New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate.

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Abstract

Green tea is rich in polyphenol flavonoids including catechins. Epigallocatechin 3-gallate (EGCG) is the most abundant and potent green tea catechin. EGCG has been extensively studied for its beneficial health effects as a nutriceutical agent. Based upon its chemical structure, EGCG is often classified as an antioxidant. However, treatment of cells with EGCG results in production of hydrogen peroxide and hydroxyl radicals in the presence of Fe (III). Thus, EGCG functions as a pro-oxidant in some cellular contexts. Recent investigations have revealed many other direct actions of EGCG that are independent from anti-oxidative mechanisms. In this review, we discuss these novel molecular mechanisms of action for EGCG. In particular, EGCG directly interacts with proteins and phospholipids in the plasma membrane and regulates signal transduction pathways, transcription factors, DNA methylation, mitochondrial function, and autophagy to exert many of its beneficial biological actions.

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Autophagy: in sickness and in health.

Ana Maria Cuervo (2004)

The degradation of intracellular components in lysosomes (autophagy) has recaptured the attention of cell biologists in recent years. The main reason for this renewed interest is the dissection of the molecular machinery that participates in this process, because the identification of new intracellular elements involved in autophagy has provided new tools to trace, quantify and manipulate autophagy in a growing number of organisms. As a result, a better understanding of the physiological roles of autophagy, the consequences of its malfunctioning and its participation in different pathological processes has emerged. This article reviews our current knowledge of the role of autophagy in disease and the efforts to reconcile its proposed dual function as both a cell protector and a cell killer.

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Autophagy and aging: the importance of maintaining "clean" cells.

Ana Maria Cuervo, Ettore Bergamini, Ulf Brunk … (2006)

A decrease in the turnover of cellular components and the intracellular accumulation of altered macromolecules and organelles are features common to all aged cells. Diminished autophagic activity plays a major role in these age-related manifestations. In this work we review the molecular defects responsible for the malfunctioning of two forms of autophagy, macroautophagy and chaperone-mediated autophagy, in old mammals, and highlight general and cell-type specific consequences of dysfunction of the autophagic system with age. Dietary caloric restriction and antilipolytic agents have been proven to efficiently stimulate autophagy in old rodents. These and other possible experimental restorative efforts are discussed.

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EGCG, a green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR.

Maria A Potenza, Flora L Marasciulo, Monica Montagnani … (2007)

Epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, may augment metabolic and vascular actions of insulin. Therefore, we investigated effects of EGCG treatment to simultaneously improve cardiovascular and metabolic function in spontaneously hypertensive rats (SHR; model of metabolic syndrome with hypertension, insulin resistance, and overweight). In acute studies, EGCG (1-100 microM) elicited dose-dependent vasodilation in mesenteric vascular beds (MVB) isolated from SHR ex vivo that was inhibitable by N(omega)-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase antagonist) or wortmannin [phosphatidylinositol (PI) 3-kinase inhibitor]. In chronic studies, 9-wk-old SHR were treated by gavage for 3 wk with EGCG (200 mg.kg(-1).day(-1)), enalapril (30 mg.kg(-1).day(-1)), or vehicle. A separate group of SHR receiving L-NAME (80 mg/l in drinking water) was treated for 3 wk with either EGCG or vehicle. Vasodilator actions of insulin were significantly improved in MVB from EGCG- or enalapril-treated SHR (when compared with vehicle-treated SHR). Both EGCG and enalapril therapy significantly lowered systolic blood pressure (SBP) in SHR. EGCG therapy of SHR significantly reduced infarct size and improved cardiac function in Langendorff-perfused hearts exposed to ischemia-reperfusion (I/R) injury. In SHR given L-NAME, beneficial effects of EGCG on SBP and I/R were not observed. Both enalapril and EGCG treatment of SHR improved insulin sensitivity and raised plasma adiponectin levels. We conclude that acute actions of EGCG to stimulate production of nitric oxide from endothelium using PI 3-kinase-dependent pathways may explain, in part, beneficial effects of EGCG therapy to simultaneously improve metabolic and cardiovascular pathophysiology in SHR. These findings may be relevant to understanding potential benefits of green tea consumption in patients with the metabolic syndrome.

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Author and article information

Journal

Journal ID (iso-abbrev): Redox Biol

Title: Redox biology

Publisher: Elsevier BV

ISSN: 2213-2317

ISSN (Print): 2213-2317

Publication date (Electronic): 2014

Volume: 2

Affiliations

[1 ] Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

[2 ] Department of Medicine, Division of Endocrinology, Diabetes & Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

[3 ] Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA ; Department of Cell, Developmental and Integrative Biology, UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Article

Publisher Item ID: S2213-2317(14)00005-6

DOI: 10.1016/j.redox.2013.12.022

PMC ID: 3909779

PubMed ID: 24494192

SO-VID: bb53cb52-dda8-4b7d-a48b-8027f191a11f

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Keywords: Anti-oxidant,EC, epicatechin,ECG, epicatechin gallate,EGC, epigallocatechin,EGCG,EGCG, epigallocatechin 3-gallate,Polyphenol,Pro-oxidant

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Keywords: Anti-oxidant, EC, epicatechin, ECG, epicatechin gallate, EGC, epigallocatechin, EGCG, EGCG, epigallocatechin 3-gallate, Polyphenol, Pro-oxidant

New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate.

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Most cited references 116

Autophagy: in sickness and in health.

Autophagy and aging: the importance of maintaining "clean" cells.

EGCG, a green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR.

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