Effects of sitagliptin and L-theanine combination therapy on testicular tissue in rats with experimental diabetes.

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.

L-Theanine Ameliorates Obesity-Related Complications Induced by High-Fat Diet in Mice: Insights from Transcriptomics and Metabolomics.

Obesity is a major public health concern globally. Plant-based ingredients have been proposed as alternative treatments for obesity. L-Theanine (THE), a unique nutraceutical component of tea, is known for its neuroprotective and cognitive benefits. However, there are few reports on THE's effects and mechanisms in improving obesity and its complications. In this study, the alleviating effects and potential mechanisms of THE on obesity-related complications (ORCs) induced by a high-fat diet(HFD) in mice were explored by performing biochemical, hepatic transcriptomics, and plasma metabolomics analyses. The results indicated THE (900 mg/kg of body weight) was effective in mitigating ORCs by decreasing body weight gain and fat deposition, improving glycolipid metabolism disorders, inflammation dysregulation, and alleviating fatty liver formation due to long-term HFD. The hepatic transcriptomics data suggested that THE intervention suppresses the lipid metabolism and inflammation pathways in HFD-fed mice, thereby inhibiting hepatic steatosis and inflammation. Moreover, plasma metabolomics analysis revealed that THE exhibited positive effects on the homeostasis of plasma metabolite balance, such as phosphatidylcholine (PC(14:0/18:1)), phosphatidylethanolamine (Lyso-PE(14:0)), phosphatidic acid (PA(16:0e/18:0)), stigmasterol, and deoxycholic acid glycine conjugate. These metabolites were strongly correlated with ORC-related indicators. Our results indicated that THE, as a functional food additive, possesses potential for ORC alleviation. However, the exact molecular mechanism of how THE alleviates ORCs needs to be investigated in the future.

Matcha Does Not Affect Electroencephalography during Sleep but May Enhance Mental Well-Being: A Randomized Placebo-Controlled Clinical Trial.

Although theanine in matcha improves sleep quality and cognitive function, the caffeine in green tea is thought to worsen sleep quality. Therefore, this study investigated the factors behind the observed improvements in subjective sleep quality in matcha. A placebo-controlled randomized double-blind parallel-group study was conducted on healthy Japanese men and women aged 27-64 years. After 4 weeks of consuming 2.7 g of matcha daily (containing 50.3 mg theanine, 301.4 mg catechins, and 71.5 mg caffeine), no significant differences were observed between the control and matcha groups on total sleep time, sleep latency, wake after sleep onset, or sleep efficiency measured by electroencephalography (EEG). However, the sleep questionnaire Oguri-Shirakawa-Azumi Sleep Inventory, the Middle-age and Aged version (OSA-MA), administered immediately after waking showed a trend toward increased satisfaction with sleep time (p < 0.1), and EEG measurements indicated significantly shortened wake-up times after waking with matcha intake (p < 0.05). The Beck Depression Inventory-II scores also tended to decrease (p < 0.1). The continuous intake of matcha may offer improved subjective sleep quality and emotional stability despite not offering significant changes in objective sleep parameters.

Novel Pink Pigments Produced by Thermal Interaction of Theaflavins, Theanine, and Glucose: Color Formation, Isolation, and Structural Characterization.

A color-deepening effect of theaflavins on the theanine-glucose thermal reaction model was revealed. Generated chromogenic intermediates in the initial stage and an accelerated browning rate through the promoted degradation of theanine-glucose Amadori rearrangement product in the intermediate and final stages are responsible for the color-deepening effect. Four pink-to-red theaflavin-theanine intermediates were verified as theaflavinies referencing the nuclear magnetic resonance and liquid chromatography-mass spectrometry information on theaflavins and l-theanine, including one accurately identified as theaflavinie 4. Theaflavinie 4 showed two maximum absorption peaks at 401 and 506 nm with parallel intensities, which resulted in a significant dichromic color change from pale pink to orange and red. Theaflavinies also could undergo further thermal reactions to yield brown polymers under higher temperatures (130 and 140 °C). This research provided new insight into realizing thermally formed polymers during black tea processing, which may be formed by oxidation products and amino acids or proteins through non-enzymatic thermal reactions.

