Neuroprotective effects of the green tea components theanine and catechins

Kakuda, Takami

doi:10.1248/bpb.25.1513

Cited by 165Tea Polyphenols and EffectsNeuroscience and Neuropharmacology ResearchMedicinal Plants and Neuroprotection

Neuroprotective effects of the green tea components theanine and catechins

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Kakuda, Takami·2002·Biological & Pharmaceutical Bulletin

DOI 10.1248/bpb.25.1513

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Abstract

The neuroprotective effects of theanine and catechins contained in green tea are discussed. Although the death of cultured rat cortical neurons was induced by the application of glutamic acid, this neuronal death was suppressed with exposure to theanine. The death of hippocampal CA1 pyramidal neurons caused by transient forebrain ischemia in the gerbil was inhibited with the ventricular preadministration of theanine. The neuronal death of the hippocampal CA3 region by kainate was also prevented by the administration of theanine. Theanine has a higher binding capacity for the AMPA/kainate receptors than for NMDA receptors, although the binding capacity in all cases is markedly less than that of glutamic acid. The results of the present study suggest that the mechanism of the neuroprotective effect of theanine is related not only to the glutamate receptor but also to other mechanisms such as the glutamate transporter, although further studies are needed. One of the onset mechanisms for arteriosclerosis, a major factor in ischemic cerebrovascular disease, is probably the oxidative alteration of low-density lipoprotein (LDL) by active oxygen species. The oxidative alterations of LDL were shown to be prevented by tea catechins. Scavenging of *O(2)(-) was also exhibited by tea catechins. The neuroprotective effects of theanine and catechins contained in green tea are a focus of considerable attention, and further studies are warranted.

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Theanine is structurally similar to glutamate and binds glutamate receptors weakly in the micromolar range, including AMPA and kainate receptors, and to a lesser extent the NMDA receptor.
“Structurally theanine is similar to the excitatory neurotransmitter glutamate which binds to glutamate receptors with weak interaction in the micromolar range, including the a-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors, and to a lesser extent, the N-methyl-D-aspartic acid receptor [15][16][17][18].”
From l -theanine: A potential multifaceted natural bioactive amide as health supplement (2017) · cites this paper as [17]

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Background
Diverse Metabolite Variations in Tea (Camellia sinensis L.) Leaves Grown Under Various Shade Conditions Revisited: A Metabolomics Study
Ji, H., Lee, Y.-R., Lee, M., Hwang, K. H., Park, C. Y., Kim, E., Park, J. S., & Hong, Y. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.7b04768 · Cited by 98 · see citing works
Neuroprotective Herbs for Stroke Therapy In Traditional Eastern Medicine
Kim, H. (2005) · Neurological Research · doi:10.1179/016164105x25234 · Cited by 93 · see citing works
Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders
Lardner, A. L. (2014) · Nutritional Neuroscience · doi:10.1179/1476830513y.0000000079 · Cited by 92 · see citing works
The role of dietary antioxidants in type 2 diabetes and neurodegenerative disorders: An assessment of the benefit profile
Fatima, M. T., Bhat, A. A., Nisar, S., Fakhro, K. A., & Akil, A. A. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e12698 · Cited by 90 · see citing works
Tea drinking and cognitive function in oldest-old Chinese
Feng, L., Li, J., Ng, T.-P., Lee, T.-S., Kua, E.-H., & Zeng, Y. (2012) · The Journal of nutrition, health and aging · doi:10.1007/s12603-012-0077-1 · Cited by 82 · see citing works
“Ltheanine, a free amino acid naturally found in tea, also possesses neuroprotective effect (13, 14).”
Background
l-theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway
Di, X., Yan, J., Zhao, Y., Zhang, J., Shi, Z., Chang, Y. Z., & Zhao, B. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.04.019 · Cited by 78 · see citing works
“revious reports have shown that green tea components uch as L-theanine have neuroprotective properties; howver, a clear cellular mechanism underlying these effects as not yet been established (Egashira et al., 2004; akuda, 2002; Nathan et al., 2006).”
