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recent advances in phytochemistry volume 33 Phytochemicals in Human Health Protection, Nutrition, and Plant Defense
recent advances in phytochemistry
volume 33
Phytochemicals in Human Health Protection, Nutrition, and Plant Defense
RECENT ADVANCES IN PHYTOCHEMISTRY
Proceedings of the Phytochemical Society of North America General Editor: John T. Romeo, University of South Florida, Tampa, Florida
Recent Volumes in the Series:
Volume 24 Biochemistry of the Mevalonic Acid Pathway to Terpenoids Proceedings of the Twenty-ninth Annual Meeting of the Phytochemical Society of North America, Vancouver, British Columbia, Canada, June, 1989
Volume 25 Modern Phytochemical Methods Proceedings of the Thirtieth Annual Meeting of the Phytochemical Society of North America, Quebec City, Quebec, Canada, August, 1990
Volume 26 Phenolic Metabolism in Plants Proceedings of the Thirty-first Annual Meeting of the Phytochemical Society of North America, Fort Collins, Colorado, June, 1991
Volume 27 Phytochemical Potential of Tropical Plants Proceedings of the Thirty-second Annual Meeting of the Phytochemical Society of North America, Miami Beach, Florida, June, 1992
Volume 28 Genetic Engineering of Plant Secondary Metabolism Proceedings of the Thirty-third Annual Meeting of the Phytochemical Society of North America, Pacific Grove, California, June-July, 1993
Volume 29 Phytochemistry of Medicinal Plants Proceedings of the Thirty-fourth Annual Meeting of the Phytochemical Society of North America, Mexico City, Mexico, August, 1994
Volume 30 Phytochemical Diversity and Redundancy in Ecological Interactions Proceedings of the Thirty-fifth Annual Meeting of the Phytochemical Society of North America, Sault Ste. Marie, Ontario, Canada, August, 1995
Volume 31 Functionality of Food Phytochemicals Proceedings of the Thirty-sixth Annual Meeting of the Phytochemical Society of North America, New Orleans, Louisiana, August, 1996
Volume 32 Phytochemical Signals and Plant-Microbe Interactions Proceedings of a jOint meeting of the Phytochemical Society of North America and the Phytochemical Society of Europe, Noordwijkerhout, The Netherlands, April, 1997
Volume 33 Phytochemicals in Human Health Protection, Nutrition, and Plant Defense Proceedings of the Thirty-eighth Annual Meeting of the Phytochemical Society of North America, Pullman, Washington, July, 1998
A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. Forfurther information please contact the publisher.
recent advances in phytochemistry
volume 33
Phytochemicals in Human Health Protection, Nutrition, and Plant Defense
Edited by
John T. Romeo University of South Florida Tampa, Florida
Springer Science+Business Media, LLC
Cover:
Library of Congress Cataloging-in-Publication Data
Phytochemicals in human health protection, nutrition and plant delense /edited by John T. Romeo.
p. cm. -(Recent advances in phytochemistry; v. 33) Includes bibliographical relerences and index.
1. Materia medica, Vegetable. 2. Pharmacognosy. 3. Plan! bioactive compounds. 4. Phytochemistry. 1. Romeo, John T. II. Series. QK861.R38 voI. 33 [RS164] 572'.2 s-dc21 [615' .32] 99-37365
CIP
Flax seed. The richest natural source 01 the plant lignan, secoisolariciresinol diglycoside (SOG), translormed to cancer-protecting mammalian lignans by intestinal bacteria. (Courtesy 01 Lilian U. Thompson)
Intsia bijuga. Heartwood. Cross section 01 vesicles, one 01 which (lighter color) is lull 01 pentahydroxy Ilavonoid, robinetin. Oarker adjacent vessel contains a mixture 01 other Ilavonoids and tri- and tetra-hydroxy stilbenes. Compounds are assumed to lunction in decay resistance (Courtesy 01 W. E. Hillis).
Proceedings 01 the 38th Annual Meeting 01 the Phytochemical Society 01 North America on Phytochemicals in Human Health Protection, Nutrition, and Plant Oelense, held July 26-31,1998, in Pullman, Washington
ISBN 978-1-4613-7123-6
© 1999Springer Science+Business Media New York Originally published by Kluwer Academic / Plenum Publishers in 1999 Softcover reprint of the hardcaver Ist editian 1999
AII rights reserved
No part 01 this book may be reproduced, s!ored in a retrieval system, or transmitted in any lorm or by any means, electronic, mechanical, photocopying, microlilming, recording, or otherwise, wi!hout written permission lrom the Publisher
ISBN 978-1-4613-7123-6 ISBN 978-1-4615-4689-4 (eBook) DOI 10.1007/978-1-4615-4689-4
To G. H. N. Towers, phytochemical pioneer.
