Volume 13 Issue 1
Jan.  2023
Turn off MathJax
Article Contents
Abstract
References
Article Navigation >  Journal of Pharmaceutical Analysis  > 2023  >  13(1): 73-87
Yanru Zhu, Feng Wang, Jiatong Han, Yunli Zhao, Miao Yu, Mingyan Ma, Zhiguo Yu. Untargeted and targeted mass spectrometry reveal the effects of theanine on the central and peripheral metabolomics of chronic unpredictable mild stress-induced depression in juvenile rats[J]. Journal of Pharmaceutical Analysis, 2023, 13(1): 73-87. doi: 10.1016/j.jpha.2022.10.001
Citation: Yanru Zhu, Feng Wang, Jiatong Han, Yunli Zhao, Miao Yu, Mingyan Ma, Zhiguo Yu. Untargeted and targeted mass spectrometry reveal the effects of theanine on the central and peripheral metabolomics of chronic unpredictable mild stress-induced depression in juvenile rats[J]. Journal of Pharmaceutical Analysis, 2023, 13(1): 73-87. doi: 10.1016/j.jpha.2022.10.001
shu

Untargeted and targeted mass spectrometry reveal the effects of theanine on the central and peripheral metabolomics of chronic unpredictable mild stress-induced depression in juvenile rats

doi: 10.1016/j.jpha.2022.10.001

  • a. Laboratory of Pharmaceutical Analysis, School of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, Zhejiang, 315100, China;