Background
Bioactivities and sensory evaluation of Pu-erh teas made from three tea leaves in an improved pile fermentation process
Chen, Y.-S., Liu, B.-L., & Chang, Y.-N. (2009) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2009.11.004 · Cited by 78 · see citing works
Effects of theanine, r-glutamylethylamide, on neurotransmitter release and its relationship with glutamic acid neurotransmission
Yamada, T., Terashima, T., Okubo, T., Juneja, L. R., & Yokogoshi, H. (2005) · Nutritional Neuroscience · doi:10.1080/10284150500170799 · Cited by 72 · see citing works
Neuroprotective activity of<scp>L</scp>-theanine on 3-nitropropionic acid-induced neurotoxicity in rat striatum
Thangarajan, S., Deivasigamani, A., Natarajan, S. S., Krishnan, P., & Mohanan, S. K. (2014) · International Journal of Neuroscience · doi:10.3109/00207454.2013.872642 · Cited by 71 · see citing works
“L-theanine has also been shown to exert a neuroprotective effect against ischemia induced by middle cerebral artery occlusion [18,10,39) and against Parkinsonrelated neurotoxicants [11].”
Background
Theanine, γ-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats
Yamada, T., Terashima, T., Kawano, S., Furuno, R., Okubo, T., Juneja, L. R., & Yokogoshi, H. (2009) · Amino Acids · doi:10.1007/s00726-007-0020-7 · Cited by 71 · see citing works
“Moreover, some reports suggested that the neuroprotective effect of theanine occurs via glutamate receptors, with theanine acting as a glutamate receptor antagonist (Kakuda et al. 2000a; Kakuda 2002b ).”
Background
Elucidation of the Corrosion Inhibition of Mild Steel in 1.0 M HCl by Catechin Monomers from Commercial Green Tea Extracts
Nofrizal, N., Rahim, A. A., Saad, B., Raja, P. B., Shah, A. M., & Yahya, S. (2011) · Metallurgical and Materials Transactions A · doi:10.1007/s11661-011-1030-3 · Cited by 70 · see citing works
Effect of Green Tea Phytochemicals on Mood and Cognition
Dietz, C., & Dekker, M. (2017) · Current Pharmaceutical Design · doi:10.2174/1381612823666170105151800 · Cited by 70 · see citing works
Glutathione and Related Molecules in Parkinsonism
Asanuma, M., & Miyazaki, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168689 · Cited by 68 · see citing works
Neuroprotective attributes of L-theanine, a bioactive amino acid of tea, and its potential role in Parkinson's disease therapeutics
Deb, S., Dutta, A., Phukan, B. C., Manivasagam, T., Thenmozhi, A. J., Bhattacharya, P., Paul, R. K., & Borah, A. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104478 · Cited by 69 · see citing works
L-theanine: an astounding sui generis amino acid in poultry nutrition
Saeed, M., Khan, M. S., Kamboh, A. A., Alagawany, M. M., Khafaga, A. F., Noreldin, A. E., Qumar, M., Safdar, M., Hussain, M., El-Hack, M. E. A., et al. (2020) · Poultry Science · doi:10.1016/j.psj.2020.07.016 · Cited by 66 · see citing works
“L-theanine offers a promising neuroprotective effect by binding to glutamate receptors and their receptor subtypes, that is, N-methyl-D-aspartate (NMDA), thereby preventing the excess calcium release into the extracellular space (Kakuda, 2002).”
BackgroundInfluential
An intervention study on the effect of matcha tea, in drink and snack bar formats, on mood and cognitive performance
Dietz, C., Dekker, M., & Piqueras‐Fiszman, B. (2017) · Food Research International · doi:10.1016/j.foodres.2017.05.002 · Cited by 68 · see citing works
Behavioral and molecular evidence for psychotropic effects in l-theanine
Wakabayashi, C., Numakawa, T., Ninomiya, M., Chiba, S., & Kunugi, H. (2012) · Psychopharmacology · doi:10.1007/s00213-011-2440-z · Cited by 65 · see citing works
“It has also been shown to exert neuroprotective effects (Kakuda 2002).”
Background
Distribution and biosynthesis of theanine in Theaceae plants
Deng, W., Ogita, S., & Ashihara, H. (2009) · Plant Physiology and Biochemistry · doi:10.1016/j.plaphy.2009.09.009 · Cited by 64 · see citing works
The science of matcha: Bioactive compounds, analytical techniques and biological properties
Devkota, H. P., Gaire, B. P., Hori, K., Subedi, L., Adhikari‐Devkota, A., Belwal, T., Paudel, K. R., Jha, N. K., Singh, S. K., Chellappan, D. K., et al. (2021) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2021.10.021 · Cited by 67 · see citing works
Neuroprotection by Radical Avoidance: Search for Suitable Agents
Hardeland, R. (2009) · Molecules · doi:10.3390/molecules14125054 · Cited by 64 · see citing works
“Interference with metabotropic glutamate receptors [254] or glutamate transporters [256] was speculated to be responsible for the effects observed.”
