茶叶成分EGCG与L-theanine联合应用的神经保护作用研究

doi:10.13305/j.cnki.jts.20240918.001

Abstract

Abstract: Differentiated neurons need to maintain axonal growth and function in a quiescent state. Previous studies have shown that epigallocatechin gallate (EGCG) and L-theanine can maintain the quiescent state of neurons and have neurorestorative effects, although the specific mechanisms are still unclear. In the Aβ_25-35-induced PC12 cell damage model, combined treatment with EGCG and L-theanine improved cell metabolism and repair capacity, enhanced cell viability and showed a significant synergistic effect. Transcriptomic and network pharmacological analyses indicate that EGCG mainly maintains the quiescent state of cells by inhibiting oxidative stress, regulating fatty acid metabolism, and mitigating amyloid protein toxicity stress. L-theanine promotes axonal growth and regulates neuronal metabolism and synaptic function. The combined application of both compounds results in a broader and milder regulation of cellular networks, reducing cellular stress. This study provided theoretical support for the neuroprotective effects of tea and its value in an aging society.

Key words: EGCG, L-theanine, neuroprotection, network pharmacology, transcriptome, joint analysis

CLC Number:

DING Shuqia, XIE Xinya, LIU Zhusheng, LIAO Xianjun, LIU Zhonghua, CAI Shuxian. A Study on the Neuroprotective Effects of Combined EGCG and L-Theanine from Tea Leaves[J]. Journal of Tea Science, 2024, 44(5): 779-792.

