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      Function of Green Tea Catechins in the Brain: Epigallocatechin Gallate and its Metabolites

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          Abstract

          Over the last three decades, green tea has been studied for its beneficial effects, including anti-cancer, anti-obesity, anti-diabetes, anti-inflammatory, and neuroprotective effects. At present, a number of studies that have employed animal, human and cell cultures support the potential neuroprotective effects of green tea catechins against neurological disorders. However, the concentration of (−)-epigallocatechin gallate (EGCG) in systemic circulation is very low and EGCG disappears within several hours. EGCG undergoes microbial degradation in the small intestine and later in the large intestine, resulting in the formation of various microbial ring-fission metabolites which are detectable in the plasma and urine as free and conjugated forms. Recently, in vitro experiments suggested that EGCG and its metabolites could reach the brain parenchyma through the blood–brain barrier and induce neuritogenesis. These results suggest that metabolites of EGCG may play an important role, alongside the beneficial activities of EGCG, in reducing neurodegenerative diseases. In this review, we discuss the function of EGCG and its microbial ring-fission metabolites in the brain in suppressing brain dysfunction. Other possible actions of EGCG metabolites will also be discussed.

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          Most cited references67

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          Tea polyphenols for health promotion.

          People have been consuming brewed tea from the leaves of the Camellia sinensis plant for almost 50 centuries. Although health benefits have been attributed to tea, especially green tea consumption since the beginning of its history, scientific investigations of this beverage and its constituents have been underway for less than three decades. Currently, tea, in the form of green or black tea, next to water, is the most widely consumed beverage in the world. In vitro and animal studies provide strong evidence that polyphenols derived from tea may possess the bioactivity to affect the pathogenesis of several chronic diseases. Among all tea polyphenols, epigallocatechin-3-gallate has been shown to be responsible for much of the health promoting ability of green tea. Tea and tea preparations have been shown to inhibit tumorigenesis in a variety of animal models of carcinogenesis. However, with increasing interest in the health promoting properties of tea and a significant rise in scientific investigation, this review covers recent findings on the medicinal properties and health benefits of tea with special reference to cancer and cardiovascular diseases.
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            Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota.

            Tea is rich in polyphenols and other phenolics that have been widely reported to have beneficial health effects. However, dietary polyphenols are not completely absorbed from the gastrointestinal tract and are metabolized by the gut microflora so that they and their metabolites may accumulate to exert physiological effects. In this study, we investigated the influence of the phenolic components of a tea extract and their aromatic metabolites upon bacterial growth. Fecal homogenates containing bacteria significantly catalyzed tea phenolics, including epicatechin, catechin, 3-O-methyl gallic acid, gallic acid and caffeic acid to generate aromatic metabolites dependent on bacterial species. Different strains of intestinal bacteria had varying degrees of growth sensitivity to tea phenolics and metabolites. Growth of certain pathogenic bacteria such as Clostridium perfringens, Clostridium difficile and Bacteroides spp. was significantly repressed by tea phenolics and their derivatives, while commensal anaerobes like Clostridium spp., Bifidobacterium spp. and probiotics such as Lactobacillus sp. were less severely affected. This indicates that tea phenolics exert significant effects on the intestinal environment by modulation of the intestinal bacterial population, probably by acting as metabolic prebiotics. Our observations provide further evidence for the importance of colonic bacteria in the metabolism, absorption and potential activity of phenolics in human health and disease. The bioactivity of different phenolics may play an important role in the maintenance of gastrointestinal health.
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              Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1.

              Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available. The objective was to examine the association between green tea consumption and cognitive function in humans. We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24. A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                25 July 2019
                August 2019
                : 20
                : 15
                : 3630
                Affiliations
                [1 ]Tea Science Center, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
                [2 ]R&D group, Mitsui Norin Co. Ltd., Shizuoka 426-0133, Japan
                Author notes
                [* ]Correspondence: gp1747@ 123456u-shizuoka-ken.ac.jp (M.P.); unno@ 123456u-shizuoka-ken.ac.jp (K.U.); Tel./Fax: +81-54-264-5822 (M.P. & K.U.)
                Author information
                https://orcid.org/0000-0002-2965-1742
                Article
                ijms-20-03630
                10.3390/ijms20153630
                6696481
                31349535
                8b1ac082-d78c-488c-a021-8c4c3bed112c
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 July 2019
                : 22 July 2019
                Categories
                Review

                Molecular biology
                blood–brain barrier,catechin,cognition,epigallocatechin gallate,green tea,microbiota,5-(3,5-dihydroxyphenyl)-γ-valerolactone

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