Background
Effects of infusion conditions and decaffeination on free amino acid profiles of green and black tea
Kocadağlı, T., Özdemir, K. S., & Gökmen, V. (2012) · Food Research International · doi:10.1016/j.foodres.2012.10.010 · Cited by 62 · see citing works
“, 1995), anti-obesity effect in mice (Zheng, Sayama, Okubo, Juneja, & Oguni, 2004), neuroprotective effect in rats (Kakuda, 2012), inhibition of caffeine stimulation in rats and anti-carcinogenic effects in human cancer cells in vitro (Friedman et al.”
Background
Effect of temperature on accumulation of chlorophylls and leaf ultrastructure of low temperature induced albino tea plant
Du, Ma, Y. Y., Chen, H, Zhong, W, L., Wu, L, Y., Ye, J, H., et al. (2008) · AFRICAN JOURNAL OF BIOTECHNOLOGY · doi:10.5897/ajb2008.000-5036 · Cited by 62 · see citing works
“Theanine has recently received much attention due to its health benefits such as promoting relaxation, reducing stress and anxiety, improving memory and learning ability, as well as suppressing high blood pressure (Yokogoshi et al., 1995; Juneja et al., 1999; Kakuda, 2002; Kim et al., 2004; Zhang et al., 2007).”
Background
Pharmacology and therapeutic uses of theanine
Eschenauer, G., & Sweet, B. V. (2006) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp050148 · Cited by 61 · see citing works
Tea and cognitive health in late life: Current evidence and future directions
Song, J., Xu, H. J., Liu, F., & Feng, L. (2011) · The journal of nutrition health & aging · doi:10.1007/s12603-011-0139-9 · Cited by 60 · see citing works
“In addition to tea polyphenols, L-theanine, a free amino acid naturally found in tea, also possess neuroprotective effect ( 36- 38 ).”
In Search of a Safe Natural Sleep Aid
Rao, T. P., Ozeki, M., & Juneja, L. R. (2015) · Journal of the American College of Nutrition · doi:10.1080/07315724.2014.926153 · Cited by 59 · see citing works
“In addition to the L-theanine research confirming the relaxation effect [37,71], memory and learning performance [51, 72], neuroprotection [61, 73, 74], and sleep [56, 62, 75], a study was conducted at the University of British Colombia in collaboration with The Canadian Center for Functional Medicine in Canada to exa…”
Background
Green Synthesis of Stable Copper Nanoparticles and Synergistic Activity with Antibiotics
Mandava, K., Kadimcharla, K., Keesara, N. R., Fatima, S. N., Bommena, P., & Batchu, U. R. (2017) · Indian Journal of Pharmaceutical Sciences · doi:10.4172/pharmaceutical-sciences.1000281 · Cited by 59 · see citing works
Protective effect of l-theanine on chronic restraint stress-induced cognitive impairments in mice
Tian, X., Sun, L., Gou, L., Ling, X., Feng, Y., Wang, L., Yin, X., & Liu, Y. (2013) · Brain Research · doi:10.1016/j.brainres.2013.01.048 · Cited by 57 · see citing works
“L-theanine has been shown to exert a neuroprotective effect against cerebral ischemia (Kakuda, 2002; Egashira, et al., 2004, 2007) and Parkinson-related neurotoxicants (Cho et al., 2008).”
Background
Diabetes and Alzheimer’s Disease: Can Tea Phytochemicals Play a Role in Prevention?
Fernando, W. M. A. D. B., Somaratne, G., Goozee, K. G., Williams, S., Singh, H., & Martins, R. N. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161200 · Cited by 55 · see citing works
“The death of hippocampal CA1 (cornus ammonis) pyramidal neurons by transient forebrain ischemia and the death of the hippocampal CA3 region by kainate was prevented by the administration of theanine [155].”
Background
Neuroprotective Effects of White Tea Against Oxidative Stress-Induced Toxicity in Striatal Cells
Almajano, M. P., Vila, I., & Ginés, S. (2011) · Neurotoxicity Research · doi:10.1007/s12640-011-9252-0 · Cited by 57 · see citing works
l -theanine: A potential multifaceted natural bioactive amide as health supplement
Adhikary, R., & Mandal, V. (2017) · Asian Pacific Journal of Tropical Biomedicine · doi:10.1016/j.apjtb.2017.08.005 · Cited by 55 · see citing works
Analysis of derivatized and underivatized theanine enantiomers by high-performance liquid chromatography/atmospheric pressure ionization-mass spectrometry.