  • b. Laboratory of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China

  • Received Date: Mar. 10, 2022
  • Accepted Date: Oct. 08, 2022
  • Rev Recd Date: Sep. 25, 2022
  • Publish Date: Oct. 13, 2022
    Abstract
  • L-theanine has been shown to have a therapeutic effect on depression. However, whether L-theanine has an excellent preventive effect on depression in children and adolescents and what its mechanism is have not been well explained. Given the complexity of the pathogenesis of depression, this study investigated the preventive effect and mechanism of L-theanine on depression in juvenile rats by combining serum and hippocampal metabolomic strategies. Behavioral tests, hippocampal tissue sections, and serum and hippocampal biochemical indexes were studied, and the results confirmed the preventive effect of L-theanine. Untargeted reversed-phase liquid chromatography-quadrupole-time-of-flight mass spectrometry and targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spectrometry were developed to analyze the metabolism changes in the serum and hippocampus to screen for potential biomarkers related to L-theanine treatment. The results suggested that 28 abnormal metabolites in the serum and hippocampus that were considered as potential biomarkers returned to near-normal levels after L-theanine administration. These biomarkers were involved in various metabolic pathways, mainly including amino acid metabolism and lipid metabolism. The levels of amino acids and neurotransmitters in the phenylalanine, tryptophan, and glutamic acid pathways were significantly reduced after L-theanine administration compared with chronic unpredictable mild stress-induced rats. In summary, L-theanine had a significant preventive effect on depression and achieved its preventive results on depression by regulating various aspects of the body, such as amino acids, lipids, and inflammation. This research systematically analyzed the mechanism of L-theanine in preventing depression and laid the foundation for applying L-theanine to prevent depression in children and adolescents.
    • FullText(HTML)
    • References(59)
  • A. Werner, Y. Perry, A. Calear, et al., School-based depression and anxiety prevention programs for young people: A systematic review and meta-analysis, Clin. Psychol. Rev. 51 (2017) 30-47
    T. Mendelson, S. Tandon, Prevention of depression in childhood and adolescence, Psychiatr. Clin. North. Am. 25 (2016) 201-218
    L. Ramsey, J. Bishop, J. Strawn, Pharmacogenetics of treating pediatric anxiety and depression, Pharmacogenomics. 20 (2019) 867-870
    Y. Han, J. Dai, Research progress in animal models and mechanism of depression, Acta Lab. Anim. Sci. Sin. 24 (2016) 321-326
    C. Raison, L. Capuron, A. Miller, Cytokines sing the blues: Inflammation and the pathogenesis of depression, Trends Immunol. 27 (2006) 24-31
    H. Chen, H. Xie, S. Huang, et al., Development of mass spectrometry-based relatively quantitative targeted method for amino acids and neurotransmitters: Applications in the diagnosis of major depression, J. Pharmaceut. Biomed. 194 (2021), 113773
    A. Cipriani, X. Zhou, C. Del Giovane, et al., Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis, Lancet. 388 (2016) 881-890
    A. Lardner, Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders, Nutr. Neurosci. 17 (2014) 145-155
    S. Hidese, S. Ogawa, M. Ota, et al., Effects of L-Theanine administration on stress-related symptoms and cognitive functions in healthy adults: A randomized controlled trial, Nutrients. 11 (2019), 2362
    S. Hidese, M. Ota, C. Wakabayashi, et al., Effects of chronic l-theanine administration in patients with major depressive disorder: An open-label study, Acta Neuropsychiatr. 29 (2017) 72-79
    T. Takarada, N. Nakamichi, T. Kakuda, 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. Pharmacol. Sci. 127 (2015) 292-297
    J. Borzelleca, D. Peters, W. Hall, A 13-week dietary toxicity and toxicokinetic study with l-theanine in rats, Food Chem. Toxicol. 44 (2006) 1158-1166
    J. Williams, J. Kellett, P. Roach, et al., l-Theanine as a functional food additive: Its role in disease prevention and health promotion, Beverages. 2 (2016) 13
    R. Beger, W. Dunn, M. Schmidt, et al., Metabolomics enables precision medicine: "A White Paper, Community Perspective", Metabolomics. 12 (2016) 149
