UNASSIGNED: L-theanine is a non-protein-forming amino acid found in tea. Limited evidence suggests that it improves selective attention. Sleep deprivation impairs attention and psychomotor reactions, affecting automobile driving. We aimed to determine whether L-theanine improves neurobehavioral measures of visual attention in acutely sleep-deprived healthy adults in a traffic-scene-based attention task.
UNASSIGNED: In a double-blind, placebo-controlled, counterbalanced, two-way crossover study, we compared the effects of a 200-mg dose of L-theanine with a placebo (150 ml of distilled water) on a computerised, traffic-scene-based visual recognition reaction task in 24 healthy volunteers (age 20-25 years; 13 males) sleep-deprived overnight. The participants made speeded button-presses to imminent accident scenes (i.e. hits), while ignoring safe scenes. They were tested pre-dose and 45 min post-dose, each treatment administered one week apart.
UNASSIGNED: Hit rates were more than 90% in all sessions, and were similar in two treatments, pre- vs post-dose. L-theanine significantly reduced false alarms (i.e. responses to safe scenes) (p = 0.014) and increased A\' (i.e. target-distractor discriminability) (p = 0.009), whereas placebo did not (p > 0.05). L-theanine reduced hit reaction time by 38.65 ms (p = 0.007), and placebo by 19.08 ms (p = 0.016), however reaction time changes from baseline were not significantly different between treatments (p > 0.05).
UNASSIGNED: L-theanine in high doses appears to improve selective visual attention by concurrently improving information processing speed and target-distractor discriminability in acutely sleep-deprived individuals. This is consistent with previous functional neuroimaging findings, where L-theanine suppressed distractor-processing and default-mode-network activity in visual selective attention tasks.

The thermal instability of γ-glutamylmethylamide synthetase (GMAS) from Methylovorus mays has imposed limitations on its industrial applications, affecting both stability and activity at reaction temperatures. In this study, disulfide bridges were introduced through a combination of directed evolution and rational design to enhance GMAS stability. Among the variants that we generated, M12 exhibited a 1.46-fold improvement in relative enzyme activity and a 6.23-fold increase in half-life at 40℃ compared to the wild-type GMAS. Employing variant M12 under optimal conditions, we achieved the production of 645.7 mM (112.49 g/L) L-theanine with a productivity of 29.3 mM/h, from 800 mM substrate in an ATP regeneration system. Our strategy significantly enhances the biosynthesis efficiency of L-theanine by preserving the structural stability of the enzyme during the catalysis process.

BACKGROUND: L-theanine is a unique non-protein amino acid in tea that is widely used as a safe food additive. We investigated the cardioprotective effects and mechanisms of L-theanine in myocardial ischemia-reperfusion injury (MIRI).
METHODS: The cardioprotective effects and mechanisms of L-theanine and the role of Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling were investigated in MIRI mice using measures of cardiac function, oxidative stress, and apoptosis.
RESULTS: Administration of L-theanine (10 mg/kg, once daily) suppressed the MIRI-induced increase in infarct size and serum creatine kinase and lactate dehydrogenase levels, as well as MIRI-induced cardiac apoptosis, as evidenced by an increase in Bcl-2 expression and a decrease in Bax/caspase-3 expression. Administration of L-theanine also decreased the levels of parameters reflecting oxidative stress, such as dihydroethidium, malondialdehyde, and nitric oxide, and increased the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD) in ischemic heart tissue. Further analysis showed that L-theanine administration suppressed the MIRI-induced decrease of phospho-JAK2 and phospho-STAT3 in ischemic heart tissue. Inhibition of JAK2 by AG490 (5 mg/kg, once daily) abolished the cardioprotective effect of L-theanine, suggesting that the JAK2/STAT3 signaling pathway may play an essential role in mediating the anti-I/R effect of L-theanine.
CONCLUSIONS: L-theanine administration suppresses cellular apoptosis and oxidative stress in part via the JAK2/STAT3 signaling pathway, thereby attenuating MIRI-induced cardiac injury. L-theanine could be developed as a potential drug to alleviate cardiac damage in MIRI.

