L-茶氨酸防治脑疾病研究进展

doi:10.13305/j.cnki.jts.2019.02.008

摘要/Abstract

摘要： 随着人口老龄化以及社会竞争日益增长带来的压力,与脑相关的神经退行性疾病及精神疾病越来越严重地影响我们的生活质量。L-茶氨酸是茶叶中一种独特的非蛋白氨基酸,大量研究表明L-茶氨酸在预防和治疗脑疾病方面有明显功效。本文综述了L-茶氨酸在机体内的吸收与代谢以及在预防和治疗脑疾病方面的研究成果,希望能为L-茶氨酸的应用和功能产品开发提供参考。

关键词: 脑疾病, L-茶氨酸, 防治, 作用机制

Abstract: With the aging of the population and the growing pressure of social competition, brain-related neurodegenerative diseases and mental disorders increasingly affect our quality of life. L-theanine is a unique non-protein amino acid in tea. Numerous studies have shown that L-theanine has significant effects on the prevention and treatment of brain diseases. In this paper, the absorption and metabolism of L-theanine in the body and the research results in the prevention and treatment of brain diseases were summarized, which would provide a reference for the application of L-theanine and development of functional products.

Key words: brain diseases, L-theanine, prevention and treatment, mechanism of action

中图分类号:

曾立, 肖文军. L-茶氨酸防治脑疾病研究进展[J]. 茶叶科学, 2019, 39(2): 193-202. doi: 10.13305/j.cnki.jts.2019.02.008.

ZENG Li, XIAO Wenjun. Advances in Brain Diseases Prevention and Treatment of L- theanine[J]. Journal of Tea Science, 2019, 39(2): 193-202. doi: 10.13305/j.cnki.jts.2019.02.008.