Acetylation participation in theanine biosynthesis: Insights from transcriptomics, proteomics, and acetylomics.

Acetylation, a crucial post-translational modification, regulates transcriptional activation, enzymatic activity, and protein interactions, playing vital roles in plant physiology and metabolism. However, the regulatory mechanism of acetylation in the biosynthesis of theanine remains unexplored. This study aims to elucidate the regulatory role of acetylation on the biosynthesis of theanine using transcriptomics, proteomics, and acetylomics in tea leaves from three tea plant cultivars with markedly different theanine content. Nineteen theanine biosynthesis-related genes were identified in the transcriptome, with ten showing significant correlation with theanine content. Proteomic analysis revealed elevated expression levels of proteins associated with the biosynthesis of theanine precursor glutamate in leaves with high theanine content, such as GOGAT and GDH. Unexpectedly, the expression level of TS was inversely correlated with the theanine content in leaves. Several highly expressed acetylated proteins and sites, such as TS, GS, and GOGAT, were found in the acetylome of leaves with high theanine content. Acetylation at lysine 304 (K304) of the TS protein may significantly contribute to the abundant accumulation of theanine in leaves. Our findings indicate that acetylation modification may play a pivotal role in theanine biosynthesis, thereby offering novel insights into the development of high-theanine tea plant germplasm resources.

Enhancing emulsion, texture, rheological and sensory properties of plant-based meat analogs with green tea extracts.

Plant-based meat analogs require improvements in taste and texture to better replicate traditional meat. L-theanine and tannin, abundant in green tea, influence food taste and physicochemical properties. This study evaluated the quality characteristics of green tea extract (GE)-supplemented plant-based patties (PP) and the mechanisms affecting taste and texture. Green tea was extracted with water (GWE) or 70 % ethanol (GEE). GEE contained higher tannin and lower L-theanine levels than GWE. Both GWE and GEE reduced protein deterioration and lipid oxidation in PP throughout the 28-day storage period. PP with 1.0 % GEE (PP-GEE1.0) showed improved emulsion stability and texture due to non-covalent interactions including hydrophobic interaction and hydrogen bonds, and increased ß-sheet structures between tannin and pea protein. PP-GEE1.0 also had superior sensory characteristics due to an optimal balance of L-theanine and tannin. Overall, the incorporation of GE, particularly GEE significantly improved physicochemical properties, sensory quality, and storage stability of PP.

Structure and evolution of alanine/serine decarboxylases and the engineering of theanine production.

Ethylamine (EA), the precursor of theanine biosynthesis, is synthesized from alanine decarboxylation by alanine decarboxylase (AlaDC) in tea plants. AlaDC evolves from serine decarboxylase (SerDC) through neofunctionalization and has lower catalytic activity. However, lacking structure information hinders the understanding of the evolution of substrate specificity and catalytic activity. In this study, we solved the X-ray crystal structures of AlaDC from Camellia sinensis (CsAlaDC) and SerDC from Arabidopsis thaliana (AtSerDC). Tyr341 of AtSerDC or the corresponding Tyr336 of CsAlaDC is essential for their enzymatic activity. Tyr111 of AtSerDC and the corresponding Phe106 of CsAlaDC determine their substrate specificity. Both CsAlaDC and AtSerDC have a distinctive zinc finger and have not been identified in any other Group II PLP-dependent amino acid decarboxylases. Based on the structural comparisons, we conducted a mutation screen of CsAlaDC. The results indicated that the mutation of L110F or P114A in the CsAlaDC dimerization interface significantly improved the catalytic activity by 110% and 59%, respectively. Combining a double mutant of CsAlaDCL110F/P114A with theanine synthetase increased theanine production 672% in an in vitro system. This study provides the structural basis for the substrate selectivity and catalytic activity of CsAlaDC and AtSerDC and provides a route to more efficient biosynthesis of theanine.

