RESUMO
OBJECTIVE: l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial. METHODS: Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS). RESULTS: HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration. CONCLUSION: Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.
Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Glutamatos/uso terapêutico , Adulto , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Cognição/efeitos dos fármacos , Transtorno Depressivo Maior/complicações , Feminino , Glutamatos/administração & dosagem , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Teste de Stroop , Resultado do TratamentoRESUMO
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.
Assuntos
Glutamatos/administração & dosagem , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Adulto , Antipsicóticos/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Sono/efeitos dos fármacos , Resultado do TratamentoRESUMO
AIM: l-Theanine (N-ethyl-l-glutamine) is an amino acid uniquely found in green tea. Growing evidence has suggested the possible effects of l-theanine on cognition. Previously, we found that l-theanine attenuates MK-801-induced deficit in prepulse inhibition (PPI) in mice. In this study, we examined the effect of l-theanine in increasing the PPI in healthy humans. METHODS: The subjects were 14 healthy adults who underwent PPI testing as a measure of sensorimotor gating 90 min after an oral intake of l-theanine (0, 200, 400, or 600 mg). PPI tests were done by examiners who were blind to the dose. RESULTS: The administration of 200 mg of l-theanine and that of 400 mg, but not 600 mg, significantly increased the % PPI compared to the baseline (0 mg). There was no significant relation between the dose of l-theanine and the startle magnitude or the habituation of startle response. The plasma concentrations of l-theanine correlated with the dose of l-theanine. CONCLUSION: The observed effect with 200-400 mg of l-theanine on PPI suggested that l-theanine at a particular dose range increases sensorimotor gating in humans.
Assuntos
Glutamatos/farmacologia , Inibição Pré-Pulso/efeitos dos fármacos , Filtro Sensorial/efeitos dos fármacos , Adulto , Relação Dose-Resposta a Droga , Feminino , Glutamatos/sangue , Habituação Psicofisiológica/efeitos dos fármacos , Voluntários Saudáveis , Humanos , MasculinoRESUMO
Endo-alpha-N-acetylgalactosaminidase catalyzes the release of Galbeta1-3GalNAc from the core 1-type O-glycan (Galbeta1-3GalNAcalpha1-Ser/Thr) of mucin glycoproteins and synthetic p-nitrophenyl (pNP) alpha-linked substrates. Here, we report the enzymatic syntheses of core 1 disaccharide-containing glycopeptides using the transglycosylation activity of endo-alpha-N-acetylgalactosaminidase (EngBF) from Bifidobacterium longum. The enzyme directly transferred Galbeta1-3GalNAc to serine or threonine residues of bioactive peptides such as PAMP-12, bradykinin, peptide-T and MUC1a when Galbeta1-3GalNAcalpha1-pNP was used as a donor substrate. The enzyme was also found to catalyze the reverse-hydrolysis reaction. EngBF synthesized the core 1 disaccharide-containing oligosaccharides when the enzyme was incubated with either glucose or lactose and Galbeta1-3GalNAc prepared from porcine gastric mucin using bifidobacterial cells expressing endo-alpha-N-acetylgalactosaminidase. Synthesized oligosaccharides are promising prebiotics for bifidobacteria.
Assuntos
Bifidobacterium/enzimologia , Mucinas Gástricas/biossíntese , Glicopeptídeos/biossíntese , Oligossacarídeos/biossíntese , alfa-N-Acetilgalactosaminidase/metabolismo , Sequência de Aminoácidos , Animais , Bifidobacterium/citologia , Galactosamina/metabolismo , Glicopeptídeos/química , Glicosilação , Hidrólise , Dados de Sequência Molecular , Serina/metabolismo , Sus scrofa , Treonina/metabolismoRESUMO
Endo-alpha-N-acetylgalactosaminidase (endo-alpha-GalNAc-ase) catalyzes the hydrolysis of the O-glycosidic bond between alpha-GalNAc at the reducing end of mucin-type sugar chains and serine/threonine of proteins to release oligosaccharides. Previously, we identified the gene engBF encoding endo-alpha-GalNAc-ase from Bifidobacterium longum, which specifically released the disaccharide Gal beta 1-3GalNAc (Fujita K, Oura F, Nagamine N, Katayama T, Hiratake J, Sakata K, Kumagai H, Yamamoto K. 2005. Identification and molecular cloning of a novel glycoside hydrolase family of core 1 type O-glycan-specific endo-alpha-N-acetylgalactosaminidase from Bifidobacterium longum. J Biol Chem. 280:37415-37422). Here we cloned a similar gene named engCP from Clostridium perfringens, a pathogenic enterobacterium, and characterized the gene product EngCP. Detailed analyses on substrate specificities of EngCP and EngBF using a series of p-nitrophenyl-alpha-glycosides chemically synthesized by the di-tert-butylsilylene-directed method revealed that both enzymes released Hex/HexNAc beta 1-3GalNAc (Hex = Gal or Glc). EngCP could also release the core 2 trisaccharide Gal beta 1-3(GlcNAc beta 1-6)GalNAc, core 8 disaccharide Gal alpha 1-3GalNAc, and monosaccharide GalNAc. Our results suggest that EngCP possesses broader substrate specificity than EngBF. Actions of the two enzymes on native glycoproteins and cell surface glycoproteins were also investigated.
Assuntos
Bifidobacterium/enzimologia , Clostridium perfringens/enzimologia , Enterobacteriaceae/enzimologia , alfa-N-Acetilgalactosaminidase/genética , alfa-N-Acetilgalactosaminidase/metabolismo , Bifidobacterium/genética , Clonagem Molecular , Clostridium perfringens/genética , Enterobacteriaceae/genética , Enterobacteriaceae/patogenicidade , Glicoproteínas/metabolismo , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/metabolismo , Modelos Biológicos , Probióticos/metabolismo , Especificidade por Substrato , alfa-N-Acetilgalactosaminidase/químicaRESUMO
PURPOSE: Theanine, an amino acid in tea, has significant anti-stress effect on experimental animals under psychosocial stress. Anti-stress effect of theanine on humans was evaluated in 5th-year university students during pharmacy practice. METHOD: The study design was a single-blind group comparison and participants (n=20) were randomly assigned to theanine or placebo groups. Theanine or placebo (lactose) tablets (200 mg, twice a day, after breakfast and lunch) were taken from 1 week prior to the pharmacy practice and continued for 10 days in the practice period. To assess the anxiety of the participants, the state-trait anxiety inventory test was carried out before the pharmacy practice. Salivary α-amylase activity (sAA) was measured as a marker of sympathetic nervous system activity. RESULTS: In the placebo-group, sAA in the morning (pre-practice sAA) was higher than in theanine-group during the pharmacy practice (p=0.032). Subjective stress was significantly lower in the theanine-group than in the placebo-group (p=0.020). These results suggest that theanine intake had anti-stress effect on students. Furthermore, students with higher pre-practice sAA showed significantly higher trait anxiety in both groups (p=0.015). Similarly, higher pre-practice sAA was correlated to shorter sleeping time in both groups (p=0.41×10(-3)). CONCLUSION: Stressful condition increased the level of sAA that was essentially affected by individual trait anxiety. The low levels of pre-practice sAA and subjective stress in the theanine-group suggest that theanine intake suppressed initial stress response of students assigned for a long-term commitment of pharmacy practice.