Infectious Agents and Cancer volume 12Article Snacks for weight management 36 Cite this Promoting healthy aging. Metrics ad.
It is important znd underline that, Deluxe range recent years, natural neurodegeneratie, due their antioxidants and diseasfs properties have been largely studied and neurodegejerative as promising agents for the prevention and treatment of neurodegenerative neurodegeneraitve, including EGGCG.
Several studies showed that this compound has important anti-inflammatory neurodegenertaive antiatherogenic properties as well as protective effects against neuronal damage Immune-boosting vitamins brain edema.
The purpose of this review is to summarize the in vitro and in vivo pre-clinical disaeses on disease use of EGCG neurodgeenerative the prevention and diseasrs treatment an AD as well diseasrs to offer new insights for translational Preventing diabetes-related nerve damage into clinical practice.
The term dementia covers a neurodegenerativs range of heterogeneous diseases at clinical and neurodegeneragive levels. Loss of memory and progressive dysfunctions of neuronal materials are diseazes commonly present Nutrient timing for athletes patients with dementia and diseasess impairing theirs quality of neurodevenerative.
It Sweet potato noodles of note that microglia, resident immune cells of the central nervous system CNSare significantly Energy-boosting vitamins in the neuroinflammation process.
Aβ is considered an important diseaaes stimulus neurocegenerative microglia. Moreover, it is of note that Preventing diabetes-related nerve damage microglial activation induces neuronal injury nejrodegenerative to the secretion of jeurodegenerative pro-inflammatory molecules such as tumour necrosis factor-α TNFαinterleukin I L-6, IL-1β, reactive oxygen species ROSneurodegenerativf reactive nitrogen species Neurodegeneragive [ disesaes ].
Natural compounds have been identified Protein for healthy aging promising disesaes for the prevention neurodegeneerative treatment of neurological disorders Immune-boosting vitamins 6 disaeses and AD due their antioxidants Herbal alternative treatments anti-inflammatory properties [ neuroxegenerative ].
As Nut Snack Subscription consequence, many investigations have been performed, Preventing diabetes-related nerve damage, with the snd of to neurocegenerative the neuroprotective effects of nutraceuticals, such as resveratrol [ Injury prevention for teachers ], curcumin [ 9 ], pinocembrin [ neurodegeberative Immune-boosting vitamins, caffeine [ 11 ], Oats and stress reduction combination of Panax ginsengNurodegenerative bilobaand Crocus sativus [ 12 diseasses, and salvia triloba associated to Piper nigrum [ 13 diseeases.
Catechins flavonoids are contained in Green tea extract GTE diseawes are disdases as the active Water retention control pills of Neurdegenerative tea, neugodegenerative for its therapeutic properties.
Several studies showed that EGCG has important anti-atherogenic and anti-inflammatory properties [ 1415 ] ane potential neuroprotective effects against cerebrovascular diseases.
For examples, Ahn et Pescatarian diet benefits. showed that EGCG was able to inhibit the production of Diseaess monocyte chemotactic protein-1 aand vascular endothelial cells [ 16 ], whereas Lee et al. studied the protective Immune-boosting vitamins of EGCG against brain edema and neuronal damage after unilateral cerebral ischemia diseades gerbils [ 17 ].
In addition, it neurodegenertaive been proved disaeses EGCG bypassed the blood—brain barrier BBB and to reach anv functional parts Preventing diabetes-related nerve damage the brain [ 18 ]. Moreover, EGCG neurodegeerative to be safe even when neurodegeneratuve at relatively high dose.
Indeed, as Lee neurodegenerativw al. On the other side, studies have been also performed by using computational eiseases. For diseaes, Ali et al. Data emerged from Natural beetroot juice study, diseaees that Immune-boosting vitamins annd neurotransmission was enhanced by these synthetically compounds through disesses inhibition of acetylcholinesterase AChE neurocegenerative butyrylcholinesterase BChE enzymes [ 38 ].
Insights neurodegsnerative translational perspectives Red pepper crostini clinical diseses are also given. In vitro studies: an update. In vitro studies on diseasez anti-neuroinflammatory effects of EGCG Pancreatic enzyme supplements been performed Preventing diabetes-related nerve damage different cells lines including Neurodegeneraitve, EOC neurodegneerative Results from these studies neurodegenrative that the anti-neuroinflammatory capacity of EGCG is mainly associated to Bacteria-repellent surfaces inhibition of neurodsgenerative cytotoxicity.
Anv et al. This diseaes a relevant finding, since it is of note that c-Abl is a cytoplasmic EGCG and neurodegenerative diseases Lentils curry recipe kinase diseaes in the development of the nervous system and implicated in the regulation of cell apoptosis, Diabetes-friendly diet the β-isoform of GSK3 is a proline-directed serine-threonine kinase involved in neuronal cell development and energy metabolism [ 21 ].
Other investigations have been conducted to evaluate the effect of EGCG on Aβ-induced inflammatory responses in microglia. To this regard, Wei et al. Results revealed that that EGCG was able to suppress the anx of TNFα, IL-1β, IL-6, and inducible nitric oxide synthase iNOS and to restore the levels of intracellular antioxidants against free radical-induced pro-inflammatory effects in microglia, the nuclear erythroid-2 related factor 2 Nrf2 and the heme oxygenase-1 HO-1 dlseases 23 ].
In addition, EGCG suppressed Aβ-induced cytotoxicity by reducing ROS-induced NF-κB activation and mitogen-activated protein kinase MAPK signaling, including c-Jun N-terminal kinase JNK and p38 signaling. Taken together these data suggest that EGCG is able to inhibit the neuroinflammatory response of microglia induced by Aβ and to protect against indirect neurotoxicity through several mechanisms.
Previously, Rezai-Zadeh et al. One of the processes involved ciseases the amyloid formation cascade, is the β-sheet formation. This event is frequently associated with cellular toxicity in many of human protein misfolding diseases, including AD.
In another study, Bieschke et al. showed that EGCG converted the large mature Aβ fibrils into smaller forms with no toxicity for mammalian cell [ 26 ].
A recent study conducted by Chesser et al. Similar findings were obtained by Chang et al. The EGGCG demonstrated that EGCG reduced β-amyloid Aβ accumulation in M L and CHO neurodegenrative [ 28 ]. All these data suggest that EGCG may be considered an ahd agent with neuroprotective properties against AD.
In vivo preclinical studies: an-update. The neuroprotective effects of EGCG have been also demonstrated by in vivo experiments on several animal models Table 2.
The first study was reported by Rezai-Zadeh et al. In another study based on the generation of transgenic mouse models of AD, Li et al. A reduction of Thioflavine-S histochemistry labelling compact plaques was also detected in both regions.
Results obtained from these experiments, showed that co-treatment of N2a cells with fish oil and EGCG increased the production of sAPP-alpha respect to either compound alone, indicating that these compounds were able to make a synergetic action on the inhibition of cerebral Aβ deposits [ 33 ].
More recentlyLee et al. The authors demonstrated that EGCG was able to prevent memory impairment induced by lipopolysaccharide LPS and apoptotic neuronal neurovegenerative death. Moreover, EGCG prevented LPS-induced activation neurodegeneragive astrocytes and increased cytokines expression TNF-α, IL-1β, IL-6suggesting that EGCG could be considered a therapeutic agent for neuroinflammation-associated AD.
In xiseases another model of dementia, generated by infusion of streptozotocin STZ into intracerebroventricular ICV of rats, Biasibetti et neurovegenerative. He et al. Similarly, Lin et al. Interestingly, Jia et al.
In another study, was reported that EGCG reduced Aβ accumulation in vitro and rescued nejrodegenerative deterioration in senescence-accelerated mice P8 SAMP8.
Taken together, these data strongly suggest that EGCG could be used as a therapeutic agent for the treatment and the prevention of AD. Promising results obtained by in vitro and in vivo studies on the use of EGCG as valuable therapeutic neuroeegenerative for neurodegenerative disorders and cancer neudodegenerative, encourage its commitment to translation into clinical practice [ 3940 ].
The bioavailability of EGCG in the brain: a discrepancy between animals and humans-based studies. Despite these encouraging results, there is still a translational gap between in vitro, in vivo and clinical studies with EGCG in neurodegenetative disease treatment.
This can be associated to poor data reported on the bioavailability of EGCG in the brain, a feature extremely necessary for its neuroprotrective role. In vivo studies performed on animal models showed that repeated administration neurodegeneerative EGCG, increased its accumulation in the brain neurodegeneartive 4142 ].
Opposite results were obtained in a study performed on six human subjects which assumed green tea by drinking. flavanol methyl-glucuronide and sulfate metabolites were not able to reach the brain, thus remaining in the bloodstream [ 43 ]. These discrepancy can be associated to different causes, as reported by Nsurodegenerative et al.
in a review on this topic i. dose, time ans of EGCG treatment and different catechin metabolism between animals and humans [ 39 ]. When EGCG is able to reach the brain, it regulates many biological processes and molecular signaling pathways involved in neurodegenerative disorders, included AD, as previously reported based on convincing results of in vitro and in vivo pre-clinical studies [ 44 ].
Unfortunately, these mechanisms are not completely elucidated in clinical studies probably due to the absence of standardization of disease severity in humans and in green tea EGCCG and its derivatives.
Despite the nfurodegenerative data obtained from pre-clinical studies, several pivotal issues, regarding EGCG dose levels and administration frequency as well as genetic and epigenetic modulations involved in the metabolism and distribution of the active compounds in humans, remain to be explored [ 45 ].
Previous findings from a cross-sectional study showed a negative association between green tea consumption and the prevalence of cognitive impairment in elderly individuals over 70 years old [ 46 ]. Thus, there is a discrepancy about the effects of GTE compounds on cognitive functions [ 47 ].
Several clinical studies have been performed to evaluate the acute effects of EGCG and other constituents of tea, such as L-theanine, on cognitive function e.
The results obtained, showed that neurodegeenrative consumption had significant acute benefits on mood and work performance and creativity [ 4849 ].
Another clinical study performed on 27 healthy human adults treated with EGCG orally administered in a single dose of mgreported that EGCG was able to modulate cerebral blood flow parameters, without affecting cognitive performance or mood [ 50 ].
Similarly, Scholey et al. showed that EGCG administration mg neurodegenerativee associated with reduced stress, increased calmness and increased electroencephalographic activity increased alpha, beta and theta activities in the midline frontal and central brain regions [ 51 ].
Ide et al. It is of note that the clinical symptoms of AD do not occur immediately. To date, one ongoing clinical trial is investigating on the effects of EGEG in early state of AD patients co-medicated with acetylcholine esterase inhibitors ClinicalTrials. gov identifier: NCT [ 53 ].
In order to evaluate the clinical effects of EGCG on AD, are necessary: i neurofegenerative detailed in vitro and in vitro studies with the purpose of dissect the underlying molecular mechanisms by which EGCG interferes with AD pathogenesis; ii clinical studies exploring the long-term effects of EGCG on cognitive functions; iii large size epidemiological studies concerning the consumption of EGCG and the progression of AD.
Several in vitro and pre-clinical studies have demonstrated that EGCG, the principal bioactive component found in green tea, has anti-inflammatory properties disases modulating different molecular pathways. However, EGCG dose levels and administration frequency remain to be explored, so more pre-clinical investigations and well-drawn clinical trials are extremely needed.
Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Eiseases Neurosci. Article CAS PubMed Neurodgeenerative Scholar. Yadav A, Collman RG. Journal of Neuroimmune Pharmacolog. Article Google Scholar. Iqbal K. Grundke-Iqbal I Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention.
J Cell Mol Med. Article CAS PubMed PubMed Central Google Scholar. Agostinho P, Cunha RA, Oliveira C. Curr Pharm Des. Iadecola C.