    S. Barnes, H. Benton, K. Casazza, et al., Training in metabolomics research. I. Designing the experiment, collecting and extracting samples and generating metabolomics data, J. Mass Spectrom. 51 (2016) 461-475
    C. Johnson, J. Ivanisevic, G. Siuzdak, Metabolomics: Beyond biomarkers and towards mechanisms, Nat. Rev. Mol. Cell Bio. 17 (2016) 451-459
    D. Hackos, P. Lupardus, T. Grand, et al., Positive allosteric modulators of GluN2A-containing NMDARs with distinct modes of action and impacts on circuit function, Neuron. 89 (2016) 983-999
    X. Liu, M. Lv, Y. Wang, et al., Deciphering the compatibility rules of traditional Chinese medicine prescriptions based on NMR metabolomics: A case study of Xiaoyaosan, J. Ethnopharmacol. 254 (2020), 112726
    U.S. Food and Drug Administration, Bioanalytical method validation guidance for industry. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioanalytical-method-validation-guidance-industry. (Accessed 24 May 2021)
    X. Han, Y. Qin, Y. Zhu, et al., Development of an underivatized LC-MS/MS method for quantitation of 14 neurotransmitters in rat hippocampus, plasma and urine: Application to CUMS induced depression rats, J. Pharmaceut. Biomed. 174 (2019) 683-695
    Q. Guo, X. Lin, Z. Di, et al., Electroacupuncture Ameliorates CUMS-induced Depression-like Behavior: Involvement of the Glutamatergic System and Apoptosis in Rats, Comb. Chem. High Throughput Screen. 24 (2021) 996-1004
    L. Yu, S. An, T. Lian, Involvement of hippocampal NMDA receptor and neuropeptide Y in depression induced by chronic unpredictable mild stress, Sheng li xue bao. 62 (2010) 14-22
    L. Liu, Y. Dong, X. Shan, et al., Anti-Depressive Effectiveness of Baicalin In Vitro and In Vivo, Molecules. 2019. https://doi.org/10.3390/molecules24020326
    W. Su, Y. Zhang, Y. Chen, et al., NLRP3 gene knockout blocks NF-κB and MAPK signaling pathway in CUMS-induced depression mouse model, Behav. Brain Res. 322 (2017) 1-8
    K. Roth, R. Katz, Stress, behavioral arousal, and open field activity--a reexamination of emotionality in the rat, Neurosci. Biobehav. Rev. 3 (1979) 247-263
    Q. Lu, A. Mouri, Y. Yang, et al., Chronic unpredictable mild stress-induced behavioral changes are coupled with dopaminergic hyperfunction and serotonergic hypofunction in mouse models of depression, Behav. Brain Res. 372 (2019), 112053
    M. Bourin, M. Hascoet, The mouse light/dark box test, Eur. J. Pharmacol. 463 (2003) 55-65
    H.E. Scharfman, The enigmatic mossy cell of the dentate gyrus, Nat. Rev. Neurosci. 17 (2016) 562-575
    K. Mizuseki, S. Royer, K. Diba, et al., Activity dynamics and behavioral correlates of CA3 and CA1 hippocampal pyramidal neurons, Hippocampus. 22 (2012) 1659-1680
    Y. Lu, C. Ho, X. Liu, et al., Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression, PloS one. 12 (2017), e0186700
    J. Tang, W. Yu, S. Chen, et al., Microglia Polarization and Endoplasmic Reticulum Stress in Chronic Social Defeat Stress Induced Depression Mouse, Neurochem. Res. 43 (2018) 985-994
    X. Zheng, A. Kang, C. Dai, et al., Quantitative analysis of neurochemical panel in rat brain and plasma by liquid chromatography-tandem mass spectrometry, Anal. Chem. 84 (2012) 10044-10051
    I. Fuertes, C. Barata, Characterization of neurotransmitters and related metabolites in Daphnia magna juveniles deficient in serotonin and exposed to neuroactive chemicals that affect its behavior: A targeted LC-MS/MS method, Chemosphere. 263 (2021), 127814
    X. Han, Y. Qin, Y. Zhu, et al., Development of an underivatized LC-MS/MS method for quantitation of 14 neurotransmitters in rat hippocampus, plasma and urine: Application to CUMS induced depression rats, J. Pharmaceut. Biomed. 174 (2019) 683-695
    J. Marcos, N. Renau, O. Valverde, et al., Targeting tryptophan and tyrosine metabolism by liquid chromatography tandem mass spectrometry, J. Chromatogr. A. 1434 (2016) 91-101
    Z. Yuan, J. Li, X. Zhou, et al., HS-GC-IMS-Based metabonomics study of Baihe Jizihuang Tang in a rat model of chronic unpredictable mild stress, J. Chromatogr. B. 1148 (2020), 122143
    L. Ding, X. Zhang, H. Guo, et al., The functional study of a chinese herbal compounded antidepressant medicine--Jie Yu Chu Fan Capsule on chronic unpredictable mild stress mouse model, PloS One. 10 (2015), e0133405
