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L-Theanine: A potential multifaceted natural bioactive amide as health supplement

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Natural bioactive compounds from plants are of great importance in modern therapeutics, which are used to prepare antibiotics, growth supplements or some other therapeutics. l-theanine is such a bioactive amide amino acid presented in different plants and fungi, especially in tea. Theanine has influential effects on lifestyle associated diseases, such as diabetes, cardiovascular disorders, hypertension, stress relief, tumor suppression, menstruation and liver injury. This amino acid can maintain normal sleep and improve memory function and nullify effect of the neurotoxins. The rate of bioavailability and its medium of ingestion in the body is one of the great concerns for its additional antioxidant properties. Pharmacokinetics of the bioactive compound and its mode of action are described herewith. The biosynthesis and industrial synthesis are also reviewed to promote accelerated production of this bioactive compound in the pharmaceutical industries.
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Review article http://dx.doi.org/10.1016/j.apjtb.2017.08.005
L
-theanine: A potential multifaceted natural bioactive amide as health supplement
Rajsekhar Adhikary, Vivekananda Mandal
*
Plant and Microbial Physiology and Biochemistry Laboratory, Department of Botany, University of Gour Banga,
Malda 732 103, W.B., India
ARTICLE INFO
Article history:
Received 11 Jul 2017
Received in revised form 27 Jul 2017
Accepted 14 Aug 2017
Available online xxx
Keywords:
Bioactive amide
Bioavailability
L
-theanine
Lifestyle associated diseases
Pharmacokinetics
ABSTRACT
Natural bioactive compounds from plants are of great importance in modern therapeutics,
which are used to prepare antibiotics, growth supplements or some other therapeutics.
L
-
theanine is such a bioactive amide amino acid presented in different plants and fungi,
especially in tea. Theanine has inuential effects on lifestyle associated diseases, such as
diabetes, cardiovascular disorders, hypertension, stress relief, tumor suppression,
menstruation and liver injury. This amino acid can maintain normal sleep and improve
memory function and nullify effect of the neurotoxins. The rate of bioavailability and its
medium of ingestion in the body is one of the great concerns for its additional antioxidant
properties. Pharmacokinetics of the bioactive compound and its mode of action are
described herewith. The biosynthesis and industrial synthesis are also reviewed to pro-
mote accelerated production of this bioactive compound in the pharmaceutical industries.
1. Introduction
Bioactive compounds of natural origin have great importance
in common days for herbal medicines, antibiotics preparation,
health supplements or some other therapeutic uses. Theanine is
one of such important non-essential amide bioactive amino acids
presented in tea (Thea sinensis, Theaceae), Ilex guayusa
(Aquifoliaceae) and Boletus badius (Basidiomycetes). The
average contents of
L
-theanine throughout the tea plants range
from 1.2 to 6.2 mg/g fresh weight. Chemically theanine is
L
-
g
-
glutamyl ethylamide or 5-N-ethyl-glutamine, with two chimeric
forms, which is principally synthesized in the root of tea and
accumulated in the leaves that are consumed as beverages.
Theanine acts on so many physiological processes of human
system in specied and limited doses
[1,2]
.
The different physiological disorders include different life-
style associated diseases, one of which is diabetes. In India,
diabetes is one of the potential epidemics with more than 62
million peoples currently suffering from this disease. In 2000,
India ranked (31.7 million) top in the world with the highest
prevalence of diabetes mellitus, followed by China (20.8
million) and United States (17.7 million). The prevalence of
diabetes is predicted to double globally from 2000 to 2030 with
a maximum increase in India followed by China and United
States
[3,4]
.
Apart from diabetes, cardio-vascular diseases (CVD) and tu-
mor for both malignant and benign are the great challenges in
modern medical therapies. World Health Organization (WHO)
have targeted 25% reduction of all non-communicable diseases
(NCD) which cause 82% death worldwide, including cardio-
vascular diseases, cancer, chronic respiratory diseases and dia-
betes. WHO also targeted 25% decrease in hypertension in young
as well as elder. To combat and successfully complete the targets,
it is necessary to search a proper potent health supplement and
theanine may be one of the potent options in medical science
[5]
.
In modern therapeutics, bioavailability of the bioactive
compound is a great concern for preparation of novel antibiotics
or health supplements. The high bioavailability and alleviation
of many physio-biological complications of human health make
theanine suitable for its acceptance as therapeutic and health
supplement. It can alleviate many physio-biological complica-
tions of human health. Advances in pharmacokinetics, pharma-
cological and physiological functions and biosynthesis of
theanine are reviewed and summarized in this article. Industrial
production of the bioactive compound has a huge nancial
prospect to ourish the economics health of a nation
[6]
.
*Corresponding author: Vivekananda Mandal, Department of Botany, University
of Gour Banga, Malda 732 103, W.B., India.
Tel: +91 9679 008986
Fax: +91 03512 223666
E-mail: vivekugb@gmail.com (V. Mandal).
Peer review under responsibility of Hainan Medical University. The journal
implements double-blind peer review practiced by specially invited international
editorial board members.
Contents lists available at ScienceDirect
Asian Pacic Journal of Tropical Biomedicine
journal homepage: www.elsevier.com/locate/apjtb
Asian Pac J Trop Biomed 2017; (): 161
2221-1691/Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://
creativecom mons.org/li censes/by-nc -nd/4.0/).
Please cite this article in press as: Adhikary R, Mandal V, L-theanine: A potential multifaceted natural bioactive amide as health supplement, Asian Pac J Trop Biomed (2017), http://dx.doi.org/10.1016/
j.apjtb.2017.08.005
2. Statement of interest
Tea, which is the second most consumed beverage in the
world, contains considerable amount of theanine (1.0%2.5%)
in dry weight of leaves, which is consumed regularly through the
preparation of green tea. Benecial bioactive property helps to
cure several biological disorders in a cost-effective manner and
act as a potential health supplement. Industrial production of
theanine has high market value and carries economic impor-
tance. The present study emphasized on the economic impor-
tance of this bioactive compound and its efcacy against
different biological and histopathological as well as psychiatric
anomalies. This review suggests the intake of Theanine both as
drugs and green tea in considerable doses and quantities
respectively in present stressful environment to live healthier
and more joyful.
3. Biosynthesis
L
-theanine contains molecular formula C
7
H
14
N
2
O
3
with
molecular weight of 174.20 Da and carries melting point of 214
215
C. The odorless, slightly sweet tasted white crystalline
L
-
theanine is transparent, colorless, water soluble in nature. The-
anine biosynthesis in tea starts with the amino acid and alanine
presented in higher amount in root, with the enzyme alanine
decarboxylate and produces ethylamine mostly found in leaves.
