; accepted, 30 August, 2015; published 01 November, 2015
REVISITING THE ROLE OF PHYCOCYANIN IN CURRENT CLINICAL PRACTICE
A. Soni *1, M. Dubey 1, M. Verma 2, R. Dhankhar 1, V. Kaushal 1, R. Atri 1 and R. Sabharwal 3
Department of Radiotherapy 1, Department of Biochemistry 2, PGIMS, Rohtak, Haryana, India.
Consultant Radiation Oncologist 3, Department of Health, Government of Haryana, Kurukshtra, Haryana
India.
ABSTRACT: C-phycocyanin (C-PC) is a biliprotein found in edible blue-green
algae. Its anti-cancer, anti-inflammatory, anti-proliferative and anti-oxidant activities
has been evidenced by many in vitro and in vivo studies. Anti-inflammatory activity
of C-PC demonstrated by free radical scavenging, inhibition of DNA damage, and
decreased ROS. Here, the effects of C-PC on cytotoxicity and cell signaling through
the apoptotic and other pathways were studied. Results indicated that anti-
proliferative effects of C-PC are mediated by inactivation of BCR-ABL signaling
and the downstream pathway PI3K/AKT. Phycocyanin induces apoptotic death, and
Bcl-2 expression inhibits it via generation of free radicals. C-PC exerted
antimelanogenic mechanisms by downregulating p38 MAPK-regulated CREB
pathway activation and upregulating MAPK/ERK-dependent degradation of MITF
protein. C-PC-mediated PDT (photodynamic therapy) is approved as a potential
therapy for cancer. Phycocyanin can be consumed as a dietary supplement or a food
component to obtain health benefits against CVD (cardiovascular disease) and
NAFLD (non-alcoholic fatty liver disease). These results suggest that phycocyanin
which had been obtained from blue green algae are potential medicaments in the
treatment of various kinds of human ailments and cancers.
INTRODUCTION: Phycocyanin extracted from
Spirulina was first marketed in 1980 by Dainippon
Ink and Chemicals under the brand name “Lina
BlueA.1 Phycocyanin is a dietary supplement
dedicated to individuals who are undergoing
chemotherapy and radiation for cancer and is used
to ease negative symptoms during treatment as well
as rejuvenate post treatment.
Phycocyanin is an important molecule extracted
from Spirulina platensis, a 3.6 billion years old blue
green algae and its nutritional values and
therapeutic values are well documented.2, 3
QUICK RESPONSE CODE
DOI:
10.13040/IJPSR.0975-8232.6(11).4588-00
Article can be accessed online on:
www.ijpsr.com
DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.6(11).4588-00
Spirulina is known to have nutritional advantages
of high-quality protein, minerals, vitamins,
essential amino acids, cyanocobalamin (B12),
tocopherols and essential fatty acids including β-
carotene and γ -linolenic acid (GLA).2, 3
Phycocyanin is a water soluble, natural and non-
toxic molecule with anticancer, antioxidant,
antiviral and anti-inflammatory activities.3,4
Phycocyanin is also a powerful agent for the
immune system in human and animals, and
provides protection from a number of diseases.3
The deep blue colour of Phycocyanin has been
widely used as a colorant in food industry for food
additive purposes.3 Various research studies also
support strong hepatoprotective, cytoprotective and
neuroprotective profile of phycocyanin.
Most of the studies are based on the laboratory
experimental results on mice and cultured cell
lines, and, still very less literature is available to
conclude any concrete result for Phycocyanin use
Keywords:
Anti-oxidant, apoptosis,
cancer, free radicals, Phycocyanin.
Correspondence to Author:
Dr. Abhishek Soni
Senior Resident, Department of
Radiotherapy, Post-graduate institute
of medical sciences, Rohtak, India
124001
E-mail: abhisheksoni246@gmail.com
Soni et al., IJPSR, 2015; Vol. 6(11): 4588-4600. E-ISSN: 0975-8232; P-ISSN: 2320-5148
International Journal of Pharmaceutical Sciences and Research 4589
in current era of medical practice. Thus, this article
reviews the role of phycocyanin in today‟s clinical
practice.
Structure:
Phycocyanin occurs as the major phycobiliprotein
in Cyanobacteria and as a secondary
phycobiliprotein in some red algae.2 C-
Phycocyanin (C-PC) is a natural compound.5 The
pigment is composed of two subunits, α and β,
which occur in equal numbers, but the exact
number may vary among the species. Both α and β
subunits contain only the PCB chromophore.2 The
structure of C-phycocyanin from the thermophilic
blue green algae Mastigocladus laminosus has been
determined at 3 Å resolution by X-ray diffraction
methods. The protein found to consist of three α-β
units arranged around a threefold symmetry axis to
form a disc with dimensions of 110 Å × 30 Å with
a central channel of 35 Å in diameter. Both
subunits, α and β, have a similar structure and are
related by a local twofold rotational axis.6 Its
molecular weight is between 70,000 and 110,000
Daltons. Phycocyanin has visible absorption
maximum between 615 and 620 nm and maximum
fluorescence emission at ~650 nm.2 Phycocyanin
accepts quanta from phycoerythrin by fluorescent
energy transfer in organisms in which it is present.2
The purity of C-PC is evaluated using the
absorbance ratio of A620/A280, and a purity of 0.7
is considered as food grade, 3.9 as reactive grade,
and more than 4.0 as analytical grade. Purity is
directly related to process costs, and, in general, the
more purified a product is, the more expensive to
obtain it.1
Fig.1 shows chemical structure of the bilin
chromophores in phycocyanin, which is very
similar to bilirubin, a heme breakdown product.2
FIG.1: CHEMICAL STRUCTURE OF PHYCOCYANIN
BILIN CHROMOPHORE (OPEN-CHAIN TETRAPYRROL) 2
Sources:
Phycocyanin can be extracted mainly from blue
green algae and may be from red algae
(rhodophytes) and cryptophytes.7 Main sources are
Spirulina platensis, Arthrospira platensis, Spirulina
maxima, Phormedium fragile, Nostoc muscorum,
Oscillatoria species, Nostoc humifusum, Anabaena
oryzae, Wollea saccata, Anabaena flous aquae,
Limnothrix and Porphyra haitanensis, thermophilic
cyanobacterium Mastigocladus laminosus,
Agmenellum quadruplicatum, Remyella
diplosiphon, Phanizomenon flos-aquae, marine
cyanobacterium Synechococcus sp. IO9201,
Galdieria sulphuraria (rhodophyte), Anabaena sp.
PCC 7120, Leptolyngbya species, Scytonema
julianum, Thermosynechococcus elongates,
Tolypothrix tenuis, Nostoc minutum, Klamath
algae, Acaryochloris marina, and Microcystis
aeruginosa.6-17
Extraction and Purification:
A number of drying methods like spray dried,
crossflow dried and oven dried methods, are used
for Spirulina processing, and results in
approximately 50% loss of phycocyanin. So fresh
biomass is suitable for extraction of phycocyanin.18
Blue green algae are grown in nutrient medium
(like Zarrouk‟s medium) containing different
amounts of nitrogen and salt. In Spirulina species,
Phycocyanin pigments increase from 12% to 22%
on increasing nitrogen levels.3 Spirulina has a wide
variety in composition of Phycocyanin pigments
ranging from R-phycocyanin (R-PC) from 5.75 to
12.35%, allophycocyanin (A-PC) from 2.53 to
6.11% and C-phycocyanin (C-PC) from 1.65 to
4.02% as a result of changing nitrogen contents and
salt stress.3, 19
The concentration of Phycocyanin pigment
including C-Phycocyanin (C-PC), allophycocyanin
(A-PC), and R-phycocanin (R-PC) are determined
spectrophotometrically at 618 and 650 nm, 650 and
618 nm, and 498, 615 and 650 nm respectively as
reported by Kursar and Alberte.20 Cyanobacteria
adjusts the contents and relative ratio of its
pigments with the light quality, like more
production under red or violet light.21 C-PC is a
natural blue pigment accounting for 14% of SP dry
weight.22 The increase in NaCl levels in nutrient
Soni et al., IJPSR, 2015; Vol. 6(11): 4588-4600. E-ISSN: 0975-8232; P-ISSN: 2320-5148
International Journal of Pharmaceutical Sciences and Research 4590
medium led to significant increase in production of
Phycocyanin contents and soluble protein in
Spirulina cells.23, 24 Phycocyanin production also
depends on iron concentration in the media.25 Thus,
Spirulina species grown under combined stress of
high NaCl and nitrogen deficient levels, produce
higher amount of Phycocyanin.3, 21, 26, 27
Many methods have been used for the separation
and purification of C-PC. C-PC is purified from
Spirulina platensis by ammonium sulfate
precipitation, ion-exchange chromatography,
modified flow cytometry and free-flow
electrophoresis (FFE).5, 28, 29 SDS-polyacrylamide
gel electrophoresis is performed to assess the
molecular weight and purity of C-PC. SDS-PAGE
analysis of the purified fraction clearly showed 2
protein bands corresponding to α and β subunits of
C-PC. The purity of C-PC, as judged by an
A620/A280 purity ratio greater than 4.0, is
sufficient for further testing. 5, 30 Femtosecond laser
spectroscopies are used to examine the electronic
structures of cyanobacteria.31
Table 1 shows the purity of C-PC after various
stages of purification which can be implied for
further analysis of grading the phycocyanin. The
table signifies that the purity can be increased and a
food grade phycocyanin was isolated.1
TABLE 1: PURIFICATION OF PHYCOCYANIN1
Sr. No.
