PMID: 

Neurobiol Dis. 2006 May ;22(2):421-34. Epub 2006 Feb 9. PMID: 16480889

Abstract Title: 

Neuroprotective and neurorescue effect of black tea extract in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

Abstract: 

In the present study, an attempt has been made to explore the neuroprotective and neuroreparative (neurorescue) effect of black tea extract (BTE) in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In the neuroprotective (BTE + 6-OHDA) and neurorescue (6-OHDA + BTE) experiments, the rats were given 1.5% BTE orally prior to and after intrastriatal 6-OHDA lesion respectively. A significant recovery in d-amphetamine induced circling behavior (stereotypy), spontaneous locomotor activity, dopamine (DA)-D2 receptor binding, striatal DA and 3-4 dihydroxy phenyl acetic acid (DOPAC) level, nigral glutathione level, lipid peroxidation, striatal superoxide dismutase and catalase activity, antiapoptotic and proapoptotic protein level was evident in BTE + 6-OHDA and 6-OHDA + BTE groups, as compared to lesioned animals. BTE treatment, either before or after 6-OHDA administration protected the dopaminergic neurons, as evident by significantly higher number of surviving tyrosine hydroxylase immunoreactive (TH-ir) neurons, increased TH protein level and TH mRNA expression in substantia nigra. However, the degree of improvement in motor and neurochemical deficits was more prominent in rats receiving BTE before 6-OHDA. Results suggest that BTE exerts both neuroprotective and neurorescue effects against 6-OHDA-induced degeneration of the nigrostriatal dopaminergic system, suggesting that possibly daily intake of BTE may slow down the PD progression as well as delay the onset of neurodegenerative processes in PD.

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PMID: 

Curr Alzheimer Res. 2007 Sep ;4(4):403-11. PMID: 17908043

Abstract Title: 

Neurorescue activity, APP regulation and amyloid-beta peptide reduction by novel multi-functional brain permeable iron- chelating- antioxidants, M-30 and green tea polyphenol, EGCG.

Abstract: 

Accumulation of iron at sites where neurons degenerate in Parkinson's disease (PD) and Alzheimer's disease (AD) is thought to have a major role in oxidative stress induced process of neurodegeneration. The novel non-toxic lipophilic brain- permeable iron chelators, VK-28 (5- [4- (2- hydroxyethyl) piperazine-1-ylmethyl]- quinoline- 8- ol) and its multi-functional derivative, M-30 (5-[N-methyl-N-propargylaminomethyl]-8-hydroxyquinoline), as well as the main polyphenol constituent of green tea (-)-epigallocatechin-3-gallate (EGCG), which possesses iron metal chelating, radical scavenging and neuroprotective properties, offer potential therapeutic benefits for these diseases. M-30 and EGCG decreased apoptosis of human SH-SY5Y neuroblastoma cells in a neurorescue, serum deprivation model, via multiple protection mechanisms including: reduction of the pro-apoptotic proteins, Bad and Bax, reduction of apoptosis-associated Ser139 phosphorylated H2A.X and inhibition of the cleavage and activation of caspase-3. M-30 and EGCG also promoted morphological changes, resulting in axonal growth-associated protein-43 (GAP-43) implicating neuronal differentiation. Both compounds significantly reduced the levels of cellular holo-amyloid precursor protein (APP) in SH-SY5Y cells. The ability of theses novel iron chelators and EGCG to regulate APP are in line with the presence of an iron-responsive element (IRE) in the 5'-untranslated region (5'UTR) of APP. Also, EGCG reduced the levels of toxic amyloid-beta peptides in CHO cells over-expressing the APP"Swedish"mutation. The diverse molecular mechanisms and cell signaling pathways participating in the neuroprotective/neurorescue and APP regulation/processing actions of M-30 and EGCG, make these multifunctional compounds potential neuroprotective drugs for the treatment of neurodegenerative diseases, such as PD, AD, Huntington's disease and amyotrophic lateral sclerosis.

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PMID: 

Neurosci Lett. 2007 Jan 16 ;411(3):222-7. Epub 2006 Nov 20. PMID: 17116366

Abstract Title: 

Epigallocatechin gallate inhibits nitric oxide-induced apoptosis in rat PC12 cells.

Abstract: 

Nitric oxide (NO) is associated with many pathophysiology of the central nervous system including brain ischemia, neurodegeneration and inflammation. Epigallocatechin gallate (EGCG) is a major compound of green tea polyphenol that has shown the protective activity against neuronal diseases. This study examined the effect of EGCG on NO-induced cell death in PC12 cells. The administration of sodium nitroprusside (SNP), a NO donor, decreased the cell viability and induced apoptosis showing characterization such as cell shrinkage and chromatin condensation as well as subG1 fraction of cell cycles. EGCG inhibited the cytotoxicity and apoptotic morphogenic changes induced by SNP. EGCG attenuated the production of reactive oxygen species (ROS) by SNP, and ameliorated the SNP-induced Bax to Bcl-2 expression ratio leading to apoptosis. In addition, EGCG prevented the release of cytochrome c from the mitochondria into the cytosol as well as the upregulation of the voltage-dependent anion channel (VDAC), a cytochrome c releasing channel, in the mitochondria of SNP-treated cells. EGCG abrogated the activation of caspase-9, caspase-8 and caspase-3 induced by SNP. These results demonstrate that EGCG has a protective effect against SNP-induced apoptosis in PC12 cells by scavenging ROS and modulating the signal molecules associated with cytochrome c, caspases, VDAC and the Bcl-2 family. These findings suggest that EGCG might be a natural neuroprotective substance.