    W. Song, Y. Guo, S. Jiang, et al., Antidepressant effects of the ginsenoside metabolite compound K, assessed by behavioral despair test and chronic unpredictable mild stress model, Neurochem. Res. 43 (2018) 1371-1382
    P. Rosa-Neto, M. Diksic, H. Okazawa, et al., Measurement of brain regional alpha-[11C]methyl-L-tryptophan trapping as a measure of serotonin synthesis in medication-free patients with major depression, Arch. Gen. Psychiat. 61 (2004) 556-563
    J. Meyer, H. McNeely, S. Sagrati, et al., Elevated putamen D(2) receptor binding potential in major depression with motor retardation: an [11C] raclopride positron emission tomography study, Am. J. Psychiat. 163 (2006) 1594-1602
    H. Cai, R. Zhu, H. Li, Determination of dansylated monoamine and amino acid neurotransmitters and their metabolites in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry, Anal. Biochem. 396 (2010) 103-111
    M. Nagasawa, Y. Ogino, K. Kurata, et al., Hypothesis with abnormal amino acid metabolism in depression and stress vulnerability in Wistar Kyoto rats, Amino acids. 43 (2012) 2101-2111
    X. Yang, G. Wang, X. Gong, et al., Effects of chronic stress on intestinal amino acid pathways, Physiol. Behav. 204 (2019) 199-209
    H. Woo, M. Chun, J. Yang, et al., Plasma amino acid profiling in major depressive disorder treated with selective serotonin reuptake inhibitors, CNS Neurosci Ther 21 (2015) 417-424
    Y. Zhu, S. Li, C. Zhu, et al., Metabolomics analysis of the antidepressant prescription Danzhi Xiaoyao Powder in a rat model of Chronic Unpredictable Mild Stress (CUMS), J. Ethnopharmacol. 260 (2020), 112832
    X. Gao, J. Cui, X. Zheng, et al., An investigation of the antidepressant action of xiaoyaosan in rats using ultra performance liquid chromatography-mass spectrometry combined with metabonomics, Phytother. Res. 27 (2013) 1074-1085
    C. Chai, B. Jin, Y. Yan, et al., Anti-depressant effect of Zhi-zi-chi decoction on CUMS mice and elucidation of its signaling pathway, J. Ethnopharmacol. 266 (2021), 113283
    Z. Liu, N. Zhou, T. Liu, et al., Progress in depression based on metabolomics, Chinese J. Pathophysiol. 36 (2020) 2264-2275
    H.M. Jia, M. Yu, L.Y. Ma, et al., Chaihu-Shu-Gan-San regulates phospholipids and bile acid metabolism against hepatic injury induced by chronic unpredictable stress in rat, J. Chromatogr. B. 1064 (2017) 14-21
    X. Li, X. Qin, J.Tian, et al., Integrated network pharmacology and metabolomics to dissect the combination mechanisms of Bupleurum chinense DC-Paeonia lactiflora Pall herb pair for treating depression, J. Ethnopharmacol. 264 (2021), 113281
    D. Kolar, L. Kleteckova, H. Brozka, et al., Mini-review: Brain energy metabolism and its role in animal models of depression, bipolar disorder, schizophrenia and autism, Neurosci. Lett. 760 (2021) 136003
    W. Ma, J. Song, H. Wang, et al., Chronic paradoxical sleep deprivation-induced depression-like behavior, energy metabolism and microbial changes in rats, Life Sci. 225 (2019) 88-97
    C. Chiarla, I. Giovannini, J. Siegel, Characterization of alpha-amino-n-butyric acid correlations in sepsis, J. Lab. Med. 158 (2011) 328-333
    J. Modica-Napolitano, P. Renshaw, Ethanolamine and phosphoethanolamine inhibit mitochondrial function in vitro: implications for mitochondrial dysfunction hypothesis in depression and bipolar disorder, Biol. Psychiatry. 55 (2004) 273-277
    T. Michel, D. Pulschen, J. Thome, The role of oxidative stress in depressive disorders, Curr. Pharm. Design. 18 (2012) 5890-2599
    X. Huang, W. Li, B. You, et al., Serum metabonomic dtudy on the antidepressant-like effects of ellagic acid in a chronic unpredictable mild stress-Induced mouse model, J. Agr. Food Chem. 68 (2020) 9546-9556
    C. Muller, M. Reichel, C. Muhle, et al., Brain membrane lipids in major depression and anxiety disorders, BBA- Mol. Cell Biol. L. 1851 (2015) 1052-1065
    T. Ali-Sisto, T. Tolmunen, E. Toffol, et al., Purine metabolism is dysregulated in patients with major depressive disorder, Psychoneuroendocrino. 70 (2016) 25-32
    W. Peng, G. Xiao, B. Li, et al., L-theanine activates the browning of white adipose tissue through the AMPK/α-Ketoglutarate/Prdm16 axis and ameliorates Diet-Induced obesity in mice, Diabetes. 70 (2021) 1458-1472
    • Relative Articles