Purification
process
Phycocyanin
concentration
(mg/ml)
1
Crude
Phycocyanin
1.94
2
Ammonium
sulphate
precipitation
2.39
3
Membrane
filtration
2.64
4
Dialysis
2.90
Cell cytotoxicity was evaluated by the 2,3-bis[2-
methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-
carboxyanilide inner salt (XTT) assay. Western
blot analysis is used to study the expression and
phosphorylation of proteins in the PI3K/AKT
pathway.5 The oxygen radical absorbance capacity
(ORAC) assay is used to assess antioxidant activity
of phycocyanin.32 C-PC concentration from G.
sulphuraria is low than cyanobacteria.33
Uses:
The spray-drying method is used to load
chitosomes with C-phycocyanin for colonic drug
delivery.34 Phycocyanin extracted from Spirulina
platensis displayed favorable health benefits such
as improving immune function, promoting zooblast
regeneration and inhibiting the growth of cancer
cells.35 Since phycocyanin is photosensitive, it has
been proposed as a new photosensitizer for
photodynamic therapy.36 C-phycocyanin is
endowed with various biological and
pharmacological properties.5 C-phycocyanin
possesses significant antioxidant activities and can
enhance immunity and inflammatory responses.5
Studies have shown that C-phycocyanin can induce
apoptosis in cancer cells such as a mouse
macrophage cell line (RAW 264.7), prostate cell
line (LNCaP), breast cell line (MCF-7), and
erythromyeloid leukemia cell line (K562).5
Phycocyanin is used in treatment of hepatocellular
carcinoma, rectal cancer, leukemia, melanoma and
used in food industry, biomedicine and cosmetics
industry. Subashini et al demonstrated that C-
phycocyanin induced apoptosis in K562 cells is
mediated by cytochrome c release, PARP cleavage,
and Bcl-2 down-regulation.5 C-phycocyanin could
be used for treating ischemia-reperfusion injury
through the activation of ERK pathway and
suppression of p38 MAPK pathway.37, 38
Phycocyanin is a potent antioxidant as well as
herbicidal agent, and possesses significant immune
enhancing and antiviral properties.1, 39, 40 It‟s
enhancing biological defense activity against
infections disease reduces allergies inflammation
by the suppression of IgE antibody.
The phycocyanin is used as coloring agent in food
item like jellies, chewing gums, ice sherbaths, and
dairy products, and it enhances antioxidant capacity
of food and beverages.1, 41 In Japan, China, and
Thailand, phycocyanin is used in cosmetics like
lipstick and eyeliners.1 It is used in biomedical
research and pharmaceutical industries.1, 42, 43 It is
used in immune diagnostic applications.1 C-PC
selectively stimulates the lymphocyte antioxidant
defence system of occupationally exposed subjects.
The activation of the antioxidant protective
mechanisms as part of the early radiation response
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International Journal of Pharmaceutical Sciences and Research 4591
is probably related to the chronic low-dose
occupational exposure. The modulating capacity of
C-PC at the molecular level may be of interest for
the protection of occupationally exposed persons.44
Antioxidative Properties of Phycocyanin:
Antioxidant activity of Phycocyanin is
demonstrated by ascorbate/iron/H2O2 assays,
DPPH (2,2 diphenyl-1-picrylhydrazyl) assay and
ABTS (2,2‟-azino-bis ethylbenzthiazoline-6-
sulfonic acid) assay.8, 45 Oxidative stress, mainly
characterized by reactive oxygen species (ROS),
damages tissues and therefore is associated with
several pathological conditions, such as
atherosclerosis, nonalcoholic steatohepatitis
(NASH), and aging. 46 Hydroxyl and peroxyl
radicals are associated with oxidative damage to
lipids and DNA.46 Human studies have reported the
protective effects of BGA against oxidative damage
in vivo and in vitro.
SP supplementation of 8 grams per day for 12
weeks significantly decreased plasma levels of
MDA (malondialdehyde), a biomarker of oxidative
stress, in diabetic patients. Similarly, healthy
elderly Korean subjects who consumed 8 grams per
day of SP for 16 weeks showed a decrease in the
lipid peroxidation level, whereas the total
antioxidant status and levels of antioxidant
enzymes, such as SOD and GPx, were elevated in
plasma, indicating that SP supplementation was
able to improve antioxidant status in the human
subjects. C-PC markedly inhibited the production
of alkoxyl radicals that are generated by the
reaction of tert-butyl hydroperoxide with ferrous
ions in the presence of luminol. In addition, C-PC
prevented DNA damage and scavenged hydroxyl
and peroxyl radicals. Furthermore, C-PC inhibited
peroxyl radical-induced oxidative hemolysis and
lipid peroxidation in normal human erythrocytes.46,
47
C-PC from AFA extract demonstrated protective
effects against cupric chloride-induced lipid
oxidation in human plasma samples. Cysteine-rich
cyanopeptide beta 2 isolated from C-PC of SF
demonstrated free radical scavenging, inhibition of
DNA damage, and decreased ROS production.48
Selenium-containing allophycocyanin (Se-APC)
extracted from selenium-enriched SP inhibited
2,20-azobis-2-methylpropanimidamide,
dihydrochloride (AAPH)-induced oxidative
hemolysis, and morphological changes in human
erythrocytes.49 Se-APC, furthermore, inhibited
AAPH-induced intracellular ROS production and
MDA accumulation.46 Treatment with C-Pc
protects the rats from Tributyltin (TBT) induced
thymic atrophy, but not proved in humans for such
a role.50 Phycocyanin may inhibit atherosclerosis by
activating heme oxygenase-1.51 Phycocyanin helps
in displacing fluoride, facilitating antioxidant
formation, reverses sodium fluoride-induced
thyroid changes, improves behaviour and protects
Purkinje cells. Phycocyanin supplementation
during pregnancy may reduce the risk of fluoride
toxicity to offspring.52
Lipid-Lowering Effect of Phycocyanin:
In human clinical trials, supplementation with
Spirulina Platensis (SP) exhibited lipid-lowering
effects. In patients with type 2 diabetes, subjects
who consumed 2 grams per day of SP for 2 months
showed significantly lower plasma triglyceride
(TG) concentrations as well as a significant
reduction in ratios of total cholesterol : HDL-C and
LDL-C : HDL-C.46 Eight grams per day of SP
supplementation for 12 weeks significantly reduced
plasma triglyceride concentrations and blood
pressure in type 2 diabetic patients with higher
initial triglyceride levels, whereas subjects with
high initial total cholesterol and LDL-C showed
significant reductions in the plasma lipids. In
patients with a hyperlipidemic nephritic syndrome,
1 gram per day of SP supplementation for 2 months
significantly decreased plasma total cholesterol,
LDL-C, and triglyceride concentrations. Up to
now, BGA dosages used in human clinical trials
have ranged from 1 to 8 grams per day for up to 24
weeks, whereas 5 gram per day is generally
recommended by the manufacturers.46
Although individual cases of discomfort or
unpleasant condition have been reported with BGA
supplementation from time to time, Dietary
Supplements Information Expert Committee (DSI-
EC) of the United States Pharmacopeial
Convention has awarded Spirulina (SM and SP) a
grade A safety rating and agreed that Spirulina is
generally safe to be consumed.53 Concern over
using BGA during pregnancy and breast feeding is
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International Journal of Pharmaceutical Sciences and Research 4592
not clearly defined in humans. However, numerous
animal studies indicated that SP consumption
during pregnancy and lactation did not induce signs
of maternal intoxication.46
In contrast, Kapoor and Mehta had demonstrated
that SP supplementation could improve iron status
during pregnancy, as evidenced by a higher
hemoglobin count, serum iron, and serum ferritin.54
Further study is necessary to evaluate the effect of
BGA supplementation in humans during specific
nutrition status and pathological conditions.46
Morcos et al perfused atherosclerotic artery
segments obtained within 5 hours postmortem with
0.1 mg/ml phycocyanin in oxygenated Krebs
Ringer solution at 30 mmHg for five minutes
followed by washout with Phycocyanin free Krebs
for ten minutes. Histologically, on light and
fluorescence microscopy, artery section revealed
fluorescence localization within the plaque
particularly at the site of elastic lamina and also at
the internal elastic lamina but not in the medial
muscle layer.
