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Astaxanthin Technical Bulletin | Brain

KEEP YOUR
MIND IN
TUNE
Advantages of Astaxanthin for
Brain Health

Clinical Benefits of Astaxanthin

• Improves age-related forgetfulness, multitasking, and alertness
• Decreases oxidation of red blood cells, which is linked to prevention of dementia
• Enhances capillary blood flow and blood antioxidant quality
• Modulates blood pressure, lowering stroke risk and vascular endothelial health

Astaxanthin: The Latest Science

• Quenches oxidative stress and inflammation in the brain’s circulatory system
• Reduces incidences of stroke and ischemia-reperfusion injury, and speeds up neurological recovery after stroke
• Modulates key cellular factors that promote neurodegenerative diseases
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THE BRAIN:

The Grand
Maestro

T he brain is the Grand Maestro of the human life: It

coordinates all the basic and complex functions that
link the body and mind. Indeed, any alteration of the brain’s intruders or the formation of internal injuries. Nevertheless,
the brain remains vulnerable to attack and damage by free
structural dynamics and biochemistry can directly disrupt
cognitive, physical, and emotional well-being. We are the radicals, especially in people over the age of 50 in whom
brain and the brain is us. the brain’s natural antioxidant enzymes progressively lose
effectiveness. In fact, excessive persistent oxidative stress
and chronic inflammation in the brain have been linked to
The Brain: A Symphony of Interrelated Cellular the development and progression of neurodegenerative
Activities conditions, such as Alzheimer’s disease and Parkinson’s
The brain contains more than 100 billion neurons, disease, and to cerebrovascular diseases, such as
which is more than 14 times the world population. It is ischemic stroke and vascular dementia. For these reasons,
interconnected with over 180,000 km of nerve fibers, long neurologists have started to pay close attention to the
enough to encircle the globe four-and-a-half times. The brain preventive and therapeutic effects of micronutrients on
is supported by more than 100 trillion tiny communication
brain health.
junctions called synapses that allow neurotransmitters to
pass information between neurons. The speed at which
information travels between neurons is roughly 400 km/h,
which is faster than a Formula 1 racing car. All this is
packed into something that has a volume of only 1,130 cm
and weighs just 1.5 kg on average, about the size of a large
grapefruit or a small head of cauliflower.

T wo clinical studies suggest that natural

astaxanthin extract from Haematococcus
pluvialis microalgae improves mental quickness,
multitasking, memory, and learning speed in
older adults who had complained of age-related
forgetfulness and loss of mental sharpness. An
additional clinical study indicates that astaxanthin
can improve mental function in older adults suffering
from symptoms of mild cognitive impairment (MCI).
Supporting studies suggest that astaxanthin maintains
Because the brain is so important it has an excellent
a healthy brain by providing antioxidant protection,
defense system. Firstly, it is well protected by the blood
and by maintaining healthy blood flow and quality.
brain barrier, which prevents harmful substances from
Other beneficial factors may include maintaining a
reaching the brain. Secondly, the brain has a specialized
healthy blood pressure.
immune system, which monitors the presence of any

2 Astaxanthin Technical Bulletin | Brain

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Why Does the Brain Need Powerful Specialized Antioxidants?

Reason 1: Among all the body’s organs, the brain Reason 3: Almost 1 liter of blood flows through the
generates the largest amount of free radicals. It capillaries of the brain every minute. The likelihood of
accounts for only 3% of body weight but requires 25% developing ischemia, stroke and vascular insufficiency are
of our total energy consumption. The brain generates dramatically increased by decades of a poor blood profile,
exceptional amounts of free radicals as a by-product of reduction of the blood antioxidant capacity, oxidation of
the energy conversion process. red blood cells, and loss of capillary integrity.

Reason 2: The brain is prone to peroxidation and Reason 4: The brain’s defense system. The brain is
inflammation. More than 60% of the brain is made of shielded by the blood brain barrier and immune system
polyunsaturated fatty acids, so neural cell membranes which stops many antioxidants from reaching the brain.
are highly vulnerable to lipid peroxidation and Therefore, for antioxidants to be effective, they must
subsequent chronic inflammation. pass the brain’s barrier and avoid inactivation by the
brain’s immune system.