BACKGROUND: L-Theanine, a nonproteinogenic amino acid derived from green tea, is being recognized as an anti-cancer candidate. However, it\'s roles in the development of cancer chemoresistance is still unknown and the molecular mechanism is urgently to be explored.
METHODS: The effects of L-Theanine on lung cancer chemoresistance were validated by Cell Counting Kit-8 (CCK-8) assay, transwell assay, and in vitro tumor spheroid formation assay; the expression of proteins was detected by using polymerase chain reaction (PCR) and western blotting. RNA-sequencing (RNA-seq) and bioinformatics analysis were used to identify differentially expressed genes induced by L-Theanine. BMAL1 knockdown and overexpression were constructed by using a lentivirus-mediated transfection system.
RESULTS: L-Theanine improved the chemoresistance to cis-diamminedichloroplatinum (DDP) and inhibited stemness of DDP-resistant lung cancer cells but not non-resistant lung cancer cells. The results from RNA-seq analysis showed that STAT3/NOTCH1 pathway was a potential dominant signaling involved in L-Theanine improving the chemoresistance in DDP-resistant lung cancer. Mechanistically, L-Theanine impeded migration and stemness activation of DDP-resistant lung cancer cells via regulating the expression of STAT3/NOTCH1/BMAL1 signaling-induced stemness markers as well as inhibiting the expression levels of drug resistance-related genes. In addition, a combination of L-Theanine and Stat3 blockade synergistically improved the chemoresistance in DDP-resistant lung cancer.
CONCLUSIONS: L-Theanine improves the chemoresistance by regulating STAT3/NOTCH1/BMAL1 signaling, reducing stemness, and inhibiting the migration of DDP-resistant lung cancer cells. The finding might provide some evidence for therapeutic options in overcoming the chemoresistance in cancers, including lung cancer.

L-theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effects, regulation of the immune response, relaxing neural tension, and reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also upregulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provides a theoretical basis for the possibility that tea drinking may prevent mitochondrial-related diseases.

UNASSIGNED: The primary objective was to compare the hypnotic efficacy of oral melatonin, oral L-theanine, and placebo in improving sleep in cancer patients with insomnia by the Athens Insomnia Scale (AIS). The secondary objective was to know the prevalence of insomnia in patients with cancer.
UNASSIGNED: A prospective, double-blinded, placebo-controlled study was conducted after obtaining Institutional Ethics Committee approval. One hundred and twenty patients were randomly assigned to either Group A (melatonin), Group B (L-theanine), or Group C (placebo). They were instructed to take the tablets for 14 consecutive days, two h (hours) before bedtime, and evaluated with AIS on the 1st day, 7th day, and 14th day.
UNASSIGNED: There were seven dropouts: Two in Group A, two in Group B, and three in Group C. Significant differences in favour of melatonin treatment were found. There were statistically significant improvements in insomnia in cancer patients on melatonin intake compared to L-theanine. L-theanine had statistically significant improvements in insomnia in comparison to placebo. The mean ± standard deviation AIS on day one in Group A was 14.82 ± 1.29; on day seven was 10.92 ± 1.12; and on day 14 was 5.00 ± 0.70. Similarly, in Group B, the mean ± standard deviation AIS was 15.39 ± 1.03, 13.05 ± 1.06, and 9.55 ± 1.01, and in Group C, the mean AIS was 14.92 ± 1.40, 14.54 ± 1.35 and 13.05 ± 1.61 on the 1st, 7th and 10th day, respectively. There was an improvement in sleep from 1 to 7 days, 7 days to 14 days, and 1 day to 14 days in all the groups (P < 0.005).
UNASSIGNED: The hypnotic efficacy of oral melatonin 3 mg was better than oral L-theanine 200 mg in cancer patients having insomnia. Furthermore, L-theanine had a better hypnotic efficacy when compared to a placebo.