These properties suggested therapeutic use of
Phycocyanin for plaque localization and
regression.55 Both C-PC and CD59 inhibit the
process of atherosclerosis, and the anti-
atherosclerotic properties of C-PC might be due to
promoting CD59 expression, preventing
proliferation of smooth muscle cell and the
apoptosis of endothelial cells, reducing lipid levels,
and finally inhibiting atherosclerosis.56
Phycocyanin prevents hypertension and endothelial
dysfunction related disease like metabolic
syndrome.57
Effect of C-PC on Lipid Peroxidation:
ROS initiate the peroxidation of membrane lipids,
leading to the accumulation of lipid peroxides and
leakage of cytosolic enzymes into circulation.46
Bhat and Madyastha reported C-PC inhibited
nearly 95% of peroxyl radical-induced lipid
peroxidation. C-PC with a reduced chromophore
can efficiently inhibit peroxyl radical-induced lipid
peroxidation in a dose-dependent manner.58
Anti-Inflammatory Effects of Phycocyanin:
Oxidative stress plays important roles in lung
disease, gastrointestinal dysfunction, endothelial
dysfunction and atherosclerosis.45 Anti-oxidative
and anti-inflammatory effects can be demonstrated
by non-alcoholic steatohepatitis model.59 C-
phycocyanin suppresses inflammation by inhibiting
the expressions of inducible cyclooxygeanase-2
(COX-2) and nitric oxide synthase, and by
inhibiting the production of pro-inflammatory
cytokines. Also, Phycocyanin scavenges free
radicals, including alkoxyl, hydroxyl and peroxyl
radicals; inhibits liver microsomal lipid
peroxidation, decreases prostaglandin E(2)
production, reduce myeloperoxidase production,
decreases nitrite production, inhibits platelets
aggregation, and uppresses the activation of nuclear
factor-κB (NF-κB) via preventing degradation of
cytosolic IκB-α. These all effects lead to anti-
inflammatory activity of Phycocyanin.60 Upto now,
the antinociceptive properties of phycocyanin have
been less thoroughly investigated.45
Consumption of BGA has been demonstrated to
promote immunity and to protect against
inflammatory diseases, such as colitis, arthritis, and
allergic rhinitis in animal and human studies.61 SP
organic extracts markedly decreased the secretion
of proinflammatory cytokines, including the
granulocyte-macrophage colony stimulating factor,
IL-6, MCP-1, and TNFa. Moreover, translocation
of NF-jB from cytoplasm to nucleus was also
inhibited. Anti-inflammatory effects of BGA have
been shown in cell studies, animal studies, and
human studies. Furthermore, understanding of the
effect of BGA on acute or chronic inflammatory
pathways is necessary because although the two
pathways share some of common mediators,
protective effects against chronic inflammation at a
low degree for a long period of time are more
relevant and beneficial to the prevention of
metabolic diseases such as CVD and NAFLD.46
Several components of BGA, including GLA and
PC, have been implicated in their anti-
inflammatory effects. SP contains 1.3% GLA. An
anti-inflammatory effect of SP is also often
associated with antioxidant and antiviral properties
of C-PC and R-PC.46 Phycocyanin supplementation
significantly reduces the salicylate-induced tinnitus
in mice.62
Antibacterial Role:
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International Journal of Pharmaceutical Sciences and Research 4593
The antibacterial activity of S. maxima extracts
were assayed against five bacterial strains (P.
aeruginosa, B. subtilis, S. aureus, E. coli and
Streptococcus sp.) by evaluation of the inhibition of
zones. Generally, all S. maxima extracts were
found to be effective with antibacterial activity and
were dose dependant. This phenomenon was in
agreement with that found by Ozdemir et al.63 The
data in Table 2 showed that the most susceptible
bacteria were Streptococcus sp. and B. subtilis to S.
maxima with highest inhibition zones ranged 613
mm at concentrations 100400 µl/disk. It is of
interest to note that all S. maxima extracts
manifested similar degrees of susceptible towards
both Gram-positive and Gram-negative bacteria.
The lower inhibition zone ranged from 6 to 9 mm
of extracts obtained for S. maxima.1
TABLE 2: ANTIBACTERIAL ACTIVITY OF
PHYCOCYANIN1
Sr.
No.
Microorganism
Zone of inhibition at various
concentrations of C-PC (mm)
100µl
200µl
300µl
400µl
1
Streptococcus
9
11
12
13
2
Pseudomonas
8
10
11
12
3
Bacillus
8
10
11
13
4
Staphylococcus
6
7
8
9
5
E. coli
7
9
10
11
Sarada et al showed that phycocyanin was able to
markedly inhibit the growth of drug resistant
bacteria Escherichia coli, Klebsiella pneumonia,
Pseudomonas aeruginosa and Staphylococcus
aureus while no activity was recorded
in Acinetobacter baumanii and Enterococcus
durans.64
Phycocyanin as Immune System Modulator:
The regular intakes of phycocyanin boost immune
responses.65-67 When used as an adjuvant to
chemotherapy Phycocyanin boost immune
system to fight cancer spread, improved cancer
response to chemotherapy and decreased risk that
chemotherapy may give rise to a new cancer.
Phycocyanin affects the stem cells in the bone
marrow, which produce white blood cells that make
the immune system and red blood cells that
oxygenate the body. Phycocyanin emulates the
affect of erythropoetin, which regulates red blod
cells production. Phycocyanin suppresses allergic
IgE antibody response and enhances secretary IgA
antibody response in mice. The immune cells
involved in cancer control, NK cells and cytotoxic
T lymphocytes, function more effectively with
intake of Phycocyanin.65, 68
Phycocyanin Mediated Apoptosis
COx-2 play a significant role in promoting tumor
growth in multiple organ systems and is
overexpressed in human lung, breast, colorectal and
prostrate tumors. C-phycocyanin from S. platensis
is a specific COx-2 inhibitor. Phycocyanin
generates free radicals, which induce damage at
macromolecular level, leading to apoptotic cell
death.60 Pardhasaradhi et al demonstrated
Phycocyanin inability to induce apoptosis in Bcl-2
transfectants which correlated well with significant
decrease in production of ROS (reactive oxygen
species) in these cells.60 Z-VAD, a pancaspase
inhibitor, inhibits phycocyanin-mediated apoptosis,
which indicates some role of caspases in apoptotic
death of BC-8 cells (monoclonal cells of rat
histiocytic tumor). Phycocyanin downregulates
Bcl-2 expression in BC-8 cells, thereby make them
vulnerable to apoptotic death. Since many tumors
are resistant to apoptosis due to Bcl-2 expression,
therefore, Phycocyanin treatment leading to Bcl-2
down-regulation, may make them sensitive to other
anticancer agents that kill the tumor cells via
apoptosis. Pardhasaradhi et al showed that
phycocyanin induce apoptosis in tumor cells via
ROS production, which is suppressed by Bcl-2.60
Anti-Cancer Effects:
Shanab et al showed that Spirulina Platensis
showed higher antioxidant activity and moderate
anticancer efficiency among various algal species
due to its total phycobiliprotein pigments, and
secondary metabolites.8 Shalaby et al revealed that
Spirulina platensis shows highest antioxidant
activity under salt stress conditions.69 Wang et al
reported that c-phycocyanin interact with the
membrane associated glyceraldehydes-3-phosphate
dehydrogenase (GADPH) and B-tubulin, causing
polymerization of microtubules and actin filaments
leading to arrest the cell cycle at G0/G1 phase, thus
exhibiting higher antiproliferative activity.70
The anticancer potential of C-PC extracted from
Spirulina platensis is very well known.71
Phycocyanin induces apoptosis in the existing as
well as proliferating cancer cells. Various
mechanisms of its anticancer activity are clear from
Table 3.71
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International Journal of Pharmaceutical Sciences and Research 4594
TABLE 3: VARIOUS MECHANISMS OF ANTITUMOR
ACTIVITY OF C-PC ISOLATED FROM SPIRULINA
PLATENSIS 71
Sr.