Nearly The global numbers of people with One new

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diagnosis
$604 improves the quality of life
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References:
World health organization, 10 facts on dementia, http://www.who.int/features/factfiles/dementia/dementia_facts/en/index5.html
Alzheimer’s Disease International, infographic, http://visual.ly/dementia-global-epidemic

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expressed permission from AstaReal Co., Ltd. Contents may not be copied or modified, in print or electronic form, without the express consent of AstaReal Co., Ltd.
Mild Cognitive Impairment Increases
with Age
Mild cognitive impairment
(MCI) is a syndrome
rather than a disease, and
encompasses a set of
symptoms including subtle
problems with memory,
planning, language,
attention, visuospatial skills,
and decision-making. The
estimated prevalence of MCI is 10%–20% for people aged
over 65, and the causes of MCI are currently unknown.
Several longitudinal studies have shown that the majority
of people affected by MCI have a substantially increased
risk of developing dementia. By 2040 more than 81 million
people worldwide will be living with MCI and Alzheimer’s
disease1, 2.
Astaxanthin Improves Cognitive
Impairment in the Elderly
MCI is a syndrome that involves cognitive impairments
exceeding those normally expected based on the
age of the individual. Symptoms include difficulty
recalling important information such as appointments,
conversations, and recent events. Decision-making and the
ability to complete complex tasks may also be affected.
The problems caused by MCI are not severe enough
to affect daily life, and thus do not meet the diagnostic
guidelines for dementia. Individuals with MCI are at
increased risk of developing Alzheimer’s disease and other
types of dementia1, 2.
In 2009, a team of researchers from Juntendo University
and Kyorin University investigated the effects of astaxanthin
on 10 healthy men aged 50-69 years, who had complained
of age-related forgetfulness3. The participants were
given 12 mg of astaxanthin daily for 12 weeks and had
their cognitive function assessed at baseline and 6 and
Figure 1. Astaxanthin Supplementation Ameliorated the Perfor-
mance of Cognitive Function3
Medium-term memory 9.1%
Working memory 14.2%
Multitasking
Mental quickness 8.1%
Reaction time
Healthy male participants (n=10, 50-69 years old) complaining age-related
forgetfulness took 12 mg daily astaxanthin for 12 weeks to observe the
response time on a cognitive function test called CogHealth.
4 Astaxanthin Technical Bulletin | Brain
12 weeks after the start of administration. The findings,
published in the Journal of Clinical Biochemistry and
Nutrition, showed that pretreatment with astaxanthin
improved the participants’ information processing, memory,
and learning. The improvement was assessed by an
internationally recognized cognitive function test called
CogHealth. The tasks tested by CogHealth are essential for
performing activities of daily living (Figure 1)3. In the same
study, astaxanthin was also found to increase the amplitude
of the P300 event related potential, a brain wave that is
used to assess cognitive function.
Taking oral astaxanthin significantly improved:
1. Reaction time [simple reaction test] – how fast a
person responds when facing a simple obstacle
2. Mental quickness [choice reaction test] – how fast
a person can match incoming words with pictures
3. Multitasking [divided attention test] – how fluently
a person can perform a physical task and a mental
task at the same time (e.g., repeating a phone number
while walking in a straight line)
4. Working memory [short-term memory test] – how
fast a person can recall a sequence of events or objects
5. Medium-term memory [delayed recall test] – how
fluently a person can recall a list of words seen a few
days before
In 2012, Juntendo University, Japan, conducted a larger
randomized, double-blind, placebo-controlled study
involving a total of 96 healthy middle-aged and elderly
participants who reported age-related forgetfulness4. The
participants took a placebo, 6 mg (low dosage), or 12 mg
(high dosage) of natural astaxanthin for 12 weeks. Despite
a strong placebo effect, participants in the high-dosage
group showed improvement in the choice reaction (mental
quickness), delayed recall (medium-term memory), and
divided attention (multitasking) tests. Working memory
(short term memory) improved significantly (p<0.05) over
baseline in the high-dosage group (Figure 2)4. Furthermore,
participants in the low-dosage and high-dosage groups
showed significantly faster learning in the short-term spatial
memory test in comparison with the placebo group, as
assessed by the Groton Maze Learning Test (GMLT). The
GMLT assesses how fast someone learns the location of
obstacles in order to avoid them when tracking a target
16.6%
destination under time pressure. It assesses spatial
memory, which is considered crucial in everyday tasks such
as remembering objects and locations.
17.5%
These clinical findings have been further validated in
experimental studies. Pretreatment with astaxanthin was
found to significantly improve learning, short term memory,
 This document contains privileged information and is for the sole use of the intended recipient. You may not disseminate the information to third parties without
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Figure 2. 12 mg of astaxanthin supplementation improves sections of the ADAS-cog test, with decreases of 15% and
cognitive function in the healthy aged individuals4
32% respectively (p ≤ 0.002) (Figure 3)7.
† p< 0.1 vs baseline, *p< 0.05 vs baseline Start 12 weeks Although the mechanism of action is unclear, the beneficial
1000 (Astaxanthin 12 mg group :n=32)
effects seen in this study may have been related to a
7.1% 880 †
800 Reduced 818 reduction in oxidative stress in the brain arising from the
Mean response time (ms)