Another free amino acid is glutamic acid, mainly found in stem,
reacts with ethylamine to produce theanine. Leaves of tea act as
sink of theanine although roots are the source of the free non-
essential amide amino acid theanine (Table 1)
[7]
.
4. Bioavailability
Theanine especially
L
-theanine when ingested either in
capsulated form or an aqueous solution of tea, is distributed not
only in human plasma level but also in the other tissues, and is
metabolized in the form of glutamate and ethylamine, because
their concentrations in plasma level are increased and found in
the urine
[8]
. Metabolic fate of
L
-theanine in rat model, after
infestation of
L
-theanine, glutamic acid and ethylamine is
found in the plasma and also in urine in dose dependent
manner
[9,10]
.In vitro, synthesis of theanine, large amount of
glutamic acid and ethylamine are produced after
L
-theanine
incubation with either glutaminase or
g
-glutamyl
transpeptidase (GGT)
[11]
. Incubation of
L
-theanine with
homogenate from rats' kidney, increased concentration of
ethylamine and glutamic acid were observed
[9,12]
, whereas
not from small intestine, liver, and brain. In the metabolic
aspect,
L
-theanine is metabolized in vitro to equimolar
amounts of ethylamine
[11]
. After intake of 24 h as capsule or
tea, the mean excretion of
L
-theanine refers 47 and 54% of
ingested one. Thus, the bioavailability of
L
-theanine remains in
between 47% and 54%
[8]
.
5. Pharmacokinetics of theanine
Theanine is chemically a chiral compound with two isomers,
L-form and D-form. In natural production, especially in tea, only
L
-theanine is found whereas in synthetic both isomers are pro-
duced. In physiological responses, there are signicant differ-
ences between Land Dforms.
L
-theanine is more readily absorbed than
D
-theanine. It has
been shown that if equal amount of Land Dform is given
separately to mammals, Lform has almost three times more
absorption capacity than Dform in the plasma level. Also, if
these two forms of this bioactive compound are given at a time
in equal content, the amount of uptake of
L
-theanine content is
much higher than
D
-theanine
[1]
.
L
-theanine and
D
-theanine have mutual antagonism when
they are administered in the system at a time. Dform inhibits
absorption of Lform in the body
[13]
.
Though these two forms of amino acid have lost from the
urinary route,
D
-theanine excretes more readily than
L
-theanine,
and the rate of excretion is about 1015 times more in Dform
than that of L form, while both are consumed either through
orally or injected in peritoneum in equal amount that resulted the
body becomes readily dehydrated
[13,14]
.
In plasma
D
-theanine degradation occurs more quickly than
L
-theanine. Both Dand Ltheanine are partially degraded into
ethylamine and glutamic acid, which is catalyzed by a
phosphate-independent glutaminase in the kidney
[13]
.
Structurally theanine is similar to the excitatory neurotrans-
mitter glutamate which binds to glutamate receptors with weak
interaction in the micromolar range, including the
a
-amino-3-
hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kai-
nate receptors, and to a lesser extent, the N-methyl-
D
-aspartic
acid (NMDA) receptor
[1518]
. Theanine acts antagonistically of
the former two sites
[16]
and as an agonist of the latter site
[19]
,
binds to group I metabotropic glutamate receptors (mGluRs)
[15,20]
and has an inhibitory activity on glutamine transporters
which accordingly blocks the reuptake of glutamine and
glutamate
[18,21,22]
. Finally, theanine elicits umami or savory
taste results direct binding and activates the T1R1 + T1R3
heterodimer or umami (savory) taste receptor
[23,24]
.
6. Mode of action of
L
-theanine
Theanine is basically non-toxic for all mammalian cells to a
certain level of intake and there has been no adverse effect in
physiological and histopathological characteristics
[1,25]
.
Theanine in Lform has very unique mode of action in the
mammalian systems, as mentioned below.
Table 1
Amino acids content value of different plant parts (
m
mol/g fresh tissues ± SD) of 6 months old seedling of tea.
Organ Ethylamine Alanine Theanine Glutamic acid Glutamine Aspartic acid Asparagine
Cotyledons 0.55 ± 0.35 2.26 ± 0.68 11.38 ± 0.81 1.79 ± 0.58 1.42 ± 0.57 1.39 ± 0.09 0.28 ± 0.05
Roots 0.66 ± 0.12 3.05 ± 0.16 39.00 ± 4.74 1.68 ± 0.32 1.56 ± 0.21 0.91 ± 0.13 0.20 ± 0.02
Leaves 0.88 ± 0.07 0.55 ± 0.06 14.96 ± 1.95 2.3 ± 0.36 1.00 ± 0.05 1.77 ± 0.26 0.44 ± 0.15
Stems 0.44 ± 0.02 0.95 ± 0.17 33.85 ± 3.68 2.39 ± 0.59 8.19 ± 1.14 1.64 ± 0.75 0.44 ± 0.02
Fresh weights (g) per organs are as follows: Cotyledons, (1.11 ± 0.18); roots, (1.05 ± 0.03); leaves (0.52 ± 0.08); stems, (0.53 ± 0.02)
[7]
.
Rajsekhar Adhikary, Vivekananda Mandal/Asian Pac J Trop Biomed 2017; (): 162
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j.apjtb.2017.08.005
L
-theanine increases dopamine and serotonin production in
the brain
[26]
and induces relaxation through the enhancement of
alpha wave activity in brain.
L
-theanine, as chemotherapeutic agent, competitively inhibits
glutamate transport into the infected tumor cells, can also
decrease intracellular glutathione (GSH) levels. The efux of
chemotherapeutic agents (e.g. doxorubicin, idarubicin, cisplatin,
irinotecan) are inhibited by theanine, which causes them to
accumulate in tumor cells and to protect normal cells from
damage by these drugs through its antioxidant property and
maintaining cellular GSH level
[22,2729]
.
L
-theanine can counteract the stimulatory effect of caffeine.
In rats, after caffeine administration intravenously with theanine
at the same dose, the stimulant effect of caffeine was blunted.
Whereas given by normal dose of caffeine with a smaller dose of
theanine administration resulted in excitatory effects of caffeine,
which suggested a dose specic dual activity of theanine
[30]
.
A dose-dependent hypotensive effect was occurred in sponta-
neously hypertensive rats injected with
L
-theanine in vivo
[31]
whereas structurally similar to theanine, glutamine administration
made unaltered blood pressure
[32]
.