Desai, M. J., & Armstrong, D. W. (2004) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.1319 · Cited by 54 · see citing works
Sports-related concussions: diagnosis, complications, and current management strategies
Hobbs, J. G., Young, J. S., & Bailes, J. E. (2016) · Neurosurgical FOCUS · doi:10.3171/2016.1.focus15617 · Cited by 53 · see citing works
Anti-obesity potential of natural methylxanthines
Carrageta, D. F., Dias, T. R., Alves, M. G., Oliveira, P. F., Monteiro, M. P., & Silva, B. M. (2018) · Journal of Functional Foods · doi:10.1016/j.jff.2018.02.001 · Cited by 52 · see citing works
The combined effect of green tea and α-glucosyl hesperidin in preventing obesity: a randomized placebo-controlled clinical trial
Yoshitomi, R., Yamamoto, M., Kumazoe, M., Fujimura, Y., Yonekura, M., Shimamoto, Y., Nakasone, A., Kondo, S., Hattori, H., Haseda, A., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-98612-6 · Cited by 59 · see citing works
Effects of l-theanine on attention and reaction time response
Higashiyama, A., Htay, H. H., Ozeki, M., Juneja, L. R., & Kapoor, M. P. (2011) · Journal of Functional Foods · doi:10.1016/j.jff.2011.03.009 · Cited by 50 · see citing works
“Related reports also support the neuroprotective effect of L-theanine in cortical neurons through an antagonistic role and thus, suggest the functional features of L-theanine in brain dynamics (De Mejia, Ramirez-Mares, & Puangpraphant, 2009; Kakuda, 2002; Kakuda, Nozawa, Unno, Okamura, & Okai, 2000; Kimura & Murata, 1…”
BackgroundResult
C-8 N -Ethyl-2-pyrrolidinone-Substituted Flavan-3-ols from the Leaves of Camellia sinensis var. pubilimba
Meng, X., Zhu, H., Yan, H., Wang, D., Yang, C., & Zhang, Y. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b02066 · Cited by 50 · see citing works
Possible involvement of group I mGluRs in neuroprotective effect of theanine
Nagasawa, K., Aoki, H., Yasuda, E., Nagai, K., Shimohama, S., & Fujimoto, S. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.05.143 · Cited by 48 · see citing works
Protective Effect of Buckwheat Polyphenols Against Long-Lasting Impairment of Spatial Memory Associated With Hippocampal Neuronal Damage in Rats Subjected to Repeated Cerebral Ischemia
Pu, F., Mishima, K., Egashira, N., Iwasaki, K., Kaneko, T., Uchida, T., Irie, K., Ishibashi, D., Fujii, H., Kosuna, K., et al. (2004) · Journal of Pharmacological Sciences · doi:10.1254/jphs.94.393 · Cited by 48 · see citing works
Colon Cancer Survival With Herbal Medicine and Vitamins Combined With Standard Therapy in a Whole-Systems Approach
McCulloch, M., Broffman, M., van der Laan, M. J., Hubbard, A., Kushi, L. H., Abrams, D. I., Gao, J. H., & Colford, J. M. (2011) · Integrative Cancer Therapies · doi:10.1177/1534735411406539 · Cited by 47 · see citing works
Theanine, r-glutamylethylamide, increases neurotransmission concentrations and neurotrophin mRNA levels in the brain during lactation
Yamada, T., Terashima, T., Wada, K., Ueda, S., Ito, M., Okubo, T., Juneja, L. R., & Yokogoshi, H. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.08.023 · Cited by 47 · see citing works
Natural compounds: evidence for a protective role in eye disease
Ritch, R. H. (2007) · Canadian Journal of Ophthalmology · doi:10.3129/can.j.ophthalmol.i07-044 · Cited by 47 · see citing works
Genome-wide identification and expression analysis of flowering-related genes reveal putative floral induction and differentiation mechanisms in tea plant (Camellia sinensis)
Liu, Y., Hao, X., Lu, Q., Zhang, W., Zhang, H., Wang, L., Yang, Y., Xiao, B., & Wang, X. (2020) · Genomics · doi:10.1016/j.ygeno.2020.01.003 · Cited by 46 · see citing works
GABA-enriched teas as neuro-nutraceuticals
Hinton, T., & Johnston, G. A. R. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104895 · Cited by 47 · see citing works
L-theanine administration results in neuroprotection and prevents glutamate receptor agonist-mediated injury in the rat model of cerebral ischemia-reperfusion
Zukhurova, M., Prosvirnina, M., Daineko, A., Simanenkova, A., Petrishchev, N., Sonin, D., Galagudza, M., Shamtsyan, M., Juneja, L. R., & Vlasov, T. (2013) · Phytotherapy Research · doi:10.1002/ptr.4868 · Cited by 42 · see citing works
“the central nervous system of mammals (Kakuda, 2002).”
