Table Of ContentPomegranates
Ancient Roots to
Modern Medicine
Medicinal and Aromatic Plants — Industrial Profiles
Individual volumes in this series provide both industry and academia with in-depth coverage of one major
genus of industrial importance.
Series Edited by Dr. Roland Hardman
Volume 1 Volume 16
Valerian, edited by Peter J. Houghton Mistletoe, edited by Arndt Büssing
Volume 2 Volume 17
Perilla, edited by He-ci Yu, Kenichi Kosuna Tea, edited by Yong-su Zhen
(cid:31)and Megumi Haga Volume 18
Volume 3 Artemisia, edited by Colin W. Wright
Poppy, edited by Jenö Bernáth Volume 19
Volume 4 Stevia, edited by A. Douglas Kinghorn
Cannabis, edited by David T. Brown Volume 20
Volume 5 Vetiveria, edited by Massimo Maffei
Neem, edited by H.S. Puri Volume 21
Volume 6 Narcissus and Daffodil, edited by Gordon R. Hanks
Ergot, edited by Vladimír Kˇren and Volume 22
(cid:31)Ladislav Cvak Eucalyptus, edited by John J.W. Coppen
Volume 7 Volume 23
Caraway, edited by Éva Németh Pueraria, edited by Wing Ming Keung
Volume 8 Volume 24
Saffron, edited by Moshe Negbi Thyme, edited by E. Stahl-Biskup and F. Sáez
Volume 9 Volume 25
Tea Tree, edited by Ian Southwell and Oregano, edited by Spiridon E. Kintzios
(cid:31)Robert Lowe Volume 26
Volume 10 Citrus, edited by Giovanni Dugo and
Basil, edited by Raimo Hiltunen and (cid:31)Angelo Di Giacomo
(cid:31)Yvonne Holm Volume 27
Volume 11 Geranium and Pelargonium, edited by
Fenugreek, edited by Georgios Petropoulos (cid:31)Maria Lis-Balchin
Volume 12 Volume 28
Ginkgo biloba, edited by Teris A. Van Beek Magnolia, edited by Satyajit D. Sarker and
Volume 13 Yuji Maruyama
Black Pepper, edited by P.N. Ravindran Volume 29
Volume 14 Lavender, edited by Maria Lis-Balchin
Sage, edited by Spiridon E. Kintzios Volume 30
Volume 15 Cardamom, edited by P.N. Ravindran and
Ginseng, edited by W.E. Court K.J. Madhusoodanan
Volume 31 Volume 38
Hypericum, edited by Edzard Ernst Aloes, edited by Tom Reynolds
Volume 32 Volume 39
Taxus, edited by H. Itokawa and K.H. Lee Echinacea, edited by Sandra Carol Miller
Volume 33 (cid:31)Assistant Editor: He-ci Yu
Capsicum, edited by Amit Krish De Volume 40
Volume 34 Illicium, Pimpinella and Foeniculum, edited by
Flax, edited by Alister Muir and (cid:31)Manuel Miró Jodral
(cid:31)Niel Westcott
Volume 41
Volume 35
Ginger, edited by P.N. Ravindran
Urtica, edited by Gulsel Kavalali
(cid:31)and K. Nirmal Babu
Volume 36
Volume 42
Cinnamon and Cassia, edited by
Chamomile: Industrial Profiles, edited by
P.N. Ravindran, K. Nirmal Babu and M. Shylaja
Volume 37 (cid:31)Rolf Franke and Heinz Schilcher
Kava, edited by Yadhu N. Singh Volume 43
Pomegranates: Ancient Roots to Modern
Medicine, edited by Navindra P. Seeram, Risa
(cid:31)N. Schulman and David Heber
9812_C000.fm Page iv Saturday, June 3, 2006 11:13 AM
Pomegranates
Ancient Roots to
Modern Medicine
Edited by
Navindra P. Seeram, Risa N. Schulman,
and David Heber
Medicinal and Aromatic Plants — Industrial Profiles
Boca Raton London New York
CRC is an imprint of the Taylor & Francis Group,
an informa business
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Library of Congress Cataloging-in-Publication Data
Pomegranates : ancient roots to modern medicine / edited by Navindra P. Seeram, Risa
N. Schulman, David Heber.
p. ; cm. -- (Medicinal and aromatic plants--industrial profiles ; 43)
“A CRC title.”