7. Dosesand physiological effects applied for
L
-theanine
in mammals
Functionally
L
-theanine especially crossing the blood brain
barrier, is measurable in a range from 30 min and up to 5 h after
ingestion
[10,11,33]
, which is metabolized in the kidneys to
glutamate and ethylamine
[34]
. Recent studies referred
anxiolytic effect of single dose of theanine up to 200250 mg
per day and it may be extended up to 1 250 mg/day
[9,12,3537]
.
But there is no such specied dosage of
L
-theanine suggested
for enhanced immune system functions in mammalian systems.
8. Physiological effects of
L
-theanine
L
-theanine has multifaceted physiological effects on human
health. A brief account of these effects is mentioned below.
8.1. Neuroprotection
Theanine helps to protect neural damage and improve function
by reduction of cerebral infarction by inhibiting different neuro-
logical functions like catalase (CAT), superoxide dismutase
(SOD), and succinate dehydrogenase (SDH) activity, thus reduces
glutathione (GSH) and oxidative damage of neuronal cells
[3638]
.
It protects brain from cerebral ischemia
[39]
, and prevents brain
injury mediated by glutamate receptor agonist
[40]
and inhibits
cerebral cortical neuron involvement in delayed neuronal death
(DND). Neuroprotective role by regulation of group I mGluR
through stimulating the expression of phospholipase C-
b
1
(PLC-
b
1) and phospholipase C-
g
1 (PLC-
g
1)
[20]
by
L
-theanine,
resulted in decrease in efcacy of neurotoxin-induced neurotox-
icity, oxidative stress and also Parkinson's (PD) and Alzheimer's
diseases (AD). DNA fragmentation and nerve cell (SH-SY5Y)
apoptosis are also reduced by
L
-theanine
[4143]
.
8.2. Hypotensive activity
In adults,
L
-theanine can serve as a hypotensive agent with
anti-stress activity, acting on suppression of cortical neuron
excitement, reduction of anxiety and control rising of blood
pressure in high stress condition
[34]
. Theanine showed
hypotensive effect on spontaneous hypertensive rat
[44,45]
.
L
-
theanine showed the hypotensive activity made by the increase
of 5-hydroxytryptamine (5-HT) levels through the regulation
of peripheral nerves and vascular system. Theanine is accumu-
lated in the animal brain and reduce the levels of brain 5-HT and
its metabolite 5-hydroxy indole acetic acid (5HIAA)
[46]
.
8.3. Anti-diabetic effects
Diabetes is principally occurred by the abnormality of zinc
metabolism, which is important for protecting heart suffering
from diabetic myocardial complications from oxidative stress.
Supplements of zinc are very crucial for treatment to prevent
cardiac-oxidative damage and delay diabetic cardiomyopathy.
Theanine-zinc compound makes a zinc complex and acts as a
zinc supplement to maintain hypoglycaemic effect
[47,48]
.
8.4. Anti-fatigue effects
L
-theanine causes rise of the concentrations of dopamine (DA)
and hepatic glycogen, and reduction of concentrations of 5-HT
and serum urea are resulted in the alleviation of physical fatigue.
Prolonged theanine treatment reduces 5-HT, serum urea and
lactate, as well as increases DA and hepatic glycogen levels
[49]
.
8.5. Anti-tumor effects
First, Theanine inhibits biosynthesis of the glutamate trans-
port protein and intracellular glutathione, resulting in less
glutathione doxorubicin conjugate (GS-DOX) of the multidrug
resistance-associated protein-5/GS-X (MRP5/GS-X) pump, and
less intercellular transport of doxorubicin (DOX), which is
benecial in effect of anti-tumor drugs
[28,50]
.
L
-theanine
enhances anti-tumor effects of cisplatin on mouse M5076 cells
[9]
, and it shows signicant suppressive effects on tumors with
combination of Irinotecan hydrochloride, whereas irinotecan
hydrochloride alone has no anti-tumor effect.
Second,
L
-theanine relieves the toxic side effects induced by
some anticancer drugs through reduction of the activity of enzyme
glutathione peroxidase and lipid peroxidation levels induced by
the drug DOX, results less super oxidative stress
[29,35]
.
And thirdly, theanine derivatives inhibit tumor growth by
targeting epidermal growth factor receptor/vascular endothelial
growth factor receptor-Akt/nuclear factor-kappa B (EGFR/
VEGFR-Akt/NF-kappa B) signaling pathways, which involves
in controlling the survival and proliferation of cells.
L
-theanine
derivatives ethyl 6-uorocoumarin-3-carboxylyl
L
-theanine
(TFC) and ethyl 6-nitrocoumarin-3-carboxylyl
L
-theanine (TNC)
can effectively inhibit the cell growth of lung cancer by targeting
these pathways
[51,52]
.
8.6. Anti-depressant effects
L
-theanine has a convincing effect on anxiety and depression.
Intake of
L
-theanine after weaning prevents mice from stress-
induced impairments of hippocampal long-term potentiation
(LTP) and improves recognition memory
[53]
. The antidepressant
mechanism of
L
-theanine involving heart rate reduction and
salivary immunoglobulin A (s-IgA) decrease responses to an
acute stress task. The reduction in heart rate and s-IgA mediate
attenuation of the sympathetic nerve activation or suppression
of the excitation of cortical neuron
[5356]
.
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8.7. Anti-oxidant activity
L
-theanine can oxidize LDL cholesterol to some extent. Lipid
peroxidation marker mediated assay of malondialdehyde inhibit
LDL oxidation with theanine in vitro, although the effect was
weaker than the potent antioxidant effect of green tea poly-
phenols
[57]
.
8.8. Improving immunity
L
-theanine with
L
-cystine can enhance serum IgG and
antigen-specic IgM levels. A combined administration of
L
-
theanine and
L
-cystine in the human system
[58]
enhances the
immunity to inuenza vaccine in elderly persons with low
hemoglobin by orally
[59]
and also alleviates post-gastrectomy
inammation and promotes recovery after surgery during the
perioperative period
[60]
.
8.9. Alleviation of liver injury induced by alcohol
Excessive alcohol uptake causes liver injury, increases free
radicals and lipid peroxide (LPO) levels, and declines the ac-
tivity of glutathione peroxidase. To alleviate alcohol-induced
liver injuries, theanine increases aldehyde dehydrogenase and
alcohol dehydrogenase activity, declines cytochrome P450 CYP
2E1
[61]
.
L
-theanine improves the hepatic indices by raising the
activities of CAT, GSH and SOD with a reduction of MDA level
in the liver. Moreover, administration of
L
-theanine signicantly
ameliorates the hepatic function and declines the level of tumor
necrosis factor-
a
in the liver
[62,63]
.