PREFACE
Since 1994, the Phytochemical Society of North America has devoted its annual symposia to topics with biological perspectives. Our last four volumes have dealt with medicinal plants (1994), plant/insect interactions (1995), food phytochemicals (1996), and plant/microbe interactions (1997), respectively. The Symposium held in Pullman, Washington, July 26-31, 1998 brought many aspects of these previous symposia once again to the forefront. This time, however, there was greater emphasis on the potential applications of phytochemistry to the diverse topics of human health and nutrition and plant defense. As we learned about innovative uses of molecular biology as it is being applied to these topics, we were reminded once again of the biochemical foundation on which these advances rest. On the occasion of the 75th birthday of G.H. Neal Towers, which we were privileged to celebrate, a perspective of where we began and how far we have advanced was made patently real for those in attendance.
The papers assembled in this volume were presented during the Symposium. Roughly grouped under three broad topics, they include: I. Drug Discovery and Pathway Engineering toward New MedicinallNutriceutical Targets (papers by Cragg, Croteau, Thompson, Costa, McLaughlin, Dixon, and Matern), 2. Roles for Polyphenols-Biosynthesis and Applications (Gross, Hillis, Haslam, and Ferreira), 3. New Chemical Prospects and Plant Defense (Asakawa, Selmar, Houghton, and Mizutani).
It is estimated that 80% of the world's population relies on traditional medicines for primary health care. For the rest of the world, about 114 of all prescriptions contain plant extracts or active principles derived from higher plants. The role of the U.S. National Cancer Institute in the development of new drugs is reviewed by Cragg. A road map through this agency is provided along with current protocols and collaborative procedures. Plant natural products continue to be major players in cancer treatment, accounting for up to 62% of commercially available drugs. Successes and prospects are discussed. Currently, approximately 1,000 Pacific yew trees must be harvested to produced a kilogram oftaxol, used for treating breast, ovarian, and other cancers. Treatment for ovarian cancer
Vll
viii PREFACE
alone would consume 90,000 trees annually. Walker and Croteau have focused their work on elucidating the biosynthesis of taxol and its related taxoids. They use a sequential approach, which examines the enzymes catalyzing each transformation, one which involves both in vivo and in vitro studies and molecular genetics. Ultimately, this information will be utilized to engineer biological systems to improve yields of taxoids.
The anticancer effects of lignans, particularly effective against mammary, colon, skin, and prostate cancers, are discussed by Thompson. Diets high in flax, the richest source, contain plant lignans that are acted upon by bacterial flora in the colon of humans to produce enterodiol and enterolactone, the putative protective agents. Epidemiological and animal studies indicate that both hormonerelated (weak or antiestrogenic effects) and non-hormone-related (antioxidant, antiangiogenic) mechanisms may be responsible. Costa and colleagues demonstrate that the major enzymatic steps for synthesizing these protective lignans are now understood. There is potential for using gene transfer and biotechnological manipulation of regulatory enzymes to enhance levels of the beneficial compounds.
McLaughlin and Chang update their studies of Annonaceous acetogenins. Since 1993, by using relatively simple bioassays, over 200 bioactive compounds have been described and evaluated. Structural/activity studies have identified
. compounds having both antitumor and pesticidal effects. Acetogenins inhibit mitochondrial electron transport systems, and, as a consequence, they are especially toxic to multiple drug resistant tumor cells and pesticide resistant insects that possess ATP-dependent xenobiotic efflux systems. In another paper which links plant defense and human health protection, Dixon and colleagues show how molecular biology can answer definitively such questions as the efficacy of phytoalexins. By cloning and manipulating genes, not only can plant resistance to disease be improved, but added human health benefits are likely. Antiestrogens, which are chemopreventive for breast cancer, and soy, which is correlated with decreased prostrate cancer, may also have hormonelike activity in plants. Matern also emphasizes structure/activity relationships in his discussion of the medicinal potential and biosynthesis of coumarins, compounds isolated from many plant and microbial sources. Coumarin roles as anti-HIV inhibitors and as treatment for skin disorders are among those singled out. He details recent developments in biosynthesis and localization, and points out that cladistic analysis of DNA sequences should lead to classification of enzymes, and mutational studies to the identification of domains responsible for catalytic specificities. Biotechnological generation of plants with modified coumarin biosynthesis and future medical applications are probable.
The importance of phenolic compounds and their potential for human betterment was apparent in several papers. The widely accepted view that tannins function as insect feeding deterrents was both reinforced and challenged by Gross. The diversity of tannins, and our recognition of new emerging roles for
PREFACE ix
them, such as viral inhibitors, which enable some insects to thrive by feeding on phenolic containing plants, forces us to rethink long-held ideas concerning their functions as feeding deterrents. Similarly, we realize their vast potential for medical applications. Extensive enzyme studies have both identified metabolic intermediates and have provided tools for the elucidation of biochemical reaction mechanisms. There is a need for cellular localization studies, information on transport vehicles, knowledge of final deposition sites, and application of molecular biology for insight into the unique structures of tannin-synthesizing enzymes. Hillis examines an often neglected source of natural products, the heartwood, a major feature of which is increased formation of secondary metabolites, especially phenolics. He examines the anatomy of heart wood and its associated tissues, and also the mechanisms by which compounds are selectively concentrated there. Potential fruit of such studies could lead toward more efficient syntheses of complex natural substances.
