Recent Advances in Polyphenol Research

Plant polyphenols are secondary metabolites that constitute one of the most common and widespread groups of natural products. They express a large and diverse panel of biological activities including beneficial effects on both plants and humans. Many polyphenols, from their structurally simplest representatives to their oligo/polymeric versions (also referred to as vegetable tannins) are notably known as phytoestrogens, plant pigments, potent antioxidants, and protein interacting agents. Sponsored by the scholarly society Groupe Polyphénols, this publication, which is the fourth volume in this highly regarded Recent Advances in Polyphenol Research series, is edited by Annalisa Romani, Vincenzo Lattanzio, and Stéphane Quideau. They have once again, like their predecessors, put together an impressive collection of cutting–edge chapters written by expert scientists, internationally respected in their respective field of polyphenol sciences. This Volume 4 highlights some of the latest information and opinion on the following major research topics about polyphenols:  • Biosynthesis and genetic manipulation • Ecological role of polyphenols in plant defense • Actions of polyphenols in human health protection • Physical organic chemistry and organic synthesis Chemists, biochemists, plant scientists, pharmacognosists and pharmacologists, biologists, ecologists, food scientists and nutritionists will all find this book an invaluable resource. Libraries in all universities and research institutions where these disciplines are studied and taught should have copies on their bookshelves.

Contributors Preface 1 Monolignol Biosynthesis and its Genetic Manipulation: the Good, the Bad and the Ugly Richard A. Dixon, M. S. Srinivasa Reddy and Lina Gallego–Giraldo 1.1 Introduction 1.2 Function and distribution of lignin in plants 1.3 Targets for modification of lignin biosynthesis 1.4 Impacts of lignin modification by targeting the monolignol biosynthetic pathway 1.5 Impacts of lignin modification by targeting TFs 1.6 Monolignol pathway modification and plant growth 1.7 Conclusions – it isn’t all that bad! 2 Perturbing Lignin Biosynthesis: Metabolic Changes in Response to Manipulation of the Phenylpropanoid Pathway Nickolas A. Anderson and Clint Chapple 2.1 Introduction 2.2 Changes in metabolism associated with phenylpropanoid pathway disruptions 2.3 Atypical lignins 2.4 Dwarfism 2.5 Conclusions 3 Function, Structure and Evolution of Flavonoid Glycosyltransferases in Plants Keiko Yonekura–Sakakibara and Kazuki Saito 3.1 Introduction 3.2 UDP–dependent glycosyltransferases 3.3 Glycoside hydrolase–type glycosyltransferases 3.4 Conclusions 4 The Chemistry and Chemical Ecology of Ellagitannins in Plant–Insect Interactions: from Underestimated Molecules to Bioactive Plant Constituents Juha–Pekka Salminen 4.1 Introduction 4.2 Definitions and chemical structures of hydrolysable tannins 4.3 Biosynthetic pathways of hydrolysable tannins in plants 4.4 Distribution of different types of tannins in plants 4.5 Tannins in plant–herbivore interactions 4.6 Conclusions 5 Diverse Ecological Roles of Plant Tannins: Plant Defense and Beyond C. Peter Constabel, Kazuko Yoshida and Vincent Walker 5.1 Introduction 5.2 Overview of Tannin Structure and Function in Defense 5.3 Tissue Localization and Ecological Function 5.4 Tannins in Plant–Soil–Environment Interactions 5.5 Conclusions 6 Epigenetics, Plant (Poly)phenolics and Cancer Prevention Clarissa Gerhauser 6.1 Overview of epigenetic gene regulation 6.2 Influence of polyphenols on DNA methylation 6.3 Influence of polyphenols on histone modifying enzymes 6.4 Influence of noncoding (micro) RNAs on gene expression 6.5 Chemopreventive polyphenols affecting the epigenome by multiple mechanisms 6.6 Summary and conclusions 7 Discovery of Polyphenol–Based Drugs for Cancer Prevention and Treatment – The Tumor Proteasome as a Novel Target Fathima R. Kona, Min Shen, Di Chen, Tak Hang Chan and Q. Ping Dou 7.1 Introduction 7.2 Secondary metabolites of plants 7.3 Plant polyphenols and their analogs 7.4 Natural polyphenols in reversing drug resistance 7.5 Conclusions 8 Flavonoid Occurrence, Bioavailability, Metabolism and Protective Effects in Humans: Focus on Flavan–3–ols and Flavonols Luca Calani, Margherita Dall’Asta, Renato Bruni and Daniele Del Rio 8.1 Introduction to flavonoids in human nutrition 8.2 Focus on flavan–3–ols and flavonols 8.3 Metabolism and bioavailability of flavonoids in humans 8.4 In vitro studies 8.5 In vivo studies 8.6 Conclusions 9 Inhibition of VEGF Signalling by Polyphenols in Relation to Atherosclerosis and Cardiovascular Disease Rebecca L. Edwards and Paul A. Kroon 9.1 Introduction 9.2 VEGF and VEGF signalling 9.3 VEGF signalling and angiogenesis 9.4 Angiogenesis in atherosclerosis 9.5 Polyphenols in foods and diets, and their absorption and metabolism 9.6 Effects of polyphenols on VEGF signalling, angiogenesis and atherosclerosis 9.7 Relationships between polyphenol consumption and cardiovascular disease risk 9.8 Conclusions 10 Phenolic Compounds in a Sex–Gender Perspective Ilaria Campesi, Annalisa Romani, Maria Marino and Flavia Franconi 10.1 Introduction 10.2 Phenolic compounds classification and molecular mechanisms 10.3 Sex–gender and xenokinetics of phenolic compounds 10.4 Sex–gender differences in xenodynamics 10.5 Conclusions 11 Thermodynamic and Kinetic Processes of Anthocyanins and Related Compounds and their Bio–Inspired Applications Fernando Pina 11.1 Why the thermodynamics and kinetics of the structural transformations of anthocyanins in aqueous solution are so important 11.2 Anthocyanins in aqueous solution 11.3 The influence of anthocyanin self–aggregation on the determination of the rate and equilibrium constants 11.4 Photochromism – Applications bio–inspired in anthocyanins 11.5 Appendix 1. Construction of the energy level diagram of the network species 11.6 Appendix 2. Calculation of the mole faction distribution of the network species 12 Synthetic Strategies and Tactics for Catechin and Related Polyphenols Ken Ohmori and Keisuke Suzuki 12.1 Introduction 12.2 Early synthetic work 12.3 Stereoselective Approaches to Flavan–3–ols 12.4 Conclusions Subject index

Annalisa Romani , board member of the « Groupe Polyphénols » (2008–2014), is Professor of Food Sciences and Technologies at the University of Florence, Italy. Her research laboratory is specialized in analytical, structural determination and biological activities of plant polyphenols, with a recent focus on food supplement and innovative extraction green technologies for the recovery of purified molecules as bio–phenols. Vincenzo Lattanzio , former President of the « Groupe Polyphénols » (2004–2008), is full Professor of Plant Biochemistry and Physiology at the University of Foggia (Italy). His research interest concerns studies of the role of phenolic compounds in resistance mechanisms of plant tissues against biotic and abiotic stresses, with a recent focus on trade–off mechanism between growth rate and adaptive response of plant tissues under nutritional stress. Stéphane Quideau , former President of the Groupe Polyphénols (2008–2012), is full Professor of Organic and Bioorganic Chemistry at the University of Bordeaux, France. His research laboratory is specialized in plant polyphenol chemistry and chemical biology, with a focus on the studies of ellagitannin chemical reactivity and synthesis, and interactions of bioactive polyphenols with their protein targets.