Product name: Theanine
Synonym name: L-Theanine
Catalogue No.: BP1388
Cas No.: 3081-61-6
Formula: C₇H₁₄N₂O₃
Mol Weight: 174.2
Botanical Source: Green Tea
Physical Description:
Type of Compound: Alkaloids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

Description:

L-Theanine is a relaxing and nondietary amino acid found pretty much exclusively in teas from Camellia sinensis. It is known to promote relaxation and improve concentration and learning ability and has neuroprotective effects. L-Theanine heals gastric ulcer and prevents CCl4-induced experimental hepatic cirrhosis in rats by blocking the main pro-inflammatory and pro-fibrogenic signals. L-Theanine can significantly alleviate the adverse oxidative effect.

References:

Hum Exp Toxicol. 2016 Feb;35(2):135-46.    

l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of nuclear factor κB and down-regulation of transforming growth factor β and connective tissue growth factor.  

Here we evaluated the ability of L-Theanine in preventing experimental hepatic cirrhosis and investigated the roles of nuclear factor-κB (NF-κB) activation as well as transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) regulation. 

METHODS AND RESULTS:

Experimental hepatic cirrhosis was established by the administration of carbon tetrachloride (CCl4) to rats (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks), and at the same time, adding L-Theanine (8.0 mg/kg) to the drinking water. Rats had ad libitum access to water and food throughout the treatment period. CCl4 treatment promoted NF-κB activation and increased the expression of both TGF-β and CTGF. CCl4 increased the serum activities of alanine aminotransferase and γ-glutamyl transpeptidase and the degree of lipid peroxidation, and it also induced a decrease in the glutathione and glutathione disulfide ratio. L-Theanine prevented increased expression of NF-κB and down-regulated the pro-inflammatory (interleukin (IL)-1β and IL-6) and profibrotic (TGF-β and CTGF) cytokines. Furthermore, the levels of messenger RNA encoding these proteins decreased in agreement with the expression levels. L-Theanine promoted the expression of the anti-inflammatory cytokine IL-10 and the fibrolytic enzyme metalloproteinase-13. Liver hydroxyproline contents and histopathological analysis demonstrated the anti-fibrotic effect of L-Theanine.

CONCLUSIONS:

In conclusion, L-Theanine prevents CCl4-induced experimental hepatic cirrhosis in rats by blocking the main pro-inflammatory and pro-fibrogenic signals.    

Acta Neuropsychiatr. 2015 Apr 21:1-6.    

Effect of l-theanine on glutamatergic function in patients with schizophrenia.   

Glutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. Previous studies suggested that L-Theanine affects the glutamatergic neurotransmission and ameliorates symptoms in patients with schizophrenia. The aims of the present study were twofold: to examine the possible effects of L-Theanine on symptoms in chronic schizophrenia patients and to evaluate the changes in chemical mediators, including glutamate + glutamine (Glx), in the brain by using 1H magnetic resonance spectroscopy (MRS). 

METHODS AND RESULTS:

The subjects were 17 patients with schizophrenia and 22 age- and sex-matched healthy subjects. L-Theanine (250 mg/day) was added to the patients' ongoing antipsychotic treatment for 8 weeks. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), Pittsburgh Sleep Quality Index scores and MRS results. There were significant improvements in the PANSS positive scale and sleep quality after the L-Theanine treatment. As for MRS, we found no significant differences in Glx levels before and after the 8 week L-Theanine treatment. However, significant correlations were observed between baseline density of Glx and change in Glx density by L-Theanine. 

CONCLUSIONS:

Our results suggest that L-Theanine is effective in ameliorating positive symptoms and sleep quality in schizophrenia. The MRS findings suggest that L-Theanine stabilises the glutamatergic concentration in the brain, which is a possible mechanism underlying the therapeutic effect.    

J Nat Med. 2014 Oct;68(4):699-708.    