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PMID: 

Brain Res. 2008 Mar 10 ;1198:141-52. Epub 2007 Dec 15. PMID: 18255049

Abstract Title: 

Orally administered epigallocatechin gallate attenuates retinal neuronal death in vivo and light-induced apoptosis in vitro.

Abstract: 

The aim of this study was to provide support for epigallocatechin gallate (EGCG), a component of green tea, to be considered in the context for neuroprotection in glaucoma, where administration by an oral route is required for adequate penetration into the retina. Ischemia was delivered to one eye of a number of rats by raising the intraocular pressure. EGCG was present in the drinking water of half of the animals 3 days before ischemia and also during the next 5 days of reperfusion. The electroretinograms (ERGs) of both eyes from all rats were recorded before ischemia and 5 days following ischemia. Seven days after ischemia retinas from both eyes of all rats were either analysed for the localisation of various antigens or extracts prepared for analysis for the level of specific proteins and mRNAs. Ischemia/reperfusion to the retina affected a number of parameters. These included the localisation of Thy-1 and choline acetyltransferase, the a- and b-wave amplitudes of the ERG, the content of certain retinal and optic nerve proteins and various mRNAs. Significantly, EGCG statistically blunted many of the effects induced by ischemia/reperfusion which included the activation of caspases. These studies demonstrate conclusively that orally administered EGCG attenuates injury to the retina caused by ischemia/reperfusion where caspases were activated. Studies were also conducted on a cell line (RGC-5 cells) where it was shown that white light (1000 lx, 48 h)-induced apoptosis is caspase-independent and can be blunted by EGCG. The present studies support the view for the use of EGCG in the treatment of glaucoma based on the premise that any potential neuroprotective agent must be administered orally, have a safe profile and poses a broad spectrum of properties that allows various risk factors (that include ischemia and light) to be attenuated.

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PMID: 

Wei Sheng Yan Jiu. 2010 Jan ;39(1):123-6. PMID: 20364607

Abstract Title: 

[Review on the neuroprotective effects of green tea polyphenols for the treatment of neurodegenerative diseases].

Abstract: 

Considering the multi-etiological characters of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, the current pharmacological approaches using drugs oriented towards a single molecular target possess limited ability to modify the course of the diseases. Green tea polyphenols have been reported to possess more than two active neuroprotective-neurorescue moieties that simultaneously manipulate multiple targets involved in neurodegeneration. This review aims to shed light on the multipharmacological neuroprotective activities and the mechanisms of green tea polyphenols on neurodegenerative diseases.

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PMID: 

PLoS One. 2010 Aug 5 ;5(8):e11951. Epub 2010 Aug 5. PMID: 20700524

Abstract Title: 

Dual beneficial effects of (-)-epigallocatechin-3-gallate on levodopa methylation and hippocampal neurodegeneration: in vitro and in vivo studies.

Abstract: 

BACKGROUND: A combination of levodopa (L-DOPA) and carbidopa is the most commonly-used treatment for symptom management in Parkinson's disease. Studies have shown that concomitant use of a COMT inhibitor is highly beneficial in controlling the wearing-off phenomenon by improving L-DOPA bioavailability as well as brain entry. The present study sought to determine whether (-)-epigallocatechin-3-gallate (EGCG), a common tea polyphenol, can serve as a naturally-occurring COMT inhibitor that also possesses neuroprotective actions.METHODOLOGY/PRINCIPAL FINDINGS: Using both in vitro and in vivo models, we investigated the modulating effects of EGCG on L-DOPA methylation as well as on chemically induced oxidative neuronal damage and degeneration. EGCG strongly inhibited human liver COMT-mediated O-methylation of L-DOPA in a concentration-dependent manner in vitro, with an average IC50 of 0.36 microM. Oral administration of EGCG moderately lowered the accumulation of 3-O-methyldopa in the plasma and striatum of rats treated with L-DOPA+carbidopa. In addition, EGCG also reduced glutamate-induced oxidative cytotoxicity in cultured HT22 mouse hippocampal neuronal cells through inactivation of the nuclear factor kappaB-signaling pathway. Under in vivo conditions, administration of EGCG exerted a strong protective effect against kainic acid-induced oxidative neuronal death in the hippocampus of rats.CONCLUSIONS/SIGNIFICANCE: These observations suggest that oral administration of EGCG may have significant beneficial effects in Parkinson's patients treated with L-DOPA and carbidopa by exerting a modest inhibition of L-DOPA methylation plus a strong neuroprotection against oxidative damage and degeneration.