Background
Medicinal plants and their isolated phytochemicals for the management of chemotherapy-induced neuropathy: therapeutic targets and clinical perspective
Oveissi, V., Ram, M., Bahramsoltani, R., Ebrahimi, F., Rahimi, R., Naseri, R., Belwal, T., Devkota, H. P., Abbasabadi, Z., & Farzaei, M. H. (2019) · DARU Journal of Pharmaceutical Sciences · doi:10.1007/s40199-019-00255-6 · Cited by 41 · see citing works
Effect of green tea (Camellia sinensis L.) extract on morphological and functional changes in adult male gonads of albino rats.
Chandra, A. K., Choudhury, S. R., De, N., & Sarkar, M. (2011) · PubMed · Cited by 41 · see citing works
l-Theanine alleviates the neuropathological changes induced by PCB (Aroclor 1254) via inhibiting upregulation of inflammatory cytokines and oxidative stress in rat brain
Sumathi, T., Asha, D., Nagarajan, G., Sreenivas, A., & Nivedha, R. (2016) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2016.01.008 · Cited by 40 · see citing works
Treatment with green tea extract attenuates secondary inflammatory response in an experimental model of spinal cord trauma
Paterniti, I., Genovese, T., Crisafulli, C., Mazzon, E., Paola, R. D., Galuppo, M., Bramanti, P., & Cuzzocrea, S. (2009) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-009-0414-z · Cited by 40 · see citing works
“Green tea polyphenols have demonstrated significant anti-oxidant, anti-carcinogenic, anti-inflammatory, thermogenic, probiotic and anti-microbial properties in numerous human, animals and in vitro studies (Choi et al. 2004; Crespy and Williamson 2004; Kakuda 2002; Sung et al. 2000).”
Background
Tea catechins’ affinity for human cannabinoid receptors
Korte, G., Dreiseitel, A., Schreier, P. H., Oehme, A., Locher, S., Geiger, S. S., Heilmann, J., & Sand, P. G. (2009) · Phytomedicine · doi:10.1016/j.phymed.2009.10.001 · Cited by 38 · see citing works
“Observational studies on neuroprotection by green tea polyphenols (Kakuda 2002; Pan et al. 2003) lend some support to putative CB1 agonistic effects but will require further confirmation, e.”
Background
Bioactive components and antioxidant properties of γ-aminobutyric acid (GABA) tea leaves
Lin, S., Mau, J., & Hsu, C.-A. (2011) · LWT · doi:10.1016/j.lwt.2011.10.025 · Cited by 38 · see citing works
Tea and Its Components Prevent Cancer: A Review of the Redox-Related Mechanism
Mao, X., Xiao, X., Chen, D., Yu, B., & He, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215249 · Cited by 37 · see citing works
Enzymatic synthesis of theanine from glutamic acid γ-methyl ester and ethylamine by immobilized escherichia coli cells with γ-glutamyltranspeptidase activity
Zhang, F., Zheng, Q.-Z., Jiao, Q.-C., Liu, J.-Z., & Zhao, G.-H. (2010) · Amino Acids · doi:10.1007/s00726-010-0553-z · Cited by 36 · see citing works
“1996, 2000), neuroprotection (Kakuda 2002; Nagasawa et al. 2004), and enhancement of defence against microbes (Bukowski and Percival 2007).”
Background
Determination of Theanine and Catechin in Camellia sinensis (Kangra Tea) Leaves by HPTLC and NMR Techniques
Kumar, D., Gulati, A., & Sharma, U. K. (2015) · Food Analytical Methods · doi:10.1007/s12161-015-0343-z · Cited by 36 · see citing works
“They also produce anti-genotoxic effect (Bhatt et al. 2010; Namita et al. 2012; Kakuda 2002).”