No.
Mechanism
Study
Year
1
Interference of DNA
synthesis in the tumor cells
Wang et al
2001
2
Activation of caspase-
dependent programmed cell
death pathways (apoptosis)
Pardhasaradhi et
al
Li et al
Roy et al
Li et al
2003
2006
2007
2010
3
Inhibition of tumor cell
growth by membrane
destruction, leading to
increased leakage of cell
constituent
Abd El-Baky
2003
4
Inhibition of tumor cell
growth by stimulation of
expression level of the proto-
oncogene c-myc
Liu et al
2000
5
Improvement of host immune
functions
Hayashi et al
Li et al
2006
2010
Gantar et al demonstrated that in contrast to the C-
PC of Spirulina platensis, the C-PC from the
cyanobacterium Limnothrix species exhibited low
activity.72 Previous studies have reported that
phycocyanin from Spirulina platensis inhibited the
growth of human hepatocellular carcinoma cell line
SMMC-7721, human rectal cancer cell line
HR8348, and human leukemia HL-60, as well as
K562 and U937 cell line. Phycocyanin from
Porphyra haitanensis was also reported to inhibit
the growth of HL-60 cells. Phycocyanin inhibits the
growth of Ehrlich Ascites Carcinoma Cells
(EACC) in a dose dependent manner, by a pathway
other than the apoptosis, by membrane destruction,
which led to increase in the leakage of cell
constituent and increase in GST and LDH enzyme
activities.3 Spirulina maxima and its protein extract
mainly C-phycocyanin provided moderate
genotoxic protection (~30%) against hydroxyurea
and some protection against the hydroxyurea
induced cytotoxicity in mice.73
C-phycocyanin attenuates cisplatin-induced
nephrotoxicity in mice.74 Hence, Phycocyanin have
antitumor activity and may be used as a
chemopreventive agent.3
Effect on Prostate Cancer:
Gantar et al reported that when only 10% of
standard dose of topotecan was combined with C-
PC, the prostate cancer cells (LNCaP) were killed
at a higher rate than when topotecan was used
alone at full dose. C-PC induce apoptosis through
generation of ROS and activation of caspase-9 and
caspase-8.72
Melanogenesis Inhibitor:
C-phycocyanin is a potential melanogenesis
inhibitor. C-phycocyanin inhibits melanin
biosynthesis by dual mechanisms; the promoted
MITF protein degradation via MAPK/ERK
signaling pathway upregulation, and the suppressed
activation of CREB via the p38 MAPK pathway
down-regulation as is clear from Table 4.37, 75
TABLE 4: PATHWAY INVOLVED FOR C-PHYCOCYANIN
AS MELANOGENESIS INHIBITOR37, 75
Negative impact
Positive impact
-C-phycocyanin may also
exert its negative impact on
p38 phosphorylation
-to restrict activation of the
CREB
-resulting in restricted MITF
gene expression
-C-phycocyanin elevates the
cellular abundance of cAMP
-which triggers the activation
of down-stream MAPK/ERK
pathway
-leading to the reduction of
MITF proteins
-activation of ERK1/2
resulted in the
phosphorylation of MITF at
S73
-induced the subsequent
ubiquitin-dependent
proteasomal degradation of
MITF
The structure resemblance of C-phycocyanin
constituents to MAPK pathway modulators (like
SB203580 and bilirubin), account for its
antimelanogenic effect.37 SB203580 [4-(4‟-
fluorophenyl)-2-(4‟- methylsulfinylphenyl)-5-(4‟-
pyridyl) imidazole] acts as a competitive inhibitor
of ATP binding of MAP kinase homologues p38a,
p38b and p38b2, and blocks a-MSH induced
melanogenesis in B16 cells.76 The prosthetic group
of C-phycocyanin, phycocyanobilin might possess
similar pyridinyl imidazole structural features to
that of SB203580, so, sharing comparable
inhibitory mechanisms.37 In constrast, a structurally
related molecule of phycocyanobilin, bilirubin,
have an anticancer activity through the
MAPK/ERK pathway activation.77
C-phycocyanin was found to be at nucleus at the
early stage of entrance and afterwards accumulated
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International Journal of Pharmaceutical Sciences and Research 4595
at the cytoplasm.37 Phycocyaniobilin, could
function as either or both an ERK activator and a
p38 MAP kinase inhibitor to regulate melanin
synthesis.37
Hematological Role:
In chronic leukemias, including chronic myeloid
leukemia (CML), Philadelphia negative
myeloproliferative neoplasms (MPNs), and chronic
lymphocytic leukemia (CLL), evidence of defects
in the regulation of cellular signaling pathways has
been reported. Currently, treatment of a CML
patient is usually based on a potent protein-tyrosine
kinase inhibitor such as imatinib. Imatinib inhibits
the kinase activity of the BCR-ABL oncoprotein,
thus hindering cell proliferation. Although imatinib
is an effective medication, drug resistance is a
problem. Therefore, an alternative medicine is
needed.5 Phycocyanin is an antioxidant protector of
human erythrocytes against peroxyl radicals.78
The anticancer effects of C-PC appear to mediated
by various mechanisms such as an increase in the
proapoptotic Fas rotein, down-regulation of Bcl-2,
and selective inhibition of COX2. The pathway
through which C-PC exerts its activities will enable
its application as a therapeutic agent for MPNs.5
Tantirapan et al found that C-PC at a micromolar
level exhibited a cytotoxic effect on human
erythromyeloid leukemia cell line (K562 cells).5
Subhashini et al demonstrated a decrease to
approximately 65% of the control growth of K562
cells treated with C-PC. Decrease in the cell growth
is a result of apoptosis via downregulation of anti-
apoptotic Bcl-2, release of cytochrome c into the
cytosol, and cleavage of poly(ADP) ribose
polymerase (PARP). C-PC induce apoptosis and
inhibit proliferation of cancer cells by altering
signal transduction related to both apoptosis
enhancement and terminated proliferation in cancer
cells, possibly through the Ras/Raf/Mek/ERK,
JAK/STAT, MAPK and PI3K/AKT pathways in
K652 cells.5
Hepatocellular Carcinoma (HCC):
Roy et al demonstrated a 50% decrease in
proliferation of doxorubicin sensitive (S-HepG2)
and doxorubicin resistant (R-HepG2) HCC cell
lines with phycocyanin. C-PC also enhanced the
sensitivity of R-hepG2 HCC cells to doxorubicin.
They showed downregulation of the anti-apoptotic
protein Bcl-2 and upregulation of the pro-apoptotic
Bax protein in the R-HepG2 cells.79 Nishanth et al
reported a significant down regulation of MDR1
(multidrug resistance-1) expression in C-PC treated
HepG2 cells through cyclooxygenase-2 (COX-2)
and reactive oxygen species mediated pathways. In
a concentration dependent manner, C-PC increased
the doxorubicin accumulation in HepG2 cells and
enhanced cells sensitivity to doxorubicin by 5
folds. Further studies reveal the involvement of
AP-1 and NF-κB in the C-PC induced down
regulation of MDR1. The inactivation of the signal
transduction pathways involving ERK, Akt, p38
and JNK by C-PC was also observed.80
Ou et al produced hepatoprotective activity of C-
phycocyanin against carbon tetrachloride-induced
hepatocyte damage in vivo and in vitro.