参考文献

[1] 熊志奇, 徐林, 周江宁. 脑重大疾病的机理和诊治[J]. 中国科学院院刊, 2016, 31(7): 765-772.
[2] Borzelleca J F, Peters D, Hall W.A 13-week dietary toxicity and toxicokinetic study with L-theanine in rats[J]. Food & Chemical Toxicology, 2006, 44(7): 1158-1166.
[3] Juneja L R, Chu D C, Okubo T, et al.L-theanine—a unique amino acid of green tea and its relaxation effect in humans[J]. Trends in Food Science & Technology, 1999, 10(6/7): 199-204.
[4] 刘洋, 李颂, 王春玲. 茶氨酸健康功效研究进展[J]. 食品研究与开发, 2016, 37(17): 211-214.
[5] Sharma E,Joshi R,Gulati A.L-theanine: an astounding sui generis integrant in tea[J]. Food Chemistry, 2018, 242: 601-610
[6] Saeed M,Naveed M, Arif M, et al.Green tea (Camellia sinensis) and L-theanine: medicinal values and beneficial applications in humans—a comprehensive review[J]. Biomedicine & Pharmacotherapy, 2017, 95: 1260-1275.
[7] 陈宗懋. 茶与健康专题(七)饮茶对脑功能的改善和神经退化性疾病的预防作用[J]. 中国茶叶, 2009, 31(10): 6-7.
[8] Başkan M H, Ayd?n M.Electron paramagnetic resonance studies of gamma-irradiated DL-alanine ethyl ester hydrochloride, L-theanine and L-glutamic acid dimethyl ester hydrochloride[J]. Spectrochimica Acta Part A Molecular & Biomolecular Spectroscopy, 2013, 112(8): 280-282.
[9] Mu W, Zhang T, Jiang B.An overview of biological production of L-theanine[J]. Biotechnology Advances, 2015, 33(4): 335-342.
[10] Scheid L, Ellinger S, Alteheld B, et al.Kinetics of L-theanine uptake and metabolism in healthy participants are comparable after ingestion of L-theanine via capsules and green tea[J]. Journal of Nutrition, 2012, 142(12): 2091-2096.
[11] Kitaoka S, Hayashi H, Yokogoshi H, et al.Transmural potential changes associated with the in vitro absorption of theanine in the guinea pig intestine[J]. Bioscience Biotechnology & Biochemistry, 1996, 60(11): 1768-1771.
[12] Desai M J, Gill M S, Hsu W H, et al.Pharmacokinetics of theanine enantiomers in rats[J]. Chirality, 2005, 17(3): 154-162.
[13] Yamamoto S, Kimura T, Tachiki T, et al.The involvement of L-type amino acid transporters in theanine transport[J]. Bioscience Biotechnology & Biochemistry, 2014, 76(12): 2230-2235.
[14] Unno T, Suzuki Y, Kakuda T, et al.Metabolism of theanine, gamma-glutamylethylamide, in rats[J]. Journal of Agricultural & Food Chemistry, 1999, 47(4): 1593-1596.
[15] Yokogoshi H, Kobayashi M, Mochizuki M, et al.Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats[J]. Neurochemical Research, 1998, 23(5): 667-673.
[16] Yamada T, Terashima T, Okubo T, et al.Effects of theanine, r-glutamylethylamide, on neurotransmitter release and its relationship with glutamic acid neurotransmission[J]. Nutritional Neuroscience, 2005, 8(4): 219-226.
[17] Kakuda T, Nozawa A, Sugimoto A, et al.Inhibition by theanine of binding of [3H]AMPA, [3H]Kainate, and [3H]MDL 105,519 to glutamate receptors[J]. Biosci Biotechnol Biochem, 2014, 66(12): 2683-2686.
[18] 李坤成, 张开元. 功能磁共振在精神病诊断中的应用[J]. 中华医学杂志, 2008, 88(23): 1589-1591.
[19] 张成. 心身疾病刚柔辨证的脑电图及脑内神经递质活性的超慢涨落图分析[D]. 北京: 中国中医科学院, 2013.
[20] Nobre A C, Rao A, Owen G N. L-theanine, a natural constituent in tea,its effect on mental state [J]. Asia Pacific Journal of Clinical Nutrition, 2008, 17 1(1): 167-168.
[21] Abdou A M, Higashiguchi S, Horie K, et al.Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans[J]. Biofactors, 2006, 26(3): 201-208.
[22] Dodd F L, Kennedy D O, Riby L M, et al.A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood[J]. Psychopharmacology, 2015, 232(14): 2563-2576.
[23] Rao T P, Ozeki M, Juneja L R.In search of a safe natural sleep aid[J]. Journal of the American College of Nutrition, 2015, 34(5): 1-12.
[24] Kobayashi K, Nagato Y, Aoi N, et al.Effects of L-theanine on the release of α-brain waves in human volunteers[J]. Nippon Nogeikagaku Kaishi, 1998, 72(2): 153-157.
[25] Lyon M R, Kapoor M P, Juneja L R.The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial[J]. Alternative Medicine Review, 2011, 16(4): 348-354.
[26] Jang H S, Jung J Y, Jang I S, et al.L-theanine partially counteracts caffeine-induced sleep disturbances in rats[J]. Pharmacology Biochemistry & Behavior, 2012, 101(2): 217-221.
[27] Ota, M, Wakabayashi, C, Sato, N, et al.Effect of L-theanine on glutamatergic function in patients with schizophrenia[J]. Acta Neuropsychiatrica, 2015, 27(5): 1-6.
[28] Ritsner M S, Miodownik C, Ratner Y, et al.L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study[J]. Journal of Clinical Psychiatry, 2011, 72(1): 34-42.