Background
Molecular interaction studies of green tea catechins as multitarget drug candidates for the treatment of Parkinson’s disease: computational and structural insights
Azam, F., Najah, M., & Alhussen, F. (2015) · Network Computation in Neural Systems · doi:10.3109/0954898x.2016.1146416 · Cited by 36 · see citing works
“Kakuda 2002 ʺ Neuroprotective Sutherland et al. 2006 Network: Computation in Neural Systems 99 enzymes of drug design.”
Background
Stable isotope dilution HILIC‐MS/MS method for accurate quantification of glutamic acid, glutamine, pyroglutamic acid, GABA and theanine in mouse brain tissues
Inoue, K., Miyazaki, Y., Unno, K., Min, J. Z., Todoroki, K., & Toyo’oka, T. (2015) · Biomedical Chromatography · doi:10.1002/bmc.3502 · Cited by 35 · see citing works
Complementary therapy for the treatment of glaucoma: a perspective.
Ritch, R. H. (2005) · PubMed · doi:10.1016/j.ohc.2005.07.004 · Cited by 35 · see citing works
“[84] Kakuda T.”
Background
Molecular Pharmacology of Honey
Afroz, R., & Tanvir, E. M. (2016) · Clinical and Experimental Pharmacology · doi:10.4172/2161-1459.1000212 · Cited by 35 · see citing works
Bioactive components of tea
Sen, G., Sarkar, N., Moutusi, N., & Maity, S. (2020) · Archive of Food and Nutritional Science · doi:10.29328/journal.afns.1001020 · Cited by 34 · see citing works
“Although caffeine can have certain negative effects on anxiety disorders, studies reveal that L-theanine neutralizes negative effects of caffeine without reducing its mind- energizing, fat-burning features [87,88].”
Background
Comprehensive Review of Nutraceuticals against Cognitive Decline Associated with Alzheimer’s Disease
Reza-Zaldívar, E. E., & Jacobo-Velázquez, D. A. (2023) · ACS Omega · doi:10.1021/acsomega.3c04855 · Cited by 27 · see citing works
Comparative effects of irradiation, fumigation, and storage on the free amino acids and sugar contents of green, black and oolong teas
Kausar, T., Akram, K., & Kwon, J. (2012) · Radiation Physics and Chemistry · doi:10.1016/j.radphyschem.2012.12.011 · Cited by 33 · see citing works
Effect of l-theanine tablets in reducing stress-related emotional signs in cats: an open-label field study
Dramard, V., Kern, L., Hofmans, J., Rème, C. A., Nicolas, C. S., Chala, V., & Navarro, C. (2018) · Irish Veterinary Journal · doi:10.1186/s13620-018-0130-4 · Cited by 33 · see citing works
Green tea modulates reserpine toxicity in animal models
Albeloushi, S., Safer, A.-M., Afzal, M., & Mousa, S. A. (2009) · The Journal of Toxicological Sciences · doi:10.2131/jts.34.77 · Cited by 30 · see citing works
“It is well-established that green tea catechins can help to reduce cholesterol, thus aiding in the prevention of cardiovascular diseases (Kakuda, 2002).”
Background
Comparison of Azorean tea theanine to teas from other origins by HPLC/DAD/FD. Effect of fermentation, drying temperature, drying time and shoot maturity
Baptista, J., Lima, E., Paiva, L. S., Andrade, A. L., & Alves, M. G. (2011) · Food Chemistry · doi:10.1016/j.foodchem.2011.12.050 · Cited by 28 · see citing works
Beneficial synergistic effects of concurrent treatment with theanine and caffeine against cerebral ischemia–reperfusion injury in rats
Sun, L., Xia, T., Gou, L., Ling, X., Wang, L., Feng, Y., Yin, X., & Liu, Y. (2013) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2012-0309 · Cited by 27 · see citing works
“Theanine, an amino acid component of tea, has been confirmed to possess antioxidative properties and neuroprotective effects against ischemia (Yokozawa and Dong 1997; Kakuda 2002; Cho et al. 2008; Nishida et al. 2008).”
Epicatechin gallate increases glutamate uptake and S100B secretion in C6 cell lineage
Abib, R. T., Quincozes‐Santos, A., Nardin, P., Wofchuk, S. T., Perry, M. L. S., Gonçalves, C., & Gottfried, C. (2007) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-007-9675-3 · Cited by 26 · see citing works
“While tea catechins are very effective in preventing atherosclerosis through their antioxidant effect and scavenging of active oxygen species, their actions in the brain remain unclear [10].”