Mechanisms involved through C-PC‟s scavenging
ability and ability to block inflammatory infiltrate
through its anti-inflammatory activities by
inhibiting HGF and TGF-β1 expression.81
Phycocyanin being COX-2 inhibitor, significantly
inhibits liver microsomal lipid peroxidation hence
protecting the liver by preventing oxidative stress
in hepatocytes.82 Phycocyanin inhibits microsomal
lipid peroxidation induced by Fe+2 ascorbic acid
or the free radical initiator 2, 2‟ azobis (2-
amidinopropane) hydrochloride (AAPH).83 C-PC
extracted from Porphyra yezoensis could develop
to new photosensitizers for cancer photodynamic
therapy.84
Colon Carcinoma:
Lu et al reported that the recombinant α-subunit of
C-phycocyanin (CpcA) inhibited the growth of
human colon carcinoma COLO 205 cells. The
apoptotic process was associated with the Bax/Bcl-
2 ratio up-regulation, mitochondrial membrane
depolarization, cytochrome c release, and caspase-9
activation. It was proven that CpcA induced the
death of COLO 205 cells through intrinsic
apoptotic pathway.85
Breast Cancer:
Phycocyanin is an ideal photosensitizer which
accumulates in breast cancer tissue and attracts He-
Ne laser to target at tumor tissues. Being natural
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International Journal of Pharmaceutical Sciences and Research 4596
and non-toxic, phycocyanin is a good substitute to
highly toxic photosensitizers or chemotherapeutic
drugs. It also causes inhibition of MCF-7 cell
proliferation and morphological changes like
chromatin condensation, blebs formation and loss
of microvilli. C-PC-mediated photodynamic
therapy activates immune system, induce pro-
apoptotic Fas genes activation, cause apoptotis of
cancer cells and down-regulates anti-apoptotic
protein expression such as P53, Bcl-2, NF-kB and
CD44 mRNA. Hence, Phycocyanin could be the
new potential anticancer drug for therapy of
Human Breast Cancer.86
Cervix Cancer:
Treatment of Human cervical cancer cell line
(HeLa) cells with Phycocyanin increases
hypodiploid cells population and DNA
fragmentation. Phycocyanin reduces antiapoptotic
proteins Bcl-2 level and promote death receptor
genes expression like Fas/FasL and ICAM.
Caspases play a central role in all apoptotic
pathways and a higher level of caspases are seen in
phycocyanin treated cells. Hence, Phycocyanin
might be the new potential anticancer agent for
Cervical Cancer therapy.87
Phycocyanin and Laser Therapy:
In this photochemical method, Phycocyanin is
injected into a patient suffering from
atherosclerosis or cancer. After being injected,
phycocyanin is taken up selectively into the
atherosclerotic plaques or the cancer cells.
Destruction of the atherosclerotic plaques or the
cancer cells occurs on subsequent irradiation.
Phycocyanin has several advantages over prior art
chemicals used for similar purposes. First, it is only
marginally sensitive to ultraviolet part of the
spectrum; consequently the patients can be
irradiated without taking concern that they will be
sensitized to subsequent sunlight exposure. Second,
phycocyanin is taken up selectively into the
atherosclerotic plaques, with little or no uptake by
the surrounding normal cells. This ensures that
upon subsequent irradiation, atherosclerotic
plaques are selectively destroyed with little or no
damage to surrounding cells or tissue.88
Effect on Pancreas:
Li et al demonstrated that cleavage of poly (ADP-
ribose) polymerase (PARP) and activation of
caspase-3 was blocked by Phycocyanin in hIAPP-
treated cells. Also, PC significantly prevented the
hIAPP-induced overproduction of malondialdehyde
(MDA) and intracellular ROS, as well as changes
in activities of glutathione peroxidase (GSH-Px)
and superoxide dismutase (SOD) enzymes.
Furthermore, hIAPP triggered mitogen-activated
protein kinases (MAPKs) activation, but these
effects were effectively suppressed by PC.89,90 So,
the study reported that PC protects INS-1E
pancreatic beta cells of rat insulinoma against
hIAPP-induced apoptotic cell death through
attenuating oxidative stress and modulating c-Jun
N-terminal kinase (JNK) and p38 pathways.89 This
is not proved in humans till now. PC may have a
potential to treat type-2 diabetes mellitus as it
enhances insulin sensitivity, regulates glucolipide
metabolism and ameliorates insulin resistance of
peripheral target tissues.91
Ischemia Reperfusion Injury:
C-phycocyanin could be used for treating ischemia-
reperfusion injury through the activation of ERK
pathway and suppression of p38 MAPK pathway.38
Phycocyanin may be used to treat ischemic stroke
as phycocyanobilin has an effective influence on
major inflammatory mediators of acute cerebral
hypoperfusion.92
Cardiovascular Disease (CVD) and Non-
Alcoholic Fatty Liver Disease (NAFLD):
Chronic diseases, such as CVD and NAFLD, are
highly related to impaired lipid metabolism,
oxidative stress, and inflammation. Phycocyanin
provides multiple health-promoting properties:
inhibition of inflammation via decreased nuclear
factor kappa B (NF-kB) activity; lowering plasma
lipid concentrations by decreasing intestinal
cholesterol absorption and hepatic lipogenesis; and
prevention of oxidative stress by blocking lipid
peroxidation and increasing free radical
scavenging.46,93 In conclusion, Phycocyanin can be
consumed as a dietary supplement or a food
component to obtain health benefits against CVD
and NAFLD.46
Neuroprotective Effects:
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International Journal of Pharmaceutical Sciences and Research 4597
The anti-inflammatory, antioxidant and immune-
modulatory properties contribute to the
neuroprotective effects of Phycocyanin. Either the
therapeutic or prophylactic application of
Phycocyanin is able to significantly reduce the
infarct volume, and also protect hippocampal
neurons from death, induced by cerebral ischemia
or reperfusion injury. Phyocyanin is platelet
aggregation inhibitor with a potential to hamper
arterial thromboembolism.94
Nephroprotective Effects:
Phycocyanin protects the renal cell integrity by
stabilizing lipid peroxidation and protecting against
oxalate induced nephro injury. Lipid peroxidation
produce aldehydes like malondialdehyde (MDA)
that are extremely active and can diffuse within or
even escape from the cell and attack targets far
from the site of the original free radical initiated
event, resulting in cell damage and therefore act as
„cytotoxic second messengers'. Phycocyanin pre-
treatment decreased the lipid peroxidation and
reversed the effects of oxalate on oxidative stress
parameters by interacting with hydroxyl radical and
by rebalancing the GSH content, catalase and
G6PD activity in oxalate treated animals.95
Acute Lung Injury:
Acute lung injury (ALI) is characterized by damage
to the epithelial and endothelial cells in lungs,
mediated by several pro-inflammatory mediators
and finally impairs respiratory function.
Phycocyanin exhibits its anti-inflammatory activity
by inhibiting inducible nitric oxide synthase
(iNOS) expression and NO production possibly by
suppressing nuclear transcription factor-kB (NF-
kB) activation, a key transcription factor promoting
proinflammatory gene expression. Leung et al
reported that posttreatment of ALI model with C-
PC significantly reduces the tissue permeability,
and protein concentration in bronchoalveolar
lavage fluid (BALF) and improves pulmonary
histological alterations.96
Wound Healing:
Phycocyanin directly enhances wound repair by its
anti-oxidant property and scavenging destructive
free radicals mechanism. Secondly, stimulation of
keratinocyte is one mechanism by which
phycocyanin might enhance wound repair
process.97
Side Effects: Phycocyanin is usually non-toxic, but
may cause liver damage, stomach pain, nausea,
vomiting, weakness, thirst, rapid heartbeat, shock,
and death. Phycocyanin may cause systemic
anaphylaxis, urticaria, labial edema, asthma,
diarrhea and diffuse erythema.98
CONCLUSION: Phycocyanin is a natural product
from cyanobacteria and is a rich source of
antioxidants. In view of current practice,
antioxidant properties of phycocyanin have been
investigated for their anti-inflammatory, anti-
proliferative and anti-cancer effects. The results
revealed for the first time that the C-phycocyanin
activities and its antitumor actions such as in
leukemia, colon cancer, pancreatic cancer etc.
could be a promising natural antitumor agent with a
potential for future pharmacological and medical
applications. In the future, these marine algae-
derived materials or compounds will be used more
often in pre-clinical studies for drug discovery. In
our review article, like other anti-cancer agents,
phycocyanin being a natural product, should be
more acceptable as an anticancer compound.
ACKNOWLEDGEMENTS: The authors are
thankful to Pubmed, BioMed Central and Google
database for providing the detailed parameters of
the articles.
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Soni A, Dubey M, Verma M, Dhankhar R, Kaushal V, Atri R and Sabharwal R: Revisiting the Role of Phycocyanin in Current Clinical
Practice. Int J Pharm Sci Res 2015; 6(11): 4588-00.doi: 10.13040/IJPSR.0975-8232.6(11).4588-00.
