New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate.
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.
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, UAB Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Hae-Suk
HS
Kim
Department of Medicine, Division of Endocrinology, Diabetes & Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Michael J
MJ
Quon
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.
Jeong-A
JA
Kim
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D020013:Calcium Signaling / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D019175:DNA Methylation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D016877:Oxidants / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013662:Tea / Q000737:chemistry; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D000975:Antioxidants; D016877:Oxidants; D059808:Polyphenols; D013662:Tea; D014157:Transcription Factors; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D000242:Cyclic AMP; D006152:Cyclic GMP
Anti-oxidant; EC, epicatechin; ECG, epicatechin gallate; EGC, epigallocatechin; EGCG; EGCG, epigallocatechin 3-gallate; Polyphenol; Pro-oxidant