6.0% 656 *
8.1% antioxidant activity of astaxanthin8. The results of this
Reduced
600 Reduced 609
study point to the potential of astaxanthin, either alone
†
480 † or combination with other antioxidants, to support and
400 451
419
7.0% 385
maintain healthy cognitive function.
Reduced
200

Figure 3. Significant improvement of ADAS-cog subscale after

0
astaxanthin-containing supplementation7
Choice reaction Working memory Delayed recall Divided attention

Healthy participants (n=96, aged 55.7±3.7) complaining age-related

forgetfulness were randomly allocated into 3 groups and given 0,6 and 12 mg * * p<0.001 Day 0 Day 60
of astaxanthin daily for 12 weeks. The cognitive functions were measured by 6

Alzheimer’s disease assessment scale-cognitine subscale

CogHealth battery in response times on a computer. 5.9

spatial memory, and development of vascular dementia 5

5.0
0
in hypertensive animal models. In 2005, researchers at
15 32
(ADAS-cog)
% * %
Toyama University in Japan found that pretreatment of
4 Decreased 4
4.1 Decreased
ischemic mice with astaxanthin significantly reduced the
time required for the mice to escape from a maze5. These
results were verified in 2007 when researchers at Qingdao 3

University in China found that healthy rats supplemented 2.8

2

with doses of astaxanthin corresponding to 10 mg/day for

2
an adult man also showed improved memory performance Word Recall Word Recognition

in maze tests6. Patients diagnosed with MCI (n=98, aged≥50, under non-pharmacological
therapy) received 4 mg of astaxanthin daily in combination with Bacopa
Monnieri and other antioxidants for 60 days. A higher score indicates greater
In 2014, a prospective cohort study examined the efficacy dysfunction.

of a combination of astaxanthin and other antioxidants for

improving memory and cognitive function in patients with
In a
MCI7. Ninety-eight participants over 50 years old received 4 Nutshell
mg of natural astaxanthin daily in combination with Bacopa
monnieri, which is a plant traditionally used as a brain tonic, Combined clinical and experimental studies
and other antioxidants for 60 days. The subjects’ cognitive have shown that supplementation with natural
function was assessed using the Alzheimer’s Disease astaxanthin may improve mental quickness,
Assessment Scale—cognitive subscale (ADAS-cog) and the multitasking, memory, and learning speed.
clock drawing test (CDT).
After 60 days of supplementation, a significant
improvement was seen in the CDT scores, which increased
Astaxanthin Improves Blood Quality
from 8.5 ± 2.3 to 9.1 ± 1.9 (p ≤ 0.001). The ADAS-cog
scores also improved significantly from Red blood cells are the principal means of delivering oxygen
13.7±5.8 at baseline to 9.7± 4.9 on and nutrients to the brain via the circulatory system. Red
day 60 (p ≤ 0.001). The greatest blood cells take up oxygen in the lungs and release it as
improvements were seen in the they travel through the brain’s capillaries. The membranes
word recall and word recognition of red blood cells are particularly susceptible to oxidation
compared with other parts of the cell. Oxidation of red blood
cells is linked to loss of mental sharpness. In fact, abnormally
What did I eat last night? high levels of phospholipid hydroperoxides (PLOOH), which
are the oxidation by-products of phospholipids, accumulate in
What’s my number?
the red blood cell membranes of dementia patients. Oxidized
What was her name? red blood cells have a decreased capacity for transporting
oxygen to the brain; therefore, the increase in PLOOH levels
is linked to the severity of dementia9.