8.10. Protective effects on the cardiovascular system
Consumption of
L
-theanine improves vascular function and
decreases the risk of cardiovascular disease. The protective ef-
cacy of the compound can reduce serum cholesterol
[64]
, rise
artery vasodilation and production of nitric oxide
[65]
, and
protect brain from cerebral ischemic injury. Alleviation of
serum cholesterol levels can reduce the risk of coronary heart
disease (CHD) by the application of
L
-theanine, which can
signicantly decrease the levels of abdominal adipose, liver
cholesterol, serum neutral fat and cholesterol
[64]
.
8.11. Improvement of memory
L
-theanine promotes the maturity of nervous centralis during
the neural maturation period, which is benecial for brain
development
[11,12]
, ameliorates learning and memorizing ability
by elimination of acquired memory disorders, oxidative stress,
and improves the brain
a
-wave
[66]
. Cognitive functions can
be enhanced by bioactive compound through the rise of brain
neurotransmitters such as dopamine, 5-hydroxytryptamine (5-
TH), glycine and
g
-aminobutyric acid (GABA)
[67,68]
.
8.12. Reduction of menstrual discomfort
The menstrual discomfort can be reduced by
L
-theanine
considerably. The target population with premenstrual syn-
drome, have experienced reduction of menstrual discomfort with
the intake of
L
-theanine
[69]
.
8.13. Maintenance of normal sleep
L
-theanine helps to maintain normal sleep for better brain
development and thus results in better mental and cognitive
health. The effect was examined on a target population and
considered benecial for maintenance of normal sleep
[69]
.
9. Side effects of
L
-theanine
L
-theanine in mammalian system is generally well tolerated,
and has a high LD
50
value (5000 mg/kg) and it is non-mutagenic
or non-carcinogenic agent in animal cells or bacteria.
10. Market demand and articial preparation of
L
-theanine
Articial chemical synthesis of
L
-theanine (purity
level 98%) comes from food-grade
L
-glutamic acid and eth-
ylamine with the solvent system as puried water and ethanol.
The major source of theanine is tea containing 1.0%2.5% of
dry weight of leaves and the average daily demand is 667
1 668 mg/day in United States according to Taiyo International,
Inc. by JHEIMBACH LLC. To mitigate the huge demand, large
scale production is very essential for smooth supply of
L
-the-
anine as a food supplement. Though there are some other fungal
sources, but the theanine content is very low compared to tea
leaves. For large scale production, the most accepted three
processes are stated here.
The rst production procedure was adopted and patented by
Taiyo International, Inc. by JHEIMBACH LLC where biolog-
ical or green synthesis of the bioactive compound was carried
out. It includes a treated organism which is aerobically cultured
in a glucose and yeast extract medium. Glutamine, ethylamine,
and glutamic acid are derived from raw materials, as well as
ammonia produced during the reaction, as impurities. The other
compounds, if presented, can be detected by the HPLC. But the
disadvantage is the total production system is completely
dependent on glutamic acid which is produced by bacterial
culture of Bacillus subtilis or Bacillus amyloliquefaciens and the
production is quite low.
The second large and facile production system of
L
-theanine
was as followed:
g
-Benzyl glutamate prepared by dissolving in
pyridine and trityl chloride (1.28 eq) was added to the solution
[70]
. To some successive treatments
L
-theanine was obtained as
white crystals through the crystallization of the residue by the
treatment of hot ethanol, and followed by re-crystallization of
ethanolwater treatment. Though in this chemical synthesis
method we get targeted product in a crystalline form, the pro-
duction method is very much time consuming.
Another efcient method of industrial production through
chemical synthesis process was developed by Zhejiang Tianrui
Chemicals Co., Ltd., where the required time is not exhaustive,
the whole system is well balanced, and a patent was awarded on
this production system.
11. Conclusion and future direction
L
-theanine, a non-essential bioactive amino acid, is very
much benecial to sustain in the stressful environment. Simul-
taneous intake of different medicine and food supplement may
reduce the health damage in a considerable limit. The mitigating
Rajsekhar Adhikary, Vivekananda Mandal/Asian Pac J Trop Biomed 2017; (): 164
Please cite this article in press as: Adhikary R, Mandal V, L-theanine: A potential multifaceted natural bioactive amide as health supplement, Asian Pac J Trop Biomed (2017), http://dx.doi.org/10.1016/
j.apjtb.2017.08.005
activity of
L
-theanine against non-communicable diseases like
cancer, cardiovascular disorder, respiratory anomalies, and dia-
betes may be useful in the current situation. High blood pressure
and the others complications can be reduced by using
L
-theanine
in a constant dose as food supplement. Pharmacokinetics,
bioavailability and mode of action in mammalian system are
discussed in this review. In accordance to the benets of
L
-
theanine, the industrial production system and the probable
effective system is discussed elaborately in this content. The
consumption of
L
-theanine can reduce the chance of application
of different drugs which have different critical side effects.
Summarily in this review the benecial role of the bioactive
compound serves as a good heath supplement in daily con-
sumption of higher combating power for both male and female.
In this regards,
L
-theanine will become a very effective supple-
ment in development of food and drugs in modern days.
Conict of interest statement
We declare that we have no conict of interest.
References
[1] Liang YR, Liu C, Xiang LP, Zheng XQ. Health benets of the-
anine in green tea: a review. Trop J Pharm Res 2015; 14(10): 1943-
9.
[2] Malongane F, McGaw LJ, Mudau FN. The synergistic potential of
various teas, herbs and therapeutic drugs in health improvement: a
review. J Sci Food Agric 2017. http://dx.doi.org/10.1002/jsfa.8472.
[3] Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of
diabetes-estimates for the year 2000 and projections for 2030.
Diabetes Care 2004; 27(3): 1047-53.
[4] Kaveeshwar SA, Cornwall J. The current state of diabetes mellitus
in India. Austral Med J 2014; 7(1): 45-8.
[5] World Health Organization (WHO). Global status report on non-
communicable diseases 2014. Geneva, Switzerland: WHO; 2014.
[Online] Available from: http://www.who.int/nmh/publications/
ncd-status-report-2014/en/.
[6] Pastoriza S, Mesías M, Cabrera C, Ru´
an-Henares JA. Healthy
properties of green and white teas: an update. Food Funct 2017.
http://dx.doi.org/10.1039/C7FO00611J.
[7] Deng WW, Ogita S, Ashihara H. Ethylamine content and theanine
biosynthesis in different organs of Camellia sinensis seedlings.
Z Naturforsch C 2009; 64(56): 387-90.
[8] Scheid L, Ellinger S, Alteheld B, Herholz H, Ellinger J, Henn T,
et al. Kinetics of L-theanine uptake and metabolism in healthy
participants are comparable after ingestion of L-theanine via cap-
sules and green tea. J Nutr 2012; 142(12): 2091-6.