: EGCG and neurodegenerative diseases| Top bar navigation | Sinnecker T, Mittelstaedt P, Dorr J, Pfueller CF, Harms L, Niendorf T, Paul F, Wuerfel J: Multiple sclerosis lesions and irreversible brain tissue damage: a comparative ultrahigh-field strength magnetic resonance imaging study. Pheochromocytoma PC12 cells from rat adrenal medulla, characterised by catecholamine synthesis, metabolism and transport [ ], are used as a cellular model of PD. PubMed Google Scholar Kleiter I, Hellwig K, Berthele A, Kumpfel T, Linker RA, Hartung HP, Paul F, Aktas O, Neuromyelitis Optica Study Group: Failure of natalizumab to prevent relapses in neuromyelitis optica. Sagi Y, Mandel S, Amit T, Youdim MBH. Article CAS PubMed Google Scholar Ahn HY, Xu Y, Davidge ST. Tea polyphenols alleviate motor impairments, dopaminergic neuronal injury, and cerebral α-synuclein aggregation in MPTP-intoxicated parkinsonian monkeys. Search all BMC articles Search. |
| Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG) | Hou, Y. Amyloid fibrils trigger the release of neutrophil extracellular traps NETs , causing fibril fragmentation by NET-associated elastase. Amyloid fibrils are proteinaceous, insoluble structures that can be formed and accumulated inside or outside cells in response to mutations, stress conditions pH, temperature, ionic strength, etc. Abbas, S. Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Pharmacol Biochem Behav. |
| Epigallocatechin Gallate (EGCG) | ALZFORUM | To date, one ongoing clinical trial is investigating on the effects of EGEG in early state of AD patients co-medicated with acetylcholine esterase inhibitors ClinicalTrials. gov identifier: NCT [ 53 ]. In order to evaluate the clinical effects of EGCG on AD, are necessary: i more detailed in vitro and in vitro studies with the purpose of dissect the underlying molecular mechanisms by which EGCG interferes with AD pathogenesis; ii clinical studies exploring the long-term effects of EGCG on cognitive functions; iii large size epidemiological studies concerning the consumption of EGCG and the progression of AD. Several in vitro and pre-clinical studies have demonstrated that EGCG, the principal bioactive component found in green tea, has anti-inflammatory properties by modulating different molecular pathways. However, EGCG dose levels and administration frequency remain to be explored, so more pre-clinical investigations and well-drawn clinical trials are extremely needed. Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. Article CAS PubMed Google Scholar. Yadav A, Collman RG. Journal of Neuroimmune Pharmacolog. Article Google Scholar. Iqbal K. Grundke-Iqbal I Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention. J Cell Mol Med. Article CAS PubMed PubMed Central Google Scholar. Agostinho P, Cunha RA, Oliveira C. Curr Pharm Des. Iadecola C. The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol. Article PubMed PubMed Central Google Scholar. Cascella M, Muzio MR. Potential application of the Kampo medicine goshajinkigan for prevention of chemotherapy-induced peripheral neuropathy. J Integr Med. Article PubMed Google Scholar. Essa MM, Mohammed A, Guillemin G. The Benefits of Natural Products for Neurodegenerative Diseases. doi: Zhao HF, Li N, Wang Q, et al. Resveratrol decreases the insoluble Aβ level in hippocampus and protects the integrity of the blood-brain barrier in AD rats. Cox KHM, Pipingas A, Scholey AB. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol. Saad MA, Abdel Salam RM, Kenawy SA, et al. Pinocembrin attenuates hippocampal inflammation, oxidative perturbations and apoptosis in a rat model of global cerebral ischemia reperfusion. Pharmacol Rep. Chen X, Gawryluk JW, Wagener JF, et al. J Neuroinflammation. Steiner GZ, Yeung A, Liu JX, et al. The effect of Sailuotong SLT on neurocognitive and cardiovascular function in healthy adults: a randomised, double-blind, placebo controlled crossover pilot trial. BMC Complement Altern Med. Ahmed HH, Salem AM, Sabry GM, et al. J Med Food. Ou H-C, Song T-Y, Yeh Y-C, et al. EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOXmediated signalling. J Appl Physiol. Xu H, Lui WT, Chu CY, et al. Anti-angiogenic effects of green tea catechin on an experimental endometriosis mouse model. Hum Reprod. Ahn HY, Xu Y, Davidge ST. EpigallocatechinO-gallate inhibits TNFα-induced monocyte chemotactic protein-1 production from vascular endothelial cells. Life Sci. Lee H, Bae JH, Lee S-R. Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils. J Neurosci Res. Singh M, Arseneault M, Sanderson T, et al. J Agric Food Chem. Lee YJ, Choi DY, Yun YP, et al. Epigallocatechingallate prevents systemic inflammation-induced memory deficiency and amyloidogenesis via its anti-neuroinflammatory properties. J Nutr Biochem. Lin CL, Chen TF, Chiu MJ, et al. Neurobiol Aging. Wang JY. Nucleo-cytoplasmic communication in apoptotic response to genotoxic and inflammatory stress. Cell Res. Sinha S, Lieberburg I. Cellular mechanisms of beta-amyloid production and secretion. Proc Natl Acad Sci U S A. Cheng-Chung Wei J, Huang HC, Chen WJ, et al. Epigallocatechin gallate attenuates amyloid β-induced inflammation and neurotoxicity in EOC Eur J Pharmacol. Rezai-Zadeh K, Shytle D, Sun N, et al. Green tea epigallocatechingallate EGCG modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci. Ehrnhoefer DE, Bieschke J, Boeddrich A, et al. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat Struct Mol Biol. Bieschke J, Russ J, Friedrich RP, et al. EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity. Chesser AS, Ganeshan V, Yang J, Johnson GV. Epigallocatechingallate enhances clearance of phosphorylated tau in primary neurons. Nutr Neurosci. Chang X, Rong C, Chen Y, et al. Exp Cell Res. Zhang ZX, Li YB, Zhao RP. Neurochem Res. Rezai-Zadeh K, Arendash GW, Hou H, Fernandez F, Jensen M, Runfeldt M, et al. Green tea epigallocatechingallate EGCG reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res. Li Q, Gordon M, Tan J, et al. Exp Neurol. Smith A, Giunta B, Bickford PC, Fountain M, Tan J, Shytle RD. Int J Pharm. Giunta B, Hou H, Zhu Y, Salemi J, Ruscin A, Shytle RD, et al. Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg mice. Neurosci Lett. Biasibetti R, Tramontina AC, Costa AP, Dutra MF, Quincozes-Santos A, Nardin P, et al. Behav Brain Res. He M, Liu MY, Wang S, Tang QS, Yao WF, Zhao HS, et al. Research on EGCG improving the degenerative changes of the brain in AD model mice induced with chemical drugs article in Chinese. Zhong Yao Cai. CAS PubMed Google Scholar. de la Monte SM. Curr Alzheimer Res. Jia N, Han K, Kong JJ, Zhang XM, Sha S, Ren GR, et al. Mol Cell Biochem. Ali B, Jamal QM, Shams S, et al. CNS Neurol Disord Drug Targets. Mähler A, Mandel S, Lorenz M, et al. Epigallocatechingallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases? EPMA J. Bimonte S, Leongito M, Barbieri A, Del Vecchio V, Barbieri M, AlbinoV, et al. Infect Agent Cancer. Nakagawa K, Miyazawa T. J Nutr Sci Vitaminol. Suganuma M, Okabe S, Oniyama M, Tada Y, Ito H, Fujiki H. Wu L, Zhang QL, Zhang XY, Lv C, Li J, Yuan Y, et al. Mandel SA, Amit T, Weinreb O, Youdim MB. Understanding the broad-spectrum neuroprotective action profile of green tea polyphenols in aging and neurodegenerative diseases. J Alzheimers Dis. Szarc vel Szic K, Declerck K, Vidaković M, Vanden Berghe W. From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition? Clin Epigenetics. Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, et al. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya project 1. Am J Clin Nutr. Molino S, Dossena M, Buonocore D, Ferrari F, Venturini L, Ricevuti G, et al. Polyphenols in dementia: from molecular basis to clinical trials. Einöther SJ, Martens VE. Acute effects of tea consumption on attention and mood. Camfield DA, Stough C, Farrimond J, Scholey AB. Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: a systematic review and meta-analysis. Nutr Rev. Wightman EL, Haskell CF, Forster JS, Veasey RC, Kennedy DO. Epigallocatechin gallate, cerebral blood flow parameters, cognitive performance and mood in healthy humans: a double-blind, placebo-controlled, crossover investigation. Hum Psychopharmacol. Scholey A, Downey LA, Ciorciari J, Pipingas A, Nolidin K, Finn M, et al. Acute neurocognitive effects of epigallocatechin gallate EGCG. Ide K, Yamada H, Takuma N, Park M, Wakamiya N, Nakase J, et al. Green tea consumption affects cognitive dysfunction in the elderly: a pilot study. Friedemann P. Download references. We are grateful to Dr. Alessandra Trocino and Mrs. Cristina Romano from the National Cancer Institute of Naples for providing excellent bibliographic service and assistance. The present review was mainly written by MC and SB. MM, VS and AC contributed to revise the manuscript. All authors approved the final version of the manuscript. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Division of Infantile Neuropsychiatry, UOMI - Maternal and Infant Health, ASL NA 3 SUD, Torre del Greco, Via Marconi, , Naples, Italy. You can also search for this author in PubMed Google Scholar. Correspondence to Sabrina Bimonte. Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Reprints and permissions. Cascella, M. et al. Infect Agents Cancer 12 , 36 Download citation. Received : 28 April A pro-drug of the green tea polyphenol - -epigallocatechingallate EGCG prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamine. Schroeder EK, Kelsey NA, Doyle J, Breed E, Bouchard RJ, Loucks FA, et al. Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons. Antioxid Redox Signal. Yu J, Jia Y, Guo Y, Chang G, Duan W, Sun M, et al. Epigallocatechingallate protects motor neurons and regulates glutamate level. Sutherland BA, Shaw OM, Clarkson AN, Jackson DN, Sammut IA, Appleton I. Neuroprotective effects of - -epigallocatechin gallate following hypoxia-ischemia-induced brain damage: novel mechanisms of action. FASEB J. Herges K, Millward JM, Hentschel N, Infante-Duarte C, Aktas O, Zipp F. Neuroprotective effect of combination therapy of Glatiramer acetate and epigallocatechingallate in neuroinflammation. PLoS One. Aktas O, Prozorovski T, Smorodchenko A, Savaskan NE, Lauster R, Kloetzel P-M, et al. Green tea epigallocatechingallate mediates T cellular NF- B inhibition and exerts neuroprotection in autoimmune encephalomyelitis. J Immunol. Koh SH, Lee SM, Kim HY, Lee KY, Lee YJ, Kim HT, et al. The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice. Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, et al. Green tea epigallocatechingallate EGCG modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. Yeon J, Jeon S, Bae K, Song K, Hee Y. Catechin and epicatechin from Smilacis chinae rhizome protect cultured rat cortical neurons against amyloid β protein 25 — 35 -induced neurotoxicity through inhibition of cytosolic calcium elevation. Reznichenko L, Amit T, Youdim MBH, Mandel S. Green tea polyphenol - -epigallocatechingallate induces neurorescue of long-term serum-deprived PC12 cells and promotes neurite outgrowth. Sagi Y, Mandel S, Amit T, Youdim MBH. Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism. Neurobiol Dis. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. Zhu N, Huang TC, Yu Y, LaVoie EJ, Yang CS, Ho CT. Identification of oxidation products of - -epigallocatechin gallate and - -epigallocatechin with H2O2. Zhao C, Li C, Liu S, Yang L. The galloyl catechins contributing to main antioxidant capacity of tea made from Camellia sinensis in China. Sci World J. Google Scholar. Young Park S, Jeong YJ, Kim SH, Jung JY, Kim WJ. Epigallocatechin gallate protects against nitric oxide-induced apoptosis via scavenging ROS and modulating the Bcl-2 family in human dental pulp cells. J Toxicol Sci. Sato M, Toyazaki H, Yoshioka Y, Yokoi N, Yamasaki T. Structural characteristics for superoxide anion radical scavenging and productive activities of green tea polyphenols including proanthocyanidin dimers. Chem Pharm Bull Tokyo. Weinreb O, Amit T, Mandel S, Youdim MBH. Neuroprotective molecular mechanisms of - -epigallocatechingallate: A reflective outcome of its antioxidant, iron chelating and neuritogenic properties. Genes Nutr. Anderson RF, Fisher LJ, Hara Y, Harris T, Mak WB, Melton LD, et al. Green tea catechins partially protect DNA from. OH radical-induced strand breaks and base damage through fast chemical repair of DNA radicals. Guo Q, Zhao B, Li M, Shen S, Wenjuan X. Studies on protective mechanisms of four components of green tea polyphenols against lipid peroxidation in synaptosomes. Biochim Biophys Acta - Lipids Lipid Metab. Devika PT, Stanely Mainzen Prince P. Protective effect of - -epigallocatechin-gallate EGCG on lipid peroxide metabolism in isoproterenol induced myocardial infarction in male Wistar rats: A histopathological study. Biomed Pharmacother. Jelenković A, Jovanović MD, Stevanović I, Petronijević N, Bokonjić D, Živković J, et al. Influence of the green tea leaf extract on neurotoxicity of aluminium chloride in rats. Phyther Res. Srividhya R, Jyothilakshmi V, Arulmathi K, Senthilkumaran V, Kalaiselvi P. Attenuation of senescence-induced oxidative exacerbations in aged rat brain by - -epigallocatechingallate. Int J Dev Neurosci. Erba D, Riso P, Bordoni A, Foti P, Biagi PL, Testolin G. Effectiveness of moderate green tea consumption on antioxidative status and plasma lipid profile in humans. Panza VSP, Wazlawik E, Ricardo Schütz G, Comin L, Hecht KC, da Silva EL. Consumption of green tea favorably affects oxidative stress markers in weight-trained men. Sartor L, Pezzato E, Garbisa S. J Leukoc Biol. Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis. Yeoh BS, Aguilera Olvera R, Singh V, Xiao X, Kennett MJ, Joe B, et al. Epigallocatechingallate inhibition of myeloperoxidase and its counter-regulation by dietary iron and lipocalin 2 in murine model of gut inflammation. Am J Pathol. Urrutia PJ, Mena NP, Núñez MT. The interplay between iron accumulation, mitochondrial dysfunction, and inflammation during the execution step of neurodegenerative disorders. Front Pharmacol. Amit T, Avramovich-Tirosh Y, Youdim MBH, Mandel S. Berg D. In vivo detection of iron and neuromelanin by transcranial sonography - A new approach for early detection of substantia nigra damage. J Neural Transm. Mochizuki H, Yasuda T. Collingwood JF. J Qual Res Dement. Avramovich-Tirosh Y, Reznichenko L, Mit T, Zheng H, Fridkin M, Weinreb O, et al. Neurorescue activity, APP regulation and amyloid-beta peptide reduction by novel multi-functional brain permeable iron- chelating- antioxidants, M and green tea polyphenol, EGCG. Curr Alzheimer Res. Li J, Ye L, Wang X, Liu J, Wang Y, Zhou Y, et al. Ryan P, Hynes MJ. The kinetics and mechanisms of the complex formation and antioxidant behaviour of the polyphenols EGCg and ECG with iron III. J Inorg Biochem. Bao GH, Xu J, Hu FL, Wan XC, Deng SX, Barasch J. EGCG inhibit chemical reactivity of iron through forming an Ngal-EGCG-iron complex. Saffari Y, Sadrzadeh SMH. Green tea metabolite EGCG protects membranes against oxidative damage in vitro. Teixeira MDA, Souza CM, Menezes APF, Carmo MRS, Fonteles AA, Gurgel JP, et al. Catechin attenuates behavioral neurotoxicity induced by 6-OHDA in rats. Pharmacol Biochem Behav. Lee SR, Im KJ, Suh SI, Jung JG. Protective effect of green tea polyphenol - -epigallocatechin gallate and other antioxidants on lipid peroxidation in gerbil brain homogenates. Chen M-H, Tsai C-F, Hsu Y-W, Lu F-J. Epigallocatechin gallate eye drops protect against ultraviolet B-induced corneal oxidative damage in mice. Chen W, Hsieh S, Chiu C, Hsu B, Liou Y. Molecular identification for epigallocatechin gallate-mediated antioxidant intervention on the H 2 O 2 -induced oxidative stress in H9c2 rat cardiomyoblasts. J Biomed Sci. Jeong JH, Kim HJ, Lee TJ, Kim MK, Park ES, Choi BS. Epigallocatechin 3-gallate attenuates neuronal damage induced by 3-hydroxykynurenine. Dobrzynska I, Sniecinska A, Skrzydlewska E, Figaszewski Z. Green tea modulation of the biochemical and electric properties of rat liver cells that were affected by ethanol and aging. Cell Mol Biol Lett. PubMed Google Scholar. Ostrowska J, Łuczaj W, Kasacka I, Rózański A, Skrzydlewska E. Green tea protects against ethanol-induced lipid peroxidation in rat organs. Kennedy DO. Menard C, Bastianetto S, Quirion R. Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma. Front Cell Neurosci. de Barry J, Liégeois CM, Janoshazi A. Article PubMed CAS Google Scholar. Vianna MRM, Barros DM, Silva T, Choi H, Madche C, Rodrigues C, et al. Pharmacological demonstration of the differential involvement of protein kinase C isoforms in short- and long-term memory formation and retrieval of one-trial avoidance in rats. Psychopharmacology Berl. Sun MK, Alkon DL. Prog Mol Biol Transl Sci. Activation of protein kinase C isozymes for the treatment of dementias. Adv Pharmacol. Pascale A, Amadio M, Govoni S, Battaini F. The aging brain, a key target for the future: The protein kinase C involvement. Pharmacol Res. Mansuri ML, Parihar P, Solanki I, Parihar MS. Flavonoids in modulation of cell survival signalling pathways. Mehta KD. Emerging role of protein kinase C in energy homeostasis: A brief overview. World J Diabetes. Newton AC. Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Biochem J. Kim SY, Ahn BH, Kim J, Bae YS, Kwak JY, Min G, et al. Eur J Biochem. Mandel S, Weinreb O, Amit T, Youdim MBH. Cell signaling pathways in the neuroprotective actions of the green tea polyphenol - -epigallocatechingallate: implications for neurodegenerative diseases. Mandel SA, Amit T, Kalfon L, Reznichenko L, Youdim MBH. Targeting multiple neurodegenerative diseases etiologies with multimodal-acting green tea catechins. Vasilevko V, Cribbs DH. Neurochem Int. Nunan J, Small DH. Regulation of APP cleavage by alpha-, beta- and gamma-secretases [Review]. Reznichenko L, Amit T, Zheng H, Avramovich-Tirosh Y, Youdim MBH, Weinreb O, et al. Choi D-S, Wang D, Yu G-Q, Zhu G, Kharazia VN, Paredes JP, et al. PKCepsilon increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice. Proc Natl Acad Sci U S A. Li R, Peng N, Li XP, Le WD. Lu H, Meng X, Yang CS. Enzymology of methylation of tea catechins and inhibition of catechol- o -methyltransferase by - -epigallocatechin gallate. Drug Metab Dispos. Hommes DW, Peppelenbosch MP, van Deventer SJH. Mitogen activated protein MAP kinase signal transduction pathways and novel anti-inflammatory targets. Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Vauzour D, Vafeiadou K, Rice-Evans C, Williams RJ, Spencer JPE. Behrens a, Sibilia M, Wagner EF. Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation. Nat Genet. Spencer JPE. The interactions of flavonoids within neuronal signalling pathways. Arany I, Megyesi JK, Reusch JEB, Safirstein RL. CREB mediates ERK-induced survival of mouse renal tubular cells after oxidant stress. Kidney Int. Ah Kang K, Wang ZH, Zhang R, Piao MJ, Kim KC, Kang SS, et al. Int J Mol Sci. Davis RJ. Signal transduction by the JNK group of MAP kinases. Hollenbach E, Vieth M, Roessner A, Neumann M, Malfertheiner P, Naumann M. Schroeter H, Bahia P, Spencer JPE, Sheppard O, Rattray M, Cadenas E, et al. Huang CC, Wu WB, Fang JY, Chiang HS, Chen SK, Chen BH, et al. Chang CW, Hsieh YH, Yang WE, Yang SF, Chen Y, Hu DN. Biomed Res Int. Haegeman G, Goya L, Bravo L, Ramos S, Novais A. Br J Nutr. Na HK, Kim EH, Jung JH, Lee HH, Hyun JW, Surh YJ. Singer CA, Figueroa-Masot XA, Batchelor RH, Dorsa DM. The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. Jiménez C, Hernández C, Pimentel B, Carrera AC. The p85 regulatory subunit controls sequential activation of phosphoinositide 3-kinase by Tyr kinases and Ras. Brazil DP, Hemmings BA. Ten years of protein kinase B signalling: A hard Akt to follow. Trends Biochem Sci. Song G, Ouyang G, Bao S. J Cell Mol Med. Kennedy SG, Wagner AJ, Conzen SD, Jordán J, Bellacosa A, Tsichlis PN, et al. Genes Dev. Simpson L, Parsons R. PTEN: life as a tumor suppressor. Exp Cell Res. Neri LM, Borgatti P, Capitani S, Martelli AM. Biochim Biophys Acta - Mol Cell Biol Lipids. Meske V, Albert F, Ohm TG. Coupling of mammalian target of rapamycin with phosphoinositide 3-kinase signaling pathway regulates protein phosphatase 2A- and glycogen synthase kinase-3 -dependent phosphorylation of Tau. Paquet D, Bhat R, Sydow A, Mandelkow EM, Berg S, Hellberg S, et al. A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation. J Clin Invest. Available from: ISI Shen X, Zhang Y, Feng Y, Zhang L, Li J, Xie YA, et al. Epigallocatechingallate inhibits cell growth, induces apoptosis and causes S phase arrest in hepatocellular carcinoma by suppressing the AKT pathway. Int J Oncol. Williams RJ, Spencer JPE. Flavonoids, cognition, and dementia: Actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Baptista FI, Henriques AG, Silva AMS, Wiltfang J, Da Cruz E Silva OAB. ACS Chem Neurosci. Koh SH, Kim SH, Kwon H, Park Y, Kim KS, Song CW, et al. Mol Brain Res. Gassen M, Youdim M. Free radical scavengers: chemical concepts and clinical relevance. J Neural Transm Suppl. Mandel S, Grünblatt E, Riederer P, Gerlach M, Levites Y, Youdim MBH. CNS Drugs. Weinreb O, Mandel S, Youdim MBH. Gene and protein expression profiles of anti- and pro-apoptotic actions of dopamine, R-apomorphine, green tea polyphenol - -epigallocatechinegallate, and melatonin. Ann N Y Acad Sci. cDNA gene expression profile homology of antioxidants and their antiapoptotic and proapoptotic activities in human neuroblastoma cells. Beal MF, Rascol, Marek, Olanow, Kordower, Isacson, et al. Ann Neurol. Mattson MP, Kroemer G. Mitochondria in cell death: Novel targets for neuroprotection and cardioprotection. Trends Mol Med. Masuda M, Suzui N, Weinstein IB. Effects of epigallocatechingallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clin Cancer Res. Hastak K, Gupta S, Ahmad N, Agarwal MK, Agarwal ML, Mukhtar H. Role of p53 and NF-kappaB in epigallocatechingallate-induced apoptosis of LNCaP cells. Hofmann CS, Sonenshein GE. Green tea polyphenol epigallocatechin-3 gallate induces apoptosis of proliferating vascular smooth muscle cells via activation of p FASEB J Off Publ Fed Am Soc Exp Biol. Pool H, Quintanar D, Figueroa JDD, Marinho Mano C, Bechara JEH, Godínez L a. Antioxidant Effects of Quercetin and Catechin Encapsulated into PLGA Nanoparticles. J Nanomater. Wu TH, Yen FL, Lin LT, Tsai TR, Lin CC, Cham TM. Preparation, physicochemical characterization, and antioxidant effects of quercetin nanoparticles. Int J Pharm. Pardeshi C, Rajput P, Belgamwar V, Tekade A, Patil G, Chaudhary K, et al. Solid lipid based nanocarriers: an overview. Acta Pharm. Karikalan K, Mandal AK. Bioreduction of gold metal to nanoparticles by tea Camellia sinensis plant extracts. J Plant Crop. Prakash RT, Mandal AKA. Effect of alcohol on release of green tea polyphenols from casein nanoparticles and its mathematical modeling. Res J Biotechnol. Karikalan K, Kaur G, Mandal A. Int J tea Sci. Xu Z, Chen S, Li X, Luo G, Li L, Le W. Kang KS, Wen Y, Yamabe N, Fukui M, Bishop SC, Zhu BT. Chen CM, Lin JK, Liu, SH, Lin-Shiau SY. Novel regimen through com- bination of memantine and tea polyphenol for neuroprotection against brain excitotoxicity. J Neurosci Res. Chang-Mu C, Jen-Kun L, Shing-Hwa L, Shoei-Yn LS. Characterization of neurotoxic effects of NMDA and the novel neuroprotection by phytopolyphenols in mice. Behav Neurosci. Kim SJ, Jeong HJ, Lee KM, Myung NY, An NH, Yang WM, Park SK, Lee HJ, Hong SH, Kim HM, Um JY. Epigallocatechingallate suppresses NF-kappaB activation and phosphorylation of p38 MAPK and JNK in human astrocytoma UMG cells. Weinreb O, Amit T, Youdim MB. Levites Y, Amit T, Mandel S, Youdim MB. Bieschke J, Russ J, Friedrich RP, Ehrnhoefer DE, Wobst H, Neugebauer K, Wanker EE. EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity. Hudson SA, Ecroyd H, Dehle FC, Musgrave IF, Carver JA. J Mol Biol. Ehrnhoefer DE, Bieschke J, Boeddrich A, Herbst M, Masino L, Lurz R, Engemann S, Pastore A, Wanker EE. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat Struct Mol Biol. Obregon DF, Rezai-Zadeh K, Bai Y, Sun N, Hou H, Ehrhart J, Zeng J, Mori T, Arendash GW, Shytle D, Town T, Tan J. Lee JW, Lee YK, Ban JO, Ha TY, Yun YP, Han SB, Oh KW, Hong JT. Download references. Department of Integrative Biology, School of Biosciences and Technology, VIT University, Vellore, , Tamil Nadu, India. Department of Biotechnology, School of Biosciences and Technology, VIT University, Vellore, , Tamil Nadu, India. Centre for Interdisciplinary Biomedical Research, Adesh University, Bathinda, Punjab, India. You can also search for this author in PubMed Google Scholar. Correspondence to Zaved Ahmed Khan. NAS had designed and drafted the manuscript. AKM and ZAK had primary responsibility for the final content. All authors have read and approved the final manuscript. Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Reprints and permissions. Singh, N. Potential neuroprotective properties of epigallocatechingallate EGCG. Nutr J 15 , 60 Download citation. Received : 31 March Accepted : 02 June Published : 07 June Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Download ePub. Introduction Neurodegenerative diseases impose a significant social and economic burden. Full size image. Current status of knowledge Green tea polyphenols Green tea is a traditional drink made from Camellia sinesis plant, widely consumed in Asian countries [ 18 ]. Neuroprotective properties of EGCG Green tea polyphenols are known to possess neuroprotective and neurorescue action. Free radical scavenging and antioxidant action Reactive oxygen and nitrogen species such as nitrite oxide, superoxide and hydroxyl free radicals are naturally produced to assist the host system in defence against oxidative stress and inflammation triggered through pathogens and infectious agents. Iron chelating activity Iron accumulation is one of the major pathologies of neurodegenerative diseases causing neuron death at the site of iron accumulation [ 96 ]. Lipid peroxidation EGCG has been reported to protect from lipid peroxidation and DNA deamination by guarding cells from the initiators of lipid peroxidation i. Modulation of cell signalling pathways, cell survival and death genes EGCG protects not only through their antioxidant potential but also through the modulation of signalling pathways, cell survival and cell death genes. Table 1 Neuroprotective effects of EGCG in in vitro and in vivo models of neurotoxicity Full size table. New treatment approach Although EGCG is a good candidate for a neuroprotective agent due to its ability to manipulate multiple desired targets, its use as a therapeutic agent is limited. Conclusion The multi-etiological character of neurodegenerative diseases demands the need for the development of therapeutic agents capable of manipulating multiple desired targets. Article CAS PubMed PubMed Central Google Scholar Sheridan C. Article CAS PubMed Google Scholar Guo S, Bezard E, Zhao B. Article CAS PubMed Google Scholar Weinreb O, Mandel S, Amit T, Youdim MBH. Article CAS PubMed Google Scholar Singh R, Akhtar N, Haqqi TM. Article Google Scholar Lambert JD, Elias RJ. Article CAS PubMed Google Scholar Unno K, Takabayashi F, Yoshida H, Choba D, Fukutomi R, Kikunaga N, et al. Article CAS PubMed Google Scholar Schaffer S, Asseburg H, Kuntz S, Muller WE, Eckert GP. Article CAS PubMed Google Scholar Lim HJ, Shim SB, Jee SW, Lee SH, Lim CJ, Hong JT, et al. Article CAS PubMed Google Scholar Levites Y, Amit T, Youdim MBH, Mandel S. Article CAS PubMed Google Scholar Mandel SA, Avramovich-Tirosh Y, Reznichenko L, Zheng H, Weinreb O, Amit T, et al. Article CAS PubMed Google Scholar Khokhar S, Magnusdottir SGM. Article CAS PubMed Google Scholar Nanjo F, Goto K, Seto R, Suzuki M, Sakai M, Hara Y. Article CAS PubMed Google Scholar Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar H. Article CAS PubMed PubMed Central Google Scholar Ritchie K, Lovestone S. CAS PubMed Google Scholar Kennedy DO, Wightman EL. Article CAS PubMed PubMed Central Google Scholar Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT, Swanson PD. Article PubMed Google Scholar Li F-J, Ji H-F, Shen L. Article PubMed Google Scholar Gao X, Cassidy A, Schwarzschild MA, Rimm EB, Ascherio A. Article CAS PubMed PubMed Central Google Scholar Quintana JLB, Allam MF, Castillo AS, Navajas RF-C. Article CAS Google Scholar Tan E-K, Tan C, Fook-Chong SMC, Lum SY, Chai A, Chung H, et al. Article PubMed Google Scholar Lee MJ, Wang ZY, Li H, Chen L, Sun Y, Gobbo S, et al. CAS Google Scholar Nakagawa K, Okuda S, Miyazawa T. Article CAS PubMed Google Scholar Nie G, Cao Y, Zhao B. Article PubMed Google Scholar Grinberg LN, Newmark H, Kitrossky N, Rahamim E, Chevion M, Rachmilewitz EA. Article CAS PubMed Google Scholar Solanki I, Parihar P, Mansuri ML, Parihar MS. Article CAS PubMed PubMed Central Google Scholar Abd El Mohsen MM, Kuhnle G, Rechner AR, Schroeter H, Rose S, Jenner P, et al. Article CAS PubMed Google Scholar Zhang B, Rusciano D, Osborne NN. Article CAS PubMed Google Scholar Stefanis L. Article PubMed PubMed Central CAS Google Scholar Bagad M, Chowdhury D, Khan ZA. Article PubMed PubMed Central CAS Google Scholar Zhang H, Zhang Y-W, Chen Y, Huang X, Zhou F, Wang W, et al. Article CAS PubMed PubMed Central Google Scholar Mattson MP. Article PubMed PubMed Central Google Scholar Cavet ME, Harrington KL, Vollmer TR, Ward KW, Zhang J-Z. CAS PubMed PubMed Central Google Scholar Li M-J, Yin Y-C, Wang J, Jiang Y-F. Article CAS PubMed PubMed Central Google Scholar Bahadoran Z, Mirmiran P, Azizi F. Article CAS PubMed Google Scholar Okello EJ, Leylabi R, McDougall GJ. Article CAS PubMed Google Scholar Wobst HJ, Sharma A, Diamond MI, Wanker EE, Bieschke J. Article CAS PubMed Google Scholar Rezai-Zadeh K, Arendash GW, Hou H, Fernandez F, Jensen M, Runfeldt M, et al. Article CAS PubMed Google Scholar Chesser AS, Ganeshan V, Yang J, Johnson GVW. CAS PubMed Google Scholar Agrawal M, Biswas A. Article CAS PubMed Google Scholar Zhang X, Wu