The health-promoting effects of tea, fruit juices, and red wine are at least partially attributable to polymeric proanthocyanidins. The chemical work of Ferreira and colleagues demonstrates how conformation analysis is leading to an understanding of the complexation of these compounds with other biomolecules, and thus, a better understanding of their salutary effects. Haslam and colleagues discuss astringency and polyphenollprotein interactions. Structure/activity relationships, the role of water, and hydrophobic effects and interactions are described. While admitting that structural problems still remain to be solved, they call for increasing emphasis on studies ranging from metabolism through ecology, to practical and applied problems.
A group of papers focus more directly, but not exclusively, on plant defense. Asakawa writes on the phytochemistry ofbryophytes. An imposing array of active terpenoids and aromatic compounds are present in Liverworts with about 80% of the sesqui- and diterpenoids being enantiomers of those found in higher plants. Only about 5% of bryophytes have been studied chemically. Many are distinguished by characteristic odors and taste, pungency and bitterness, antimicrobial and antifungal activity, insect antifeedant activity, nematocidal and piscicidal activity, and plant growth inhibitory activity. Increasing medical applications are being discovered, ranging from cytotoxic and anti-HIV activity to possible chemoprevention of osteoporosis and allergy. Similarly, interest in the genus Buddleja is relatively recent. A number of uses of extract of this plant, which include wound healing, treatment for liver and bronchial complaints, and antifungal, antibacterial, analgesic, and sedative effects are known. Houghton and Mensah show that an understanding ofthe role ofthe plant's contained iridoids, f1avonoids, and phenylethanoids is emerging. Selmar summarizes the biology of cyanogenic glucosides and related nutritional problems. The idea that high concentrations in certain plants function as repellents is generally accepted, but the role of low concentrations, widespread in most food plants, is less understood. A putative function as a metabolic mediator involved in signaling and influencing plant
x PREFACE
metabolism and development has been proposed. Finally, Mizutani summarizes years of study of isolations and characterizations of ecochemicals. Sequiterpenes, oligostilbenes, and isoflavonoids are emphasized, and evidence for a variety of traditional ecological roles is provided.
The Symposium was organized by Norman G. Lewis and G.H. Neal Towers. Their success in bringing together such a distinguished group of speakers was exceptional. The array of friendly people at Washington State University who made our stay pleasant are especially thanked. As in past years, my editing of this volume was greatly facilitated by the assistance, patience, and friendship of Dawn McGowan.
John T. Romeo University of South Florida
CONTENTS
I. Natural Product Drug Discovery and Development: The United States National Cancer Institute Role .................... .
Gordon M. Cragg, Michael R. Boyd, Rita Khanna, David 1. Newman, and Edward A. Sausville
2. Taxol Biosynthesis: A Review of Some Determinant Steps . . . . . . . . .. 31 Kevin Walker and Rodney Croteau
3. Role of Lignans in Carcinogenesis ............................. 51 Lilian U. Thompson
4. Toward Engineering the Metabolic Pathways of Cancer-Preventing Lignans in Cereal Grains and Other Crops ................ 67
Michael A. Costa, Zhi-Qiang, Laurence B. Davin, and Norman G. Lewis
5. Simple (Bench-Top) Bioassays and the Isolation of New Chemically Diverse Antitumor and Pesticidal Agents from Higher Plants ................................... 89
Jerry L. McLaughlin and Ching-Jer Chang
6. Molecular Controls for Isoflavonoid Biosynthesis in Relation to Plant and Human Health ............................... 133
Richard A. Dixon, Pedro Canovas, Ze-Jian Guo, Xian-Zhi He, Chris Lamb, and Fiona McAlister
7. Medical Potential and Biosynthesis of Plant Coumarins ............. 161 Ulrich Matern
8. Biosynthesis, Biodegradation, and Cellular Localization of Hydrolyzable Tannins ................................. 185
Georg G. Gross
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9. The Formation of Heartwood and Its Extractives: An Overview ...... 215 WE. Hillis
10. Recent Advances in the Chemistry of Proanthocyanidins ............ 255 Daneel Ferreira, Hendrik van Rensburg, Elfranco Malan, Johan
Coetzee, and Reinier J. J. Nel
11. Astringency and Polyphenol Protein Interactions .................. 289 Edwin Haslam, Michael P. Williamson, Nicola J. Baxter,
and Adrian J. Charlton
12. Phytochemistry of Bryophytes: Biologically Active Terpenoids and Aromatic Compounds from Liverworts ................... 319
Yoshinori Asakawa
13. Biologically Active Compounds from Buddleja Species ............. 343 Peter J. Houghton and Abraham Y. Mensah
14. Cyanide in Foods: Biology of Cyanogenic Glucosides and Related Nutritional Problems ........................ 369
Dirk Selmar
15. Plant Ecochemicals from the Viewpoint of Plant Defense ........... 393 Junya Mizutani
Index ....................................................... .421