BACKGROUND: Overactivation of receptors that respond to excitatory neurotransmitters can result in various harmful outcomes, such as the inability to properly modulate calcium levels, generation of free radicals, initiation of the mitochondrial permeability transition, and subsequent secondary damage caused by excitotoxicity. A non-proteinogenic amino acid of tea, L-theanine, is structurally related to glutamate, the major stimulatory neurotransmitter in the brain. Previous reports have emphasised its ability to bind with glutamate receptors.
OBJECTIVE: An in-depth understanding of the binding compatibility between ionotropic glutamate receptors and L-theanine is a compelling necessity.
METHODS: In this molecular docking study, the antagonistic effect of L-theanine and its possible therapeutic benefit in GluR5 kainate receptor inhibition has been evaluated and compared to the familiar AMPA and kainite receptor antagonists, cyanoquinoxaline (CNQX) and dinitroquinoxaline (DNQX), using Molegro Virtual Docker 7.0.0.
RESULTS: The capacity of L-theanine to cohere with the GluR5 receptor was revealed to be higher than that of glutamate, although it could not surpass the high binding tendency of competitive antagonists CNQX and DNQX. Nonetheless, the drug-likeness score and the blood-brain barrier traversing potential of L-theanine were higher than CNQX and DNQX.
CONCLUSIONS: The study provides an inference to the advantage of L-theanine, which can be a safe and effective alternative natural therapy for rescuing neuronal death due to excitotoxicity.

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.

L-theanine, an amino acid component of the tea leaves of Camellia sinensis, is sold in Japan as a supplement for good sleep. Although several studies in humans and mice have reported the effects of L-theanine on brain function, only a few reports have comprehensively clarified the disposition of theanine administered to mice and its effects on concentrations of other blood amino acids. In this study, we aimed to determine the changes in the blood levels of L-theanine administered to mice and amino acid composition of the serum. L-theanine were administered to four-week-old Std-ddY male mice orally or via tail vein injection. L-theanine and other amino acids in serum prepared from blood collected at different time points post-dose were labeled with phenylisothiocyanate and quantified. The serum concentration of orally administered L-theanine peaked 15 min after administration. The area under the curve for tail vein injection revealed the bioavailability of L- theanine to be approximately 70%. L-theanine administration did not affect any amino acid levels in the serum, but a significant increase in the peak area overlapping the Glycine (Gly) peak was observed 30 min after administration. L-theanine administered to mice was rapidly absorbed and eliminated, suggesting that taking L-theanine as a supplement is safe without affecting its own levels or serum levels of other amino acids. However, considering that Gly, similar to L-theanine, is used as a dietary supplement for its anxiolytic effects and to improve sleep, determining the effects of L-theanine administration on Gly is important and needs further research.

Tea grey blight disease is one of the most destructive diseases that infects tea and is caused by the pathogen Pestalotiopsis theae (Sawada) Steyaert. L-theanine is a unique non-protein amino acid of the tea plant. Different concentrations of L-theanine exhibit significant inhibitory effects on the growth and sporulation ability of the pathogen causing tea grey blight disease. To understand the effect mechanism of L-theanine on P. theae, transcriptome profiling was performed on the pathogenic mycelium treated with three different concentrations of L-theanine: no L-theanine treatment (TH0), 20 mg/mL theanine treatment (TH2), and 40 mg/mL theanine treatment (TH4). The colony growths were significantly lower in the treatment with L-theanine than those without L-theanine. The strain cultured with a high concentration of L-theanine produced no spores or only a few spores. In total, 2344, 3263, and 1158 differentially expressed genes (DEGs) were detected by RNA-sequencing in the three comparisons, Th2 vs. Th0, Th4 vs. Th0, and Th4 vs. Th2, respectively. All DEGs were categorized into 24 distinct clusters. According to GO analysis, low concentrations of L-theanine primarily affected molecular functions, while high concentrations of L-theanine predominantly affected biological processes including external encapsulating structure organization, cell wall organization or biogenesis, and cellular amino acid metabolic process. Based on KEGG, the DEGs of Th2 vs. Th0 were primarily involved in pentose and glucuronate interconversions, histidine metabolism, and tryptophan metabolism. The DEGs of Th4 vs. Th0 were mainly involved in starch and sucrose metabolism, amino sugar, and nucleotide sugar metabolism. This study indicated that L-theanine has a significant impact on the growth and sporulation of the pathogen of tea grey blight disease and mainly affects amino acid metabolism, carbohydrate metabolism, and cellular structure-related biosynthesis processes of pathogenic fungi. This work provides insights into the direct control effect of L-theanine on pathogenic growth and also reveals the molecular mechanisms of inhibition of L-theanine to P. theae.