... Allophycocyanin, phycocyanin and phycoerythrin consist of α and β protein subunits and different isomeric linear tetrapyrrole prosthetic groups (bilin chromophores) [14,15]. These bilin chromophores differ in the arrangement of their double bonds. ...
... Phycocyanin is stable in the pH range of 4.5 to 8.0 [5]. The purified phycocyanin has the highest absorption at 610-625 nm [2,3,5,6,9,12,15,17]. The absorption maximum at a wavelength of 610-625 nm is attributed to the absorption of the chromophore [9]. ...
... The phycocyanin concentration and purity are determined by spectrophotometric method as described by Bennet and Bogard in 1973 [3]. The concentration (C−PC) is calculated according to the formula below, using the absorbances at the clue wavelengths of 620 nm and 652 nm [3,6,8,12,20]: [2,15,16,21] phycocyanin in mg. From our experience, it is necessary to select appropriate weight and volume of water for the spectrophotometric evaluation of the phycocyanin content in the obtained powder. ...
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c-phycocyanin (phycocyanin) is a pigment-protein complex of the light-harvesting phycobiliprotein family that takes part in the primary phase of photosynthesis in lower plants. The phycocyanin content depends on such factors as the species of microalgae, physical state of biomass, extraction techniques, etc. The main methods for obtaining phycocyanin from biomass include chemical, physical and enzyme treatments with the following purification by such methods as precipitation with ammonium sulfate, ion exchange chromatography, and gel filtration chromatography. The commercial value of phycocyanin is directly related to the methods of its obtaining, purification and purity. The ratio of absorbances A620/A280 indicates the grade of phycocyanin and is the principal index of its purity. If the ratio of A620/A280 is greater than 4, phycocyanin can be used for pharmaceutical and analytical studies; at not less than 0.7, phycocyanin can be used for the food industry and at not less than 3.9 phycocyanin can be used as a reagent. The purified phycocyanin has some absorption maxima at the wavelengths of 610–625 nm, 353 nm and 277 nm. Its molecular mass ranges from 110 to 220 kDa. The search for extraction methods is aimed at obtaining a high yield of phycocyanin of an appropriate purity in industrial scale. This will allow a wider introduction of phycocyanin into the food, cosmetics and pharmaceutical industries as a safe product with many positive biological properties, in particular, antioxidant, antitumor, antiplatelet, antibacterial, hypotensive, anti-inflammatory, etc
... Consiste en una enzima oxidante endógena que genera especies reactivas de oxígeno y puede ser liberada fuera de la célula, aumentando el potencial de daño a un objetivo extracelular [61]. La C-ficocianina inhibe tanto la peroxidación lipídica microsomal del hígado como la agregación de plaquetas, disminuyendo la producción de PGE2 y de nitritos, reduciendo la producción de mieloperoxidasa y suprimiendo la activación del NF-κB a través de la prevención de la degradación del inhibidor kappa B alfa (IκB-α) citosólico [62]. ...
... Esto se ha visto a través de su ingesta. Cuando se usa como adyuvante de la quimioterapia, impulsa al sistema inmune a combatir la propagación de las células tumorales, mejora su respuesta frente a la quimioterapia y reduce el riesgo de que esta dé lugar a un nuevo cáncer [62]. En adición, puede estimular directamente la formación de la unidad formadora de colonias eritroide, incrementando la hematopoyesis de la médula ósea [57]. ...
... Adicionalmente, hay estudios que demuestran que suprime la respuesta alérgica de anticuerpos IgE y mejora la de anticuerpos secretores IgA en ratones. Las células inmunes involucradas en el control del cáncer (células NK y linfocitos T citotóxicos) funcionan de manera más efectiva con la ingesta de esta proteína [62]. ...
Article
Full-text available
El cáncer es una enfermedad compleja, heterogénea y dinámica, caracterizada por una mitosis descontrolada. Históricamente, se ha tratado con cirugía, radioterapia y quimioterapia, y en años más recientes mediante la inmunoterapia. Para ello, se han investigado distintas proteínas para la modulación de la respuesta inmune. Un grupo de estas son las C-ficocianinas, biliproteinas proveniente de microalgas verde azuladas como Spirulina platensis. El ambiente antiinflamatorio en personas sanas es una medida profiláctica para disminuir el riesgo de desarrollar un determinado tipo de cáncer. Su ingesta ha mostrado ese comportamiento, al suprimir la liberación de sustancias proinflamatorias. También se ha apreciado un efecto inmunomodulador al aumentar o disminuir la expresión de CD59, así como al ocasionar la proliferación de macrófagos y la liberación de sustancias inflamatorias. Esto último es un indicativo de que no se cuenta con información suficiente para corroborar su uso como opción profiláctica o terapéutica contra el cáncer. Por ello, es trascendental la información sobre sustancias naturales como esta, porque aunque se ven más atractivas para tratar esta enfermedad, no existen efectos terapéuticos totalmente comprobados.
... The Pharma Innovation Journal http://www.thepharmajournal.com [36] ; mcg = microgram, mg = milligram, IU = international unit (Moorhead et al. 2005) [22] Components Protein 6 times higher than egg, 3 times higher than beef or pork, 2 times than soyabean Fibre 4 times higher than flour or corn and oat Vitamin B12 3-4 times higher than animal liver Beta Carotene 40 times higher than spinach, 2 times higher than carrots chlorophyll 20 times higher than wheatgrass Calcium 14 times higher than milk, 2 times higher than yogurt Iron 9 times higher than spinach, 5 times than soyabean Potassium 4 times higher than banana Pharmacological actions of Spirulina  Anti-inflammatory and immunomodulatory effect-Spirulina comprises a pigment known as phycocyanobilin, which is a powerful inhibitor of an enzyme that is necessary for causing an inflammation (Soni et al., 2015) [42] . Spirulina enhances immunity by producing a huge amount of antibodies, interferongamma, and cytosine. ...
... The Pharma Innovation Journal http://www.thepharmajournal.com [36] ; mcg = microgram, mg = milligram, IU = international unit (Moorhead et al. 2005) [22] Components Protein 6 times higher than egg, 3 times higher than beef or pork, 2 times than soyabean Fibre 4 times higher than flour or corn and oat Vitamin B12 3-4 times higher than animal liver Beta Carotene 40 times higher than spinach, 2 times higher than carrots chlorophyll 20 times higher than wheatgrass Calcium 14 times higher than milk, 2 times higher than yogurt Iron 9 times higher than spinach, 5 times than soyabean Potassium 4 times higher than banana Pharmacological actions of Spirulina  Anti-inflammatory and immunomodulatory effect-Spirulina comprises a pigment known as phycocyanobilin, which is a powerful inhibitor of an enzyme that is necessary for causing an inflammation (Soni et al., 2015) [42] . Spirulina enhances immunity by producing a huge amount of antibodies, interferongamma, and cytosine. ...
Article
Full-text available
Limited consumption of natural food stuff in the 21 st century has led to deficiency of vitamins and other important minerals in the human body. Due to excess and repetitive use of chemical fertilizers, the crop productivity is declining day by day. Spirulina is multi-cellular and filamentous blue-green algae biomass which belongs to the class of cyanobacteria discovered by non-referenced Mexicans in the 16 th century can be a viable solution of all these problems. In recent years, Spirulina has gained enormous attention from research point of view as well as industries as a flourishing source of nutraceutical and pharmaceuticals. It has a very high content of macro as well as micronutrients, essential amino acids, proteins, lipids, vitamins, minerals and anti-oxidants. It is among the most nutritious, concentrated whole food sources that exists in nature, and is known as a superfood. Spirulina exhibits anticancer, antidiabetic, anti-inflammatory, immunomodulatory and many other properties. Spirulina has the potential of reducing the negative impacts of wastewater discharge through bioremediation. Two major technologies are being considered for the cultivation of Spirulina: closed photobioreactors (PBR) and open raceway ponds. In developing countries like India where malnutrition is a renowned social challenge and it can be defeated by the supplementation of Spirulina products in the diet. The commercial cultivation of Spirulina and converting it to consumable forms (tablets or powder) can be a new way of agribusiness. Therefore, Spirulina is emerging as a cost-effective means of improving livestock and crop productivity in a sustainable manner to ensure food and nutritional security.