References

[1] Powers E T, Morimoto R I, Dillin A, et al.Biological and chemical approaches to diseases of proteostasis deficiency[J]. Annual Review of Biochemistry, 2009, 78(1): 959-991.
[2] Taylor R C, Dillin A.Aging as an event of proteostasis collapse[J]. Cold Spring Harbor Perspectives in Biology, 2011, 3(5): 328-342. doi: 10.1101/cshperspect.a004440.
[3] Mok K H, Pettersson J, Orrenius S, et al.HAMLET, protein folding, and tumor cell death[J]. Biochemical & Biophysical Research Communications, 2007, 354(1): 1-7.
[4] Chiti F, Dobson C M.Protein misfolding, functional amyloid, and human disease[J]. Annual Review of Biochemistry, 2006, 75(1): 333-366.
[5] Soto C.Alzheimer's and prion disease as disorders of protein conformation: implications for the design of novel therapeutic approaches[J]. Journal of Molecular Medicine, 1999, 77(5): 412-418.
[6] Wallace R A, Dalton A J.What can we learn from study of Alzheimer's disease in patients with down syndrome for early-onset Alzheimer's disease in the general population?[J]. Alzheimer's Reseach &Therapy, 2011, 3(2): 13. doi: 10.1186/alzrt72.
[7] Asaad M, Lee J H. A guide to using functional magnetic resonance imaging to study Alzheimer's disease in animal models [J]. Disease Models and Mechanisms, 2018, 11(5): dmm031724. doi: 10.1242/dmm.031724.
[8] Sheng J G, Zhou X Q, Mrak R E, et al.Progressive neuronal injury associated with amyloid plaque formation in Alzheimer disease[J]. Journal of Neuropathology and Experimental Neurology, 1998(7): 714-717.
[9] Inglis F.The tolerability and safety of cholinesterase inhibitors in the treatment of dementia[J]. International Journal of Clinical Practice Supplement, 2002, 127(127): 45.doi: .1016/S0924-8579(02)00114-0.
[10] Pervin M, Unno K, Takagaki A, et al.Function of green tea catechins in the brain: epigallocatechin gallate and its metabolites[J]. International Journal of Molecular Sciences, 2019, 20(15): 3630. doi: 10.3390/ijms20153630.
[11] Afzal O, Dalhat M H, Altamimi A S A, et al. Green tea catechins attenuate neurodegenerative diseases and cognitive deficits[J]. Molecules, 2022, 27(21): 7604. doi: 10.3390/molecules27217604.
[12] Youn K, Ho C T, Jun M.Multifaceted neuroprotective effects of (-)-epigallocatechin-3-gallate (EGCG) in Alzheimer's disease: an overview of pre-clinical studies focused onβ-amyloid peptide[J]. Food Science and Human Wellness, 2022, 11(3): 11. doi:10.1016/j.fshw.2021.12.006.
[13] Miren E, Amanda C, Patricia R M, et al.Epigallocatechin-3-gallate (EGCG) improves cognitive deficits aggravated by an obesogenic diet through modulation of unfolded protein response in APPswe/PS1dE9 mice[J]. Molecular Neurobiology, 2020, 57(4): 1814-1827.
[14] Walker J M, Klakotskaia D, Ajit D, et al.Beneficial effects of dietary EGCG and voluntary exercise on behavior in an Alzheimer's disease mouse model[J]. Journal of Alzheimers Disease, 2015, 44(2): 561-572.
[15] Unno K, Pervin M, Nakagawa A, et al.Blood-brain barrier permeability of green tea catechin metabolites and their neuritogenic activity in human neuroblastoma SH-SY5Y cells[J]. Molecular Nutrition & Food Research, 2017, 61(12): 1700294. doi:10.1002/mnfr.201700294.
[16] Pervin M, Unno K, Nakagawa A, et al.Blood brain barrier permeability of (-)-epigallocatechin gallate, its proliferation-enhancing activity of human neuroblastoma SH-SY5Y cells, and its preventive effect on age-related cognitive dysfunction in mice[J]. Biochemistry and Biophysics Reports, 2017, 9: 180-186.
[17] Du A Z, Rong D, Cyrollah L, et al.Epigallocatechin-3-gallate, an active ingredient of traditional Chinese medicines, inhibits the 3CLpro activity of SARS-CoV-2[J]. International Journal of Biological Macromolecules, 2021, 176(1): 1-12.
[18] Wu Z, Yu W, Ni W, et al.Improvement of obesity by Liupao tea is through the IRS-1/PI3K/AKT/GLUT4 signaling pathway according to network pharmacology and experimental verification[J]. Phytomedicine, 2023, 110: 154633. doi:10.1016/j.phymed.2022.154633
[19] Gong Z, Liu Q, Lin L, et al.L-Theanine prevents ETEC-induced liver damage by reducing intrinsic apoptotic response and inhibiting ERK1/2 and JNK1/2 signaling pathways[J]. European Journal of Pharmacology, 2017, 818: 184-190.
[20] Tsai, Wen H, Chung H, et al. L-Theanine inhibits proinflammatory PKC/ERK/ICAM-1/IL-33 signaling, apoptosis, and autophagy formation in substance P-Induced hyperactive bladder in rats[J]. Neurourology and Urodynamics, 2017, 36(2): 297-307.
[21] Unno T, Suzuki Y, Kakuda T, et al.Metabolism of theanine, gamma-glutamylethylamide, in rats[J]. Journal of Agricultural and Food Chemistry, 1999, 47(4): 1593-1596.
[22] Nedergaard M, Takano T, Hansen A J.Beyond the role of glutamate as a neurotransmitter[J]. Nature Reviews Neuroscience, 2002, 3(9): 748-755.
[23] 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.
[24] Lipinski C A, Lombardo F, Dominy B W, et al.Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings[J]. Advanced Drug Delivery Reviews, 2001, 46(1/2/3): 3-26.
[25] Daina A, Michielin O, Zoete V.SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules[J]. Scientific Reports. 2017, 7: 42717. doi: 10.1038/srep42717.
[26] Wang Y X, Zhang S, Li F C, et al.Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics[J]. Nucleic Acids Research, 2020, 48(D1): 1031-1041.
[27] Bader G D, Hogue C W V. An automated method for finding molecular complexes in large protein interaction networks[J]. BMC Bioinformatics, 2003, 4: 2. doi: 10.1186/1471-2105-4-2.
[28] Zhou Y, Zhou B, Pache L, et al.Metascape provides a biologist-oriented resource for the analysis of systems-level datasets[J]. Nature Communications, 2019, 10(1): 1523. doi: 10.1038/s41467-019-09234-6.
[29] Papassotiropoulos A, Gerhards C, Heck A, et al.Human genome-guided identification of memory-modulating drugs[J]. Proceedings of the National Academy of Sciences, 2013, 110(46): 4369-4374.
[30] Gonçalves P B, Sodero A C R, Cordeiro Y. Green tea epigallocatechin-3-gallate (EGCG) targeting protein misfolding in drug discovery for neurodegenerative diseases[J]. Biomolecules, 2021, 11(5): 767. doi: 10.3390/biom11050767.
[31] 刘宝贵, 陈致印, 张杨玲, 等. L-茶氨酸与表没食子儿茶素没食子酸酯预防肥胖及高胆固醇血症的协同调节作用[J]. 食品工业科技, 2022, 43(3): 341-350.
Liu B G, Chen Z Y, Zhang Y L,et al.Synergistic moderating effects of L-theanine and EGCG for the prevention of obesity and Hypercholesterolemia[J]. Science and Technology of Food Industry, 2022, 43(3): 341-350.
[32] 彭影琦, 袁冬寅, 林玲, 等. 表没食子儿茶素没食子酸酯对L-茶氨酸调节小鼠血清及肠道游离氨基酸的影响[J]. 食品科学, 2020, 41(19): 154-160.
Peng Y Q, Yuan D Y, Lin L, et al.Influence of epigallocatechin gallate on the regulation effect of L-theanine on eerum and intestinal free amino acids in mice[J]. Food Science, 2020, 41(19): 154-160.
[33] Bianchi V E, Herrera P F, Laura R.Effect of nutrition on neurodegenerative diseases. A systematic review[J]. Nutr Neurosci, 2021, 24(10): 810-834.
[34] Zhang W, Bai Y, Wang Y, et al.Polypharmacology in drug discovery: a review from systems pharmacology perspective[J]. Current Pharmaceutical Design, 2016, 22(21): 3171-3181.
[35] Xie X, Wan J, Zheng X, et al.Synergistic effects of epigallocatechin gallate and L-theanine in nerve repair and regeneration by anti-amyloid damage, promoting metabolism, and nourishing nerve cells[J]. Frontiers in Nutrition, 2022, 9: 951415.doi: 10.3389/fnut.2022.951415.
[36] Mandel S, Amit T, Reznichenko L, et al.Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders[J]. Molecular Nutrition & Food Research, 2006, 50(2): 229-234.
[37] Unno K, Yamada H, Iguchi K, et al.Anti-stress effect of green tea with lowered caffeine on humans: a pilot study[J]. Biological & Pharmaceutical Bulletin, 2017, 40(6): 902. doi: 10.1248/bpb.b17-00141.
[38] Kim T I, Lee Y K, Park S G, et al.L-Theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-kappaB pathways[J]. Free Radical Biology and Medicine, 2009, 47(11): 1601-1610.
[39] Morley J E, Armbrecht H J, Farr S A, et al.The senescence accelerated mouse (SAMP8) as a model for oxidative stress and Alzheimer's disease[J]. Biochim Biophys Acta, 2012, 1822(5): 650-656

A Study on the Neuroprotective Effects of Combined EGCG and L-Theanine from Tea Leaves

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