L-Theanine

The leaves of Camellia sinensis

L-Theanine healed NSAID-induced gastric ulcer by modulating pro/antioxidant balance in gastric ulcer margin.[Pubmed:24981317]

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

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

An overview of biological production of L-theanine.[Pubmed:25871834]

Biotechnol Adv. 2015 May-Aug;33(3-4):335-42.

L-Theanine (gamma-glutamylethylamide) is a unique non-protein amino acid that is naturally found in tea plants. It contributes to the umami taste and unique flavor to green tea infusion, and thus its content in tea leaves highly impacts the tea quality and price. In addition to the graceful taste, it has been proved to have many beneficial physiological effects, especially promoting relaxation and improving concentration and learning ability. Based on these promising advantages, L-Theanine has been commercially developed as a valuable ingredient for use in food and beverages to improve and/or maintain human health. L-Theanine can be obtained by chemical synthesis or isolation from tea, while chemical synthesis of L-Theanine is hard to be accepted by consumers and is not allowed to use in food industry, and isolation of L-Theanine in high purity generally involves time-consuming, cost-ineffective, and complicated operational processes. Accordingly, the biological production of L-Theanine has recently attracted much attention. Four kinds of bacterial enzymes, including L-glutamine synthetase, gamma-glutamylmethylamide synthetase, gamma-glutamyltranspeptidase, and L-glutaminase, have been characterized to have L-Theanine-producing ability. Herein, an overview of recent studies on the biological production of L-Theanine was presented.

l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of nuclear factor kappaB and down-regulation of transforming growth factor beta and connective tissue growth factor.[Pubmed:25852135]

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

Here we evaluated the ability of L-Theanine in preventing experimental hepatic cirrhosis and investigated the roles of nuclear factor-kappaB (NF-kappaB) activation as well as transforming growth factor beta (TGF-beta) and connective tissue growth factor (CTGF) regulation. 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-kappaB activation and increased the expression of both TGF-beta and CTGF. CCl4 increased the serum activities of alanine aminotransferase and gamma-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-kappaB and down-regulated the pro-inflammatory (interleukin (IL)-1beta and IL-6) and profibrotic (TGF-beta 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. In conclusion, L-Theanine prevents CCl4-induced experimental hepatic cirrhosis in rats by blocking the main pro-inflammatory and pro-fibrogenic signals.

Effect of L-theanine on glutamatergic function in patients with schizophrenia.[Pubmed:25896423]

Acta Neuropsychiatr. 2015 Oct;27(5):291-6.

OBJECTIVES: 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). METHOD: 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. 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.

Protective effect of L-Theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain - histopathological, and biochemical approach.[Pubmed:24654859]

Drug Chem Toxicol. 2015 Jan;38(1):22-31.

L-Theanine is an amino acid derivative primarily found in tea. It has been reported to promote relaxation and have neuroprotective effects. The present study was designed to investigate the role of oxidative stress and the status of antioxidant system in the management of aluminum chloride (AlCl3) induced brain toxicity in various rat brain regions and further to elucidate the potential role of L-Theanine in alleviating such negative effects. Aluminium administration significantly decreased the level of reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, Na(+)/K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase and increased the level of lipid peroxidation and the activities of alkaline phosphatase, acid phosphatase, alanine transaminase and aspartate transaminase in all the brain regions when compared with control rats. Pre-treatment with L-Theanine at a dose of 200 mg/kg b.w. significantly increased the antioxidant status and activities of membrane bound enzymes and also decreased the level of LPO and the activities of marker enzymes, when compared with aluminium induced rats. Aluminium induction also caused histopathological changes in the cerebral cortex, cerebellum and hippocampus of rat brain which was reverted by pretreatment with L-Theanine. The present study clearly indicates the potential of L-Theanine in counteracting the damage inflicted by aluminium on rat brain regions.

High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells.[Pubmed:18522853]

Cell Stem Cell. 2008 Jun 5;2(6):602-12.

High-throughput screening (HTS) of chemical libraries has become a critical tool in basic biology and drug discovery. However, its implementation and the adaptation of high-content assays to human embryonic stem cells (hESCs) have been hampered by multiple technical challenges. Here we present a strategy to adapt hESCs to HTS conditions, resulting in an assay suitable for the discovery of small molecules that drive hESC self-renewal or differentiation. Use of this new assay has led to the identification of several marketed drugs and natural compounds promoting short-term hESC maintenance and compounds directing early lineage choice during differentiation. Global gene expression analysis upon drug treatment defines known and novel pathways correlated to hESC self-renewal and differentiation. Our results demonstrate feasibility of hESC-based HTS and enhance the repertoire of chemical compounds for manipulating hESC fate. The availability of high-content assays should accelerate progress in basic and translational hESC biology.

Theanine prevents memory impairment induced by repeated cerebral ischemia in rats.[Pubmed:17705146]

Phytother Res. 2008 Jan;22(1):65-8.

The present study investigated the neuroprotective effect of gamma-glutamylethylamide (theanine), a component Japanese green tea (Camellia sinensis), on memory impairment induced by twice-repeated cerebral ischemia in rats. Theanine was injected i.p. immediately after the first occlusion. Theanine (0.3 and 1 mg/kg) significantly prevented the impairment of spatial memory in rats subjected to repeated cerebral ischemia, 7 days after the second reperfusion. Moreover, theanine (1 mg/kg) significantly inhibited the decrease in the number of surviving cells in the hippocampal CA1 field in the same rats. These results suggest that theanine prevents memory impairment induced by repeated cerebral ischemia, in part by protecting against neuronal cell death, and that it might be useful for preventing cerebrovascular disease.

Inhibition by theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors.[Pubmed:12596867]

Biosci Biotechnol Biochem. 2002 Dec;66(12):2683-6.

In an investigation of the mechanisms of the neuroprotective effects of theanine (gamma-glutamylethylamide) in brain ischemia, inhibition by theanine of the binding of [3H](RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), [3H]kainate, and [3H](E)-3-(2-phenyl-2-carboxyethenyl)-4,6-dichloro-1-H-indole-2-carboxylic acid (MDL 105,519) to glutamate receptors was studied in terms of its possible inhibiting effects on the three receptor subtypes (AMPA, kainate, and NMDA glycine), with rat cortical neurons. Theanine bound the three receptors, but its IC50 of theanine was 80- to 30,000-fold less than that of L-glutamic acid.

L-Theanine (L-Glutamic Acid γ-ethyl amide）is a non-protein amino acid contained in green tea leaves, which blocks the binding of L-glutamic acid to glutamate receptors in the brain, and with neuroprotective and anti-oxidative activities. L-Theanine causes anti-stress effects via the inhibition of cortical neuron excitation by oral intake.

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