Flavonoids: Biosynthesis, Biological Effects and Dietary Sources

388 Pages·2009·7.14 MB·English

by  Keller R.B. (ed.)

NUTRITION AND DIET RESEARCH PROGRESS SERIES

F : B ,
LAVONOIDS IOSYNTHESIS
B E
IOLOGICAL FFECTS
AND DIETARY SOURCES

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Flavonoids: Biosynthesis,
Biological Effects and Dietary Sources
Raymond B. Keller
2009. ISBN: 978-1-60741-622-7
NUTRITION AND DIET RESEARCH PROGRESS SERIES

F : B ,
LAVONOIDS IOSYNTHESIS
B E
IOLOGICAL FFECTS
AND DIETARY SOURCES

RAYMOND B. KELLER
EDITOR

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LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA
Flavonoids : biosynthesis, biological effects and dietary sources / [edited by] Raymond B. Keller.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-61761-914-4 (Ebook)

Published by Nova Science Publishers, Inc. (cid:30)  New York
CONTENTS

Preface vii
Chapter 1 Bioavailability and Metabolism of Dietary Flavonoids –
Much Known – Much More to Discover 1
David E. Stevenson, Arjan Scheepens and Roger D. Hurst
Chapter 2 Cytoprotective Activity of Flavonoids in Relation
to Their Chemical Structures and Physicochemical Properties 53
Jingli Zhang and Margot A. Skinner
Chapter 3 Oligomeric Nature, Colloidal State, Rheology,
Antioxidant Capacity and Antiviral Activity of Polyflavonoids 97
A.Pizzi
Chapter 4 Grapefruit Flavonoids: Naringin and Naringinin 141
Ricky W. K. Wong and A. Bakr M. Rabie
Chapter 5 Development of Promising Naturally Derived
Molecules to Improve Therapeutic Strategies 181
Dominique Delmas, Frédéric Mazué, Didier Colin,
Patrick Dutartre and Norbert Latruffe
Chapter 6 Effect of a Diet Rich in Cocoa Flavonoids on
Experimental Acute Inflammation 213
M. Castell, A. Franch, S. Ramos-Romero,
E. Ramiro-Puig, F. J. Pérez-Cano and C. Castellote
Chapter 7 Mechanisms at the Root of Flavonoid Action in Cancer:
A Step Toward Solving the Rubik's Cube 231
Maria Marino and Pamela Bulzomi
Chapter 8 Antiophidian Mechanisms of Medicinal Plants 249
Rafael da Silva Melo, Nicole Moreira Farrapo,
Dimas dos Santos Rocha Junior, Magali Glauzer Silva,
José Carlos Cogo, Cháriston André Dal Belo,
Léa Rodrigues-Simioni, Francisco Carlos Groppo
and Yoko Oshima-Franco
vi Contents
Chapter 9 Molecular Targets of Flavonoids during Apoptosis
in Cancer Cells 263
Kenichi Yoshida
Chapter 10 Flavan-3-ol Monomers and Condensed Tannins
in Dietary and Medicinal Plants 273
Chao-Mei Ma and Masao Hattori
Chapter 11 Chemotaxonomic Applications of Flavonoids 291
Jacqui M. McRae, Qi Yang, Russell J. Crawford
and Enzo A. Palombo
Chapter 12 Bioanalysis of the Flavonoid Composition
of Herbal Extracts and Dietary Supplements 301
Shujing Ding and Ed Dudley
Chapter 13 Antibacterial Effects of the Flavonoids
of the Leaves of Afrofittonia Silvestris 315
Kola’ K. Ajibesin
Chapter 14 Why Is Bioavailability of Anthocyanins So Low? 323
Sabina Passamonti
Index 331
PREFACE