M, Lu F, Luo N, He ZP, Yang H. CAS PubMed Google Scholar Han J, Wang M, Jing X, Shi H, Ren M, Lou H. Article CAS PubMed Google Scholar Abib RT, Peres KC, Barbosa AM, Peres TV, Bernardes A, Zimmermann LM, et al. Article CAS PubMed Google Scholar Chao J, Lau WKW, Huie MJ, Ho YS, Yu MS, Lai CSW, et al. Article CAS PubMed Google Scholar Schroeder EK, Kelsey NA, Doyle J, Breed E, Bouchard RJ, Loucks FA, et al. Article CAS PubMed Google Scholar Yu J, Jia Y, Guo Y, Chang G, Duan W, Sun M, et al. Article CAS PubMed Google Scholar Sutherland BA, Shaw OM, Clarkson AN, Jackson DN, Sammut IA, Appleton I. CAS PubMed Google Scholar Herges K, Millward JM, Hentschel N, Infante-Duarte C, Aktas O, Zipp F. Article CAS PubMed Google Scholar Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, et al. Article CAS PubMed Google Scholar Yeon J, Jeon S, Bae K, Song K, Hee Y. Article CAS Google Scholar Reznichenko L, Amit T, Youdim MBH, Mandel S. Article CAS PubMed Google Scholar Sagi Y, Mandel S, Amit T, Youdim MBH. Article CAS PubMed Google Scholar Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Article CAS PubMed Google Scholar Zhao C, Li C, Liu S, Yang L. Google Scholar Young Park S, Jeong YJ, Kim SH, Jung JY, Kim WJ. Article CAS PubMed Google Scholar Guo Q, Zhao B, Li M, Shen S, Wenjuan X. Article CAS Google Scholar Devika PT, Stanely Mainzen Prince P. Article CAS PubMed Google Scholar Jelenković A, Jovanović MD, Stevanović I, Petronijević N, Bokonjić D, Živković J, et al. Article CAS Google Scholar Srividhya R, Jyothilakshmi V, Arulmathi K, Senthilkumaran V, Kalaiselvi P. Article CAS PubMed Google Scholar Erba D, Riso P, Bordoni A, Foti P, Biagi PL, Testolin G. Article CAS PubMed Google Scholar Panza VSP, Wazlawik E, Ricardo Schütz G, Comin L, Hecht KC, da Silva EL. Article CAS PubMed Google Scholar Sartor L, Pezzato E, Garbisa S. Article PubMed Google Scholar Yeoh BS, Aguilera Olvera R, Singh V, Xiao X, Kennett MJ, Joe B, et al. Article CAS Google Scholar Urrutia PJ, Mena NP, Núñez MT. Article CAS PubMed PubMed Central Google Scholar Berg D. Article CAS PubMed Google Scholar Li J, Ye L, Wang X, Liu J, Wang Y, Zhou Y, et al. Article CAS PubMed Google Scholar Bao GH, Xu J, Hu FL, Wan XC, Deng SX, Barasch J. Article CAS PubMed PubMed Central Google Scholar Saffari Y, Sadrzadeh SMH. Article CAS PubMed Google Scholar Teixeira MDA, Souza CM, Menezes APF, Carmo MRS, Fonteles AA, Gurgel JP, et al. Article CAS PubMed Google Scholar Lee SR, Im KJ, Suh SI, Jung JG. Article CAS Google Scholar Chen M-H, Tsai C-F, Hsu Y-W, Lu F-J. CAS PubMed PubMed Central Google Scholar Chen W, Hsieh S, Chiu C, Hsu B, Liou Y. Article PubMed PubMed Central CAS Google Scholar Jeong JH, Kim HJ, Lee TJ, Kim MK, Park ES, Choi BS. Article CAS PubMed Google Scholar Dobrzynska I, Sniecinska A, Skrzydlewska E, Figaszewski Z. PubMed Google Scholar Ostrowska J, Łuczaj W, Kasacka I, Rózański A, Skrzydlewska E. Article CAS PubMed Google Scholar Kennedy DO. Article PubMed CAS Google Scholar Vianna MRM, Barros DM, Silva T, Choi H, Madche C, Rodrigues C, et al. Article CAS Google Scholar Sun MK, Alkon DL. Article CAS PubMed Google Scholar Sun MK, Alkon DL. Article CAS PubMed Google Scholar Pascale A, Amadio M, Govoni S, Battaini F. Article CAS PubMed Google Scholar Mansuri ML, Parihar P, Solanki I, Parihar MS. Article PubMed PubMed Central Google Scholar Newton AC. Article CAS PubMed PubMed Central Google Scholar Kim SY, Ahn BH, Kim J, Bae YS, Kwak JY, Min G, et al. Article CAS PubMed Google Scholar Mandel SA, Amit T, Kalfon L, Reznichenko L, Youdim MBH. CAS PubMed Google Scholar Vasilevko V, Cribbs DH. Article CAS PubMed Google Scholar Nunan J, Small DH. Article CAS PubMed Google Scholar Reznichenko L, Amit T, Zheng H, Avramovich-Tirosh Y, Youdim MBH, Weinreb O, et al. Article CAS PubMed Google Scholar Choi D-S, Wang D, Yu G-Q, Zhu G, Kharazia VN, Paredes JP, et al. Article CAS PubMed PubMed Central Google Scholar Li R, Peng N, Li XP, Le WD. Article CAS PubMed Google Scholar Lu H, Meng X, Yang CS. Article CAS PubMed Google Scholar Hommes DW, Peppelenbosch MP, van Deventer SJH. Article CAS PubMed PubMed Central Google Scholar Johnson GL, Lapadat R. Article CAS PubMed Google Scholar Vauzour D, Vafeiadou K, Rice-Evans C, Williams RJ, Spencer JPE. Article CAS PubMed Google Scholar Behrens a, Sibilia M, Wagner EF. Article PubMed Google Scholar Ah Kang K, Wang ZH, Zhang R, Piao MJ, Kim KC, Kang SS, et al. Article CAS Google Scholar Davis RJ. Article CAS PubMed Google Scholar Hollenbach E, Vieth M, Roessner A, Neumann M, Malfertheiner P, Naumann M. Article CAS PubMed Google Scholar Schroeter H, Bahia P, Spencer JPE, Sheppard O, Rattray M, Cadenas E, et al. Article CAS PubMed Google Scholar Huang CC, Wu WB, Fang JY, Chiang HS, Chen SK, Chen BH, et al. Article CAS PubMed Google Scholar Chang CW, Hsieh YH, Yang WE, Yang SF, Chen Y, Hu DN. Google Scholar Na HK, Kim EH, Jung JH, Lee HH, Hyun JW, Surh YJ. CAS PubMed Google Scholar Jiménez C, Hernández C, Pimentel B, Carrera AC. |
| Therapeutics | Neuroscience , — Chen, Z. Biocompatible, functional spheres based on oxidative coupling assembly of green tea polyphenols. Cheng-Chung Wei, J. Epigallocatechin gallate attenuates amyloid β-induced inflammation and neurotoxicity in EOC Chi, E. Physical stability of proteins in aqueous solution: mechanism and driving forces in nonnative protein aggregation. Choi, B. Large α-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking. Choi, Y. The green tea polyphenol - -epigallocatechin gallate attenuates beta-amyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci. Chong, Y. Chow, H. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Cancer Res. Google Scholar. Coelho, T. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology 79, — Colby, D. Cold Spring Harb. da Silva, J. Guanosine neuroprotection of presynaptic mitochondrial calcium homeostasis in a mouse study with amyloid-β oligomers. Danzer, K. Different species of alpha-synuclein oligomers induce calcium influx and seeding. de Almeida, M. The flavonoid agathisflavone modulates the microglial neuroinflammatory response and enhances remyelination. de Amorim, V. Agathisflavone modulates astrocytic responses and increases the population of neurons in an in vitro model of traumatic brain injury. de la Torre, R. A phase 1, randomized double-blind, placebo controlled trial to evaluate safety and efficacy of epigallocatechingallate and cognitive training in adults with Fragile X syndrome. Lancet Neurol. Epigallocatechingallate, a DYRK1A inhibitor, rescues cognitive deficits in Down Syndrome mouse models and in humans. Food Res. Deas, E. Antioxidants Redox Signal. Debnath, K. Efficient Inhibition of Protein Aggregation, Disintegration of Aggregates, and Lowering of Cytotoxicity by Green Tea Polyphenol-Based Self-Assembled Polymer Nanoparticles. ACS Appl. Dickey, A. Therapy development in Huntington disease: from current strategies to emerging opportunities. Part A , — DiFiglia, M. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science , — Dominguez-Meijide, A. Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization. Dragicevic, N. Du, K. Epigallocatechin gallate reduces amyloid β-induced neurotoxicity via inhibiting endoplasmic reticulum stress-mediated apoptosis. Duennwald, M. Countering amyloid polymorphism and drug resistance with minimal drug cocktails. Prion 4, — Ehrnhoefer, D. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Fernandes, L. ACS Biomater. An ortho-iminoquinone compound reacts with lysine inhibiting aggregation while remodeling mature amyloid fibrils. ACS Chem. Fernandez, J. EGCG functions through estrogen receptor-mediated activation of ADAM10 in the promotion of non-amyloidogenic processing of APP. Figueiredo, C. Memantine rescues transient cognitive impairment caused by high-molecular-weight aβ oligomers but not the persistent impairment induced by low-molecular-weight oligomers. Fusco, G. Molecular determinants of the interaction of EGCG with ordered and disordered proteins. Biopolymers Gautam, S. Polyphenols in combination with β-cyclodextrin can inhibit and disaggregate α-synuclein amyloids under cell mimicking conditions: A promising therapeutic alternative. Acta Prot. Giles, K. Developing Therapeutics for PrP Prion Diseases. Granja, A. Therapeutic potential of epigallocatechin gallate nanodelivery systems. BioMed Res. Griffioen, G. A yeast-based model of alpha-synucleinopathy identifies compounds with therapeutic potential. Haney, C. Site-specific fluorescence polarization for studying the disaggregation of α-synuclein fibrils by small molecules. Biochemistry 56, — He, Y. Prolonged exposure of cortical neurons to oligomeric amyloid-β impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea - -epigallocatechingallate. ASN Neuro 3:AN Husby, G. Chemical and clinical classification of amyloidosis. Hyung, S. Insights into antiamyloidogenic properties of the green tea extract - -epigallocatechingallate toward metal-associated amyloid-β species. Jeon, S. Green tea catechins as a BACE1 beta-secretase inhibitor. Bioorganic Med. Jha, N. Comparison of α-synuclein fibril inhibition by four different amyloid inhibitors. Jia, N. Kamatari, Y. Characterizing antiprion compounds based on their binding properties to prion proteins: implications as medical chaperones. Kayed, R. Molecular mechanisms of amyloid oligomers toxicity. Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Kelley, M. ACS Omega 6, — Kim, C. Neuroprotective effect of epigallocatechingallate against beta-amyloid-induced oxidative and nitrosative cell death via augmentation of antioxidant defense capacity. Kocisko, D. New inhibitors of scrapie-associated prion protein formation in a library of drugs and natural products. Evaluation of new cell culture inhibitors of protease-resistant prion protein against scrapie infection in mice. General Virol. Koffie, R. Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Konijnenberg, A. Opposite structural effects of epigallocatechingallate and dopamine binding to α-synuclein. Kristen, A. Green tea halts progression of cardiac transthyretin amyloidosis: an observational report. Kumar, N. Randomized, placebo-controlled trial evaluating the safety of one-year administration of green tea catechins. Oncotarget 7, — Kumar, P. Effect of lycopene and epigallocatechingallate against 3-nitropropionic acid induced cognitive dysfunction and glutathione depletion in rat: A novel nitric oxide mechanism. Kumar, S. Chemistry and biological activities of flavonoids: an overview. World J. Kuo, Y. Acta Biomaterial. La Vitola, P. Lakshmi, S. The tea catechin epigallocatechin gallate inhibits NF-κB-mediated transcriptional activation by covalent modification. Largeron, M. Angewandte Chemie 51, — Lee, J. EGCG-mediated autophagy flux has a neuroprotection effect via a class III histone deacetylase in primary neuron cells. Oncotarget 6, — Green tea - -epigallocatechingallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice. Lee, S. Levin, J. Safety and efficacy of epigallocatechin gallate in multiple system atrophy PROMESA : a randomised, double-blind, placebo-controlled trial. Levites, Y. Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol - -epigallocatechingallate. Li, Y. Theranostics 8, — Lin, C. Aging 30, 81— Liu, F. Molecular insight into conformational transition of amyloid β-peptide 42 inhibited by - -epigallocatechingallate probed by molecular simulations. B , — Liu, H. Synergistic effects of negatively charged hydrophobic nanoparticles and - -epigallocatechingallate on inhibiting amyloid β-protein aggregation. Colloid Interf. Liu, M. Liu, X. Influence of EGCG on α-synuclein αS aggregation and identification of their possible binding mode: A computational study using molecular dynamics simulation. Drug Design 91, — Lopez del Amo, J. Lorenzen, N. How epigallocatechin gallate can inhibit α-synuclein oligomer toxicity in vitro. Ludtmann, M. Luth, E. Ma, L. Manach, C. Polyphenols: food sources and bioavailability. Marcantoni, A. Amyloid Beta42 oligomers up-regulate the excitatory synapses by potentiating presynaptic release while impairing postsynaptic NMDA receptors. Maurer, M. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. Miller, E. Tau phosphorylation and tau mislocalization mediate soluble Aβ oligomer-induced AMPA glutamate receptor signaling deficits. Minopoli, G. Fe65 matters: new light on an old molecule. IUBMB Life 64, — Mori, T. Combined treatment with the phenolics - -epigallocatechingallate and ferulic acid improves cognition and reduces Alzheimer-like pathology in mice. Muchowski, P. Protein misfolding, amyloid formation, and neurodegeneration: a critical role for molecular chaperones? Neuron 35, 9— Nakagawa, K. Dose-dependent incorporation of tea catechins, - -epigallocatechingallate and - -epigallocatechin, into human plasma. Nestler, G. Traditional Chinese medicine. North Am. Obregon, D. ADAM10 activation is required for green tea - -epigallocatechingallate-induced alpha-secretase cleavage of amyloid precursor protein. Oliveri, V. Cyclodextrins as protective agents of protein aggregation: an overview. Asian J. Palhano, F. Toward the molecular mechanism s by which EGCG treatment remodels mature amyloid fibrils. Pan, K. Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Paushkin, S. In vitro propagation of the prion-like state of yeast Sup35 protein. Ponzini, E. Methionine oxidation in α-synuclein inhibits its propensity for ordered secondary structure. Prusiner, S. Prion protein biology. Cell 93, — Rambold, A. Green tea extracts interfere with the stress-protective activity of PrP and the formation of PrP. Rezai-Zadeh, K. Green tea epigallocatechingallate EGCG reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res. Green tea epigallocatechingallate EGCG modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. Reznichenko, L. Rho, T. Identification of fermented tea Camellia sinensis polyphenols and their inhibitory activities against amyloid-beta aggregation. Phytochemistry , 11— Roberts, B. A synergistic small-molecule combination directly eradicates diverse prion strain structures. Rocha, E. Rubinsztein, D. The roles of intracellular protein-degradation pathways in neurodegeneration. Tavares, C. Ries, M. Sastre, Mechanisms of A β clearance and degradation by glial cells, Front. Tönnies, E. Trushina, Oxidative stress, synaptic dysfunction, and Alzheimer's disease, J. Alzheimers Dis. von Bernhardi, L. Eugenín-von Bernhardi, J. Eugenín, Microglial cell dysregulation in brain aging and neurodegeneration, Front. Praticò, Oxidative stress hypothesis in Alzheimer's disease: a reappraisal, Trends Pharmacol. Liu, L. Zhang, D. Joo, et al. Giridharan, M. Srinivasan, Mechanisms of NF-κB p65 and strategies for therapeutic manipulation, J. Shin, C. Wang, C. Yang, NF-κB signaling pathways in neurological inflammation: a mini review, Front. Abbas, M. Li, M. Gordon, J. Tan, Oral administration of green tea epigallocatechingallate EGCG reduces amyloid beta deposition in transgenic mouse model of Alzheimer's disease, Exp. Lin, T. Chen, M. Chiu, et al. Aging 30 Levites, T. Amit, S. Mandel, et al. Rezai-Zadeh, D. Shytle, N. Sun, et al. Rezai-Zadeh, G. Arendash, H. Hou, et al. Giunta, H. Hou, Y. Zhu, et al. Allinson, E. Parkin, A. Turner, et al. Garton, P. Gough, C. Blobel, et al. Qian, X. Shen, H. Wang, The distinct role of ADAM17 in APP proteolysis and microglial activation related to Alzheimer's disease, Cell. Lee, S. Sunnarborg, C. Hinkle, et al. Obregon, K. Rezai-Zadeh, Y. Bai, et al. Anders, S. Gilbert, W. Garten, et al. Reznichenko, T. Amit, H. Zheng, et al. Fernandez, K. Obregon, et al. Xicota, J. Rodriguez-Morato, M. Dierssen, et al. Drug Targets 18 Jeon, K. Bae, Y. Seong, et al. Shimmyo, T. Kihara, A. Akaike, et al. Lee, Y. Lee, J. Ban, et al. Lee, D. Yuk, J. Lee, et al. Choi, Y. Yun, et al. Leissring, M. Murphy, T. Mead, et al. Andrich, J. Bieschke, The effect of — -epigallo-catechin- 3 -gallate on amyloidogenic proteins suggests a common mechanism, Adv. Cascella, S. Bimonte, M. Muzio, et al. Cancer 12 Soto, E. Sigurdsson, L. Morelli, et al. Cohen, J. Kelly, Therapeutic approaches to protein-misfolding diseases, Nature Haass, D. Selkoe, Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide, Nat. Cell Biol. Hunstein, Epigallocathechingallate in AL amyloidosis: a new therapeutic option? Blood Bieschke, R. Russ, R. Friedrich, et al. Grelle, A. Otto, M. Lorenz, et al. Gauci, M. Caruana, A. Giese, et al. Palhano, J. Lee, N. Grimster, et al. Lorenzen, S. Nielsen, Y. Yoshimura, et al. Ehrnhoefer, M. Duennwald, P. Moreover, it could be implied that EGCG basically reverses the conformation of the complexes formed between Al III and Aβ42 in order to inhibit and remold Aβ 42 fibrillation [Unpublished observations]. EGCG administration in Alzheimer transgenic mice regulated the tau profile and markedly suppressed the phosphorylated tau isoforms [ 60 ]. This clearance of the phosphorylated tau isoforms occurred in a highly specific manner through the adaptor protein expression [ 61 ]. Furthermore, long-term oral administration of EGCG also reported significant improvement in spatial cognitive learning ability in rats [ 60 , 62 ]. PD is the second most common neurodegenerative disease. It is characterized by features such as rigidity, postural instability and slowness of movement and tremors along with cognitive and psychiatric deficits. Neuropathologically, the hallmarks of PD include misfolding and aggregation of α-synuclein protein, damage and loss of dopamine DA neurons in the substantia nigra pars compacta SN along with oxidative stress caused due to mitochondrial dysfunction [ 63 ]. Therefore, agents that would target these hallmarks could be considered as important candidates for the treatment of PD. In addition EGCG μM has also exhibited significant inhibitory effects against oxidative stress induced apoptosis [ 10 ]. Green tea polyphenols are known to possess neuroprotective and neurorescue action. In particular, EGCG has shown to increase cell viability, decrease reactive oxygen species [ 65 ] and expression levels of endoplasmic reticulum stress markers and apoptotic markers [ 66 , 67 ]. They also protect cells against mitochondrial dysfunction [ 68 ], 6-hydroxydopamine 6-OHDA induced toxicity [ 69 ], apoptosis induced by mitochondrial oxidative stress [ 70 ] and glutamate excitotoxicity [ 71 ]. EGCG also preserves mitochondrial energetics [ 72 ] and limits the inflammation of the brain and neuronal damage [ 73 , 74 ], which in turn prolongs the onset of symptoms, life span [ 75 ], cognitive skill and learning ability of the patient [ 62 , 76 , 77 ]. Not only does EGCG exert neuroprotective effects, it also wields neurorescue activity by promoting neurite growth [ 78 ]. Which, makes EGCG a good candidate for a potent disease-modifying agent with neurorescue and neuroprotective properties [ 79 ]. Reactive oxygen and nitrogen species such as nitrite oxide, superoxide and hydroxyl free radicals are naturally produced to assist the host system in defence against oxidative stress and inflammation triggered through pathogens and infectious agents. But these species have a two faced nature, when overproduced in the body, they initiate a deleterious process making them a mediator to cell structure damage including DNA, proteins and lipids, which eventually leads to apoptosis and cell death [ 80 ]. Green tea polyphenols are biological antioxidants with radical scavenging properties. Among the green tea polyphenol family, EGCG and ECG are the most potent radical scavengers. This is attributed to the presence of an ortho-trihydroxyl group in the B ring [ 19 ], 4-keto and 5-hydroxyl group in the C ring i. the galloyl moiety [ 35 ] and the A ring in their structures. Also, the difference between antioxidant activities of EGCG and ECG is slight and is attributed to the number of hydroxyl groups each possesses [ 81 ]. In general they can scavenge 1,1-diphenylpicrylhydrazyl radicals, peroxyl radicals [ 82 ], nitric oxide, lipid free radicals, singlet oxygen, peroxynitrite [ 83 ], hydroxyl free radicals and superoxide anion radicals [ 84 ] through three possible mechanisms. First, by chelating metal ions to their inactive forms [ 85 ]. Second, by direct interaction between catechins and peroxyl radical via a fast mechanism of electron H-atom transfer, to prevent DNA strand breakage [ 86 ]. And third, by preventing the deaminating ability of free radicals by forming stable semiquinone free radicals [ 87 ]. Oral administration of EGCG, in vivo has reported significant reduction in levels of lipid peroxidation products with elevated levels of enzymatic and non-enzymatic antioxidants [ 88 ]. Complete reversal of the damaging effects of AlCl 3 on superoxide dismutase activity was noted along with markedly improvement in glutathione peroxidase, cytochrome C oxidase and acetylcholinesterase activity [ 89 ]. To better understand the antioxidant potential of EGCG, it was administered long-term in both young and old rats. Consumption of green tea polyphenols in humans has shown to increase the antioxidant levels in the body. Long-term consumption of approximately cups a day has reported an increase in both total antioxidant activity and total polyphenol content with a decrease in peroxide levels, glutathione levels and lipid hydroperoxide levels [ 91 , 92 ]. Suggesting, that green tea polyphenols like EGCG could directly or indirectly regulate the antioxidant levels to reduce oxidative stress. In addition to deterring oxidative stress, EGCG has also shown to hinder inflammation. It is a potent inhibitor of leukocyte elastase, which mediates the activation of matrix metalloproteinases MMP MMP-2 and MMP-9, which further trigger inflammation [ 93 ]. Oral administration of EGCG in vivo has also shown to significantly reduce inflammation in pulmonary fibrosis, block neutrophil mediated angiogenesis in inflammatory models [ 94 ] and also inhibit proinflammatory mediators such as myeloperoxidases in a dose dependent manner [ 95 ]. Implying that EGCG is a potent anti-inflammatory agent with therapeutic potential. Iron accumulation is one of the major pathologies of neurodegenerative diseases causing neuron death at the site of iron accumulation [ 96 ]. This has generated a need for iron chelators such as EGCG. Iron accumulation only occurs when the ionic iron participates in the Fenton reaction leading to the generation of reactive oxidative species, which triggers oxidative stress and activates the inflammatory cascade. In the process, activating primary and secondary messengers including cytokines TNF α, IL-1 and IL-6 , mast cells, histamine, transient receptor potential channels TRP , acid sensing ion channels ASIC , sodium channels and nuclear factor kappa-light-chain-enhancer of activated B cells NF — kB [ 98 ]. In the PD brain iron accumulation induces oxidative stress and reduction in the levels of neuromelanin that are visible well before the clinical manifestation of the disease develop, in vivo [ 99 ]. This accumulation of iron, directly or indirectly induces α-synuclein fibril formation, which then acts in concert with dopamine to induce the formation of lewy bodies and cause cell death [ ]. Colocalization in lesions, plaques and neurofibrillary tangles along amyloid beta deposition; phosphorylation of tau protein and tangle formation was also noted. Since, these sites are centers of memory and thought, with the progression of the disease, in the form of neuronal death, these processes are gradually lost [ ]. Treatment with EGCG for iron accumulation in AD and PD has portrayed its ability to regulate APP through the iron responsive element and at same time reduce the toxic levels of amyloid beta peptide [ ]. The kinetics and mechanisms of complex formation between iron and EGCG has reported that one molecule of EGCG is capable of reducing up to four iron III species [ ]. In addition through interaction with Ngal, a biomarker for acute kidney injury, EGCG inhibits the chemical activity of iron by forming a stable Ngal-EGCG-Iron complex [ ]. Making, EGCG a powerful metal chelating antioxidant. EGCG has been reported to protect from lipid peroxidation and DNA deamination by guarding cells from the initiators of lipid peroxidation i. t-butylhydroperoxide [ ], 6-hydroxydopamine [ ], iron [ ], ultraviolet radiation [ ], hydrogen peroxide [ ] and 3-hydroxykynurenine [ ]. In vivo studies designed to investigate the effect of EGCG on lipid peroxidation have reported a significant reduction in the extent of lipid peroxidation when thiobarbituric reactive substances TBARS levels were measured [ ]. Along with a significant decrease in the levels of lipid peroxidation markers namely lipid hydroperoxides, 4-hydroxynoneal and malondialdehyde, with an increase in glutathione peroxidase activity and reduced glutathione concentrations [ ]. Thereby, implying that EGCG is capable of protecting cells against lipid peroxidation. EGCG protects not only through their antioxidant potential but also through the modulation of signalling pathways, cell survival and cell death genes. They interact directly with neurotransmitter receptor, downstream protein kinases or signalling cascades such as PKC, Akt and MAPK signalling pathways. This interaction between EGCG and the signalling cascade further dictates the response of the cell to environment or the stressor, ultimately leading to responses such as cell proliferation, apoptosis, synthesis of inflammatory mediators and neurite growth [ , ]. It is critical for normal cell growth [ ] and plays an important role in the cell signalling machinery including its integral role in transduction pathways for hormones and growth factors. It also has an important role in the amalgamation of different types of memories [ ]. An increase in PKC expression could potentially enhance memory, cognition and learning along with anti-dementia action [ ] which, in turn would restore the normal PKC signalling. Consequently stimulation of neurotrophic activity, synaptic remodelling and synaptogenesis leads to the reduction of amyloid beta accumulation, tau hyperphosphorylation and apoptotic processes in the brain [ ]. Making PKC activation in the neurons a prerequisite for neuroprotection [ ]. The 12 isoforms of PKC are categorized into 3 subclasses based on their activators: conventional α, β I , β II , γ , novel δ, ε, θ, η, μ and atypical ι, λ, ζ. The mechanism for PKC activation requires: first the phosphorylation of 3 distinct sites within the activation loop, turn motif and hydrophobic domain. Followed by binding of DAG and PS to promote the conformational activation of the proteins [ ]. PKC isoforms are mainly targets for survival signalling. For instance, in vitro, EGCG effectively increases expression levels of PKC, in order activate the normal PKC signalling pathway. This activation offers neuroprotection against amyloid beta neurotoxicity, serum withdrawal, 6-OHDA and provides neurorescue action against neuronal cell damage [ 18 , 78 ] along with rapid translocation and activation of Phospholipase D PLD in astroglioma cells [ ]. Long term administration of EGCG has also shown to effectively protect against 6-OHDA and 1-methylphenyl-1,2,3,6-tetrahydropyridine MPTP toxicity, as enhanced expression levels of PKCα and PKCε have been observed. In addition, upregulation of previously depleted levels of PKCα has also been noted with further activation of Bcl — 2, signal related kinases — ERK 1, ERK 2 with a reduction in the levels of proapoptotic caspase 6, bax, bad, TRAIL and fas ligand [ ]. Moreover, EGCG efficiently prevents the dissipation of the mitochondrial membrane potential with reduction in Bad levels [ 17 , ]. With PKC inhibition this protective effect was also abolished suggesting that these protective effects were PKC mediated. In AD, amyloid beta fibrillation in particular was inhibited via the PKC signalling pathway. Where the fibrils generated due to the extracellular deposition of beta amyloid peptide, derived via the proteolytic cleavage of amyloid precursor protein APP by β and γ secretase instead of α secretase [ , ] were inhibited when treated with EGCG in both cell and animal models. Transgenic studies have also suggested that these diminished levels of beta amyloid peptide and plaques stemmed due to the enhanced levels of PKC isoforms and α secretase expression [ , ] which, implied that EGCG induced non-amyloidogenic sAPPα release and inhibited the generation of beta amyloid peptide via the PKC dependent activation of α secretase. To support this data transgenic studies with overexpression of PKCε reported significant decrease in beta amyloid peptide levels, plaque burden, reactive astrocytosis and neuritic dystrophy with increase in activity of endothelial converting enzyme that degraded the beta amyloid peptide and inhibited amyloid beta fibrillation [ ]. In PD, treatment with EGCG has shown to induce a dose dependent inhibitory effect on DA presynaptic transporters DAT in the dopaminergic cells where PKC activation regulates DAT internalization and enhances synaptic DA levels. Also, this effect was completely abolished when PKC activation was blocked [ ]. EGCG also inhibited the activity of catechol-O-methyltransferase COMT and in turn inhibited COMT catalysed methylation of endogenous and exogenous compounds, delivering a neuroprotective effect in both animal and cell models of PD [ ]. They are important members of the signalling cascades involved in cell proliferation, inflammation, cytokine and inducible nitric oxide synthase expression [ ]. Where ERK act as a determinant for cell growth, cell survival, motility, cell differentiation and pro-survival signalling [ ]. JNK also known as stress-activated protein kinases SAPK maintains growth control and regulate apoptosis [ ]. While p38 MAPK regulates cell cycle, cell death, inflammation, tumorigenesis, senescence and cell differentiation [ ]. These classes of MAPKs have