[9] Sadzuka Y, Yamashita Y, Kishimoto S, Fukushima S, Takeuchi Y,
Sonobe T. Glutamate transporter mediated increase of antitumor
activity by theanine, an amino acid in green tea. Yakugaku Zasshi
2002; 122(11): 995-9.
[10] Cho HS, Kim S, Lee SY, Park JA, Kim SJ, Chun HS. Protective
effect of the green tea component, L-theanine on environmental
toxins-induced neuronal cell death. Neurotoxicology 2008; 29(4):
656-62.
[11] Yamada T, Terashima T, Wada K, Ueda S, Ito M, Okubo T, et al.
Theanine,
g
-glutamylethylamide, increases neurotransmission
concentrations and neurotrophin mRNA levels in the brain during
lactation. Life Sci 2007; 81: 1247-55.
[12] Tian X, Sun L, Gou L, Ling X, Feng Y, Wang L, et al. Protective
effect of L-theanine on chronic restraint stress-induced cognitive
impairments in mice. Brain Res 2013; 1503: 24-32.
[13] Desai MJ, Gill MS, Hsu WH, Armstrong DW. Pharmacokinetics of
theanine enantiomers in rats. Chirality 2005; 17(3): 154-62.
[14] Tsuge H, Sano S, Hayakawa T, Kakuda T, Unno T. Theanine,
gamma-glutamylethylamide, is metabolized by renal phosphate-
independent glutaminase. Biochim Biophys Acta 2003; 1620: 47-
53.
[15] Nathan P, Lu K, Gray M, Oliver C. The neuropharmacology of L-
theanine (N-ethyl-L-glutamine): a possible neuroprotective and
cognitive enhancing agent. J Herb Pharmacother 2006; 6(2): 21-
30.
[16] Kakuda T, Nozawa A, Sugimoto A, Niino H. Inhibition by the-
anine of binding of (
3
H) AMPA, (
3
H) kainate, and (
3
H) MDL 105,
519 to glutamate receptors. Biosci Biotechnol Biochem 2002;
66(12): 2683-6.
[17] Kakuda T. Neuroprotective effects of the green tea components
theanine and catechins. Biol Pharm Bull 2002; 25(12): 1513-8.
[18] Kakuda T. Neuroprotective effects of theanine and its preventive
effects on cognitive dysfunction. Pharmacol Res 2011; 64(2): 162-8.
[19] Wakabayashi C, Numakawa T, Ninomiya M, Chiba S, Kunugi H.
Behavioral and molecular evidence for psychotropic effects in
Ltheanine. Psychopharmacology 2012; 219(4): 1099-109.
[20] Nagasawa K, Aoki H, Yasuda E, Nagai K, Shimohama S,
Fujimoto S. Possible involvement of group I mGluRs in neuro-
protective effect of theanine. Biochem Biophys Res Commun 2004;
320(1): 116-22.
[21] Sugiyama T, Sadzuka Y, Tanaka K, Sonobe T. Inhibition of
glutamate transporter by theanine enhances the therapeutic efcacy
of doxorubicin. Toxicol Lett 2001; 121(2): 89-96.
[22] Sugiyama T, Sadzuka Y. Theanine and glutamate transporter in-
hibitors enhance the antitumor efcacy of chemotherapeutic agents.
Biochim Biophys Acta 2003; 1653(2): 47-59.
[23] Narukawa M, Toda Y, Nakagita T, Hayashi Y, Misaka T. L-the-
anine elicits umami taste via the T1R1 + T1R3 umami taste re-
ceptor. Amino Acids 2014; 46(6): 1583-7.
[24] T¨
urk¨
oz¨
uD,S
¸anlier N. L-theanine, unique amino acid of tea, and its
metabolism, health effects, and safety. Crit Rev Food Sci Nutr
2017; 57(8): 1681-7.
[25] Borzelleca JF, Peters D, Hall W. A 13-week dietary toxicity and
toxicokinetic study with L-theanine in rats. Food Chem Toxicol
2006; 44(7): 1158-66.
[26] Yokogoshi H, Mochizuki M, Saitoh K. Theanine induced reduction
of brain serotonin concentration in rats. Biosci Biotech Biochem
1998; 62(4): 816-7.
[27] Sadzuka Y, Sugiyama T, Suzuki T, Sonobe T. Enhancement of the
activity of doxorubicin by inhibition of glutamate transporter.
Toxicol Lett 2001; 123: 159-67.
[28] Sugiyama T, Sadzuka Y, Nagasawa R. Membrane transport and
antitumor activity of pirarubicin, and comparison with those of
doxorubicin. Jpn J Cancer Res 1999; 90(7): 775-80.
[29] Sugiyama T, Sadzuka Y. Theanine, a specic glutamate derivative
in green tea, reduces the adverse reactions of doxorubicin by
changing the glutathione level. Cancer Lett 2004; 212(2): 177-84.
[30] Kakuda T, Nozawa A, Unno T. Inhibiting effects of theanine on
caffeine stimulation evaluated by EEG in the rat. Biosci Biotechnol
Biochem 2000; 64: 287-93.
[31] Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T. Effect of
theanine,
g
-glutamylethylamide, on brain monoamines and striatal
dopamine release in conscious rats. Neurochem Res 1998; 23(5):
667-73.
[32] Yokogoshi H, Kato Y, Sagesaka YM, Takihara-Matsuura T,
Kakuda T, Takeuchi N. Reduction effect of theanine on blood
pressure and brain 5-hydroxyindoles in spontaneously hypertensive
rats. Biosci Biotech Biochem 1995; 59(4): 615-8.
[33] Eschenauer G, Sweet BV. Pharmacology and therapeutic uses of
theanine. Am J Health Syst Pharm 2006; 63(1): 28-30.
[34] Yoto A, Motoki M, Murao S, Yokogoshi H. Effects of L-theanine
or caffeine intake on changes in blood pressure under physical and
psychological stresses. J Physiol Anthropol 2013; 31:28.
[35] Sadzuka Y, Sugiyama T, Miyagishima A, Nozawa Y, Hirota S.
The effects of theanine, as a novel biochemical modulator, on the
antitumor activity of adriamycin. Cancer Lett 1996; 105: 203-9.
[36] Thangarajan S, Deivasigamani A, Natarajan SS, Krishnan P,
Mohanan SK. Neuroprotective activity of L-theanine on 3-
nitropropionic acid-induced neurotoxicity in rat striatum. Int J
Neurosci 2014; 124(9): 673-84.