Background
A multifunctional cytoprotective agent that reduces neurodegeneration after ischemia
Jiang, Z.-G., Lu, X., Nelson, V. M., Yang, X., Pan, W., Chen, R., Lebowitz, M., Almassian, B., Tortella, F. C., Brady, R. O., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510573103 · Cited by 26 · see citing works
Characterization of <scp>l</scp>-Theanine Excitatory Actions on Hippocampal Neurons: Toward the Generation of Novel N-Methyl-<scp>d</scp>-aspartate Receptor Modulators Based on Its Backbone
Sebih, F., Rousset, M., Bellahouel, S., Rolland, M., de Jesus Ferreira, M. C., Guiramand, J., Cohen-Solal, C., Barbanel, G., Cens, T., Abouazza, M., et al. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00036 · Cited by 24 · see citing works
Lung Cancer Survival With Herbal Medicine and Vitamins in a Whole-Systems Approach
McCulloch, M., Broffman, M., van der Laan, M. J., Hubbard, A., Kushi, L. H., Kramer, A., Gao, J. H., & Colford, J. M. (2011) · Integrative Cancer Therapies · doi:10.1177/1534735411406439 · Cited by 24 · see citing works
Effect of green tea (camellia sinensis l.) leaf extract on reproductive system of adult male albino rats.
Das, S. K., & Karmakar, S. N. (2015) · Europe PMC (PubMed Central) · Cited by 23 · see citing works
A new epigallocatechin gallate derivative isolated from Anhua dark tea sensitizes the chemosensitivity of gefitinib via the suppression of PI3K/mTOR and epithelial-mesenchymal transition
Liu, J., Zhong, T., Yi, P., Fan, C., Zhang, Z., Liang, G., Xu, Y., & Fan, Y. (2020) · Fitoterapia · doi:10.1016/j.fitote.2020.104590 · Cited by 23 · see citing works
Altered levels of oxidation and phospholipase c isozyme expression in the brains of theanine-administered rats
Nishida, K., Yasuda, E., Nagasawa, K., & Fujimoto, S. (2008) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.31.857 · Cited by 21 · see citing works
Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial
Kardashev, A., Ratner, Y., & Ritsner, M. S. (2018) · Clinical Schizophrenia & Related Psychoses · doi:10.3371/csrp.kara.070415 · Cited by 18 · see citing works
Neuroprotective effect of L-theanine on Aβ-induced neurotoxicity through anti-oxidative mechanisms in SK-N-SH and SK-N-MC cells
Jo, M.-R., Park, M.-H., Choi, D.-Y., Yuk, D.-Y., Lee, Y.-M., Lee, J.-M., Jeong, J.-H., Oh, K.-W., Lee, M.-S., Han, S.-B., et al. (2011) · Biomolecules and Therapeutics · doi:10.4062/biomolther.2011.19.3.288 · Cited by 18 · see citing works
“…its components possess neuroprotective effects on several neurodegenerative diseases including middle cerebral artery occlusion-induced ischemia (Kakuda, 2002; Egashira et al., 2004; Egashira et al., 2007) as well as Alzheimer’s diseases (Nathan et al., 2006; Egashira et al., 2008; Yamada et…”
BackgroundResultInfluential
Antimicrobial effects of copper nanoparticles with green tea and neem formulation
Thomas, A. A. (2022) · Bioinformation · doi:10.6026/97320630018284 · Cited by 18 · see citing works
Dietary Green Tea Extract Prior to Spinal Cord Injury Prevents Hepatic Iron Overload but Does Not Improve Chronic Hepatic and Spinal Cord Pathology in Rats
Goodus, M. T., Sauerbeck, A. D., Popovich, P. G., Bruno, R. S., & McTigue, D. M. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2018.5771 · Cited by 18 · see citing works
Direct interaction of natural and synthetic catechins with signal transducer activator of transcription 1 affects both its phosphorylation and activity
Menegazzi, M., Mariotto, S., Bosco, M. D., Darra, E., Vaiana, N., Shoji, K., Abdel‐Azeim, S., Maréchal, J., Pérahia, D., Suzuki, H., et al. (2013) · FEBS Journal · doi:10.1111/febs.12618 · Cited by 17 · see citing works
Centella asiatica modulates neuron cell survival by altering caspase-9 pathway
Omar, N. S., Zakaria, Z. A. C., Then, S., Ngah, W. Z. W., & Mazlan, M. (2011) · Journal of Medicinal Plants Research · doi:10.5897/jmpr.9000323 · Cited by 17 · see citing works
The effects of L-theanine supplementation on the outcomes of patients with mental disorders: a systematic review
Moshfeghinia, R., Sanaei, E., Mostafavi, S., Assadian, K., Sanaei, A., & Ayano, G. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-06285-y · Cited by 17 · see citing works
Novel HPLC Method to Evaluate the Quality and Identify the Origins of Longjing Green Tea
Song, M., Li, Q., Guan, X., Wang, T., & Kai-shun, B. (2012) · Analytical Letters · doi:10.1080/00032719.2012.704532 · Cited by 16 · see citing works
“2005), antimutagenic (Ioannides and Yoxall 2003; Hernaez, Xu, and Dashwood 1999), antimicrobial (Bancirov 2010), antidiabetic (Sabu, Smitha, and Kuttan 2002), antiarteriosclerosis (Kakuda 2002), and anti-influenza (Furuta, Hirooka, and Abea 2007) have been reported.”