[29] Miodownik C, Maayan R, Ratner Y, et al.Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone molar ratio associated with clinical response to L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients[J]. Clinical Neuropharmacology, 2011, 34(4): 155-160.
[30] Lu K, Gray M A, Oliver C, et al.The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans[J]. Human Psychopharmacology Clinical & Experimental, 2004, 19(7): 457-465.
[31] Heese T, Jenkinson J, Love C, et al.Anxiolytic effects of L-theanine-a component of green tea-when combined with midazolam, in the male Sprague-Dawley rat[J]. Aana J, 2009, 77(6): 445-449.
[32] Lee W K, Kim T I, Park S, et al.Anxiolytic effect of a combination of green tea extract and L-theanine[J]. Laboratory Animal Research, 2010, 26(1): 63-68.
[33] Tian X, Sun L, Gou L, et al.Protective effect of L-theanine on chronic restraint stress-induced cognitive impairments in mice[J]. Brain Research, 2013, 1503(1): 24-32.
[34] Everett J M, Gunathilake D, Dufficy L, et al.Theanine consumption, stress and anxiety in human clinical trials: A systematic review[J]. Journal of Nutrition & Intermediary Metabolism, 2016, 4: 41-42.
[35] Kardashev A, Ratner Y, Ritsner M S.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[J]. Clinical Schizophrenia & Related Psychoses, 2018, 12(1): 31-41.
[36] Shinsuke H, Miho O, Chisato W, et al.Effects of chronic L-theanine administration in patients with major depressive disorder: an open-label study[J]. Acta Neuropsychiatrica, 2016, 29(2): 1-8.
[37] 彭彬, 刘仲华, 林勇, 等. L-茶氨酸改善慢性应激大鼠抑郁行为作用研究[J]. 茶叶科学, 2014, 34(04): 355-363.
[38] Cui Y, L G, Liu Y, et al. Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice[J]. Phytotherapy Research, 2011, 25(11): 1636-1639.
[39] Wakabayashi C, Numakawa T, Ninomiya M, et al.Behavioral and molecular evidence for psychotropic effects in L-theanine[J]. Psychopharmacology, 2012, 219(4): 1099-1109.
[40] Hidese S, Ota M, Wakabayashi C, et al.Effects of chronic L-theanine administration in patients with major depressive disorder: an open-label study[J]. Acta neuropsychiatrica, 2017, 29(2): 72-79.
[41] Haskell C F, Kennedy D O, Milne A L, et al.The effects of L-theanine, caffeine and their combination on cognition and mood[J]. Biological Psychology, 2008, 77(2): 113-122.
[42] Park S K, Jung I C, Lee W K, et al.A combination of green tea extract and L-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study[J]. Journal of Medicinal Food, 2011, 14(4): 334-343.
[43] Higashiyama A, Htay H H, Ozeki M, et al.Effects of L-theanine on attention and reaction time response[J]. Journal of Functional Foods, 2011, 3(3): 171-178.
[44] Dimpfel W, Kler A, Kriesl E, et al.Source density analysis of the human EEG after ingestion of a drink containing decaffeinated extract of green tea enriched with L-theanine and theogallin[J]. Nutritional Neuroscience, 2013, 10(3/4): 169-180.
[45] Owen G N, Parnell H, De Bruin E A, et al. The combined effects of L-theanine and caffeine on cognitive performance and mood[J]. Nutritional Neuroscience, 2013, 11(4): 193-198.
[46] Kelly S P, Gomez-Ramirez M, Montesi J L, et al.L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance[J]. Journal of Nutrition, 2008, 138(8): 1572S-1577S.
[47] Einöther S J, Martens V E, Rycroft J A, et al.L-theanine and caffeine improve task switching but not intersensory attention or subjective alertness[J]. Appetite, 2010, 54(2): 406-409.
[48] Kahathuduwa C N, Dassanayake T L, Amarakoon A M T, et al. Acute effects of theanine, caffeine and theanine-caffeine combination on attention[J]. Nutritional Neuroscience, 2016(2): 1-9.
[49] Kahathuduwa C N, Dhanasekara C S, Chin S H, et al.l-Theanine and caffeine improve target-specific attention to visual stimuli by decreasing mind wandering: a human functional magnetic resonance imaging study[J]. Nutrition Research, 2018, 49: 67-78.
[50] White D J, Klerk S D, Woods W, et al.Anti-stress, behavioural and magnetoencephalography effects of an l-theanine-based nutrient drink: a randomised, double-blind, placebo-controlled, crossover trial[J]. Nutrients, 2016, 8(1): 53-71.
[51] Giles G E, Mahoney C R, Brunyé T T, et al.Caffeine and theanine exert opposite effects on attention under emotional arousal[J]. Canadian Journal of Physiology & Pharmacology, 2017, 95(1): 93-100.
[52] Nathan P J, Lu K, Gray M, et al.The neuropharmacology of L-theanine (N-Ethyl-L-Glutamine)[J]. J Herb Pharmacother, 2006, 6(2): 21-30.