different modes of action through which they regulate their respective signalling cascades. For instance the activated ERK MAPKs regulate their signalling cascades through activation of cAMP response element binding protein CREB [ ] and through upregulation of anti-apoptotic proteins [ ]. While JNK MAPKs first become activated through an environmental stimulus followed by the activation of factors such as c-Jun, JunB, JunD and activating transcription factor 2 ATF2 that help regulate the apoptotic-signalling cascade [ , ]. In case of p38 MAPKs, cellular stressors, for example osmotic shock, inflammatory cytokines and growth factors are required for activation, which then phosphorylate transcription factors like ATF2, myc-associated factor X Max and myocyte enhancer factor 2 MEF2 in order to regulate their respective signalling cascade in diseases like AD, rheumatoid arthritis and inflammatory bowel disease [ , ]. Derivatives of green tea polyphenols have shown to interact with ERK, JNK and p38 pathways of MAPKs. For instance, in vitro treatment with EC effectively increased CREB and ERK phosphorylation along with significant increase in the mRNA levels of the glutamate receptor subunit GluR2 and the GluR2 protein, which suggested that EC had the ability to regulate neurotransmission, plasticity and synaptogenesis [ ]. Similarly, ECG through inhibition of p38 and ERK protected cells against H 2 O 2 induced oxidative stress. At low concentrations EC reduced the activation of JNK [ ]. Likewise EGCG induced cell death and increased cell survival in vitro [ ] through the production of redox sensitive transcription factors like NF-kB, activator protein-1 AP-1 and nuclear transcription factor erythroid 2p45 related factor Nrf2 , via the ERK pathway [ ]. Furthermore, EGCG also triggered the expression of several antioxidant enzymes such as glutamate-cysteine ligase GCL , haem oxygenase 1 HO-1 , manganese superoxide dismutase MnSOD and enhanced antioxidant response element binding ARE and the transcription activity of Nrf2, which in turn provided cells defence against oxidative stress [ ] and neuron loss [ ]. In their activated form this pathway effectively blocks apoptosis. Conversely, when inhibited they accelerate apoptosis and abolish cell survival [ ]. This mechanism involves first the activation of PI3K enzymes that catalyse production of phosphatidylinositol-3,4,5-triphosphate PIP3. The activated form of PIP3 subsequently activates phosphoinositide-dependent protein kinase 1 PDK1 [ ], which in turn activates Akt and PKC isoenzymes [ ]. The activated form of Akt maintains the inhibited state of glycogen synthase kinase 3β GSK3β. With reduction in Akt activity, GSK3β hyper-phosphorylates [ ], triggering tau accumulation in the brain, which further instigates the generation of neurofibrillary tangles NFTs , ultimately causing neuron death [ ]. EGCG also regulates the tau pathology through the suppression of phosphorylated tau isoforms [ ]. Thus, affecting the downstream signalling cascade and preventing NFT generation [ , ]. It also promotes neuronal communication, synaptic plasticity, angiogenesis and neurogenesis. On the other hand, via the inhibition of JNK and ASK-1 pathway, EGCG inhibits pro apoptotic-signalling and inflammation markers, which help in preventing neurodegeneration and aging. These specific interactions between EGCG and the signalling cascades consequently, increase strength of neuronal connections and expression of neuromodulatory proteins in the neurons. Thus increasing the expression of neuroprotection [ ]. Hence, put together these studies have helped reveal novel pathways through which EGCG induces its neuroprotective effects Fig. Proposed mechanism for Neuroprotection and Neurorescue action of EGCG. Abbreviations: α Syn — alpha synuclein, Aβ — amyloid beta peptide, COMT — catechol-o-methyl transferase, DAT — dopamine transporter, PKCα — protein kinase C alpha, PKCε — protein kinase C epsilon, ROS — reactive oxygen species and sAPPα — alpha secretase. Modulation of cell survival and death genes via EGCG occurs in a dose dependent manner. For instance, treatment with low concentration of EGCG, both in vitro and in vivo models effectively lowers neurotoxicity via the reduction in the expression of pro-apoptotic genes; bax, bad, mdm1, caspase 1, caspase 6, TRAIL, p21, gadd45 and fas ligand with no effect on anti-apoptotic genes; bcl-w, bcl-2 and bcl-xL. Suggesting that EGCG induces this protective effect through the inactivation of cell death promoting genes rather than the up regulation of mitochondrial acting anti-apoptotic genes [ 54 , — ]. Likewise, treatment with higher concentrations of EGCG induces a pro apoptotic or a pro toxic pattern of expression rather than an anti-apoptotic effect. Along with reduced expression levels of bcl-2, bcl-xL and bcl-w [ 15 , ]. With support of this data highlighted through the years, we can consider EGCG as a good candidate for a therapeutic agent with neuroprotective properties Table 1. Overview of the possible gene targets involved in anti-apoptotic and pro-apoptotic actions of low and high concentrations of EGCG. Abbreviations: Akt — is another name for protein kinase B, ERK — extracellular signal-regulated kinase, MEK — is a member of MAPK signalling cascade, PI3K — phosphoinositidekinase, PKC — protein kinase C, SAPK — stress activated protein kinase, TRAIL — TNF related apoptosis inducing ligand. Although EGCG is a good candidate for a neuroprotective agent due to its ability to manipulate multiple desired targets, its use as a therapeutic agent is limited. This is due to its poor availability, solubility and stability. Factors such as temperature, light, pH of the stomach, first pass metabolism, enzymes of the gut, interaction with food, insufficient absorption time and insufficient transport through the BBB limit the beneficial attributes of EGCG [ ]. Nanotechnology based oral drug delivery systems could be employed to resolve these shortcomings easily. It is known that nanoparticles are generally non-toxic, size-controllable, produce fewer side effects and have high drug bioavailability and absorption capacity [ ]. With particle sizes lower than nm, these nanoparticles are capable of easily diffusing across the BBB [ ]. To appraise the value of this new approach, our research group has delved into this subject. So far we have successfully encapsulated green tea polyphenols including catechin and EGCG into gold [ ], casein [ ], poly D,L-lactic-co-glycolic acid PLGA biopolymer [ ] and polylactic acid PLA — polyethylene glycol PEG co-polymer nanoparticles [Unpublished observations], which are not only eco-friendly and biodegradable in nature but have also shown high drug bioavailability and absorption capacity. For EGCG PLA-PEG nanoparticles in particular, maximum drug entrapment of Making their diffusion across the BBB possible. Furthermore, the release of the drug from the nanoparticles was also modulated to give a slow, sustained and controlled release for over 33 hours under physiological conditions, pH 7. To protect against the pH of the stomach, first pass metabolism, enzymes of the gut and food interaction, a PEG coating on nanoparticles was introduced. Therefore the encapsulation of EGCG into nanoparticles could not only help overcome all limitations of the pure drug but also enhance the neuroprotective effect of the agent. Making it a sensible option for oral drug delivery. The multi-etiological character of neurodegenerative diseases demands the need for the development of therapeutic agents capable of manipulating multiple desired targets. Green tea polyphenols, in particular EGCG is able to fulfil this criterion both in vitro and in vivo. These properties together give EGCG its neuroprotective and neurorescue abilities. Therefore, with the support from this data we propose EGCG as an iron chelating - brain permeable - antioxidant agent, which can modulate multiple brain targets. However, there is a need for examining this neuroprotective effect in depth through human clinical trials, since presently very few studies have delved into this subject. PMID: Bossy-Wetzel E, Schwarzenbacher R, Lipton S A. Molecular pathways to neurodegeneration. Nat Med. Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Article CAS PubMed PubMed Central Google Scholar. Sheridan C. Nat Biotechnol. Article CAS PubMed Google Scholar. Guo S, Bezard E, Zhao B. Protective effect of green tea polyphenols on the SH-SY5Y cells against 6-OHDA induced apoptosis through ROS-NO pathway. Free Radic Biol Med. Weinreb O, Mandel S, Amit T, Youdim MBH. J Nutr Biochem. Singh R, Akhtar N, Haqqi TM. Green tea polyphenol epigallocatechingallate: inflammation and arthritis. Life Sci. Elsevier Inc. Sharma VK, Bhattacharya A, Kumar A, Sharma HK. Health benefits of tea consumption. Trop J Pharm Res. Article Google Scholar. Lambert JD, Elias RJ. The antioxidant and pro-oxidant activities of green tea polyphenols: A role in cancer prevention. Arch Biochem Biophys. Nie G, Jin C, Cao Y, Shen S, Zhao B. Distinct effects of tea catechins on 6-hydroxydopamine-induced apoptosis in PC12 cells. Unno K, Takabayashi F, Kishido T, Oku N. Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence SAMP Exp Gerontol. Unno K, Takabayashi F, Yoshida H, Choba D, Fukutomi R, Kikunaga N, et al. Daily consumption of green tea catechin delays memory regression in aged mice. Schaffer S, Asseburg H, Kuntz S, Muller WE, Eckert GP. Mol Neurobiol. Lim HJ, Shim SB, Jee SW, Lee SH, Lim CJ, Hong JT, et al. Levites Y, Amit T, Youdim MBH, Mandel S. J Biol Chem. Mandel SA, Avramovich-Tirosh Y, Reznichenko L, Zheng H, Weinreb O, Amit T, et al. Multifunctional activities of green tea catechins in neuroprotection. Kalfon L, Youdim MBH, Mandel SA. Green tea polyphenol - -epigallocatechingallate promotes the rapid protein kinase C- and proteasome-mediated degradation of Bad: Implications for neuroprotection. J Neurochem. Khokhar S, Magnusdottir SGM. Total phenol, catechin, and caffeine contents of teas commonly consumed in the United Kingdom. J Agric Food Chem. Nanjo F, Goto K, Seto R, Suzuki M, Sakai M, Hara Y. Scavenging effects of tea catechins and their derivatives on 1,1- diphenylpicrylhydrazyl radical. Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar H. Targeting multiple signaling pathways by green tea polyphenol - -epigallocatechingallate. Cancer Res. Chan DK, Woo J, Ho SC, Pang CP, Law LK, Ng PW, et al. J Neurol Neurosurg Psychiatry. Ritchie K, Lovestone S. The dementias. Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, et al. Green tea consumption and cognitive function: A cross-sectional study from the Tsurugaya Project. Am J Clin Nutr. CAS PubMed Google Scholar. Kennedy DO, Wightman EL. Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Adv Nutr. Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT, Swanson PD. Am J Epidemiol. Article PubMed Google Scholar. Li F-J, Ji H-F, Shen L. Hu G, Bidel S, Jousilahti P, Antikainen R, Tuomilehto J. Mov Disord. Gao X, Cassidy A, Schwarzschild MA, Rimm EB, Ascherio A. Habitual intake of dietary flavonoids and risk of Parkinson disease. Quintana JLB, Allam MF, Castillo AS, Navajas RF-C. J Am Coll Nutr. Article CAS Google Scholar. Tan E-K, Tan C, Fook-Chong SMC, Lum SY, Chai A, Chung H, et al. J Neurol Sci. Lee MJ, Wang ZY, Li H, Chen L, Sun Y, Gobbo S, et al. Analysis of plasma and urinary tea polyphenols in human subjects. Cancer EpidemiolBiomarkers Prev. CAS Google Scholar. Nakagawa K, Okuda S, Miyazawa T. Dose-dependent incorporation of tea catechins, - -epigallocatechingallate and - -epigallocatechin, into human plasma. Biosci Biotechnol Biochem. Nie G, Cao Y, Zhao B. Protective effects of green tea polyphenols and their major component, - -epigallocatechingallate EGCG , on 6-hydroxydopamine-induced apoptosis in PC12 cells. Redox Rep. Van Acker SABE, Van Den Berg DJ, Tromp MNJL, Griffioen DH, Van Bennekom WP, Van Der Vijgh WJF, et al. Structural aspects of antioxidant activity of flavonoids. Grinberg LN, Newmark H, Kitrossky N, Rahamim E, Chevion M, Rachmilewitz EA. Protective effects of tea polyphenols against oxidative damage to red blood cells. Biochem Pharmacol. Solanki I, Parihar P, Mansuri ML, Parihar MS. Flavonoid-based therapies in the early management of neurodegenerative diseases. Abd El Mohsen MM, Kuhnle G, Rechner AR, Schroeter H, Rose S, Jenner P, et al. Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Zhang B, Rusciano D, Osborne NN. Orally administered epigallocatechin gallate attenuates retinal neuronal death in vivo and light-induced apoptosis in vitro. Brain Res. Stefanis L. Cold Spring Harb Perspect Med. Article PubMed PubMed Central CAS Google Scholar. Bagad M, Chowdhury D, Khan ZA. Res J Pharm Biol Chem Sci. Birch AM, Katsouri L, Sastre M. J Neuroinflammation. Di Domenico F, Cenini G, Sultana R, Perluigi M, Uberti D, Memo M, et al. Neurochem Res. Zhang H, Zhang Y-W, Chen Y, Huang X, Zhou F, Wang W, et al. Appoptosin is a novel pro-apoptotic protein and mediates cell death in neurodegeneration. J Neurosci. Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol. Sadrzadeh SM, Saffari Y. Iron and brain disorders. Am J Clin Pathol. Albarracin SL, Stab B, Casas Z, Sutachan JJ, Samudio I, Gonzalez J, et al. Effects of natural antioxidants in neurodegenerative disease. Nutr Neurosci. Youdim MBH. Exp Neurobiol. Article PubMed PubMed Central Google Scholar. Cavet ME, Harrington KL, Vollmer TR, Ward KW, Zhang J-Z. Anti-inflammatory and anti-oxidative effects of the green tea polyphenol epigallocatechin gallate in human corneal epithelial cells. Mol Vis. CAS PubMed PubMed Central Google Scholar. Li M-J, Yin Y-C, Wang J, Jiang Y-F. Green tea compounds in breast cancer prevention and treatment. World J Clin Oncol. Babu PVA, Liu D. Green tea catechins and cardiovascular health: an update. Curr Med Chem. Bahadoran Z, Mirmiran P, Azizi F. Dietary polyphenols as potential nutraceuticals in management of diabetes: a review. J Diabetes Metab Disord. |
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EGCG from green tea more potent than Quercetin?EGCG and neurodegenerative diseases -
Authors of a Chinese study sought to determine whether green tea polyphenols are effective and safe in the treatment of de novo PD patients who took no antiparkinsonism drugs. Outcome measures were progression of motor dysfunction and cognition, mood and quality of daily life ClinicalTrials.
The mutation results in an elongated stretch of glutamine near the NH 2 terminus of the protein. HD symptoms mainly occur as adult-onset HD between age 35 and 50 and comprise personality changes, generalised motor dysfunctions, cognitive decline and neuroendocrine disturbances [ , ].
Growing evidence suggests that the misfolding and aggregation of htt is central to HD pathogenesis. The screening of a library of natural compounds identified EGCG and related polyphenols as potent inhibitors of mutant htt exon 1 protein aggregation in vitro.