Rajsekhar Adhikary, Vivekananda Mandal/Asian Pac J Trop Biomed 2017; (): 165
Please cite this article in press as: Adhikary R, Mandal V, L-theanine: A potential multifaceted natural bioactive amide as health supplement, Asian Pac J Trop Biomed (2017), http://dx.doi.org/10.1016/
j.apjtb.2017.08.005
[37] Jo M, Park MH, Choi DY, Yuk DY, Lee YM, Lee JM, et al.
Neuroprotective effect of L-theanine on A
b
-induced neurotoxicity
through anti-oxidative mechanisms in SK-N-SH and SK-N-MC
cells. Biomol Ther 2011; 19: 288-95.
[38] Sumathi T, Shobana C, Thangarajeswari M, Usha R. Protective effect
of L-theanine against aluminium induced neurotoxicity in cerebral
cortex, hippocampus and cerebellum of rat brain histopathological,
and biochemical approach. Drug Chem Toxicol 2015; 38: 22-31.
[39] Egashira N, Hayakawa K, Mishima K, Kimura H, Iwasaki K,
Fujiwara M. Neuroprotective effect of gamma-glutamylethylamide
(theanine) on cerebral infarction in mice. Neurosci Lett 2004;
363(1): 58-61.
[40] Zukhurova M, Prosvirnina M, Daineko A, Simanenkova A,
Petrishchev N, Sonin D, et al. L-theanine administration results in
neuroprotection and prevents glutamate receptor agonist-mediated
injury in the rat model of cerebral ischemia-reperfusion. Phyt-
other Res 2013; 27: 1282-7.
[41] Jamwal S, Singh S, Gill JS, Kumar P. L-theanine prevent quino-
linic acid induced motor decit and striatal neurotoxicity: reduction
in oxido-nitrosative stress and restoration of striatal neurotrans-
mitters level. Eur J Pharmacol 2017. http://dx.doi.org/10.1016/
j.ejphar.2017.06.016.
[42] Yoneda Y. An L-glutamine transporter isoform for neurogenesis
facilitated by L-theanine. Neurochem Res 2017. http://dx.doi.org/
10.1007/s11064-017-2317-6.
[43] Takeshima M, Miyazaki I, Murakami S, Kita T, Asanuma M. l-
Theanine protects against excess dopamine-induced neurotoxicity in
the presence of astrocytes. J Clin Biochem Nutr 2016; 59(2): 93-9.
[44] Yokogoshi H, Kobayashi M. Hypotensive effect of gamma-
glutamylmethylamide in spontaneously hypertensive rats. Life Sci
1998; 62(12): 1065-8.
[45] Rogers PJ, Smith JE, Heatherley SV, Pleydell-Pearce CW. Time
for tea: mood, blood pressure and cognitive performance effects of
caffeine and theanine administered alone and together. Psycho-
pharmacology 2008; 195: 569-77.
[46] Chen ZM. Theanine has antihypertensive function. Chin Tea 1997;
2:27.
[47] Matsumoto K, Yamamoto S, Yoshikawa Y, Doe M, Kojima Y,
Sakurai H, et al. Antidiabetic activity of Zn (II) complexes with a
derivative of L-glutamine. Bull Chem Soc Jpn 2005; 78: 1077-81.
[48] Kajiwara N, Yoshikawa Y, Yasui H, Matsumoto K. Experimental
observations of anti-diabetic activity of zinc complexes with the-
anine. Ann Nutr Metab 2013; 63. 16321632.
[49] Tan J, Lin Z, Peng Q, Guo L, Lv H. Evaluation on the alleviating
physical fatigue function of theanine compound preparation. J Tea
Sci 2012; 32: 530-4.
[50] Zhang G, Miura Y, Yakasaki K. Effects of dietary powdered green
tea and theanine on tumor growth and endogenous hyperlipidemia in
hepatoma-bearing rats. Biosci Biotechnol Biochem 2002; 66: 711-6.
[51] Zhang GY, Ye XS, Ji DX, Zhang HR, Sun FJ, Shang CQ, et al.
Inhibition of lung tumor growth by targeting EGFR/VEGFR-Akt/
NFkappa B pathways with novel theanine derivatives. Onco-
target 2014; 5: 8528-43.
[52] Liu J, Sun Y, Zhang H, Ji D, Wu F, Tian H, et al. Theanine from
tea and its semi-synthetic derivative TBrC suppress human cervical
cancer growth and migration by inhibiting EGFR/Met-Akt/NF-
k
B
signaling. Eur J Pharmacol 2016; 791: 297-307.
[53] Tamano H, Fukura K, Suzuki M, Sakamoto K, Yokogoshi H,
Takeda A. Preventive effect of theanine intake on stress-induced
impairments of hippocamapal longterm potentiation and recogni-
tion memory. Brain Res Bull 2013; 95: 1-6.
[54] Kimura K, Ozeki M, Juneja LR, Ohira H. L-theanine reduces
psychological and physiological stress responses. Biol Psychol
2007; 74: 39-45.
[55] Hidese S, Ota M, Wakabayashi C, Noda T, Ozawa H, Okubo T,
et al. Effects of chronic l-theanine administration in patients with
major depressive disorder: an open-label study. Acta Neuro-
psychiatr 2017; 29(2): 72-9.
[56] Unno K, Hara A, Nakagawa A, Iguchi K, Ohshio M, Morita A,
et al. Anti-stress effects of drinking green tea with lowered caffeine
and enriched theanine, epigallocatechin and arginine on psycho-
social stress induced adrenal hypertrophy in mice. Phytomedicine
2016; 23(12): 1365-74.
[57] Yokozawa T, Dong E. Inuence of green tea and its three major
components upon low density lipoprotein oxidation. Exp Toxicol
Pathol 1997; 49(5): 329-35.
[58] Takagi Y, Kurihara S, Higashi N, Morikawa S, Kaset, Maeda A,
et al. Combined administration of L-cystine and L-theanine en-
hances immune functions and protects against inuenza virus
infection in aged mice. J Vet Med Sci 2010; 72(2): 157-65.
[59] Miyagawa K, Hayashi Y, Kurihara S, Maeda A. Coadministration
of L-cystine and L-theanine enhances efcacy of inuenza vacci-
nation in elderly persons: nutritional status-dependent immunoge-
nicity. Geriatr Gerontol Intl 2008; 8: 243-50.
[60] Miyachi T, Tsuchiya T, Oyama A, Tsuchiya T, Abe N, Sato A,
et al. Perioperative oral administration of cystine and theanine
enhances recovery after distal gastrectomy: a prospective ran-
domized trial. JPEN Parenter Enter 2013; 37: 384-91.