Theanine enhances resistance to Botrytis cinerea in postharvest strawberry fruit via modulating cell-wall and phenylpropanoid metabolisms.

Theanine (N-ethyl-γ-glutamine), as a unique non-protein amino acid, plays vital roles in abiotic stress resistance, while its roles in biotic stress resistance are still unclear. Gray mold caused by Botrytis cinerea is a major disease in strawberries. Effects of theanine on the development of gray mold, cell-wall and phenylpropanoid metabolisms in strawberries were investigated in this study. Results showed that 5 mmol L-1 theanine treatment reduced disease incidence and severity of gray mold in strawberries with antifungal activity in vitro. Meanwhile, theanine treatment enhanced the accumulation of phenolic compounds and lignin, especially ellagic acid, cyanidin, and quercetin, which was associated with increased phenylpropanoid pathway related enzyme activities. Moreover, theanine induced callose deposition and suppressed cell- wall disassembling enzymes, accompanied by higher levels of water insoluble pectin, hemicellulose and cellulose. Therefore, theanine treatment could alleviate decay of B. cinerea-inoculated strawberries by regulating phenylpropanoid and cell-wall metabolisms, maintaining higher levels of phenolic compounds and cell-wall components, thereby contributing to disease resistance and cell-wall structure integrity.

l-Theanine Alleviates Ulcerative Colitis by Regulating Colon Immunity via the Gut Microbiota in an MHC-II-Dependent Manner.

Alterations to the gut microbiota are associated with ulcerative colitis (UC), whereas restoration of normobiosis can effectively alleviate UC. l-Theanine has been shown to reshape the gut microbiota and regulate gut immunity. To investigate the mechanisms by which l-theanine alleviates UC, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice. In this study, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice to explore the mechanism by which l-theanine alleviates UC. By reducing inflammation in the colon, we demonstrated that l-theanine alleviates symptoms of UC. Meanwhile, l-theanine can improve the abundance of microbiota related to short-chain fatty acid, bile acid, and tryptophan production. Single-cell sequencing results indicated that l-theanine-mediated suppression of UC was associated with immune cell changes, especially regarding macrophages and T and B cells, and validated the immune cell responses to the gut microbiota. Further, flow cytometry results showed that the ability of dendritic cells, macrophages, and monocytes to present microbiota antigens to colonic T cells in an MHC-II-dependent manner was reduced after treating normal mouse fecal donors with l-theanine. These results demonstrate that l-theanine modulates colon adaptive and innate immunity by regulating the gut microbiota in an MHC-II-dependent manner, thereby alleviating UC.

Improvement of both human and animal memory by synergy between fructooligosaccharide and L-theanine function establishing a safe and effective food supplement.

Aging is classically associated with a decline of cognitive abilities, especially in relation to memory. While the development of potential treatments for neurodegenerative diseases has been in sharp focus, mild cognitive impairment (MCI), a form of age-related memory loss, in the absence of severe functional impairment, a condition experienced by many healthy adults, has received relatively little attention. Advances in this space would make significant contributions to the goal of healthy aging and may also help promote cognitive performance across the wider population. The individual action of either fructooligosaccharide (FOS) or L-theanine, both natural plant-derived molecules, has been tentatively linked with improvements in cognition, but our understanding remains far from complete. We therefore determined the effect of different dose combinations of FOS and L-theanine (termed MT-01/GBL-Memory1) in mice against FOS and L-theanine monotherapy. FOS and L-theanine were found to synergistically enhance murine memory in our animal tests at a dose of 100 mg/kg (coefficient of drug interaction (CDI) < 1). In a subsequent human trial, we demonstrated that MT-01 improved the memory of healthy adults after 1 month of consumption. Our results suggest that a combination of FOS and L-theanine synergistically enhances murine memory within a specific dose range. We show that this plant natural product regimen also improves human memory in a population of healthy adults. MT-01 therefore represents a novel, safe, and effective dietary supplement to promote human memory and cognition.