[53] Cho H S, Kim S, Lee S Y, et al.Protective effect of the green tea component, L-theanine on environmental toxins-induced neuronal cell death[J]. Neurotoxicology, 2008, 29(4): 656-662.
[54] 吴波拉, 虞希冲, 杜冠华. L-茶氨酸减轻叠氮钠诱导的人神经母细胞瘤SH-SY5Y细胞线粒体损伤[J]. 基础医学与临床, 2013, 33(11): 1465-1469.
[55] Taeil K, Yongkyung L, Sanggi P, et al.L-theanine, an amino acid in green tea, attenuates β-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-κB pathways[J]. Free Radical Biology & Medicine, 2009, 47(11): 1601-1610.
[56] Mi-Ran Jo, Mi-Hee Park, Dong-Young Choi, et al.Neuroprotective effect of L-theanine on Aβ-induced neurotoxicity through anti-oxidative mechanisms in SK-N-SH and SK-N-MC cells[J]. Biomolecules & Therapeutics, 2011, 19(3): 288-295.
[57] Di X, Yan J, Zhao Y, et al.L-theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway[J]. Neuroscience, 2010, 168(3): 778-786.
[58] Kim T I, Dong Y Y, Sang G P, et al.Improvement of memory impairment by the combination of green tea extract and L-theanine through inhibition of acetylcholinesterase activity in mice[J]. Laboratory Animal Research, 2008, 24: 87-92.
[59] Jamwal S, Kumar P.L-theanine, a component of green tea prevents 3-nitropropionic acid (3-NP)-induced striatal toxicity by modulating nitric oxide pathway[J]. Molecular Neurobiology, 2016, 54(3): 2327-2337.
[60] Jamwal S, Singh S, Gill J S, et al.L-theanine prevent quinolinic acid induced motor deficit and striatal neurotoxicity: Reduction in oxido-nitrosative stress and restoration of striatal neurotransmitters level[J]. European Journal of Pharmacology, 2017, 811: 171-179.
[61] 王玉芬, 李春雨, 秦志祥, 等. 茶氨酸对脑缺血再灌注损伤保护作用的实验研究[J]. 中华神经医学杂志, 2006(6): 562-565.
[62] 王庆利, 张力军, 吴明春, 等. 茶氨酸对脑缺血损伤大鼠自由基代谢的影响[J]. 实用医学杂志, 2008(11): 1898-1900.
[63] 张燕辉, 吴明春, 王庆利. 茶氨酸对大鼠局灶性脑缺血性损伤后炎性细胞因子表达的影响[J]. 中国临床神经外科杂志, 2010, 15(9): 544-546.
[64] Ceremuga T E, Martinson S, Washington J, et al.Effects of L-theanine on posttraumatic stress disorder induced changes in rat brain gene expression[J]. The Scientific World Journal, 2014(4): 1-10.
[65] Egashira N, Hayakawa K, Osajima M, et al.Involvement of GABA(A) receptors in the neuroprotective effect of theanine on focal cerebral ischemia in mice[J]. Journal of Pharmacological Sciences, 2007, 105(2): 211-214.
[66] Egashira N, Ishigami N, Pu F, et al.Theanine prevents memory impairment induced by repeated cerebral ischemia in rats[J]. Phytotherapy Research, 2008, 22(1): 65-68.
[67] Zukhurova M, Prosvirnina M, Daineko A, et al.L-theanine administration results in neuroprotection and prevents glutamate receptor agonist-mediated injury in the rat model of cerebral ischemia-reperfusion[J]. Phytotherapy Research Ptr, 2013, 27(9): 1282-1287.
[68] 王宁, 吕建瑞, 张珍妮, 等. 茶氨酸对全脑缺血再灌注大鼠JNK信号通路与DNA修复的影响[J]. 山西医科大学学报, 2016, 47(5): 415-418, 454.
[69] 梁宇. 茶氨酸对神经干细胞增殖和分化的影响[D]. 济南: 山东大学, 2015.
[70] Ben P, Zhang Z, Zhu Y, et al.L-theanine attenuates cadmium-induced neurotoxicity through the inhibition of oxidative damage and tau hyperphosphorylation[J]. Neurotoxicology, 2016, 57: 95-103.
[71] Takarada T, Nakamichi N, Kakuda T, et al.Daily oral intake of theanine prevents the decline of 5-bromo-2'-deoxyuridine incorporation in hippocampal dentate gyrus with concomitant alleviation of behavioral abnormalities in adult mice with severe traumatic stress[J]. Journal of Pharmacological Sciences, 2015, 127(3): 292-297.
[72] Takarada T, Nakamichi N, Nakazato R, et al.Possible activation by the green tea amino acid theanine of mammalian target of rapamycin signaling in undifferentiated neural progenitor cells in vitro [J]. Biochemistry & Biophysics Reports, 2016, 5: 89-95.
[73] Sumathi T, Asha D, Nagarajan G, et al.L-theanine alleviates the neuropathological changes induced by PCB (Aroclor 1254) via inhibiting upregulation of inflammatory cytokines and oxidative stress in rat brain[J]. Environmental Toxicology & Pharmacology, 2016, 42: 99-117.
[74] Takeshima M, Miyazaki I, Murakami S, et al.L-theanine protects against excess dopamine-induced neurotoxicity in the presence of astrocytes[J]. Journal of Clinical Biochemistry & Nutrition, 2016, 59(2): 93-99.
[75] Schallier A, Vermoesen K, Loyens E, et al.L-theanine intake increases threshold for limbic seizures but decreases threshold for generalized seizures[J]. Nutritional Neuroscience, 2013, 16(2): 78-82.
[76] 滕安国. 功能因子与免疫调控机制及功能食品开发[J]. 天津科技大学学报, 2017, 32(5): 2.