[61] Sadzuka Y, Inoue C, Hirooka S, Sugiyama T, Umegaki K,
Sonobe T. Effects of theanine on alcohol metabolism and hepatic
toxicity. Biol Pharm Bull 2005; 28: 1702-6.
[62] Liu Y, Sun LY, Gou LS, Jia GG, Fu XB, Li S, et al. Inhibitory
effect of theanine on hepatic and renal injury in mice exposed to
unpredictable chronic mild stress. Lat Am J Pharm 2013; 32:
833-89.
[63] Hintzpeter J, Stapelfeld C, Loerz C, Martin HJ, Maser E. Green tea
and one of its constituents, epigallocatechine-3-gallate, are potent
inhibitors of human 11b-hydroxysteroid dehydrogenase type 1.
PLoS One 2014; 9(1). e84468.
[64] Ma XL. Research progress in studies on cardiovascular system
function of tea. Chin Tea 2008; 11: 12-3.
[65] Siamwala JH, Dias PM, Majumder S, Joshi MK, Sinkar VP,
Banerjee G, et al. L-Theanine promotes nitric oxide production in
endothelial cells through eNOS phosphorylation. J Nutr Biochem
2013; 24: 595-605.
[66] Egashira N, Ishigami N, Pu F, Mishima K, Iwasaki K, Orito K,
et al. Theanine prevents memory impairment induced by repeated
cerebral ischemia in rats. Phytother Res 2008; 22(1): 65-8.
[67] Sebih F, Rousset M, Bellahouel S, Rolland M, de Jesus
Ferreira MC, Guiramand J, et al. Characterization of l-theanine
excitatory actions on hippocampal neurons: toward the generation
of novel N-Methyl-d-aspartate receptor modulators based on its
backbone. ACS Chem Neurosci 2017. http://dx.doi.org/10.1021/
acschemneuro.7b00036.
[68] Dietz C, Dekker M. Effect of green tea phytochemicals on mood
and cognition. Curr Pharm Des 2017; 23(19): 2876-905. PMID:
28056735.
[69] Anonymous European Food Safety Authority (EFSA) Panel on
Dietetic Products. Nutrition and Allergies (NDA). Scientic
opinion on the substantiation of health claims related to L-theanine
from Camellia sinensis (L.) Kuntze (tea) and improvement of
cognitive function (ID 1104, 1222, 1600, 1601, 1707, 1935, 2004,
2005), alleviation of psychological stress (ID 1598, 1601), main-
tenance of normal sleep (ID 1222, 1737, 2004) and reduction of
menstrual discomfort (ID 1599) pursuant to Article 13(1) of
Regulation (EC) No 1924/2006. EFSA J 2011; 9(6): 2238.
[70] Kawagishi H, Sugiyama K. Facile and large-scale synthesis of L-
theanine. Biosci Biotech Biochem 1992; 56(4): 689.
Rajsekhar Adhikary, Vivekananda Mandal/Asian Pac J Trop Biomed 2017; (): 166
Please cite this article in press as: Adhikary R, Mandal V, L-theanine: A potential multifaceted natural bioactive amide as health supplement, Asian Pac J Trop Biomed (2017), http://dx.doi.org/10.1016/
j.apjtb.2017.08.005
... Yaşlılık: Bireyin fiziksel açıdan kayba uğradığı, statü kaybettiği, kişiler arası desteğin zayıfladığı, artan fiziksel hastalıklar ve özürlülük nedeniyle bireyin çevreye bağımlı hale geldiği aynı zamanda ruhsal sorunların da daha fazla gözlemlendiği bir dönemdir (1,23). ...
... Sağlık Kalite Standartları, ''Türk Sağlık Kalite Sistemi''nin dört temel bileşeninden biridir ve geliştirilme sebebi, Türkiye'de faaliyet gösteren tüm sağlık kurum ve kuruluşlarının hedef kalite düzeylerini belirtmek ve pratik kılavuz sağlamak içindir. SKS seti, Türkiye'de, üniversite, kamu veya özel sağlık hizmeti sunan bütün kurum ve kuruluşlar için oluşturulmuş aynı zamanda tıbbi hizmetlerin sunumunda ve risk yönetiminin sağlanmasında oluşabilecek risklerin en aza indirilmesi için bir araç olurken, değerlendirme sistemleri, standartları ve değerlendirme kriterleri için de bir rehber niteliğindedir [1]. ...
... Buna istinaden, acil durumlarda süreç yönetimi için bir takım araçlara ihtiyaç vardır ve bunlar için bazı uyarı sistemleri geliştirilmiştir. Bu amaçla dünya çapında en yaygın kullanılan araçlardan biri de renkli kodlardır [1]. ...
... Yaşlılık: Bireyin fiziksel açıdan kayba uğradığı, statü kaybettiği, kişiler arası desteğin zayıfladığı, artan fiziksel hastalıklar ve özürlülük nedeniyle bireyin çevreye bağımlı hale geldiği aynı zamanda ruhsal sorunların da daha fazla gözlemlendiği bir dönemdir (1,23). ...
... Sağlık Kalite Standartları, ''Türk Sağlık Kalite Sistemi''nin dört temel bileşeninden biridir ve geliştirilme sebebi, Türkiye'de faaliyet gösteren tüm sağlık kurum ve kuruluşlarının hedef kalite düzeylerini belirtmek ve pratik kılavuz sağlamak içindir. SKS seti, Türkiye'de, üniversite, kamu veya özel sağlık hizmeti sunan bütün kurum ve kuruluşlar için oluşturulmuş aynı zamanda tıbbi hizmetlerin sunumunda ve risk yönetiminin sağlanmasında oluşabilecek risklerin en aza indirilmesi için bir araç olurken, değerlendirme sistemleri, standartları ve değerlendirme kriterleri için de bir rehber niteliğindedir [1]. ...
... Buna istinaden, acil durumlarda süreç yönetimi için bir takım araçlara ihtiyaç vardır ve bunlar için bazı uyarı sistemleri geliştirilmiştir. Bu amaçla dünya çapında en yaygın kullanılan araçlardan biri de renkli kodlardır [1]. ...
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... Theanine is a natural bioactive compound derived from the tea plant (Thea sinesis, Theaceae) that has gained popularity as a stress-relief supplement in humans [30]. Naturally available predominately in the L-form stereoisomer, L-theanine is structurally similar to the excitatory neurotransmitter glutamate and has been shown to bind to glutamate receptors and act as an antagonist [31]. ...
... This is in contrast to the response seen in humans which shows a short-term decrease in HR following L-th administration (2 mg mL −1 ) which returns to baseline after ∼25 min [52]. Theanine's structural similarity to glutamate leads to a decrease in excitatory neurotransmission through its antagonism of glutamate receptors and inhibition of glutamine import for glutamate production [30,52,53]. Theanine has been shown to antagonize the action of glutamate at the crayfish neuromuscular junction [54]. ...