... Natural dyes decrease the use of synthetic dyes that can cause serious diseases. The natural dye in various products decreases the chances of life-threatening disease and it has the least side effects than synthetic dye [13,16]. C-Phycocyanin and C-Phycoerythrin pigments from cyanobacteria have the unique potential to act as antibacterial, antifungal, antioxidant (as they can scavenge the free radicle from ROS), anti-inflammatory (by prohibiting the pro-inflammatory signals and modifying the function of macrophages), anti-diabetic and anti-cancer (kill the cancerous cell without disturbing healthy cells) agent. ...
... C-Phycocyanin and C-Phycoerythrin pigments from cyanobacteria have the unique potential to act as antibacterial, antifungal, antioxidant (as they can scavenge the free radicle from ROS), anti-inflammatory (by prohibiting the pro-inflammatory signals and modifying the function of macrophages), anti-diabetic and anti-cancer (kill the cancerous cell without disturbing healthy cells) agent. Phycocyanin is used to treat hepatocellular carcinoma, rectal carcinoma, melanoma; leukaemia, etc. [16,17]. The studies on the antibacterial activity of cyanobacterial phycobiliprotein, are less reported. ...
Article
The pigments are vital parts of photosynthetic machinery in algae and exhibit a myriad of applications as nutraceuticals, cosmetics, colorants, which find huge applications in many industires, including the paint industry and paper industry. The antimicrobial, antioxidative, anti-inflammatory, and anti-cancer potential of microalgal pigments contribute towards their varied industrial applications. In this study, pigments (Fucoxanthin, C-phycocyanin, and C-phycoerythrin), extracted from microalgae were investigated to check the antimicrobial efficacy using agar well diffusion and disc diffusion methods against pathogenic bacteria: Staphylococcus aureus and Escherichia coli. The fucoxanthin pigment isolated from diatom Thalassiosira sp. exhibited the highest antibacterial activity against Staphylococcus aureus (17 ± 1.53 mm) and in contrast fucoxanthin pigment isolated from Chaetoceroes sp. exhibited the highest bactericidal activity against Escherichia coli (18 ± 1). The pigment extract of Spirulina plantesis showed the highest antibacterial activity against E. coli (41 ± 0.3) and S. elongatus also exhibited high antibacterial activity against E. coli (32 ± 0.5) while Anabaena variabilis showed the highest antibacterial activity against Staphylococcus aureus (34 ± 0.5). The potential of microalgal pigments is highly valuable and further extensive studies can elaborate the underlying mechanisms.
... The chemical purity of C-PC was monitored according to the A 620 /A 280 ratio. The absorbance at a wavelength of 620 nm indicates maximum absorption of C-PC, while the absorbance at a wavelength of 280 nm is related to proteins and nucleic acids in the solution [9,21,[24][25][26][27][28]. ...
Article
Full-text available
The physicochemical characteristics of phycocyanin extracted from cyanobacteria collected in Kaunas Lagoon were studied (spectrum characteristics, C-PC content in the dry mass and chemical purity). It was determined that the tested concentrations of C-PC in purified water should be in the range of 0.02–0.16% for measuring C-PC content in the dry mass and its spectrum characteristics. The two clear absorption maxima were detected in the spectrum of C-PC at the wavelengths of 277 and 619 nm. The content of C-PC in the dry powder form was in the range of 7.25% to 9.30% depending on its concentration in the solution and type of spectrophotometer. Furthermore, a purity factor of 1.5 was calculated, which indicated the food qualification of the obtained biomass of C-PC. Finally, the analytical procedure for studying the pro- and anti-oxidant activity of C-PC was developed and the antioxidant activity of C-PC was measured for the available markers. It was revealed that C-PC has dual properties (pro- and anti-oxidant ones) depending on its concentration, more exactly, its content in reaction mixtures with 2,2-diphenyl-1-picrylhydrazyl (DPPH). The following issues were resolved during the research: the concentration of ethanol in the DPPH solution was chosen in order to avoid precipitation of proteins in the reaction mixtures (50%); the ratio of the solution of C-PC to the DPPH solution was selected; the selected concentrations of the markers for the construction of their calibration curves were chosen for quercetin and for rutin. The antioxidant activity of the obtained C-PC sample was determined. Keywords: antioxidant activity, C-phycocyanin, cyanobacteria, DPPH, quercetin, rutin
... Their remarkable biological activity as antioxidant, 232À234 immune stimulator, 235,236 antidiabetes, 237 anticholesterolemic, 238,239 antiviral, 240 anti-inflammatory, 241,242 or antitumor agent 12,25,233,243À246 have indeed aroused interest within the nutraceutical, pharmaceutical, and cosmetic industries. 12,25,233,244,247 Cosmetic uses β-carotene Formulation as a UV filter and antioxidant protection (protector skin against external aggression); creams and topical formulations to promote hydration, skin discoloration (i.e., spots or uneven coloring), anti-aging properties 219 Lutein Sunscreen formulations as UV filters; creams and formulations to promote skin hydration and elasticity, reduction of wrinkling; anti-aging sera 186,220 Astaxanthin Sunscreen formulations as UV filters; creams and formulations to promote skin hydration and elasticity, reduction of hyperpigmentation; antiaging property creams 221 PBPs have been extensively recognized for their antioxidant and protective properties, both in vitro and in vivo using different models. 232,241,248 For instance, PC obtained from Arthrospira species was demonstrated protection when peroxyl radicals attack human erythrocytes, by preventing hemolysis-probably derived from their scavenging action. ...
Book
Cyanobacteria are among the most successful and ancient forms of life ever known. These photosynthetic autotrophs have been studied for decades as model organisms in various aspects, from photosynthesis to biotechnological applications and, more recently, for their pharmacological potential in umpteen fields. In fact, cyanobacteria are now recognized as top metabolic producers of a huge number of bioactive compounds with medical interest and that can revolutionize drug discovery and development. Allied to their metabolic capabilities, cyanobacteria benefit from a cost-effective energy-capturing ability, and high cultivation yields with minimum nutritional requirements, being extremely attractive in terms of industrial-scale production processes. This book was designed to bring together fields in which cyanobacteria derived compounds most stood out, with a special focus on those related to therapeutics, cosmetics, and nutrition, emphasizing unique molecules not found in higher organisms. Of the most promising compounds isolated so far, those acting as anti-inflammatories, anti-carcinogens, antimicrobials, and UV protectors fill a prominent place within drug discovery programs. The metabolic richness of cyanobacteria has also been upholding their key role in the field of cosmetics and nutraceuticals, with the last occupying a prominent place in a rapidly expanding market. Apart from the pharmacological and biotechnological approach, this book does not set aside the well-known cyanobacterial toxins, warning to their substantial economic and social impacts, and drawing attention to the urgency of fully addressing algal blooms and their systematic monitoring. Additionally, and given its extreme importance, this book provides a distinctive approach to cyanobacteria systematics, by exploring general aspects and biodiversity of these organisms to discuss trends in cyanobacterial taxonomy. Overall, The Pharmacological Potential of Cyanobacteria is intended to be a useful resource for students, researchers, and professionals working in the field of cyanobacteria, serving as a guide in the discovery, research, and application of these unique microorganisms. Graciliana Lopes, Marisa Silva and Vitor Vasconcelos
... Their remarkable biological activity as antioxidant, 232À234 immune stimulator, 235,236 antidiabetes, 237 anticholesterolemic, 238,239 antiviral, 240 anti-inflammatory, 241,242 or antitumor agent 12,25,233,243À246 have indeed aroused interest within the nutraceutical, pharmaceutical, and cosmetic industries. 12,25,233,244,247 Cosmetic uses β-carotene Formulation as a UV filter and antioxidant protection (protector skin against external aggression); creams and topical formulations to promote hydration, skin discoloration (i.e., spots or uneven coloring), anti-aging properties 219 Lutein Sunscreen formulations as UV filters; creams and formulations to promote skin hydration and elasticity, reduction of wrinkling; anti-aging sera 186,220 Astaxanthin Sunscreen formulations as UV filters; creams and formulations to promote skin hydration and elasticity, reduction of hyperpigmentation; antiaging property creams 221 PBPs have been extensively recognized for their antioxidant and protective properties, both in vitro and in vivo using different models. 232,241,248 For instance, PC obtained from Arthrospira species was demonstrated protection when peroxyl radicals attack human erythrocytes, by preventing hemolysis-probably derived from their scavenging action. ...