Enhanced L-theanine production through semi-rational design of γ-glutamylmethylamide synthetase from Methylovorus mays.

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.

Effect of L-theanine on selective attention in a traffic-related reaction task in sleep-deprived young adults: a double-blind placebo-controlled, crossover study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

L-Theanine Prolongs the Lifespan by Activating Multiple Molecular Pathways in Ultraviolet C-Exposed Caenorhabditis elegans.

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.

Cystine and theanine for chemoradiotherapy-induced esophagitis in non-small cell lung cancer: a prospective observational study.

PURPOSE: Although several potential radioprotectants have been explored, radiation esophagitis is still difficult to control. Further development of supportive therapies is required. Our purpose was to investigate the efficacy and safety of cystine and theanine for esophagitis in non-small cell lung cancer (NSCLC) patients undergoing chemoradiotherapy (CRT). METHODS: This study is a prospective observational study. The participants were recruited from unresectable locally advanced NSCLC who had scheduled to receive weekly paclitaxel or nab-paclitaxel/carboplatin plus radiation therapy (60 Gy in 30 fractions) for 6 weeks. They took an oral amino acid supplement containing 700 mg cystine and 280 mg theanine once daily regardless of CRT timing from the start of CRT until completion. The primary endpoint was the incidence of any grade esophagitis. The secondary endpoints were quality of life (QoL) and adverse events (AEs). RESULTS: A total of 26 patients were evaluated. All participants completed 60 Gy of RT in 30 fractions. The overall incidence of esophagitis was 73%; however, no ≥ grade 3 was reported. There were no AEs likely to be related to cystine and theanine. The mean EuroQoL 5-Dimension 5-Level health index score before and after chemoradiotherapy was 0.952 ± 0.0591 and 0.952 ± 0.0515 (P = 0.89), and the mean Visual Analogue Scale scores before and after treatment were 67.9 ± 15.4 and 79.4 ± 13.2 (P = 0.0047), respectively. CONCLUSION: Our study showed no severe esophagitis, any AEs, nor QoL decrease in NSCLC patients receiving CRT. Cystine and theanine are potentially effective to reduce severe CRT-induced esophagitis. TRIAL REGISTRATION: UMIN000052622, 26 October 2023, retrospectively registered.

Effect of Dietary L-Theanine on Protein Expression in the Hippocampus of Senescence-Accelerated Mice (SAMP8).

L-Theanine is contained in green tea at 1-3% per dry matter as an amino acid with an umami taste, and the antidepressant effect and protective effect against stress-induced brain atrophy in mice, as well as the related mechanism have been reported. However, effects of theanine on the hippocampus from the proteome analysis and the action mechanism have not been examined. In this study, we mainly investigated the possibility of theanine's cognitive impairment-preventing function and the action mechanism by proteomics in the hippocampus of SAMP8 administered with theanine. In addition to improvement in the aging score with theanine administration, in proteomics, significant suppressions in the expressions of synapsin 2, α-synuclein, ß-synuclein, and protein tau were observed by theanine administration, and the expression of CAM kinase II beta and alpha exhibited a significant increase and increasing tendency with theanine administration, respectively. The expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein tended to increase by theanine administration. On the other hand, serotonin/tryptophan, GABA/glutamic acid and glutamine/glutamic acid ratios in the hippocampus showed an increasing tendency, a significant increase, and an increasing tendency with theanine administration, respectively. These results suggested that theanine might have been involved in the improvement of neurodegeneration or cognitive impairment by suppressing the productions of synapsin, synuclein and protein tau which are considered to be produced along with aging and oxidation, and by enhancing the production of serotonin by increasing the expression of CAM kinase II, and further by affecting the metabolism of glutamate.

L-Theanine Inhibits Chemoresistance of Lung Cancer Cells to Cisplatin by Regulating STAT3/NOTCH1-BMAL1 Signaling.