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PMID: 

J Pathol. 2010 Dec ;222(4):329-34. PMID: 20922714

Abstract Title: 

AMP-activated protein kinase: 'a cup of tea' against cholesterol-induced neurotoxicity.

Abstract: 

Disturbances in brain cholesterol metabolism have been linked to Alzheimer's disease (AD) pathology. A high-cholesterol diet increases fibrillar amyloidβ peptide (Aβ) deposition, inflammation, and apoptosis that eventually results in neurodegeneration and learning and memory impairments. In the October 2010 issue of The Journal of Pathology, Lu and colleagues provided a novel and interesting mechanism that explains how quercetin, a flavonoid found at high concentrations in green and black teas, may help to protect against cholesterol-induced neurotoxicity through activation of AMP-activated protein kinase (AMPK), a metabolic energy gauge. Further work will be necessary to address whether AMPK may be a potential target to combat neurodegenerative diseases.

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PMID: 

Brain Res. 2012 Jan 18 ;1433:104-13. Epub 2011 Nov 13. PMID: 22138428

Abstract Title: 

Theaflavin, a black tea polyphenol, protects nigral dopaminergic neurons against chronic MPTP/probenecid induced Parkinson's disease.

Abstract: 

Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by loss of dopominergic neurons in substantia nigra pars compacta, and can be experimentally induced by the neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Chronic administration of MPTP/probenecid (MPTP/p) leads to oxidative stress, induction of apoptosis, and loss of dopominergic neurons which results in motor impairments. Epidemiological studies have shown an inverse relationship between tea consumption and susceptibility to PD. Theaflavin is a black tea polyphenol, which possess a wide variety of pharmacological properties including potent anti oxidative, anti apoptotic and anti inflammatory effects. The current study is aimed to assess the effect of theaflavin against MPTP/p induced neurodegenaration in C57BL/6 mice. We found that the theaflavin attenuates MPTP/p induced apoptosis and neurodegeneration as evidenced by increased expression of nigral tyrosine hydroxylase (TH), dopamine transporter (DAT) and reduced apoptotic markers such as caspase-3, 8, 9 accompanied by normalized behavioral characterization. This may be due to anti oxidative and anti apoptotic activity and these data indicate that theaflavin may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative diseases such as PD.

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PMID: 

Foods. 2020 Feb 12 ;9(2). Epub 2020 Feb 12. PMID: 32059406

Abstract Title: 

Enhancement of the Anti-Inflammatory Effect of Mustard Kimchi on RAW 264.7 Macrophages by theFermentation-Mediated Generation of Phenolic Compound Derivatives.

Abstract: 

Mustard leaf kimchi contains numerous functional compounds that have various health benefits. However, the underlying mechanisms of their anti-inflammatory effects are unclear. In this study, changes in the mustard leaf kimchi phenolics profile after fermentation with or withoutwere determined using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). To correlate changes in phenolic profiles with anti-inflammatory activities of the fermentation extracts, lipopolysaccharides (LPS)-stimulated RAW 264.7 cells were treated with the extracts. We identified 12 phenolic acids in mustard leaf kimchi fermented with. Caffeic acid, chlorogenic acid, epicatechin, and catechin substituted the metabolite abundance. Extracts of mustard leaf kimchi fermented by(MLKL) markedly inhibited nitric oxide production by decreasing interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2) expression levels in LPS-treated RAW 264.7 cells. Thus, fermentation withpotentially improves the anti-inflammatory activities of mustard leaf and mustard leaf fermented with this microorganism may serve as a proper diet for the treatment of inflammation.

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PMID: 

Front Biosci (Schol Ed). 2012 Jan 1 ;4:581-98. Epub 2012 Jan 1. PMID: 22202078

Abstract Title: 

Molecular mechanisms of the neuroprotective/neurorescue action of multi-target green tea polyphenols.

Abstract: 

Mounting evidence suggests that lifestyle factors, especially nutrition are essential factor for healthy ageing. However, as a result of the increase in life expectance, neurodegenerative diseases like Alzheimer's and Parkinson's (AD and PD, respectively) are becoming an increasing burden, as aging is their main risk factor. Brain aging and neurodegenerative diseases of the elderly are characterized by oxidative damage, dysregulation of redox metals homeostasis and inflammation. Thus, it is not surprising that a large amount of drugs/agents in therapeutic use for these conditions are antioxidants/metal complexing, bioenergetic and anti-inflammatory agents. Natural plant polyphenols (flavonoids and non-flavonoids) are the most abundant antioxidants in the diet and as such, are ideal nutraceuticals for neutralizing stress-induced free radicals and inflammation. Human epidemiological and new animal data suggest that green and black flavonoids named catechins, may help protecting the aging brain and reduce the incidence of dementia, AD and PD. This review will present salient features of the beneficial multi-pharmacological actions of black and green tea polyphenols in aging and neurodegeneration, and speculate on their potential in drug combination to target distinct pathologies as a therapeutic disease modification approach.

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