L-Theanine healed NSAID-induced gastric ulcer by modulating pro/antioxidant balance in gastric ulcer margin.   

L-Theanine is a unique non-protein-forming amino acid present in tea [Camellia sinensis (L.) O. Kuntze]. In the present work, we evaluated the healing effect of L-Theanine on NSAID (indomethacin)-induced gastric ulcer. 

METHODS AND RESULTS:

Histology of the stomach tissues revealed maximum ulceration on the third day after indomethacin administration (18 mg/kg, single dose p.o.) which was accompanied by increased lipid peroxidation; protein carbonylation; Th1 cytokine synthesis, and depletion of thiol, mucin, prostaglandin (PG) E, Th2 cytokine synthesis; and total antioxidant status in mice. L-Theanine healed gastric ulcer at a dose of 10 mg/kg b.w. but aggravated the ulcerated condition at a higher dose of 40 mg/kg b.w. At 10 mg/kg b.w., L-Theanine significantly alleviated the adverse oxidative effect of indomethacin through enhanced synthesis of PGE2 by modulation of cyclo-oxygenase-1 and 2 [COX-1 and COX-2] expression, Th1/Th2 cytokine balance, and restoration of cellular antioxidant status at the gastric ulcer margin.

CONCLUSIONS:

The present study revealed for the first time the dose-dependent biphasic effect of a natural neuroprotective agent, L-Theanine, on gastric ulcer disease.    

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Theanine, also known as N (5) - ethyl-L-glutamine, is a unique non protein amino acid mainly found in Camellia sinensis plants, with the highest content found in green tea leaves. Since the first isolation and identification of theanine from green tea by Japanese scientist Mijiro Sakato in 1950, it has rapidly become a research hotspot in the fields of natural product pharmacology, neuroscience, and nutrition due to its unique chemical structure and extensive physiological activity. Its CAS number is 3081-61-6.

Traditionally, green tea has been widely consumed due to its refreshing and fatigue relieving effects, and modern research has revealed that theanine is one of the key active ingredients for these benefits. Unlike caffeine, another major component in tea, theanine does not have an excitatory effect on the central nervous system, but instead exhibits significant relaxation, anti anxiety, and neuroprotective properties. Pharmacological studies have shown that theanine has various potential biological activities such as elderly protection, neuroprotection, immune regulation, and anti-tumor assistance. Among them, its regulatory role in mental and neurological disorders, especially anxiety related disorders, has received the most extensive attention. With the increasing number of stress-related diseases in modern society, the search for safe and effective natural anti anxiety substances has become an important research direction. Due to its good safety and multi-target effects, theanine has shown great potential for development. This article aims to systematically review the chemical properties, sources, pharmacological activities, mechanisms of action, medicinal properties, and clinical application prospects of theanine, in order to provide comprehensive scientific references for the in-depth research and development of this natural product.

Chemical structure and physicochemical properties

The chemical structural formula of theanine is C7H14N2O3, with a molecular weight of 174.20 g/mol. Its chemical essence is a derivative of glutamine, specifically L-glutamine with an ethyl group (- CH2CH3) attached to the gamma amide nitrogen atom, hence the system name N (5) - ethyl-L-glutamine. The molecular structure contains a chiral carbon atom, and naturally occurring theanine is mainly in the L-configuration, which is also its main form of biological activity.

In terms of physical and chemical properties, theanine is a white crystalline or crystalline powder with a slightly sweet taste and a umami taste similar to monosodium glutamate (MSG). It contains both amino and carboxyl groups in its molecule, belonging to zwitterionic compounds and exhibiting tautomerization. The calculated lipid water partition coefficient (LogP) is approximately -0.98, indicating its high hydrophilicity. Its topological polar surface area (TPSA) is 92.42 Å ², further confirming its polar molecular properties. These parameters determine the excellent water solubility of theanine, and experimental data shows that its water solubility is as high as 21.24 mg/mL, providing favorable conditions for its absorption and distribution in organisms. Theanine is relatively stable under acidic conditions, but may undergo hydrolysis under strong acid, strong base, or high temperature conditions, producing glutamic acid and ethylamine.