Includes bibliographical references and index.
ISBN-13: 978-0-8493-9812-4 (alk. paper)
ISBN-10: 0-8493-9812-6 (alk. paper)
1. Pomegranate--Therapeutic use. I. Seeram, Navindra P. II. Schulman, Risa N. III.
Heber, David. IV. Series: Medicinal and aromatic plants--industrial profiles ; v. 43.
[DNLM: 1. Plant Preparations--therapeutic use. 2. Punicaceae. 3. Phytotherapy--
methods. QV 766 P785 2006]
RM666.P798P66 2006
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9812_Discl.indd 1 5/3/06 12:31:42 PM
9812_C000.fm Page vii Saturday, June 3, 2006 11:13 AM
Preface
Wilt thou be gone? It is not yet near day.
It was the nightingale, and not the lark,
That pierced the fearful hollow of thine ear.
Nightly she sings on yon pomegranate-tree.
Believe me, love, it was the nightingale.
Romeo and Juliet, III, 5
The pomegranate is an ancient fruit that has not changed much throughout the history
of man. After the discovery of agriculture about 10,000 years ago, we know that it
was grown in Egypt. It was found in the Indus Valley so early that there is a word
in Sanskrit for pomegranate. Indian royalty began their banquets with pomegranate,
grape, and jujube.
The pomegranate is also significant in Jewish tradition. The pomegranate is said
to have 613 seeds to represent the 613 commandments in the Torah. While this has
not been confirmed in modern times, the image of the pomegranate was woven into
the high priest’s robes, and brass representations were part of the ancient Temple’s
pillars. The pomegranate is mentioned six times in the Song of Solomon, and even
today silver-plated representations of pomegranates are used to cover the wooden
handles of the Torah scrolls.
The pomegranate appeared in China during the Han and Sung dynasties, prob-
ably brought from the Middle East by traders. It was slowly adopted in medieval
Europe but was known in Elizabethan England, as can be seen by the quote above
from Romeo and Juliet. The Spanish conquistadores brought the pomegranate to
America. Jesuit missionaries carried it north to California, where it now grows in
abundance in that state’s mild Mediterranean-like climate.
The biochemistry of the pomegranate is fascinating, and its several very different
classes of compounds are discussed in detail in this book. The red/purple color of
anthocyanins provides the rich color of the skin. Anthocyanins are also found in the
arils (the botanical term for the part commonly consumed, including the flesh and
the seed) along with traces of an astringent family of compounds known as the
hydrolyzable tannins. Among these, pomegranate juice made by squeezing the whole
fruit is a rich source of a large polyphenol antioxidant — an ellagitannin known as
punicalagin. This molecule with a molecular weight of over 1000 Daltons does not
enter the human body intact. Instead, it is broken up into ellagic acid moieties
released into the bloodstream over several hours. It is also metabolized by colonic
bacteria to urolithins and their conjugates, which appear in the blood and urine. The
family of phytochemicals found in pomegranate juice extracts, made by squeezing
the whole fruit, act together with greater potency than any of the single constituents
9812_C000.fm Page viii Saturday, June 3, 2006 11:13 AM
alone, as is the case with many different fruits, vegetables, and herbs. The seeds
also contain a rare lipid called punicic acid that is similar to conjugated linoleic acid
but has an additional double bond.
The physiological effects of pomegranate juice constituents are remarkable in
their preventive potential against two of the major chronic diseases of aging — heart
disease and cancer.