Book
PREFACE Cyanobacteria are among the most successful and ancient forms of life ever known. These photosynthetic autotrophs have been studied for decades as model organisms in various aspects, from photosynthesis to biotechnological applications and, more recently, for their pharmacological potential in umpteen fields. In fact, cyanobacteria are now recognized as top metabolic producers of a huge number of bioactive compounds with medical interest and that can revolutionize drug discovery and development. Allied to their metabolic capabilities, cyanobacteria benefit from a cost-effective energy-capturing ability, and high cultivation yields with minimum nutritional requirements, being extremely attractive in terms of industrial-scale production processes. This book was designed to bring together fields in which cyanobacteria derived compounds most stood out, with a special focus on those related to therapeutics, cosmetics, and nutrition, emphasizing unique molecules not found in higher organisms. Of the most promising compounds isolated so far, those acting as anti-inflammatories, anti-carcinogens, antimicrobials, and UV protectors fill a prominent place within drug discovery programs. The metabolic richness of cyanobacteria has also been upholding their key role in the field of cosmetics and nutraceuticals, with the last occupying a prominent place in a rapidly expanding market. Apart from the pharmacological and biotechnological approach, this book does not set aside the well-known cyanobacterial toxins, warning to their substantial economic and social impacts, and drawing attention to the urgency of fully addressing algal blooms and their systematic monitoring. Additionally, and given its extreme importance, this book provides a distinctive approach to cyanobacteria systematics, by exploring general aspects and biodiversity of these organisms to discuss trends in cyanobacterial taxonomy. Overall, The Pharmacological Potential of Cyanobacteria is intended to be a useful resource for students, researchers, and professionals working in the field of cyanobacteria, serving as a guide in the discovery, research, and application of these unique microorganisms. Graciliana Lopes, Marisa Silva and Vitor Vasconcelos
... their anti-aging, anti-Alzheimer and anti-cancer activities (Batista et al., 2006; Sonani et al., 2016. Phycoerythrin has been reported to have antifungal, antibacterial, antioxidant and dermatoprotective activities (Verma et al., 2018), whereas antibacterial, immune system modulating, anti-cancer (prostate, breast and cervix), melanogenesis inhibiting and hematological roles have been reported for PC (Soni et al., 2015). Additionally, the consumption of edible algae containing PC has health promoting activities including prevention of inflammation, degradation of plasma lipid concentration through reduction in cholesterol absorption and inhibition of oxidative stress via blocking lipid peroxidation (Ku et al., 2013). ...
Article
Full-text available
Microalgae produce a variety of bioactive components that provide benefits to human and animal health. Cryptophytes are one of the major groups of microalgae, with more than 20 genera comprised of 200 species. Recently, cryptophytes have attracted scientific attention because of their characteristics and biotechnological potential. For example, they are rich in a number of chemical compounds, such as fatty acids, carotenoids, phycobiliproteins and polysaccharides, which are mainly used for food, medicine, cosmetics and pharmaceuticals. This paper provides a review of studies that assess protective algal compounds and introduce cryptophytes as a remarkable source of bioactive components that may be usable in biomedical and pharmaceutical sciences.
Chapter
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The effects of C-phycocyanin (C-PC) on atherosclerosis and the regulatory effects of CD59 gene on anti-atherosclerotic roles of C-PC were investigated. Apolipoprotein E knockout (ApoE(-/-)) mice were randomly divided into four groups: control group, C-PC treatment group, CD59 transfection group and C-PC+CD59 synergy group. The mice were fed with high-fat-diet and treated with drug intervention at the same time. Results showed the atherosclerotic mouse model was successfully established. CD59 was over-expressed in blood and tissue cells. Single CD59 or C-PC could reduce blood lipid levels and promote the expression of anti-apoptotic Bcl-2 but inhibit pro-apoptotic Fas proteins in endothelial cells. The expression levels of cell cycle protein D1 (Cyclin D1) and mRNA levels of cyclin dependent protein kinase 4 (CDK4) in smooth muscle cells were restrained by CD59 and C-PC. CD59 or C-PC alone could inhibit the formation of atherosclerotic plaque by suppressing MMP-2 protein expression. In addition, C-PC could promote CD59 expression. So both CD59 and C-PC could inhibit the progress of atherosclerosis, and the anti-atherosclerotic effects of C-PC might be fulfilled by promoting CD59 expression, preventing smooth muscle cell proliferation and the apoptosis of endothelial cells, reducing blood fat levels, and at last inhibiting the development of atherosclerosis.
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The experimental data on the study of the antibacterial activity of purified phycocyanin, a protein-bound pigment isolated from blue-green alga, Spirulina platensis (Nordstedt) Geitler, Oscillatoriaceae are generalized and it was shown that phycocyanin was able to markedly inhibit the growth of drug resistant bacteria Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus while, no activity was recorded in Acinetobacter baumanii and Enterococcus durans, this is the first report of the activity of purified C-phycocyanin against drug resistant bacteria. The possible use of phycocyanin as a drug with associated antibacterial activity is discussed. KeywordsDrug resistant bacteria–MIC–Phycocyanin– Spirulina platensis
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Light has bilateral effects on phototrophic organisms. As cyanobacteria in Roman hypogea are long acclimatized to dim environment, moderate intensity of illumination can be used to alleviate biodeterioration problems on the stone substrata. Moderate intensity of light inactivates cyanobacteria by causing photoinhibition, photobleaching and photodamage to the cells. The effectiveness of light depends not only on its intensity but also on the composition and pigmentation of the component cyanobacteria in the biofilms. Red light is the most effective for the species rich in phycocyanin and allophycocyanin, such as Leptolyngbya sp. and Scytonema julianum, whereas green light is effective to inhibit the species rich in phycoerythrin, like Oculatella subterranea. White light is effective to control the grayish and the black cyanobacteria, such as Symphyonemopsis sp. and Eucapsis sp. abundant in all of these pigments. Blue light is the least effective. 150 μmol photons m(-2) s(-1) of blue light cannot cause biofilm damage while the same intensity of red, green or white irradiation for 14 days can severely damage the cyanobacterial cells in the biofilms due to ROS formation. Electron spin resonance spectroscopy detected the formation of radicals in different cyanobacterial cellular extracts exposed to 80 μmol photons m(-2) s(-1) of light.
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Cyanobacterial phycobiliproteins have evolved to capture light energy over most of the visible spectrum due to their bilin chromophores, which are linear tetrapyrroles that have been covalently attached by enzymes called bilin lyases. We report here the crystal structure of a bilin lyase of the CpcS family from Thermosynechococcus elongatus (TeCpcS-III). TeCpcS-III is a 10-stranded beta barrel with two alpha helices and belongs to the lipocalin structural family. TeCpcS-III catalyzes both cognate as well as non-cognate bilin attachment to a variety of phycobiliprotein subunits. TeCpcS-III ligates phycocyanobilin, phycoerythrobilin and phytochromobilin to the alpha and beta subunits of allophycocyanin and to the beta subunit of phycocyanin at the Cys82-equivalent position in all cases. The active form of TeCpcS-III is a dimer, which is consistent with the structure observed in the crystal. Using the UnaG protein and its association with bilirubin as a guide, a model for the association between the native substrate, phycocyanobilin, and TeCpcS was produced.
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Abstract The purpose of the present report was to determine the inhibitory effect of Spirulina maxima (Sm) and its protein extract (PE), mainly consisting of C-phycocyanin, on the increase in micronuclei and bone marrow cytotoxicity induced by hydroxyurea (HU) in pregnant mice and their fetuses. The two tested antimutagenic agents were administered daily from day 10 to day 18 of pregnancy, and HU (300 mg/kg) was administered once on day 16 of the assay. The experimental design also included mice that were administered only Sm or PE (1000 and 400 mg/kg, respectively), two control groups that were administered with vehicles (water and 0.5% Tween 80), and one additional group that was treated solely with HU. Blood samples from the pregnant mice and their fetuses were examined at day 19 of pregnancy. Significant increases in the number of micronucleated polychromatic erythrocytes and in the total number of micronucleated erythrocytes were observed in all HU-treated animals. In contrast, similarly low numbers of micronuclei were observed in the two control groups and in the groups treated with Sm and PE alone. The administration of Sm (100, 500, and 1000 mg/kg) and PE (100, 200, and 400 mg/kg) to HU-treated animals conferred moderate genotoxic protection (∼30%) and some protection against the cytotoxicity induced by HU in mice. The obtained results provide new information regarding the capacity of the tested agents to confer protection to adult mice and transplacentally, as well as on a specific subclass of micronuclei.