FLAVONOIDS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
ii
ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Flavonoids: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00434-8 1. Flavonoids-Popular works. I. Title.
iii
Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail:
[email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.
iv
Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on flavonoids. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
v
About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
vi
About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
vii
Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON FLAVONOIDS ............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Flavonoids ..................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 27 The National Library of Medicine: PubMed ................................................................................ 30 CHAPTER 2. NUTRITION AND FLAVONOIDS ................................................................................... 75 Overview...................................................................................................................................... 75 Finding Nutrition Studies on Flavonoids.................................................................................... 75 Federal Resources on Nutrition ................................................................................................... 80 Additional Web Resources ........................................................................................................... 80 CHAPTER 3. ALTERNATIVE MEDICINE AND FLAVONOIDS ............................................................. 87 Overview...................................................................................................................................... 87 National Center for Complementary and Alternative Medicine.................................................. 87 Additional Web Resources ........................................................................................................... 95 General References ..................................................................................................................... 112 CHAPTER 4. DISSERTATIONS ON FLAVONOIDS ............................................................................. 113 Overview.................................................................................................................................... 113 Dissertations on Flavonoids....................................................................................................... 113 Keeping Current ........................................................................................................................ 114 CHAPTER 5. PATENTS ON FLAVONOIDS ....................................................................................... 115 Overview.................................................................................................................................... 115 Patents on Flavonoids ................................................................................................................ 115 Patent Applications on Flavonoids ............................................................................................ 118 Keeping Current ........................................................................................................................ 138 CHAPTER 6. BOOKS ON FLAVONOIDS ........................................................................................... 139 Overview.................................................................................................................................... 139 Book Summaries: Online Booksellers......................................................................................... 139 CHAPTER 7. PERIODICALS AND NEWS ON FLAVONOIDS ............................................................. 141 Overview.................................................................................................................................... 141 News Services and Press Releases.............................................................................................. 141 Academic Periodicals covering Flavonoids ................................................................................ 143 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 147 Overview.................................................................................................................................... 147 NIH Guidelines.......................................................................................................................... 147 NIH Databases........................................................................................................................... 149 Other Commercial Databases..................................................................................................... 151 APPENDIX B. PATIENT RESOURCES ............................................................................................... 153 Overview.................................................................................................................................... 153 Patient Guideline Sources.......................................................................................................... 153 Finding Associations.................................................................................................................. 155 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 157 Overview.................................................................................................................................... 157 Preparation................................................................................................................................. 157 Finding a Local Medical Library................................................................................................ 157 Medical Libraries in the U.S. and Canada ................................................................................. 157 ONLINE GLOSSARIES................................................................................................................ 163 Online Dictionary Directories ................................................................................................... 163
viii Contents
FLAVONOIDS DICTIONARY ................................................................................................... 165 INDEX .............................................................................................................................................. 227
1
FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with flavonoids is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about flavonoids, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to flavonoids, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on flavonoids. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to flavonoids, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on flavonoids. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
3
CHAPTER 1. STUDIES ON FLAVONOIDS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on flavonoids.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and flavonoids, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “flavonoids” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Dietary Intake of Antioxidants and Risk of Alzheimer Disease Source: JAMA. Journal of the American Medical Association. 287(24): 3223-3229. 2002. Summary: This article examines the association between dietary intake of antioxidants and the risk of Alzheimer's disease (AD) in a population- based study conducted in the Netherlands. At baseline (1990-1993), the 5,395 participants were aged 55 years or older, free of dementia, noninstitutionalized, and had reliable dietary assessment. They were reassessed in 1993-1994 and 1997-1999 and were continuously monitored for incident dementia. After a mean follow-up of 6 years, 197 participants developed dementia, of whom 146 had AD. After adjusting for age, sex, baseline cognitive function, alcohol intake, education, smoking status, body mass index, total energy intake, presence of carotid plaques, and use of antioxidative supplements, high intakes of vitamin C and vitamin E were associated with a lower risk of AD. Among current smokers, this
4
Flavonoids
relationship was most pronounced and also present for intakes of beta carotene and flavonoids. The associations did not vary by education or apolipoprotein E genotype. Results suggest that high dietary intakes of vitamin C and vitamin E may lower the risk of AD. 6 tables, 34 references. (AA-M). •
Get Your Disease Fighters From Food Source: Health. p. 20. January/February 2001. Summary: This article recommends getting beta-carotene, an antioxidant, and flavonoids, a group of powerful antioxidants, from food rather than supplements. Research indicates that when beta-carotene is taken in pill form, the risk of cancer increases even though eating foods high in this antioxidant lowers cancer and heart disease risk. Now scientists are concerned that flavonoid supplements may also be risky. Martyn Smith, a toxicologist at the University of California at Berkeley, reviewed the research on flavonoids. He found evidence that in food sources such as vegetables, fruits, grains, and wine, the nutrients protect against heart disease and cancer. However, there were no studies demonstrating the safety or efficacy of supplements. Taking the amount suggested by some flavonoid supplement manufacturers could cause more harm than good, according to Smith. Until more is known, he advises sticking with flavonoid-rich foods such as onions and apples.