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. CONCLUSION: 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.

Comparison Between Efficacy of Oral Melatonin and Oral L-theanine in Improving Sleep in Cancer Patients Suffering From Insomnia: A Randomised Double-blinded Placebo-controlled Study.

Objectives: 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. Materials and Methods: 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. Results: 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). Conclusion: 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.

Theanine Capture of Reactive Carbonyl Species in Humans after Consuming Theanine Capsules or Green Tea.

Acrolein (ACR), methylglyoxal (MGO), and glyoxal (GO) are a class of reactive carbonyl species (RCS), which play a crucial role in the pathogenesis of chronic and age-related diseases. Here, we explored a new RCS inhibitor (theanine, THE) and investigated its capture capacity on RCS in vivo by human experiments. After proving that theanine could efficiently capture ACR instead of MGO/GO by forming adducts under simulated physiological conditions, we further detected the ACR/MGO/GO adducts of theanine in the human urine samples after consumption of theanine capsules (200 and 400 mg) or green tea (4 cups, containing 200 mg of theanine) by using ultraperformance liquid chromatography-time-of-flight-high-resolution mass spectrometry. Quantitative assays revealed that THE-ACR, THE-2ACR-1, THE-MGO, and THE-GO were formed in a dose-dependent manner in the theanine capsule groups; the maximum value of the adducts of theanine was also tested. Furthermore, besides the RCS adducts of theanine, the RCS adducts of catechins could also be detected in the drinking tea group. Whereas, metabolite profile analysis showed that theanine could better capture RCS produced in the renal metabolic pathway than catechins. Our findings indicated that theanine could reduce RCS in the body in two ways: as a pure component or contained in tea leaves.

Hepatoprotective effects and mechanisms of l-theanine and epigallocatechin gallate combined intervention in alcoholic fatty liver rats.

BACKGROUND: Chronic excessive alcohol consumption can lead to alcoholic fatty liver, posing substantial health risks. l-Theanine (LTA) and epigallocatechin gallate (EGCG) in tea exert antioxidant and hepatoprotective effects. However, the combined effects of LTA and EGCG on rats with alcoholic fatty liver, and the underlying mechanisms of such effects, remain unclear. In this study, Sprague Dawley (SD) rats were fed with alcohol for 6 weeks to induce alcoholic fatty liver. Subsequently, for another 6 weeks, the rats were administered LTA (200 mg kg-1 day-1), EGCG (200 mg kg-1 day-1), or a combination of LTA with EGCG (40 mg kg-1 day-1 l-Thea +160 mg kg-1 day-1 EGCG), respectively. RESULTS: The combined use of LTA and EGCG for alcoholic fatty liver disease had more significant effects than their individual administration. This combination reduced the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as the levels of hepatic triglyceride (TG), malondialdehyde (MDA), and reactive oxygen species (ROS) in the rats. The combined intervention also increased hepatic superoxide dismutase (SOD) and glutathione peroxidase activity. Reductions in hepatic fat accumulation and inflammatory responses were observed. The mechanism underlying these effects primarily involved the inhibition of fatty acid synthesis and the alleviation of lipid peroxidation through the downregulation of the mRNA and protein expression of TNF-α, SREBP1c, and CYP2E1 and the upregulation of the mRNA and protein expression of ADH1, ALDH2, Lipin-1, PPARαPPARα, AMPK, and PGC-1α, thereby promoting the oxidative decomposition of fatty acids and reducing the synthesis of cholesterol and glucose. CONCLUSION: l-Theanine and EGCG appear to be able to alleviate alcoholic fatty liver by modulating lipid metabolism and ameliorating oxidative stress, indicating their potential as natural active ingredients in anti-alcoholic fatty liver food products. © 2024 Society of Chemical Industry.

L-theanine alleviates myocardial ischemia/reperfusion injury by suppressing oxidative stress and apoptosis through activation of the JAK2/STAT3 pathway in mice.

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.