  • Relative Articles

    • Supplements(0)
    • Cited By

  • Cited by

    Periodical cited type(11)

    1. Xu, R., Yu, H., Wang, Y. et al. Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract. Journal of Pharmaceutical Analysis, 2025, 15(2): 101101. doi:10.1016/j.jpha.2024.101101
    2. Yang, L., Liu, Z., Xiong, L. et al. Caenorhabditis elegans in the biological activity research of tea: From “little transparent” to “big star”. Journal of Functional Foods, 2025, 125: 106673. doi:10.1016/j.jff.2025.106673
    3. Jiang, M., Sha, Y., Zou, Y. et al. Integration of deep neural network modeling and LC-MS-based pseudo-targeted metabolomics to discriminate easily confused ginseng species. Journal of Pharmaceutical Analysis, 2025, 15(1): 101116. doi:10.1016/j.jpha.2024.101116
    4. Gao, Y., Zhou, T. Depressive disorder prevention by DIET crosslink: Diet, intestinal microbiota, enzyme and traits of metabolism. Trends in Food Science and Technology, 2024, 150: 104596. doi:10.1016/j.tifs.2024.104596
    5. Deng, X., Lin, Q., Zhu, S. et al. Effect of group counseling integrating tea-drinking on mental health improvement of college students | [茶饮团体心理辅导改善大学生心理健康状况效果]. Chinese Journal of School Health, 2024, 45(6): 826-830. doi:10.16835/j.cnki.1000-9817.2024184
    6. Wang, Z., Guo, S., Cai, Y. et al. Decoding active compounds and molecular targets of herbal medicine by high-throughput metabolomics technology: A systematic review. Bioorganic Chemistry, 2024, 144: 107090. doi:10.1016/j.bioorg.2023.107090
    7. Chen, J., Li, T., Huang, D. et al. Integrating UHPLC-MS/MS quantitative analysis and exogenous purine supplementation to elucidate the antidepressant mechanism of Chaigui granules by regulating purine metabolism. Journal of Pharmaceutical Analysis, 2023, 13(12): 1562-1576. doi:10.1016/j.jpha.2023.08.008
    8. Zhao, C., Cai, Z. Mass Spectrometry-Based Omics and Imaging Technique: A Novel Tool for Molecular Toxicology and Health Impacts. Reviews of Environmental Contamination and Toxicology, 2023, 261(1): 10. doi:10.1007/s44169-023-00032-2
    9. Liu, M., Ma, W., He, Y. et al. Recent Progress in Mass Spectrometry-Based Metabolomics in Major Depressive Disorder Research. Molecules, 2023, 28(21): 7430. doi:10.3390/molecules28217430
    10. Chen, C., Gong, W., Tian, J. et al. Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase. Journal of Pharmaceutical Analysis, 2023, 13(6): 640-659. doi:10.1016/j.jpha.2023.04.016
    11. Wang, W., Mu, Q., Feng, X. et al. Sweet Taste Receptor T1R3 Expressed in Leydig Cells Is Closely Related to Homeostasis of the Steroid Hormone Metabolism Profile. Journal of Agricultural and Food Chemistry, 2023, 71(20): 7791-7802. doi:10.1021/acs.jafc.3c01110

    Other cited types(0)

  • Created with Highcharts 5.0.7Amount of accessChart context menuAbstract Views, HTML Views, PDF Downloads StatisticsAbstract ViewsHTML ViewsPDF Downloads2024-052024-062024-072024-082024-092024-102024-112024-122025-012025-022025-032025-0401020304050
    Created with Highcharts 5.0.7Chart context menuAccess Class DistributionFULLTEXT: 31.1 %FULLTEXT: 31.1 %META: 64.6 %META: 64.6 %PDF: 4.3 %PDF: 4.3 %FULLTEXTMETAPDF
    Created with Highcharts 5.0.7Chart context menuAccess Area Distribution其他: 14.5 %其他: 14.5 %Belarus: 0.4 %Belarus: 0.4 %Canada: 0.9 %Canada: 0.9 %China: 63.4 %China: 63.4 %Colombia: 0.4 %Colombia: 0.4 %Egypt: 0.8 %Egypt: 0.8 %Gate City: 0.1 %Gate City: 0.1 %India: 0.8 %India: 0.8 %Macau: 0.6 %Macau: 0.6 %Netherlands: 0.8 %Netherlands: 0.8 %Poland: 0.8 %Poland: 0.8 %Russian Federation: 0.8 %Russian Federation: 0.8 %Saudi Arabia: 0.5 %Saudi Arabia: 0.5 %United Kingdom: 1.4 %United Kingdom: 1.4 %United States: 13.6 %United States: 13.6 %麦地那: 0.4 %麦地那: 0.4 %其他BelarusCanadaChinaColombiaEgyptGate CityIndiaMacauNetherlandsPolandRussian FederationSaudi ArabiaUnited KingdomUnited States麦地那

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article has an altmetric score of 1
    Article views (511) PDF downloads(34) Cited by(11)
    Proportional views
    Related

    Copyright © Journal of Pharmaceutical Analysis

    E-mail: jpasubmit@126.com;  jpaeditor@xjtu.edu.cn   Tel:+86-029-88960092

    Address: Western China Science and Technology Innovation Harbour, Xixian New Area, Xi’an, 712000, China

    Email alert RSS

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return