•
Slim Pickings Source: Runner's World. p.29. October 2000. Summary: This article summarizes two studies indicating that spicy food and green tea can boost metabolism and blunt appetite. In the first study, from the British Journal of Nutrition, women ate one of four different breakfasts: one was high in fat and hot red pepper, another high in fat without red pepper, a third high in carbohydrate, and the last high in carbohydrate and hot red pepper. Three hours later, the women consuming the meals high in red pepper were not hungry, whereas the others were. The second study was published in the American Journal of Clinical Nutrition. Six out of 10 men who took a green tea supplement (the equivalent of a cup of tea) with their meals burned about 80 more calories during the following 24 hours than those who took a caffeine pill or placebo. The researchers believe that the flavonoids in tea may be responsible for the increase in metabolism.
•
Herbal Therapies and Diabetes Complications Source: Diabetes Self-Management. 18(1): 87-88, 91-92, 95-96, 98. January-February 2001. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Website: www.diabetes-self-mgmt.com. Summary: This article, the third of a series of articles on herbal therapies, reviews herbal and alternative therapy supplements for the treatment of diabetic complications. Both the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Trial (UKPDS) demonstrated that keeping blood glucose levels as close to normal as possible can delay or prevent the development of complications in people with either type 1 or type 2 diabetes. Some of the new, experimental treatments for complications of diabetes include nutritional and herbal supplements. Many supplements may be of potential benefit in the treatment or prevention of heart disease, including fish oil, fenugreek, garlic, red yeast, antioxidants, and several herbs that inhibit blood clotting such as ginger, garlic, gingko biloba, and ginseng. The symptoms
Studies
5
of peripheral neuropathy may be eased with alpha lipoic acid, capsaicin, and evening primrose oil. Although bilberry and gingko biloba have both been proposed as potential treatments for diabetic retinopathy, neither is currently recommended for this use. The herb yohimbe has a reputation as a aphrodisiac and a treatment for impotence, but clinical trials do not support its use. There are several experimental drugs and some herbal supplements that may prevent damage caused by the conversion of extra glucose in the cells into sorbitol, including flavonoids, quercetin, and extracts from licorice root. Although being overweight is not considered a complication of diabetes, it can make controlling blood glucose levels more difficult. Losing a small amount of weight can lower both blood glucose and blood cholesterol levels. Numerous herbal and nutritional supplements exist for people who are trying to lose weight. Common ingredients found in herbal weight loss preparations include various diuretics and laxatives, guarana, ephedra, and garcinia. The article reviews studies on these products, identifies their adverse effects, and presents typical dosing regimens. In addition, the article provides guidelines for safe supplement use and lists suggestions for further reading. 1 table. •
Health Nuts Source: Cooking Light. p.96-101,154. March 1999. Summary: Thornton reports on research indicating that nuts may actually improve heart health, regardless of other risk factors such as weight, blood pressure, exercise, or gender. This may spring from the nature of the fat in nuts, which is both monounsaturated and polyunsaturated. These are the healthy forms of fat, found in such foods as olive and canola oils. In addition, nuts contain Omega-3 fatty acids, and are nutritionally dense with such nutrients as vitamin E, folic acid, niacin, copper, potassium, and magnesium. According to Thornton, nuts also contain flavonoids and isoflavones, compounds thought to prevent cancer and cardiovascular disease. Finally, since nuts have a high satiety factor, most people find a small amount filling, which contributes to weight loss. Recipes containing nuts are included, such as pork, cashew, and green bean stir-fry, Persian poached pears, hazelnut-fig quick bread, fruit and nut granola, and chicken tetrazzini with almonds.