Flavonoids, also referred to as bioflavonoids, are polyphenol antioxidants found naturally
in plants. They are secondary metabolites, meaning they are organic compounds that have no
direct involvement with the growth or development of plants. Flavonoids are plant nutrients
that when consumed in the form of fruits and vegetables are non-toxic as well as potentially
beneficial to the human body. Flavonoids are widely disbursed throughout plants and are
what give the flowers and fruits of many plants their vibrant colors. They also play a role in
protecting the plants from microbe and insect attacks. More importantly, the consumption of
foods containing flavonoids has been linked to numerous health benefits. Though research
shows flavonoids alone provide minimal antioxidant benefit due to slow absorption by the
body, there is indication that they biologically trigger the production of natural enzymes that
fight disease.
Recent research indicates that flavonoids can be nutritionally helpful by triggering
enzymes that reduce the risk of certain cancers, heart disease, and age-related degenerative
diseases. Some research also indicates flavonoids may help prevent tooth decay and reduce
the occurrence of common ailments such as the flu. These potential health benefits, many of
which have been proven, have become of particular interest to consumers and food
manufacturers.
Foods that contain high amounts of flavonoids include blueberries, red beans, cranberries,
and blackberries. Many other foods, including red and yellow fruits and vegetables and some
nuts, also contain flavonoids. Red wine and certain teas also are rich in flavonoids.
Chapter 1 - There have been many epidemiological studies linking flavonoid intake to
health benefits and many in vitro studies demonstrating various biological effects of
flavonoids that should be reflected by health benefits. It has been widely assumed that these
observations are linked and dietary flavonoids are readily absorbed into the circulation and
influence many regulatory and signalling pathways in tissues. More recently, it has become
apparent that only a small proportion of dietary flavonoid intake is actually absorbed directly
and measured relative absorption varies about 2 orders of magnitude between different
compounds.
It is also apparent that most of the dietary load of flavonoids finds its way to the colon
where the numerous and varied microflora metabolise them into simpler but much more
bioavailable compounds. Further complications to the bioavailability of flavonoids are added
by human Phase II conjugative metabolism, which is thought to convert most absorbed
flavonoids into polar conjugates.
viii Raymond B. Keller
There is no doubt that some unconjugated flavonoids do get into the circulation at low
concentrations, but they are quantitatively swamped by the bulk of flavonoid conjugates and
colonic metabolites.
In contrast with the much-studied metabolism of flavonoids, relatively little is known
about the biological activities of their conjugates and metabolites, although what is known
comes from a predominance of in vitro studies and suggests that the metabolites do have
numerous and significant biological activities. Hence very little is known about the real and
mostly indirect benefits and mechanisms of action of dietary flavonoids.
In this review, the current state of knowledge in this area is discussed, with the aim of
stimulating further research (especially by intervention studies) to aid greater understanding.
Chapter 2 - Flavonoids are widely distributed in fruit and vegetables and form part of the
human diet. These compounds are thought to be a contributing factor to the health benefits of
fruit and vegetables in part because of their antioxidant activities. Despite the extensive use of
chemical antioxidant assays to assess the activity of flavonoids and other natural products that
are safe to consume, their ability to predict an in vivo health benefit is debateable. Some are
carried out at non-physiological pH and temperature, most take no account of partitioning
between hydrophilic and lipophilic environments, and none of them takes into account
bioavailability, uptake and metabolism of antioxidant compounds and the biological
component that is targeted for protection. However, biological systems are far more complex
and dietary antioxidants may function via multiple mechanisms. It is critical to consider
moving from using ‘the test tube’ to employing cell-based assays for screening foods,
phytochemicals and other consumed natural products for their potential biological activity.
The question then remains as to which cell models to use. Human immortalized cell lines
derived from many different cell types from a wide range of anatomical sites are available
and are established well-characterized models.
The cytoprotection assay was developed to be a more biologically relevant measurement
than the chemically defined antioxidant activity assay because it uses human cells as a
substrate and therefore accounts for some aspects of uptake, metabolism and location of
flavonoids within cells. Knowledge of structure activity relationships in the cytoprotection
assay may be helpful in assessing potential in vivo cellular protective effects of flavonoids.