Plant sources and extraction methods

Theanine is a characteristic amino acid in tea (especially green tea), accounting for 1-2% of the dry weight of tea and more than 50% of the total free amino acids in tea. Its content is significantly affected by factors such as tea tree variety, growth environment, picking season, and processing technology. Generally speaking, high-quality green teas such as Yulu tea and matcha grown under shade have the highest content of theanine, as shading conditions inhibit the synthesis of bitter components such as catechins and promote the accumulation of theanine. In addition to Camellia plants, theanine has also been detected in a few mushrooms (such as Boletus badius), but the content is much lower than in tea leaves.

Extracting and purifying theanine from tea leaves is the main way to obtain this compound. Traditional extraction methods include hot water extraction, solvent extraction, etc. The hot water extraction method utilizes the good water solubility of theanine to repeatedly extract tea leaves with hot water. After combining the filtrate, the crude extract is obtained through concentration, decolorization (commonly using activated carbon), and alcohol precipitation to remove impurities. To further obtain high-purity theanine, column chromatography technology is often used for separation and purification. For example, cation exchange resin (such as 732 type) is used for adsorption, and then gradient elution is carried out using ammonia water or sodium chloride solution to collect the fraction rich in theanine. Finally, the product is obtained by concentration, crystallization, and drying.

With the development of biotechnology, microbial fermentation and enzymatic synthesis of theanine have become promising green production pathways. For example, using glutamine synthetase or gamma glutamyltransferase, efficient synthesis of theanine can be achieved in microbial cells or enzyme reaction systems using glutamic acid and ethylamine as substrates. These methods have the advantages of mild conditions, high yield, and environmental friendliness, and are important directions for future industrial production.

Pharmacological activity research

A large number of pharmacological studies both in vitro and in vivo have confirmed that theanine has multiple biological activities, with its core effects concentrated in the fields of nervous system and mental health.

1. Anti anxiety and sedative effects:
This is the most notable pharmacological activity of theanine. A large number of animal experiments (such as elevated cross maze experiments, light and dark box experiments) and human clinical trials have shown that theanine can effectively alleviate anxiety like behavior and mental stress, without causing sedation or motor dysfunction. Its effect is mild, usually taking effect 30-60 minutes after ingestion, and the effect can last for several hours. Compared with traditional anti anxiety drugs such as benzodiazepines, theanine has no addiction, withdrawal symptoms, or significant side effects, and is extremely safe.

2. Neuroprotective effect:
Theanine has a protective effect on the central nervous system. Research has shown that it can alleviate neuronal damage caused by glutamate excitotoxicity, which is related to the pathological mechanisms of neurodegenerative diseases such as cerebral ischemia and Alzheimer's disease. In animal models, pre-treatment with theanine can reduce the area of cerebral ischemia-reperfusion injury and improve cognitive function. Its neuroprotective effect may be related to regulating neurotransmitters, inhibiting oxidative stress, and resisting apoptosis.

3. Improvement of cognitive function:
Theanine can affect cognitive processes such as attention and memory. Research has shown that when used alone or in combination with caffeine, theanine can improve an individual's attention span and reaction accuracy in complex tasks, while reducing the tension and anxiety that caffeine may cause, achieving a state of "awake relaxation".

4. Other activities:
In addition, theanine also has immunomodulatory effects, which can enhance the body's resistance to pathogens; As an adjuvant in tumor treatment, it can enhance the anti-tumor effect of certain chemotherapy drugs (such as doxorubicin) and reduce their side effects; It also has the potential to lower blood pressure and regulate lipid metabolism.