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Live crustaceans, especially lobsters, crabs, and shrimp, fetch premium prices in many international seafood markets, especially in parts of Asia. To access these market opportunities, live crustaceans frequently need to be transported over long distances, which can involve prolonged air exposure resulting in elevated stress and increased morbidity and mortality. Interventions which deliver metabolic suppression to live crustaceans during their transport have the potential to improve outcomes from live shipping. In this study, the administration of adenosine (Ado) and L-theanine (L-th) were assessed for metabolic suppression in the New Zealand scampi, Metanephrops challengeri, a deep sea lobster which is highly prized as seafood, and with excellent prospects for supply into premium live seafood markets. The administration to scampi of Ado and L-th in isolation or as a mixture (Ado/L-th), caused a significant decrease in heart rate (HR) with a lasting effect for the 4 hr experimental period. However, this depression of HR did not translate into a systemic downregulation of metabolism, as measured by the key metabolites, i.e., glycogen utilization and the accumulation of lactate and ammonia. The lack of systematic metabolic downregulation would preclude the potential use of Ado and L-th for commercial application in live shipping of crustaceans.
... It makes up 1-2% of the dry weight of fresh tea leaves and contributes to the favorable umami taste of tea [10,11]. L-theanine also offers several physiological effects, including relaxation, cognitive enhancement, and potential neuroprotective properties [12]. Moreover, emerging evidence suggests that L-theanine could perform antioxidant, anti-inflammatory, L-theanine (purity > 98%) and EGCG (purity > 95%) were generously provided by Hunan Sanfu Biological Technology Co., LTD (Changsha, China). ...
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Epigallocatechin-3-gallate (EGCG) is a main bioactive constituent in green tea. Being a redox-active polyphenol, high-dose EGCG exhibits pro-oxidative activity and could cause liver injury. L-theanine is a unique non-protein amino acid in green tea and could provide liver-protective effects. The purpose of this study was to investigate the hepatoprotective effects of L-theanine on EGCG-induced liver injury and the underlying mechanisms. A total of 300 mg/kg L-theanine was administrated to ICR mice for 7 days. Then, the acute liver injury model was established through intragastric administration of 1000 mg/kg EGCG. Pretreatment with L-theanine significantly alleviated the oxidative stress and inflammatory response caused by high-dose EGCG through modulation of Nrf2 signaling and glutathione homeostasis. Furthermore, metabolomic results revealed that L-theanine protects mice from EGCG-induced liver injury mainly through the regulation of amino acid metabolism, especially tryptophan metabolism. These findings could provide valuable insights into the potential therapeutic applications of L-theanine and highlight the importance of the interactions between dietary components.
... 92 Moreover, Ltheanine can cross the BBB, probably by the leucine-preferring transport, and accumulates in the brain parenchyma within a time window of 0.5 up to 5 h. 93,94 As a natural glutamate antagonist with a higher binding capacity for the AMPA/ kainite and NMDA receptors, L-theanine inhibits the glutamate reuptake in the synaptic cleft, attenuating the glutamate toxicity. 95,96 Although the underlying therapeutic mechanisms are unclear, L-theanine treatment can benefit patients with cognitive impairment. ...
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Nowadays, nutraceuticals are being incorporated into functional foods or used as supplements with nonpharmacological approaches in the prevention and management of several illnesses, including age-related conditions and chronic neurodegenerative diseases. Nutraceuticals are apt for preventing and treating such disorders because of their nontoxic, non-habit-forming, and efficient bioactivities for promoting neurological well-being due to their ability to influence cellular processes such as neurogenesis, synaptogenesis, synaptic transmission, neuro-inflammation, oxidative stress, cell death modulation, and neuronal survival. The capacity of nutraceuticals to modify all of these processes reveals the potential to develop food-based strategies to aid brain development and enhance brain function, prevent and ameliorate neurodegeneration, and possibly reverse the cognitive impairment observed in Alzheimer’s disease, the most predominant form of dementia in the elderly. The current review summarizes the experimental evidence of the neuroprotective capacity of nutraceuticals against Alzheimer’s disease, describing their mechanisms of action and the in vitro and in vivo models applied to evaluate their neuroprotective potential.
... The combination of Ltheanine and L-cystine can increase IgG serum and levels of antigen-specific IgM. In the human body system, combining L-theanine and L-cystine improves immunity to influenza vaccination in older people with low hemoglobin levels, as well as alleviates postgastrectomy inflammation, and promotes healing post surgery in the perioperative period [18]. Molecular docking analysis of this compound found that it had the largest number for binding energy (-3.62 kcal/mol) and inhibition constant (2.22 mM) out of the four compounds studied. ...
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This study examines the impact of the combination of sitagliptin and L-theanine on the testis tissue of rats with experimental diabetes. Diabetes mellitus, a chronic metabolic illness, significantly reduces quality of life and can cause male infertility by decreasing sperm count, motility, and testosterone levels. Rats were allocated to five separate groups: control, diabetes, L-theanine, sitagliptin, and combination therapy. The measurements encompassed blood glucose levels, body weight, serum insulin levels, and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The histological examination of testicular tissue was conducted using H&E, PASH, caspase-12, and PCNA staining techniques, in addition to a TUNEL assay to detect apoptosis. Levels of oxidative stress indicators, including glutathione peroxidase (GPX), malondialdehyde (MDA), and catalase, were also evaluated. The results showed that the group of individuals with diabetes had significantly higher levels of blood glucose, apoptotic indices, GPX, catalase, and MDA levels and activities in comparison with the control group. Although both the L-theanine and sitagliptin groups exhibited some improvement, the combination therapy demonstrated the most significant decrease in histopathological damage and apoptotic markers. These results indicate that the combination of sitagliptin and L-theanine may significantly decrease testicular damage caused by diabetes, making it a promising therapeutic strategy.
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Non-communicable diseases, such as cardiovascular disease, cancer, diabetes, obesity, and hypertension, represent the cause of 60% of all deaths around the globe. With proper diet and natural dietary antioxidant supplements, these diseases can be prevented by up to 40% according to the British Nutrition Foundation. This book provides a comprehensive overview of the literature on the health benefits of natural dietary antioxidant supplements. It presents state-of-the-art research and information as well as the global regulations, labelling, and health claims of natural dietary antioxidant supplements. Written by expert authors, the wealth of research is arranged by disease type rather than by supplement type making it much more useful to the reader. Filling a gap in the literature, the book is aimed at researchers and professionals working in food chemistry, nutrition, and health benefits.
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