Mini Review New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate $ Hae-Suk Kim a , Michael J. Quon c , Jeong-a Kim a,b,n a Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA b Department of Cell, Developmental and Integrative Biology, UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA c Department of Medicine, Division of Endocrinology, Diabetes & Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA article info Article history: Received 12 December 2013 Received in revised form 20 December 2013 Accepted 20 December 2013 Available online 10 January 2014 Keywords: Polyphenol EGCG Anti-oxidant Pro-oxidant 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. & 2014 The Authors. Published by Elsevier B.V. All rights reserved. Contents Introduction............................................................................................................ 187 Pro-oxidant or anti-oxidant? .............................................................................................. 188 Cell surface receptor ..................................................................................................... 189 Intracellular signaling pathways ............................................................................................ 189 Calcium ........................................................................................................... 190 Cyclic-nucleotides (cAMP/cGMP) ....................................................................................... 190 Other signaling pathways ............................................................................................. 191 Nuclear function ........................................................................................................ 192 Regulation of transcription factors ...................................................................................... 192 DNA methylation .................................................................................................... 192 Mitochondrial function ................................................................................................... 192 Autophagy ............................................................................................................. 192 Summary and perspectives ................................................................................................ 193 Acknowledgments ....................................................................................................... 193 References ............................................................................................................. 193 Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/redox Redox Biology 2213-2317/$ - see front matter & 2014 The Authors. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.redox.2013.12.022 Abbreviations: EGCG, epigallocatechin 3-gallate; ECG, epicatechin gallate; EGC, epigallocatechin; EC, epicatechin ☆ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. n Corresponding author at: Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Tel.: þ205 934 4128; fax 205 975 9372. E-mail address: jakim@uab.edu (J.-a. Kim). Redox Biology 2 (2014) 187–195