Mechanism of action and molecular targets

The various pharmacological effects of theanine, especially its anti anxiety and neuroprotective effects, are achieved through synergistic action on multiple molecular targets and signaling pathways, reflecting the multi-target nature of natural products.

1. Neurotransmitter system regulation:
This is the core mechanism by which theanine exerts its central role.
* Gamma aminobutyric acid (GABA) system: GABA is the main inhibitory neurotransmitter in the central nervous system. The structure of theanine is similar to that of glutamate, and it can penetrate the blood-brain barrier and may affect the metabolism of GABA. Research has shown that theanine can upregulate GABA levels and regulate the expression or function of GABA receptor subtypes (such as GABRA1, GABRB2, GABRG2), thereby enhancing central inhibition and producing anti anxiety and sedative effects.
* Monoamine neurotransmitter system: Theanine can affect the levels of monoamine neurotransmitters such as dopamine and serotonin (5-HT) in the brain. It may reduce the degradation of these neurotransmitters by inhibiting the activity of monoamine oxidase A (MAOA), thereby increasing their concentration in synaptic cleft and improving mood. Its anti anxiety effect is related to the activation of 5-HT1A receptor (HTR1A) and the regulation of 5-HT2A receptor (HTR2A), as well as the regulation of dopamine D2 receptor (DRD2).
* Glutamate system: As a derivative of glutamine, theanine can antagonize the excessive excitation of certain receptors (such as NMDA receptors) by glutamate, preventing excitotoxicity, which is a key link in its neuroprotective effect.

2. Neurotrophic factors and signaling pathways:
Theanine can promote the expression of brain-derived neurotrophic factor (BDNF). BDNF is crucial for the survival, growth, differentiation, and synaptic plasticity of neurons. Theanine may also activate transcription factors such as cAMP response element binding protein (CREB1) to initiate downstream gene expression related to cell survival and stress resistance, thereby exerting neuroprotective and anti anxiety effects.

3. Other targets:
Theanine may have a regulatory effect on serotonin transporter (SLC6A4), affecting the reuptake of 5-HT. In addition, its antioxidant and anti-inflammatory effects also participate in overall neuroprotection and emotional regulation.

In summary, theanine comprehensively regulates the GABAergic, 5-HT, dopaminergic, and glutamatergic systems through a "multi-target, micro regulatory" approach, and enhances neural nutritional support, ultimately synergistically producing physiological effects that stabilize emotions, protect nerves, and improve cognition.

Evaluation of drug properties and pharmacokinetics

The evaluation of drug like parameters shows that theanine has good potential for development. Its molecular weight is moderate (174.20), with strong hydrophilicity (LogP-0.98, TPSA 92.42) and excellent water solubility, which is beneficial for its oral absorption. The key toxicity screening indicators show that theanine has no inhibitory effect on hERG potassium channels, indicating a very low risk of causing QT interval prolongation in the heart; The Ames test result is negative, indicating no mutagenicity and high safety.

Pharmacokinetic studies (mainly conducted in rats and humans) revealed the dynamic process of theanine in vivo:
* Absorption: After oral administration, it is mainly actively absorbed in the small intestine through sodium ion coupled amino acid transporters, and the absorption is rapid. The peak blood drug concentration is reached about 1 hour after oral administration.
* Distribution: Theanine can penetrate the blood-brain barrier, although its prediction of "blood-brain barrier: low" may suggest limited permeability, actual research has shown that it can enter brain tissue and accumulate in specific areas of the brain (such as the thalamus and hippocampus) within a few hours after ingestion, which directly supports its central activity.
* Metabolism: In the body, some theanine is hydrolyzed into glutamate and ethylamine in the kidneys; The other part exists in its original form. It may also undergo modifications such as ethylation or acetylation, but the main metabolic pathway is relatively simple.
* Excretion: Theanine is mainly excreted from urine through the kidneys, with a clearance half-life of approximately 1-2 hours. Within about 24 hours after ingestion, it is basically completely excreted without any risk of accumulation in the body.