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expressed permission from AstaReal Co., Ltd. Contents may not be copied or modified, in print or electronic form, without the express consent of AstaReal Co., Ltd.
In 2011, Tohoku University in Japan conducted a
randomized, double-blind, placebo-controlled study, involving
30 older adults who took 6 or 12 mg of astaxanthin daily
for 12 weeks9. In this study, published in the British Journal
of Nutrition, astaxanthin supplementation reduced oxidative
by-products in red blood cells, attenuated lipid peroxidation
of the red blood cell membranes, and improved the
antioxidant status of the red blood cells. The results suggest
that astaxanthin may help prevent vascular dementia by
improving the quality of the blood and the quantity of oxygen
and nutrients that reach the brain tissues (Figure 4)9.
Figure 4. 12 mg of astaxanthin supplementation significantly
decreased the concentration of PLOOH in red blood cells9
Start
20
PLOOH Concentration (pmol/ml)
48%
18.6
15
13.9 14.9
Reduced
10
9.7
5
0 Nutshell
Placebo Group Astaxanthin (12 mg)
Healthy participants (n=30, 56.3 mean years old) were randomly received 0
(placebo), 6 or12 mg of daily astaxanthin for 12 weeks to measure the level of
PLOOH in red blood cells. This figure shows changes of placebo and 12 mg group.
Astaxanthin Improves Circulation and
Blood Flow
In addition to blood
quality, good circulation
and capillary blood flow
is essential to deliver
antioxidant and nutrient rich
blood to all portions of the
brain. In 2005, Nagaki et
al. conducted a randomized double-blind study in which
36 subjects who received 6 mg/day of astaxanthin for 4
weeks experienced a 4% improvement in capillary blood
flow10. These results were complemented by a 2008 study
by Miyawaki et al. in which adult men taking 6 mg/day of
astaxanthin for 10 days showed a 10% increase in blood
flow as measured by blood transit times11.
Astaxanthin Reduces Blood Pressure
High blood pressure is the most important risk factor
for stroke and a leading cause of cerebrovascular
complications, including hardening and narrowing of
6 Astaxanthin Technical Bulletin | Brain
the brain capillaries. A series of experimental and
clinical studies suggest that astaxanthin can modulate
blood pressure; therefore, it is considered a promising
micronutrient for the prevention and alleviation of the
effects of hypertension.
Two clinical studies were conducted in Japan to determine
the effects of astaxanthin in humans. In an open clinical
study conducted at Doshisha University in Japan, 20
healthy postmenopausal women took 12 mg of astaxanthin
daily for 8 weeks and their systolic blood pressure and
diastolic blood pressure were reduced by 7% and 4%,
respectively12. In a second clinical study conducted at
Juntendo University, 73 participants aged 20-60 years
took 4 mg of astaxanthin daily for 4 weeks and showed a
12 weeks 5% decrease in systolic blood pressure3. Overall, studies
suggest that astaxanthin can combat hypertension because
it improves vascular integrity, vessel dilation/constriction,
and blood rheology or capillary circulation13. These finding
are supported by a series of experimental studies involving
hypertensive animal models5, 14-17.
In a
Clinical studies also suggest that astaxanthin
fights vascular dementia by reducing the
amount of oxidative by-products in red blood
cells, improving circulation in capillaries, and
by reducing blood pressure—major factors in
preventing vascular dementia.
Latest Science
Experimental studies using animal and in vitro models have
shown that astaxanthin supplementation helps prevent and
alleviate neurodegenerative and cerebrovascular diseases.
Astaxanthin has been shown to:
1. Reduce the incidence of stroke, limit neurological
damage in the areas affected by ischemia, and
scavenge oxidative by-products during ischemic
reperfusion5, 18, 19.
2. Inhibit aggressive immune-inflammatory responses that
can accelerate capillary disintegration and neural cell
death after a stroke20-23.
3. Limit the inflammatory responses and premature
senescence of dopaminergic cells typically observed in
Parkinson’s patients24-26.
4. Attenuate the biochemical disruption, cytotoxicity,
and oxidative stress associated with the abnormal
presence of beta-amyloid peptides in Alzheimer’s
disease27, 28.
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Outlook
Human clinical studies have shown that astaxanthin can
improve mental function and memory in middle aged and
elderly adults experiencing age related forgetfulness as well
in persons suffering from the symptoms of mild cognitive
impairment. The mechanism of action for these benefits
are likely related to astaxanthin’s strong antioxidant and
anti-inflammatory effects. Astaxanthin’s positive effects on
blood quality, circulation, and blood pressure also support
brain health. Experimental studies with animal models
strongly suggest that astaxanthin has the potential to
prevent and support recovery from strokes, and to improve
biomarkers associated with the development of Parkinson’s
and Alzheimer’s disease; additional research is needed
in these areas. The totality of the evidence suggests that
astaxanthin is an excellent choice as natural, side effect
free supplement to support and maintain brain health and to
improve mental function and memory.
Recommended daily dosage: 6-12 mg
Warning: Consult your physician prior to use if you are pregnant
or nursing, or if you have any medical condition or are taking any
medication or other dietary supplements.
AstaREAL® Natural Algae Astaxanthin
Astaxanthin is a naturally occurring pigment that
gives the reddish pink color to marine organisms
such as crabs, shrimp, and salmon. It is often called
the King of Carotenoids because of its powerful
antioxidant potency. Astaxanthin also possesses
a unique molecular structure that spans the cell
membrane’s hydrophillic and hydrophobic layers,
attracting and quenching free radicals. AstaREAL®
astaxanthin is derived from a wholly natural source,
the microalgae Haematococcus pluvialis, and
contains the same form of astaxanthin found in wild
salmon.
Singlet Oxygen Quenching Power
Astaxanthin is
ATB-Brain
1409-01
References
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Lancet. 366:2112–2117.
2. Lopez OL et al., (2003). Prevalence and classification of mild cognitive impairment
in the Cardiovascular Health Study Cognition Study: Part 1. Arch Neurol. 2003; 63
(4):494-506.
3. Satoh et al., (2009). Preliminary Clinical Evaluation of Toxicity and Efficacy of A New
Astaxanthin-rich Haematococcus pluvialis Extract. J Clin Biochem Nutr. May;44(3):280-4.
4. Katagiri et al., (2012). Effects of astaxanthin-rich Haematococcus pluvialis extract on
cognitive function: a randomised, double-blind, placebo-controlled study. J Clin Biochem
Nutr. Sep;51(2):102-7.
5. Hussein et al., (2005). Antihypertensive and neuroprotective effects of astaxanthin in
experimental animals. Biol Pharm Bull. Jan;28(1):47-52.
6. Zhang et al., (2007). Impact of astaxanthin-enriched algal powder of Haematococcus
pluvialis on memory improvement in BALB/c mice. Environ Geochem Health.
Dec;29(6):483-9.
7. Zanotta D et al., (2014). Cognitive effects of a dietary supplement made from extract
of Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild
cognitive impairment: a noncomparative, explorative clinical study. Neuropsychiatr Dis