Background
Theogallin and L-theanine as active ingredients in decaffeinated green tea extract: I. electrophysiological characterization in the rat hippocampus in-vitro
Dimpfel, W., Kler, A., Kriesl, E., & Lehnfeld, R. (2007) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.59.8.0011 · Cited by 16 · see citing works
“The mechanism of action seems to involve glutamate receptors (Kakuda 2002).”
Background
Isolation of <scp>L</scp>‐Theanine from Plant Material using a Molecularly Imprinted Polymer
Lachová, M., Lehotay, J., Karasová, G., Skačáni, I., & Armstrong, D. W. (2007) · Journal of Liquid Chromatography & Related Technologies · doi:10.1080/10826070701435053 · Cited by 15 · see citing works
“A number of papers have documented the inhibition of peroxidation of low density lipoproteins (LDL) by tea extract.([9]) Another study using electroencephalography (EEG) also showed an inhibiting effect of theanine on caffeine stimulation.”
Background

Chemoprevention effect of tea against neuronal death-dementia.
Kakuda, T. (2006) · CABI eBooks · doi:10.1079/9781845931124.0182
Self-citation
Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction
Kakuda, T. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.03.010 · Cited by 124 · see citing works
Self-citation
Theanine prevents memory impairment induced by repeated cerebral ischemia in rats
Egashira, N., Ishigami, N., Pu, F., Mishima, K., Iwasaki, K., Orito, K., Oishi, R., & Fujiwara, M. (2008) · Phytotherapy Research · doi:10.1002/ptr.2261 · Cited by 40 · see citing works
Multifunctional Activities of Green Tea Catechins in Neuroprotection
Mandel, S. A., Avramovich‐Tirosh, Y., Reznichenko, L., Zheng, H., Weinreb, O., Amit, T., & Youdim, M. B. H. (2005) · Neurosignals · doi:10.1159/000085385 · Cited by 347 · see citing works
Biomolecules of Tea
Sebih, F., Guiramand, J., Cohen‐Solal, C., Vignes, M., & Rolland, V. (2014) · HAL

Authors: Kakuda, T.
Affiliations: Central Research Institute (IN)
Corresponding author: Kakuda, Takami
Venue: Biological & Pharmaceutical Bulletin
Publisher: Pharmaceutical Society of Japan
Published: 2002
Volume: 25
Issue: 12
Pages: 1513-1518
ISSN: 0918-6158 (ISSN-L)
1347-5215
DOI: 10.1248/bpb.25.1513
OpenAlex: W2085517462
Cited by: 165
References: 56
Citations by year: 2026: 3 · 2025: 7 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 9 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 6 · 2015: 10 · 2014: 4 · 2013: 9 · 2012: 9
FWCI: 0.66
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Biological and Pharmaceutical Bulletin (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Tea Polyphenols and Effects
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Keywords: theanine, tea catechins, green tea, neuroprotection, glutamate excitotoxicity, transient forebrain ischemia, NMDA receptor, glutamate transporters, superoxide radical scavenging, arteriosclerosis, ischemic cerebrovascular disease
MeSH terms: Animals, Catechin, Cell Survival, Glutamates, Humans, Tea, Cell Death, Neuroprotective Agents

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Neuroprotective effects of the green tea components theanine and catechins

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