Overall, theanine has ideal pharmacokinetic characteristics such as good oral bioavailability, brain entry, rapid metabolism and excretion, and a wide safety window, laying a solid foundation for its development as a functional food ingredient or drug.

Clinical application prospects and prospects

Based on its excellent safety and clear pharmacological activity, theanine has shown broad clinical application prospects in multiple fields.

1. Healthy foods and dietary supplements:
At present, theanine has been approved as a food additive or dietary supplement ingredient in multiple countries such as the United States, Japan, and China. It is widely used in functional beverages, candies, tablets, and other products that relieve mental stress, improve sleep quality, and enhance attention. This is its most mature market application.

2. Auxiliary treatment for neurological and psychiatric disorders:
* Anxiety disorder: As a natural intervention for mild to moderate anxiety, theanine can be used as an adjunct or alternative to first-line medications, especially for patients who are unwilling or unable to tolerate the side effects of traditional anti anxiety drugs.
* Cognitive impairment: In the early intervention of diseases such as mild cognitive impairment (MCI) and Alzheimer's disease (AD), the neuroprotective and cognitive improving effects of theanine make it potentially valuable as part of a comprehensive management strategy.
* Attention Deficit Hyperactivity Disorder (ADHD): Its characteristic of improving attention without sedative side effects has been studied in the auxiliary management of ADHD.
* Management of side effects of psychotropic drugs: Research and explore its use to alleviate some of the side effects caused by antipsychotic drugs.

3. Other medical fields:
As an adjuvant for reducing toxicity and enhancing efficacy in tumor radiotherapy and chemotherapy; Used in the cardiovascular field to assist in the management of stress-induced hypertension; Used in immune regulation to enhance the body's resistance.

Future prospects and challenges:
Despite the bright prospects, the in-depth development and clinical application of theanine still face some challenges and directions that need to be explored:
1. Deepening mechanism of action: It is necessary to more accurately elucidate its specific targets and signaling pathways at the molecular and neural network levels, especially the intrinsic connections between its various effects.
2. Clinical evidence upgrade: At present, most human trials have small sample sizes and short cycles. More large-scale, multicenter, randomized double-blind long-term clinical trials are needed in the future to confirm their efficacy and optimal dosage regimen for specific diseases.
3. Formulation innovation: Develop new delivery systems (such as nano formulations, transdermal patches) to improve their bioavailability, brain targeting, or provide sustained release.
4. Combination therapy research: Systematically study the synergistic effects of theanine with other drugs (such as antidepressants, cognitive enhancers) or natural products (such as caffeine, catechins), and develop more effective compound products.
5. Synthetic Biology Production: Optimize enzymatic or microbial fermentation production processes to reduce costs and meet the growing market demand.

Conclusion

Theanine, a natural amino acid derived from green tea, has evolved from a flavor component to a star molecule with important biological activity after decades of scientific research. Its unique chemical structure endows it with the ability to cross the blood-brain barrier, regulate the neurotransmitter system and neurotrophic pathways through multiple targets, resulting in multiple beneficial effects such as anti anxiety, neuroprotection, and cognitive improvement. The excellent medicinal properties and extremely high safety provide strong support for its transition from dietary supplements to clinical drugs.

Currently, theanine has been widely used in relieving daily stress and improving sub-health conditions. In the future, with further elucidation of its mechanism of action and continuous accumulation of high-level clinical evidence, theanine is expected to play an important role in a wider range of medical fields such as anxiety disorders and neurodegenerative diseases. It represents a successful example of discovering modern therapeutic value from traditional medicinal and edible plants, and its research process also enlightens us that there are still countless treasures similar to theanine in nature, waiting for us to unlock them with the key of science. The continuous exploration of theanine will not only promote its own development, but also provide valuable experience and ideas for pharmacological research and innovative drug development of natural products.