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Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res

Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, and Department of Neurosurgery, University of South Florida, Tampa, FL 33613, USA.
Brain Research (Impact Factor: 2.84). 07/2008; 1214(C):177-87. DOI: 10.1016/j.brainres.2008.02.107
Source: PubMed

ABSTRACT

We previously reported that intraperitoneal (i.p.) injection (20 mg/kg) of (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, decreased beta-amyloid (Abeta) levels and plaques via promotion of the non-amyloidogenic alpha-secretase proteolytic pathway in "Swedish" mutant amyloid precursor protein overexpressing (APPsw, Tg) mice. Here, we find that EGCG administered orally in drinking water (50 mg/kg) similarly reduces Abeta deposition in these mice. Following a six month treatment of an 8 month old cohort, immunohistochemical analysis of coronal sections reveals that plaque burdens were reduced in the cingulate cortex, hippocampus, and entorhinal cortex by 54%, 43%, and 51%, respectively. Congo red plaque burdens were decreased in the cingulate cortex, hippocampus, and entorhinal cortex by 53%, 53%, and 58%, respectively as well. ELISA of brain homogenates of the treatment Tg mice revealed consistent reductions in both Abeta1-40 and 1-42 soluble and insoluble forms. In the present study we also investigated the effect EGCG administration had on tau pathology and cognition in Tg mice. Both i.p. and orally-treated Tg animals were found to have modulated tau profiles, with markedly suppressed sarkosyl-soluble phosphorylated tau isoforms. Radial arm water maze (RAWM) testing for working memory indicated that EGCG provided cognitive benefit to Tg mice with both i.p. and oral administration, although i.p.-treated animals showed a more pronounced benefit because of the greater impairment of their Tg controls at the time of testing. Taken together, these data further the notion of EGCG dietary supplementation as a potentially safe and effective prophylaxis for Alzheimer's disease.

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    • "Tea contains various bioactive compounds such as epigallocatechin-3-gallate (EGCG), l-theanine, and caffeine [6] [7]. These compounds may protect the brain through antioxidant and anti-inflammatory mechanisms and through their effects on the modification associated with Alzheimer's disease (AD) and its pathology [8] [9] [10] [11]. There are also other biological mechanisms by which tea exerts neuroprotective effects, such as regulating the secretion of stress hormones and the production of catecholamines, regulating the cAMP-response element binding protein signaling cascade, and inhibiting acetylcholinesterase activity, as well as the regulatory role of l-theanine in brain neurotransmitter systems [8]. "

    Full-text · Chapter · Dec 2015
    • "(À)-Epigallocatechin-3-gallate (EGCG) has been said to have beneficial effects in cancer[41], human immunodeficiency virus infection[42]and neurodegenerative diseases[43]. EGCG also reportedly interacted with various amyloidogenic proteins and induced non-toxic stable oligomers[17,18,23,44]. Here, we showed that EGCG inhibited the formation of apoA-I Iowa fibrils and disaggregated apoA-I Iowa fibrils. "
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    ABSTRACT: Introduction: Apolipoprotein A-I (apoA-I) amyloidosis is either a non-hereditary form with deposits of wild-type apoA-I proteins in atherosclerotic plaques or a hereditary form with progressive accumulation of mutant apoA-I proteins in different tissues. Several small polyphenolic molecules reportedly inhibited formation of fibrillar assemblies of some amyloidogenic proteins and their cytotoxicity, but small molecules that inhibit apoA-I fibril formation have never been reported.Methods: Our methods included a thioflavin-T-binding assay, atomic force microscopy and dot blot and cell-based assays.Results: We showed that (−)-epigallocatechin-3-gallate (EGCG), a tea-derived flavanol, inhibited in vitro fibril formation and disaggregated fibrils preformed by the N-terminal 1–83 fragments of wild-type (WT) apoA-I and the G26R point mutation of apoA-I (apoA-IIowa). We eliminated a common structure recognized by the anti-amyloid antibody OC by incubating apoA-IIowa with EGCG or treating apoA-IIowa fibrils with EGCG, which supported the above observation. In addition, EGCG rescued human embryonic kidney 293 cells from cytotoxicity and attenuated production of reactive oxygen species, which were induced by apoA-IIowa fibrils.Conclusions: Our results support the concept that EGCG inhibits amyloid fibril formation of various amyloidogenic proteins. Thus, EGCG may be a candidate for providing a structure to develop de novo inhibitors for amyloidosis treatment.
    No preview · Article · Dec 2015 · Amyloid
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    • "It has been shown that EGCG specifically interferes with phospholipids and proteins from plasma membrane and controls transcription factors, mitochondrial function, signal transduction pathways, DNA methylation , and autophagy [6]. Green tea exerts protective effects in arterial hypertension [7], obesity [8] [9] [10] [11], type 2 diabetes mellitus [12] [13] [14], metabolic syndrome (MetS) [15] [16] [17] [18], ischemic stroke [19], Alzheimer's disease [20] [21], Parkinson's disease [22], oral cancer [23], and breast cancer [24] [25]. In vitro, it has been extensively proven that polyphenols have anti-inflammatory activities, exerted through the modulation of enzymes and mediated by antioxidative effects. "
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    ABSTRACT: Introduction: Promising experimental and clinical trials suggest that green tea decrease inflammatory process in cardiometabolic diseases, but evidence from epidemiologic studies about the effects on plasma C-reactive protein (CRP) seems inconsistent and ambiguous. Therefore the aim of the meta-analysis was to evaluate the impact of green tea supplementation on plasma CRP concentrations. Methods: We searched selected database up to October 26, 2014 to identify randomized controlled trials (RCTs) investigating the impact of green tea supplementation on plasma CRP concentrations. Two independent reviewers extracted data on study characteristics, methods and outcomes. Results: Meta-analysis of data from 11 RCTs arms did not indicate a significant effect of supplementation with green tea catechins on plasma CRP concentrations (WMD: 0.085 mg/L, 95%CI: -0.225, 0.395, p=0.592). This effect size was robust in sensitivity analysis and omission of each individual study did not have a significant effect. The non-significant effects of green tea catechins on plasma CRP concentrations were also observed in subgroups of studies with green tea supplementation duration of <8 weeks (WMD: 0.029 mg/L, 95%CI: -0.229, 0.286, p=0.828) and ≥8 weeks (WMD: 0.099 mg/L, 95%CI: -0.555, 0.754, p=0.766). Likewise there was no significant effect in subgroups of studies with total catechins doses <400 mg/day (WMD: 0.073 mg/L, 95%CI: -0.251, 0.398, p=0.658) and ≥400 mg/day (WMD: 0.213 mg/L, 95%CI: -0.148, 0.574, p=0.247). The effect size were not significant after stratification of studies to those recruiting healthy subjects (WMD: -0.028 mg/L, 95%CI:-0.216, 0.160, p=0.769), and those recruiting subjects with cardiometabolic diseases (WMD: 0.260 mg/L, 95%CI: -0.815, 1.334, p=0.636). Conclusions: This meta-analysis of data from 11 RCT arms did not indicate a significant effect of supplementation with green tea catechins on plasma CRP concentrations. Further, well-designed trials are necessary to validate these results.
    Full-text · Article · Feb 2015 · Nutrition
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