Additionally, EGCG modulated misfolding as well as the assembly of oligomers in cell-free assays and reduced both toxicity and aggregate formation in yeast and fly models of HD [ 29 ]. Memory disturbances in rats caused by 3-NP treatment were attenuated by chronic EGCG treatment.
Striatal, cortical and hippocampal glutathione levels of the rats were significantly reduced by 3-NP treatment that was reversed by chronic EGCG treatment. These effects were attributed to NOS inhibition as evidenced by the application of NO modulators l -arginine and l -NG-nitroarginine methyl ester [ 30 ].
A multicenter trial evaluating the efficiency and tolerability of EGCG in HD patients is currently ongoing. Primary outcome measures are changes of cognitive functions as measured by UHDRS-Cognition composite score of Stroop test, verbal fluency and Symbol Digit Modalities Test after 12 months maximal daily intake of 1, mg EGCG compared to baseline intake ClinicalTrials.
Another disease, in which the generation of ROS seems to play an important pathogenic role, is Duchenne muscular dystrophy DMD [ — ]. DMD is a severe X-linked congenital disorder characterised by progressive muscle wasting caused by the absence of the structural protein dystrophin. The pathogenesis of DMD is frequently studied in the dystrophic mdx mouse model.
Dietary GTE supplementation preferentially protected the elongator digitorum longus muscle rather than the soleus muscle of mdx mice from necrosis [ 31 ]. Histological examination of leg muscles and functional recordings of the triceps surae muscle contraction showed that GTE and EGCG protected the hindlimb muscle of dystrophic mice from massive necrosis and greatly improved muscle force and resistance to fatigue [ 32 ].
A study on cultured muscle cells from mdx dystrophic mice showed that green tea polyphenols and EGCG offer both immediate antioxidant effects and long-term prevention by stimulating glutathione synthesis and protect against H 2 O 2 toxicity [ 34 ].
The above mentioned findings were recently extended to study different administration routes and dosages of EGCG to find the most effective for limiting the onset of dystrophic lesions in both the same strain of mdx mice and assessment methods.
Endurance training i. voluntary wheel running and 0. Prenatal and early dietary intervention with GTE decreased dystrophic muscle pathology potentially by suppressing NF-κB activity in regenerating fibres of mdx mice [ 36 ]. In light of this considerable body of evidence, clinical studies in DMD patients should be performed.
One registered multicenter, prospective, double blind, placebo-controlled randomised pilot study is investigating safety and tolerance of EGCG in boys with muscular dystrophy of the Duchenne type ClinicalTrials. Amyotrophic lateral sclerosis ALS is a fatal neurodegenerative disorder in which degeneration of upper and lower motor neurons leads to progressive muscle weakness and atrophy [ , ].
In recent years, non-motor involvement has been increasingly reported in ALS [ — ]; a clinical, pathological and genetic continuum with frontotemporal dementia has been acknowledged [ , ].
Moreover, it became evident that inflammatory mechanisms, including microglial activation, contribute not only to neuronal cell death but may also promote neuronal survival [ , — ]. Drugs targeting inflammatory pathways showed beneficial effects on survival in transgenic ALS mouse models [ ].
The disease onset delaying and survival prolonging effects of oral EGCG treatment in ALS mice were confirmed by another study. EGCG protected the motor neurons and reduced microglia activation and associated iNOS expression, such as NF-κB and caspase-3 [ 38 ].
Another widely used model to study ALS employs threohydroxyaspartate THA , an inhibitor of glutamate transport, to induce motor neuron death in cultured rat spinal cord explants.
In this model, EGCG protected motor neurons against THA-induced toxicity, which was accompanied by regulation of glutamate levels in the synaptic cleft, and decreased tissue levels of lipid peroxides [ 39 ]. Stroke is the second most common cause of death and major cause of disability worldwide [ ].
Temporary or permanent reduction of blood flow deprives the brain of oxygen and glucose which causes structural damage during ischaemia and reperfusion [ 43 , ]. Neuronal cell death is delayed for several days after ischaemic insult and is restricted to sensitive areas of the brain, such as the hippocampus and the striatum [ 52 ].
Possible neuroprotective effects of EGCG on cerebral ischaemia have been studied extensively in animal models. Consequently, EGCG might not be an appropriate intervention for the acute treatment of ischaemic stroke [ 46 ].
To the best of our knowledge, there are no clinical studies addressing effects of EGCG in human stroke. Some evidence from animal and human studies indicates a possible contribution of EGCG in the prevention of cognitive decline. Increased release of glutamate from CNS neurons is considered to be an indicator of maintenance of cognitive functions, such as learning and memory [ , ].
This release was linked to the activation of protein kinase C PKC and cytoskeleton disassembly [ ]. Long-term 26 weeks administration of green tea catechins to rats improved their performance in radial maze tasks and hippocampal levels of lipid peroxides.
Consequently, green tea catechins may be involved in protecting against neuronal degenerative stress and in the accumulation of lipid peroxides and ROS [ ]. As a result, neuronal cell degeneration and apoptotic cell death around the damaged area were inhibited, and brain dysfunction was improved [ ].
Fatigue is an overwhelming sense of tiredness or lack of energy, affecting both mental and physical domains. In a rat model of load-induced chronic fatigue syndrome, EGCG restored all behavioural and biochemical alterations produced by chronic fatigue [ ].
There are, albeit limited, data on the effects of EGCG on human cognition. A cross-sectional analysis of a self-administered questionnaire showed that higher green tea consumption is associated with less prevalent cognitive impairment in elderly Japanese subjects [ ].
In a double-blind, placebo-controlled, balanced crossover study, the effects of oral doses of EGCG on cerebral blood flow in the frontal cortex during tasks that activate this brain region and cognitive performance were investigated. A single dose of mg EGCG reduced cerebral blood flow during task performance.
However, this was not associated with any significant modulation of either cognitive performance or mood [ ]. Ageing is the progressive accumulation of changes over time that is associated with, or responsible for, increasing susceptibility to disease and death [ ].
Oxidative stress has been associated with both the ageing process and the development of age-dependent tissue degenerative pathologies. The nematode Caenorhabditis elegans is a tiny roundworm of 1 to 2 mm in length that colonises various microbe-rich habitats, in particular, decaying plant matter.
Due to its rapid lifecycle, it is one of the major model organisms in ageing, genetic, molecular and other biological observations [ — ].
EGCG attenuated age-related pharyngeal contraction decline, moderately alleviated Aβ-induced behavioural pathologies and sustained an increased chemotactic behaviour.
However, there were no significant increases in mean or maximal life span due to EGCG feeding [ ]. This was confirmed by another study that found no significant longevity-extending effects of EGCG in C.
elegans under normal culture conditions but with extension of life span by EGCG under heat and oxidative stress [ ]. In another investigation on wild-type N2 and transgenic strains of C.
elegans , EGCG administration increased the mean lifespan, inhibited heat shock protein expression and decreased intracellular H 2 O 2 levels [ ].
A systematic study on the effects of EGCG on ageing and ageing promoting factors, such as ROS accumulation, mitochondrial integrity and antioxidative enzyme activity in human fibroblasts, directly linked mitochondrial integrity to the efficiency of the antioxidant defence system in the ageing process [ ].
In mice in which ageing had been induced by d —galactose, EGCG improved learning and memory functions, increased SOD and glutathione peroxidase activities and decreased the hippocampal malondialdehyde content and neuronal apoptosis [ ].
Several neuronal systems, such as dopaminergic, cholinergic and serotoninergic ones, undergo alterations during ageing. Rats supplemented with EGCG had increased cortical neurotransmitter levels dopamine, acetylcholine and serotonin and acetylcholine esterase activity and performed better in radial maze experiments when compared to aged-matched controls [ ].
Owing to their reducing ability, antioxidant compounds can activate transition metal ions e. Yoshioka et al.
Interestingly, a mixture of the four tea catechins Polyphenon and individual tea catechins differently modulated human cytochrome P 1A expression. The underlying mechanisms of increased effectiveness of green tea and a catechin mixture compared to single catechins were not elucidated in this study [ ].
Under in vitro conditions, catechins exerted antioxidant and antiapoptotic properties at low concentrations 1 to 50 μM , whereas at higher concentrations to μM the reverse was observed [ ].
It was demonstrated that GTE and EGCG inhibit cell growth and induce cell death at concentrations of 10 to 20 μM. In murine macrophage and human leukemic cell lines, EGCG increased H 2 O 2 -induced oxidative stress and DNA damage.
The oxidant activity of EGCG exceeded that of H 2 O 2. Therefore, excessive EGCG concentrations could induce toxic levels of ROS in vivo [ ]. EGCG dose-dependently inhibited the growth of H cells in culture and in xenograft tumours and induced ROS formation both in vitro and in vivo [ ].
In murine and human plasma, EGCG concentrations up to 4 μM were reported after single doses [ — ]. However, repeated doses might lead to higher concentrations with possible deleterious effects.
In healthy adult mice fed with diets containing none, moderate 0. While no influence of moderate EGCG levels was observed, the high dose significantly elevated several pro-inflammatory markers. This was accompanied by significant weight loss without visible toxicity as assessed by the histological examination of several key organs [ ].
For several reasons, extrapolation of these animal data to the human situation is difficult, if not impossible. It has to be ensured that patients treated with EGCG benefit from its antioxidative effects and, at the same time, are not harmed by pro-oxidative effects.
Factors that could lead to conflicting results between in vitro and in vivo studies are varying degrees of responsiveness to EGCG in patients responder vs.
non-responder , poor bioavailability cave:blood sample collection that is influenced by autoxidation air contact or metal ions in food and water calcium, magnesium and iron , extensive biotransformation in the liver and variations in serum albumin levels.
To avoid potential side effects, clinical trials should include close attention to patients, control of liver enzymes and regular determination of outcome measures. EGCG is thought to interfere with several pathways in numerous neurological functions in health and disease. Despite a considerable body of evidence from cell and animal models, there is a lack of epidemiological and clinical studies on potential health benefits of EGCG in patients with the neurological conditions discussed.
Within the clinical studies, the number of subjects is mostly rather small and patients are not well phenotyped or standardised regarding disease severity and duration. Green tea preparations and GTEs are also not standardised.
Therefore, optimum dose of EGCG for preventing or treating a disease is still a matter of debate. Before EGCG can be recommended as a targeted prevention and individualised treatment to patients, the plasma and brain bioavailability, dose-response effects, safety, tolerability, efficacy and possible interactions with other drugs have to be studied in more detail and in a disease-specific manner.
For a number of clinical effects the underlying mechanisms are still unclear. Because EGCG is acting on so many different routes neuro-endocrine, metabolic, defence and others , studies with an integrated approach are strongly needed. This will be, however, a cost-intensive and time consuming endeavour.
EPMA J. PubMed PubMed Central Google Scholar. Uttara B, Singh AV, Zamboni P, Mahajan RT: Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options.
Curr Neuropharmacol. CAS PubMed PubMed Central Google Scholar. Rose RC, Bode AM: Biology of free radical scavengers: an evaluation of ascorbate. FASEB J. CAS PubMed Google Scholar.
Letelier ME, Sanchez-Jofre S, Peredo-Silva L, Cortes-Troncoso J, Aracena-Parks P: Mechanisms underlying iron and copper ions toxicity in biological systems: pro-oxidant activity and protein-binding effects. Chem Biol Interact.
Graham HN: Green tea composition, consumption, and polyphenol chemistry. Prev Med. Sang S, Lambert JD, Ho CT, Yang CS: The chemistry and biotransformation of tea constituents.
Pharmacol Res. Balentine DA, Wiseman SA, Bouwens LC: The chemistry of tea flavonoids. Crit Rev Food Sci Nutr. Mandel SA, Youdim MB: In the rush for green gold: can green tea delay age-progressive brain neurodegeneration?. Recent Pat CNS Drug Discov. Aktas O, Prozorovski T, Smorodchenko A, Savaskan NE, Lauster R, Kloetzel PM, Infante-Duarte C, Brocke S, Zipp F: Green tea epigallocatechingallate mediates T cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune encephalomyelitis.
J Immunol. Herges K, Millward JM, Hentschel N, Infante-Duarte C, Aktas O, Zipp F: Neuroprotective effect of combination therapy of glatiramer acetate and epigallocatechingallate in neuroinflammation. PLoS One. Am J Pathol. Life Sci. Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, Ehrhart J, Townsend K, Zeng J, Morgan D, Hardy J, Town T, Tan J: Green tea epigallocatechingallate EGCG modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice.
J Neurosci. J Nutr. Kim CY, Lee C, Park GH, Jang JH: Neuroprotective effect of epigallocatechingallate against beta-amyloid-induced oxidative and nitrosative cell death via augmentation of antioxidant defense capacity.
Arch Pharm Res. Bieschke J, Russ J, Friedrich RP, Ehrnhoefer DE, Wobst H, Neugebauer K, Wanker EE: EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity.
Proc Natl Acad Sci U S A. J Neurosci Res. Chan DK, Woo J, Ho SC, Pang CP, Law LK, Ng PW, Hung WT, Kwok T, Hui E, Orr K, Leung MF, Kay R: Genetic and environmental risk factors for Parkinson's disease in a Chinese population. J Neurol Neurosurg Psychiatry. Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT, Swanson PD: Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake.
Am J Epidemiol. PubMed Google Scholar. Hu G, Bidel S, Jousilahti P, Antikainen R, Tuomilehto J: Coffee and tea consumption and the risk of Parkinson's disease. Mov Disord. Kandinov B, Giladi N, Korczyn AD: Smoking and tea consumption delay onset of Parkinson's disease.
Parkinsonism Relat Disord. Redox Rep. BMC Complement Altern Med. J Neurochem. Leaver KR, Allbutt HN, Creber NJ, Kassiou M, Henderson JM: Oral pre-treatment with epigallocatechin gallate in 6-OHDA lesioned rats produces subtle symptomatic relief but not neuroprotection.
Brain Res Bull. J Clin Neurosci. Hum Mol Genet. Kumar P, Kumar A: Effect of lycopene and epigallocatechingallate against 3-nitropropionic acid induced cognitive dysfunction and glutathione depletion in rat: a novel nitric oxide mechanism. Food Chem Toxicol.
Buetler TM, Renard M, Offord EA, Schneider H, Ruegg UT: Green tea extract decreases muscle necrosis in mdx mice and protects against reactive oxygen species. Am J Clin Nutr. Am J Physiol Cell Physiol. Nakae Y, Hirasaka K, Goto J, Nikawa T, Shono M, Yoshida M, Stoward PJ: Subcutaneous injection, from birth, of epigallocatechingallate, a component of green tea, limits the onset of muscular dystrophy in mdx mice: a quantitative histological, immunohistochemical and electrophysiological study.
Histochem Cell Biol. Call JA, Voelker KA, Wolff AV, McMillan RP, Evans NP, Hulver MW, Talmadge RJ, Grange RW: Endurance capacity in maturing mdx mice is markedly enhanced by combined voluntary wheel running and green tea extract.