First, in heart disease, the pioneering work of Michael Aviram on pomegranate
polyphenols has demonstrated their ability to reduce lipid peroxidation and the
progression of atherosclerosis in animal models. One clinical study demonstrated
improved cardiac muscle perfusion in a group of patients with heart disease. Nobel
Prize winner Lou Ignarro demonstrated marked enhancement of nitric oxide pro-
duction in endothelial cells, which reveals another exciting and perhaps primary
mode for the prevention of cardiovascular disease.
Second, there are significant new findings suggesting that pomegranate juice
may be active against common forms of cancer. In basic laboratory studies, pome-
granate juice extracts and the tannins as well as anthocyanins have significant
antiproliferative and proapoptotic effects in several different types of cancer cells
in vitro including colon cancer, prostate cancer, and head and neck cancer. In colon
cancer cell lines that express cyclo-oxygenase 2 enzyme, we have demonstrated
together with Bharat Aggarwal the inhibition of proliferation and Nuclear Factor
kappa-B activation by pomegranate ellagitannins. In prostate cancer xenografts,
pomegranate juice has been shown by Hasan Mukhtar and coworkers to reduce
tumor growth. Finally, in a preliminary study of men with advanced prostate cancer
and rising PSA levels performed at UCLA by Allan Pantuck, pomegranate juice
reduced the rate of rise of PSA by 50% over a 1-year period. Ongoing basic and
clinical research is being pursued by a number of research groups to examine the
potential preventive effects of pomegranates in common forms of cancer.
Pomegranate seeds in many traditions have led to the idea that pomegranates
promote fertility, but there is no evidence to that effect as yet. However, what is
known of its potential phytoestrogenic effects is reviewed in some detail.
Unlocking the secrets hidden within this ancient fruit will require the application
of all of our modern methods of nutritional science including nutrigenomics, proteo-
mics, and detailed studies of subcellular signaling pathways in normal and diseased
cells.
David Heber, MD, PhD, FACP, FACN
Professor of Medicine and Public Health
UCLA Center for Human Nutrition
9812_C000.fm Page ix Saturday, June 3, 2006 11:13 AM
Editors
Navindra P. Seeram, Ph.D. is assistant director
of the UCLA Center for Human Nutrition and
adjunct assistant professor at the David Geffen
School of Medicine at the University of Califor-
nia, Los Angeles. His doctorate, in natural prod-
uct chemistry, was obtained from the University
of the West Indies and he conducted postdoctoral
research at the Bioactive Natural Products and
Phytoceuticals Laboratory at Michigan State
University. In addition to his membership in
numerous professional societies, Dr. Seeram
serves on several scientific advisory boards and
on editorial boards of scientific journals. His
research has been widely reported in peer-
reviewed journals, book chapters, and trade
magazines and he is regularly invited to speak at
national and international scientific conferences. He has 15 years of experience in
phytochemicals and his research interests are currently focused on the evaluation of
foods, spices, and herbal medicines in laboratory, animal, and human studies, for
the prevention and treatment of chronic human illnesses such as cancer and heart
disease.
Risa N. Schulman, Ph.D. is dedicated to the
prevention of chronic disease using natural com-
pounds found in plants and foods, and the
empowerment of the individual to take control
of his or her health and well-being. As the former
director of research for POM Wonderful in Los
Angeles, California, she built and managed an
international team of researchers studying the
health effects of pomegranates, making signifi-
cant contributions to the development of the
field, including 11 publications by the team in
3 years. At Wyeth’s Solgar Vitamins, she devel-
oped plant-based nutritional supplements, pat-
enting one formula, and managed claim substantiation for 450 products. She acted
as guest curator for an exhibit on plant-based medicines in conjunction with Bristol-
Myers Squibb at the New Jersey Museum of Agriculture in New Brunswick, New
Jersey. Dr. Schulman’s field experience includes studies of plants and ecosystems