Treat. Feb 3; 10:225-30.
8. Nakajima Y et al., (2008). Astaxanthin, a dietary carotenoid, protects retinal cells against
oxidative stress in vitro and in mice in vivo. J. Pharm. Pharmacol. 60, 1365–1374.
9. Nakagawa et al., (2011). Antioxidant effect of astaxanthin on phospholipid peroxidation
in human erythrocytes. Br J Nutr. Jun;105(11):1563-71.
10. Nagaki et al., (2005). The Effect of Astaxanthin on Retinal Capillary Blood Flow
in Normal Volunteers. Journal of Clinical Therapeutics & Medicines (Rinsho Iyaku).
21(5):537-42.
11. Miyawaki et al., (2005). Effects of Astaxanthin on Human Blood Rheology. Journal of
Clinical Therapeutics and Medicines., 21(4):421-429.7.
12. Iwabayashi et al., (2009). Efficacy and safety of eight-week treatment with astaxanthin in
individuals screened for increased oxidative stress burden. Anti-aging Med. 6:15-21.
13. Kidd et al., (2011). Astaxanthin, cell membrane nutrient with diverse clinical benefits and
anti-aging potential. Altern Med Rev. Dec;16(4):355-64.
14. Hussein et al., (2005). Antihypertensive potential and mechanism of action of
astaxanthin: II. Vascular reactivity and hemorheology in spontaneously hypertensive rats.
Biol Pharm Bull. Jun;28(6):967-71.
15. Hussein et al., (2006). Antihypertensive potential and mechanism of action of
astaxanthin: III. Antioxidant and histopathological effects in spontaneously hypertensive
rats. Biol Pharm Bull. Apr;29(4):684-8.
16. Monroy-Ruiz et al., (2011). Astaxanthin-enriched-diet reduces blood pressure and
improves cardiovascular parameters in spontaneously hypertensive rats. Pharmacol
Res. Jan;63(1):44-50.
17. Preuss et al., (2011). High dose astaxanthin lowers blood pressure and increases insulin
sensitivity in rats: are these effects interdependent? Int J Med Sci. Feb 9;8(2):126-38.
18. Shen et al., (2009). Astaxanthin reduces ischemic brain injury in adult rats. FASEB J.
Jun;23(6):1958-68.
19. Sasaki et al., (2011). Astaxanthin inhibits thrombosis in cerebral vessels of stroke-prone
spontaneously hypertensive rats. Nutr Res. 2011 Oct;31(10):784-9.
20. Kudo et al., (2002). Effects of astaxanthin on brain damages due to ischemia.
Carotenoid Science. 5(25).
21. Lee et al., (2010). Neuroprotective Effects of Astaxanthin in Oxygen-Glucose
Deprivation in SH-SY5Y Cells and Global Cerebral Ischemia in Rat. J Clin Biochem Nutr.
Sep;47(2):121-9.
22. Chan et al., (2009). Antioxidative and anti-inflammatory neuroprotective effects of
astaxanthin and canthaxanthin in nerve growth factor differentiated PC12 cells. J Food
Sci. Sep;74(7):H225-31.
23. Lu et al., (2010). Neuroprotective effect of astaxanthin on H(2)O(2)-induced neurotoxicity
in vitro and on focal cerebral ischemia in vivo. Brain Res. Nov 11;1360:40-8.
24. Ikeda et al., (2008). Protective effects of astaxanthin on 6-hydroxydopamine-induced
apoptosis in human neuroblastoma SH-SY5Y cells. J Neurochem. Dec;107(6):1730-40.
25. Liu et al., (2009). Astaxanthin inhibits reactive oxygen species-mediated cellular toxicity
in dopaminergic SH-SY5Y cells via mitochondria-targeted protective mechanism. Brain
Res. Feb 13;1254:18-27.
26. Lee et al., (2011). Astaxanthin protects against MPTP/MPP+-induced mitochondrial
dysfunction and ROS production in vivo and in vitro. Food Chem Toxicol. Jan;49(1):271-80.
27. Wang et al., (2010). Astaxanthin upregulates heme oxygenase-1 expression through
ERK1/2 pathway and its protective effect against beta-amyloid-induced cytotoxicity in
SH-SY5Y cells. Brain Res. Nov 11;1360:159-67.
28. Chang et al., (2010). Astaxanthine secured apoptotic death of PC12 cells induced by
beta-amyloid peptide 25-35: its molecular action targets. J Med Food. Jun;13(3):548-56.
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