This chapter will discuss the cytoprotective properties of flavonoids and focuses on the
relationship between their cytoprotective activity, physicochemical properties such as
lipophilicity (log P) and bond dissociation enthalpies (BDE), and their chemical structures.
The factors influencing the ability of flavonoids to protect human gut cells are discussed, and
these support the contention that the partition coefficients of flavonoids as well as their rate of
reaction with the relevant radicals help define the protective abilities in cellular environments.
By comparing the geometries of several flavonoids, its possible to explain the structural
dependency of the antioxidant action of these flavonoids.
Chapter 3 - The determination by Matrix-Assisted Laser Desorption/Ionization time–of-
flight (MALDI-TOF) mass spectroscopy of the oligomeric nature of the two major industrial
polyflvonoid tannins which exist, namely mimosa and quebracho tannins, and some of their
modified derivatives indicates that: (i) mimosa tannin is predominantly composed of
prorobinetinidins while quebracho is predominantly composed of profisetinidins, that (ii)
mimosa tannin is heavily branched due to the presence of considerable proportions of
"angular" units in its structure while quebracho tannin is almost completely linear. These
structural differences also contribute to the considerable differences in viscoity of water
Preface ix
solutions of the two tannins. (iii) the interflavonoid link is more easily hydrolysable, and does
appear to sometime hydrolyse in quebracho tannin and profisetinidins, partly due to the linear
structure of this tannin, and confirming NMR findings that this tannin is subject to
polymerisation/depolymerisation equilibria. This tannin hydrolysis does not appear to occur
in mimosa tannin in which the interflavonoid link is completely stable to hydrolysis. (iv)
Sulphitation has been shown to influence the detachment of catechol B-rings much more than
pyrogallol-type B-rings. (vi) The distribution of tannin oligomers, and the tannins number
average degree of polymerisation obtained by MALDI-TOF, up to nonamers and decamers,
appear to compare well with the results obtained by other techniques. As regards procyanidin
tannins, it has been possible to determine for mangrove polyflavonoid tannins that: (i)
procyanidins oligomers formed by catechin/epicatechin, epigallocatechin and epicatechin
gallate monomers are present in great proportions. (ii) oligomers, up to nonamers, in which
the repeating unit at 528-529 Da is a catechin gallate dimer that has lost both the gallic acid
residues and an hydroxy group are the predominant species. (iii) oligomers of the two types
covalently linked to each other also occur.
Water solution of non-purified polyflavonoid extracts appear to be incolloidal state, this
being due mainly to the hydrocolloid gums extracted with the tannin as well as to the tannin
itself.
Commercial, industrially produced mimosa, quebracho, pine and pecan polyflavonoid
tannin extracts water solutions of different concentrations behave mainly as viscous liquids at
the concentrations which are generally used for their main industrial applications. Clear
indications of viscoelastic response are also noticeable, among these the cross-over of the
elastic and viscous moduli curves at the lower concentrations of the range investigated, with
some differences being noticeable between each tannin and the others, pine and quebracho
tannin extracts showing the more marked viscoelastic behaviour. Other than pH dependence
(and related structural considerations), the parameters which were found to be of interest as
regards the noticeable viscoelastic behaviour of the tannin extracts were the existence in the
solutions of labile microstructures which can be broken by applied shear. This is supported by
the well known thixotropic behaviour of concentrated, commercial polyflavonoid tannin
extracts water solutions.
Such microstructures appear to be due or (i) to the known colloidal interactions of these
materials, or (ii) to other types of secondary interactions between tannin oligomers and
particularly between tannin and carbohydrate oligomers. The latter is supported by the
dependence of this effect from both the average molecular masses of the tannin and of the
carbohydrate oligomers.
The behaviour of polyflavonoid tannins as regards their antioxydant capacity and radical
scavenging ability has been examined. Radical formation and radical decay reactions of some
polyflavonoid and hydrolysable tannins has been followed, and comparative kinetics
determined, for both light induced radicals and by radical transfer from a less stable chemical
species to the tannin as part of an investigation of the role of tannin as antioxidants.
The five parameters which appear to have a bearing on the very complex pattern of the
rates of tannin radical formation and radical decay were found to be (i) the extent of the
colloidal state of the tannin in solution (ii) the stereochemical structure at the interflavonoid
units linkage (iii) the ease of heterocyclic pyran ring opening, (iv) the relative numbers of A-
and B-rings hydroxy groups and (v) solvation effects when the tannin is in solution. It is the