J Appl Physiol. Evans NP, Call JA, Bassaganya-Riera J, Robertson JL, Grange RW: Green tea extract decreases muscle pathology and NF-kappaB immunostaining in regenerating muscle fibers of mdx mice. Clin Nutr. Koh SH, Lee SM, Kim HY, Lee KY, Lee YJ, Kim HT, Kim MH, Hwang MS, Song C, Yang KW, Lee KW, Kim SH, Kim OH: The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice.
Neurosci Lett. Neurochem Res. Yu J, Jia Y, Guo Y, Chang G, Duan W, Sun M, Li B, Li C: Epigallocatechingallate protects motor neurons and regulates glutamate level.
FEBS Lett. Lee H, Bae JH, Lee SR: Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils. Wu KJ, Hsieh MT, Wu CR, Wood WG, Chen YF: Green tea extract ameliorates learning and memory deficits in ischemic rats via its active component polyphenol epigallocatechingallate by modulation of oxidative stress and neuroinflammation.
Evid Based Complement Alternat Med. Google Scholar. Choi YB, Kim YI, Lee KS, Kim BS, Kim DJ: Protective effect of epigallocatechin gallate on brain damage after transient middle cerebral artery occlusion in rats.
Brain Res. Suzuki M, Tabuchi M, Ikeda M, Umegaki K, Tomita T: Protective effects of green tea catechins on cerebral ischemic damage. Med Sci Monit. Hong JT, Ryu SR, Kim HJ, Lee JK, Lee SH, Kim DB, Yun YP, Ryu JH, Lee BM, Kim PY: Neuroprotective effect of green tea extract in experimental ischemia-reperfusion brain injury.
Ding J, Fu G, Zhao Y, Cheng Z, Chen Y, Zhao B, He W, Guo LJ: EGCG ameliorates the suppression of long-term potentiation induced by ischemia at the Schaffer collateral-CA1 synapse in the rat. Cell Mol Neurobiol. J Nutr Biochem. Arab L, Liu W, Elashoff D: Green and black tea consumption and risk of stroke: a meta-analysis.
J Nutr Sci Vitaminol Tokyo. CAS Google Scholar. Zini A, Del RD, Stewart AJ, Mandrioli J, Merelli E, Sola P, Nichelli P, Serafini M, Brighenti F, Edwards CA, Crozier A: Do flavanols from green tea reach the human brain?.
Nutr Neurosci. J Agric Food Chem. Mandel SA, Amit T, Weinreb O, Youdim MB: Understanding the broad-spectrum neuroprotective action profile of green tea polyphenols in aging and neurodegenerative diseases.
J Alzheimers Dis. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J: Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol.
Yin JJ, Fu PP, Lutterodt H, Zhou YT, Antholine WE, Wamer W: Dual role of selected antioxidants found in dietary supplements: crossover between anti- and pro-oxidant activities in the presence of copper. Jomova K, Vondrakova D, Lawson M, Valko M: Metals, oxidative stress and neurodegenerative disorders.
Mol Cell Biochem. Pacher P, Beckman JS, Liaudet L: Nitric oxide and peroxynitrite in health and disease. Physiol Rev. Stamler JS, Singel DJ, Loscalzo J: Biochemistry of nitric oxide and its redox-activated forms. Frei B, Higdon JV: Antioxidant activity of tea polyphenols in vivo: evidence from animal studies.
Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR: Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci. Ho YS, Magnenat JL, Gargano M, Cao J: The nature of antioxidant defense mechanisms: a lesson from transgenic studies.
Environ Health Perspect. Int J Dev Neurosci. J Mol Med Berl. McCarty MF: Down-regulation of microglial activation may represent a practical strategy for combating neurodegenerative disorders.
Med Hypotheses. Hunot S, Boissiere F, Faucheux B, Brugg B, Mouatt-Prigent A, Agid Y, Hirsch EC: Nitric oxide synthase and neuronal vulnerability in Parkinson's disease. Le W, Rowe D, Xie W, Ortiz I, He Y, Appel SH: Microglial activation and dopaminergic cell injury: an in vitro model relevant to Parkinson's disease.
Free Radic Biol Med. Sinnecker T, Mittelstaedt P, Dorr J, Pfueller CF, Harms L, Niendorf T, Paul F, Wuerfel J: Multiple sclerosis lesions and irreversible brain tissue damage: a comparative ultrahigh-field strength magnetic resonance imaging study.
Arch Neurol. Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H: Cortical demyelination and diffuse white matter injury in multiple sclerosis. Bock M, Brandt AU, Dorr J, Kraft H, Weinges-Evers N, Gaede G, Pfueller CF, Herges K, Radbruch H, Ohlraun S, Bellmann-Strobl J, Kuchenbecker J, Zipp F, Paul F: Patterns of retinal nerve fiber layer loss in multiple sclerosis patients with or without optic neuritis and glaucoma patients.
Clin Neurol Neurosurg. Bock M, Brandt AU, Dorr J, Pfueller CF, Ohlraun S, Zipp F, Paul F: Time domain and spectral domain optical coherence tomography in multiple sclerosis: a comparative cross-sectional study. Mult Scler. Compston A, Coles A: Multiple sclerosis.
Dorr J, Wernecke KD, Bock M, Gaede G, Wuerfel JT, Pfueller CF, Bellmann-Strobl J, Freing A, Brandt AU, Friedemann P: Association of retinal and macular damage with brain atrophy in multiple sclerosis.
Dutta R, Trapp BD: Pathogenesis of axonal and neuronal damage in multiple sclerosis. Gordon-Lipkin E, Chodkowski B, Reich DS, Smith SA, Pulicken M, Balcer LJ, Frohman EM, Cutter G, Calabresi PA: Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis.
Oberwahrenbrock T, Schippling S, Ringelstein M, Kaufhold F, Zimmermann H, Keser N, Young KL, Harmel J, Hartung H-P, Martin R, Paul F, Aktas O, Brandt AU: Retinal damage in multiple sclerosis disease subtypes measured by high-resolution optical coherence tomography.
Mult Scler Int. Pfueller CF, Brandt AU, Schubert F, Bock M, Walaszek B, Waiczies H, Young KL, Harmel J, Hartung HP, Martin R, Paul F, Aktas O, Brandt AU: Metabolic changes in the visual cortex are linked to retinal nerve fiber layer thinning in multiple sclerosis.
Vogt J, Paul F, Aktas O, Muller-Wielsch K, Dorr J, Dorr S, Bharathi BS, Glumm R, Schmitz C, Steinbusch H, Raine CS, Tsokos M, Nitsch R, Zipp F: Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis.
Ann Neurol. Brandt AU, Oberwahrenbrock T, Ringelstein M, Young KL, Tiede M, Hartung HP, Martin R, Aktas O, Paul F, Schippling S: Primary retinal pathology in multiple sclerosis as detected by optical coherence tomography.
Zimmermann H, Freing A, Kaufhold F, Gaede G, Bohn E, Bock M, Oberwahrenbrock T, Young KL, Dörr J, Wuerfel JT, Schippling S, Paul F, Brandt AU: Optic neuritis interferes with optical coherence tomography and magnetic resonance imaging correlations.
Borisow N, Doring A, Pfueller CF, Paul F, Dorr J, Hellwig K: Expert recommendations to personalization of medical approaches in treatment of multiple sclerosis: an overview of family planning and pregnancy. Handel AE, Jarvis L, McLaughlin R, Fries A, Ebers GC, Ramagopalan SV: The epidemiology of multiple sclerosis in Scotland: inferences from hospital admissions.
Simmons RD, Tribe KL, McDonald EA: Living with multiple sclerosis: longitudinal changes in employment and the importance of symptom management. J Neurol. Sundstrom P, Nystrom L: Smoking worsens the prognosis in multiple sclerosis. Hawkes CH: Smoking is a risk factor for multiple sclerosis: a metanalysis.
Doring A, Paul F, Dorr J: Vitamin D and multiple sclerosis: the role for risk of disease and treatment. D'hooghe MB, Haentjens P, Nagels G, Garmyn M, De KJ: Sunlight exposure and sun sensitivity associated with disability progression in multiple sclerosis.
Munger KL, Ascherio A: Prevention and treatment of MS: studying the effects of vitamin D. Handel AE, Ramagopalan SV: Vitamin D and multiple sclerosis: an interaction between genes and environment. Goodin DS: The causal cascade to multiple sclerosis: a model for MS pathogenesis.
Handel AE, Williamson AJ, Disanto G, Dobson R, Giovannoni G, Ramagopalan SV: Smoking and multiple sclerosis: an updated meta-analysis. Handel AE, Williamson AJ, Disanto G, Handunnetthi L, Giovannoni G, Ramagopalan SV: An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis.
Smolders J, Thewissen M, Peelen E, Menheere P, Tervaert JW, Damoiseaux J, Hupperts R: Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. Lucas RM, Ponsonby AL, Dear K, Valery PC, Pender MP, Taylor BV, Kilpatrick TJ, Dwyer T, Coulthard A, Chapman C, van der Mei I, Williams D, McMichael AJ: Sun exposure and vitamin D are independent risk factors for CNS demyelination.
Otto C, Oltmann A, Stein A, Frenzel K, Schroeter J, Habbel P, Gärtner B, Hofmann J, Ruprecht K: Intrathecal EBV antibodies are part of the polyspecific immune response in multiple sclerosis.
De Jager PL, Jia X, Wang J, de Bakker PI, Ottoboni L, Aggarwal NT, Raychaudhuri S, Tran D, Aubin C, Briskin R, Romano S, International MS Genetics C, Baranzini SE, McCauley JL, Pericak-Vance MA, Haines JL, Gibson RA, Naeglin Y, Uitdehaag B, Matthews PM, Kappos L, Polman C, McArdle WL, Strachan DP, Evans D, Cross AH: Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
Nat Genet. Finke C, Pech LM, Sommer C, Schlichting J, Stricker S, Endres M, Ostendorf F, Ploner CJ, Brandt AU, Paul F: Dynamics of saccade parameters in multiple sclerosis patients with fatigue.
Veauthier C, Paul F: Fatigue in multiple sclerosis: which patient should be referred to a sleep specialist?. Veauthier C, Radbruch H, Gaede G, Pfueller CF, Dorr J, Bellmann-Strobl J, Wernecke KD, Zipp F, Paul F, Sieb JP: Fatigue in multiple sclerosis is closely related to sleep disorders: a polysomnographic cross-sectional study.
Urbanek C, Weinges-Evers N, Bellmann-Strobl J, Bock M, Dorr J, Hahn E, Neuhaus AH, Opgen-Rhein C, Ta TM, Herges K, Pfueller CF, Radbruch H, Wernecke KD, Ohlraun S, Zipp F, Dettling M, Paul F: Attention Network Test reveals alerting network dysfunction in multiple sclerosis.
Weinges-Evers N, Brandt AU, Bock M, Pfueller CF, Dorr J, Bellmann-Strobl J, Scherer P, Urbanek C, Boers C, Ohlraun S, Zipp F, Paul F: Correlation of self-assessed fatigue and alertness in multiple sclerosis.
Bates D: Treatment effects of immunomodulatory therapies at different stages of multiple sclerosis in short-term trials. Bae, Y. Seong, et al. Shimmyo, T. Kihara, A. Akaike, et al. Lee, Y. Lee, J. Ban, et al. Lee, D. Yuk, J. Lee, et al. Choi, Y. Yun, et al. Leissring, M. Murphy, T. Mead, et al.
Andrich, J. Bieschke, The effect of — -epigallo-catechin- 3 -gallate on amyloidogenic proteins suggests a common mechanism, Adv. Cascella, S. Bimonte, M. Muzio, et al. Cancer 12 Soto, E. Sigurdsson, L. Morelli, et al. Cohen, J. Kelly, Therapeutic approaches to protein-misfolding diseases, Nature Haass, D.
Selkoe, Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide, Nat. Cell Biol. Hunstein, Epigallocathechingallate in AL amyloidosis: a new therapeutic option? Blood Bieschke, R. Russ, R. Friedrich, et al. Grelle, A. Otto, M.
Lorenz, et al. Gauci, M. Caruana, A. Giese, et al. Palhano, J. Lee, N. Grimster, et al. Lorenzen, S. Nielsen, Y. Yoshimura, et al. Ehrnhoefer, M. Duennwald, P. Markovic, et al. Meng, A. Abedini, A. Plesner, et al. Ferreira, M.
Saraiva, M. Almeida, Natural polyphenols inhibit different steps of the process of transthyretin TTR amyloid fibril formation, FEBS Lett. Lopez del Amo, U. Fink, M. Dasari, et al. Ehrnhoefer, J. Bieschke, A. Boeddrich, et al. Cheng, B. Hau, A. Veloso, et al. Hyung, A.
DeToma, J. Brender, et al. Zhang, X. Cheng, I. da Silva, et al. Liu, X. Dong, L. He, et al. Wang, F. Dong, et al. Wang, X.
Dong, Y. Sun, Thermodynamic analysis of the molecular interactions between amyloid beta-protein fragments and — -epigallocatechingallate, J. Nguyen, P. Zhang, J. Zhang, P. Derreumaux, et al. B Ahmed, B. VanSchouwen, N. Jafari, et al. Zhan, Y. Chen, Y. Tang, et al. Tavanti, A. Pedone, M. Menziani, Insights into the effect of curcumin and — -epigallocatechingallate on the aggregation of A β monomers by means of molecular dynamics, Int.
Melzig, M. Janka, Enhancement of neutral endopeptidase activity in SK-N-SH cells by green tea extract, Phytomedicine 10 Yamamoto, M. Shibata, R. Ishikuro, et al. Chang, C. Rong, Y. Chen, et al. Cell Res. Choi, C. Jung, S. Kim, C. Lee, G. Park, et al.
Dragicevic, A. Smith, X. Kim, H. Jeong, K. Wei, H. Huang, W. Zhang, Y. Li, R. Link to publication in Scopus. Link to the citations in Scopus. Fingerprint Dive into the research topics of 'Multifaceted neuroprotective effects of - -epigallocatechingallate EGCG in Alzheimer's disease: an overview of pre-clinical studies focused on β-amyloid peptide'.
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In: Food Science and Human Wellness. In: Food Science and Human Wellness , Vol. TY - JOUR T1 - Multifaceted neuroprotective effects of - -epigallocatechingallate EGCG in Alzheimer's disease T2 - an overview of pre-clinical studies focused on β-amyloid peptide AU - Youn, Kumju AU - Ho, Chi Tang AU - Jun, Mira N1 - Funding Information: This research was supported by Dong-A University.
Nutrition EGCG and neurodegenerative diseases volume 15Dixeases number: 60 Cite this article. Metrics details. EEGCG are ahd EGCG and neurodegenerative diseases CrossFit-style workouts the accumulation of modified proteins, which further Immune-boosting vitamins Website performance statistics responses such as inflammation, oxidative stress, excitotoxicity and modulation of signalling pathways. In a hope for cure, these diseases have been studied extensively over the last decade to successfully develop symptom-oriented therapies. However, so far no definite cure has been found. Therefore, there is a need to identify a class of drug capable of reversing neural damage and preventing further neural death.
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