Federally Funded Research on Flavonoids The U.S. Government supports a variety of research studies relating to flavonoids. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to flavonoids. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use 2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
6
Flavonoids
animals or simulated models to explore flavonoids. The following is typical of the type of information found when searching the CRISP database for flavonoids: •
Project Title: ANALYSIS OF PHENOLIC PHYTOCHEMICAL BY ESI-MS Principal Investigator & Institution: Brodbelt, Jennifer S.; Professor; Chemistry and Biochemistry; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 15-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The proposed work is aimed at the development of electrospray ionization/quadrupole ion trap mass spectrometry for the sensitive detection and characterization of phenolic phytochemicals and their metabolites in urine, tissue and food, especially soybeans, kale and citrus fruit. Many phenolic compounds are plant pigments that are known to yield health benefits as dietary phytochemicals, having antioxidant and estrogen-like properties that give antitumor activities. Three primary objectives are described. 1) Solid phase extraction and HPLC separation methods will be developed for the phenolic compounds. Samples of interest include soybeans, kale, citrus fruit, urine, plasma and tissue. 2) Novel metal complexation methods using various transition and alkaline earth metals and auxiliary ligands will be developed as an alternative to conventional protonation, which is often inefficient for the phenolic compounds. 3) The fragmentation patterns of the phenolic compounds and metabolites will be characterized by both low energy collisional activated dissociation (CAD) and infrared dissociation (IRPD). Many phenolic phytochemicals exist naturally as glycosides in plants, so the site of glycosylation and identification of the attached sugars are critical structural issues that will be probed. The diagnostic utility of, the fragmentation patterns obtained from by CAD will be compared to those obtained by IRPD. Special attention will be focused on comparing the dissociation patterns obtained for metal cationized vs. protonated vs. deprotonated complexes. Several new ways to make the IRPD method more tunable, i.e. the ability to vary the fragmentation pattern, will be examined, including implementation of tandem IRPD/CAD methods. This work will be aimed at solving specific problems from four collaborations: one involving the detection and quantitation of flavonoids in kale, soy, and urine, the second involving the identification and quantitation of coumarins in urine and tissue, the third involving the quantitation and identification of tocopherol compounds in tissue, and the fourth involving the quantitation and identification of flavonoids in citrus fruit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ANTIOXIDANT POLYPHENOLS FROM FRUITS OF THE MYRTLE FAMILY Principal Investigator & Institution: Reynertson, Kurt A.; Biological Sciences; Herbert H. Lehman College 250 Bedford Park Blvd. West Bronx, Ny 10468 Timing: Fiscal Year 2002; Project Start 17-SEP-2002 Summary: Many species of the Myrtle family (Myrtaceae) are popular edibles throughout the tropical and subtropical world. In addition, some are used medicinally in divergent traditional practices from South America to Southeast Asia. The fruits of two species of Eugenia (Myrtaceae) have shown a strong antioxidant activity in the 1,1diphenyl-2- picrylhydrazyl (DPPH) assay, and subsequent ethnomedical and chemotaxonomic study of related plants in the subtribe Eugeniinae have led to the hypothesis that these fruits contain flavonoids or other polyphenolic compounds that exhibit an oxidative protection to biomolecules in humans. The fruits of ten popular
Studies
7
edible species from this taxa will be analyzed for antioxidant activity using the DPPH assay. The most active extracts will be studied in greater detail to isolate and identify specific polyphenolic antioxidant phytochemicals. It is expected that novel antioxidant compounds will be discovered, and their chemical structures will be fully elucidated. This research will then use the analytical tools developed to look closely at beverages and vinegar made from the most active fruit to ascertain whether the beneficial phytochemicals in the fruit can be detected in commercial products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIOXIDANTS AND OXIDATIVE DAMAGE IN MITOCHONDRIA Principal Investigator & Institution: Giulivi, Cecilia; Chemistry; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JAN-2004 Summary: (provided by applicant) The focus of this project resides on the role of small antioxidant molecules on the prevention and/or repair of nitrated proteins in mitochondria. Protein nitration occurs in biological systems exposed to nitric oxide. The addition of a nitro group to a tyrosine residue, yielding 3-nitrotyorosine, has been claimed to be a post-translational modification, part of signal transduction pathways, or a result of "normal" oxidative stress. In this study, the investigators will characterize the mechanism underlying the nitration of proteins in nitric oxide-producing mitochondria, given the important role that these organelles have in the maintenance of cellular ATP, beta-oxidation, heme synthesis, and other functions. The studies will be aimed at understanding the kinetic and structural changes caused by nitration, and how naturally- occurring antioxidants present in fruits and vegetables may prevent/reverse this effect. The antioxidant effect of flavonoids, coumarins, and catechins will be studied in terms hydroxyl substitution, conjugation of rings, and o- methylation of hydroxyl groups to elucidate an association between structure and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CARDIOVASCULAR EFFECTS OF SCUTELLARIA BAICELENSIS Principal Investigator & Institution: Yuan, Chun-Su; Anesthesiology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 20-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): Cardiovascular disease remains a leading cause of death throughout the world, with many dying outside the hospital due to cardiac arrest. Although oxidants may play an important role in this major cardiovascular disease, little has been done to examine what role traditional vs. nontraditional antioxidants may play in its acute treatment. During the past year, our group investigated cardioprotective effects of Scutellaria baicalensis, a Chinese medicinal herb. We reported that an extract of Scutellaria baicalensis dose-dependently attenuated reactive oxygen species in cardiomyocytes and decreased cell death. We were particularly excited to observe that Scutellaria baicalensis extract rapidly quenched reactive oxygen species generated in mitochondria. The ability to gain rapid access to intracellular sites, such as mitochondria, and attenuate reactive oxygen species is a significant advantage, a characteristic that may be lacking in antioxidants currently in use. In separate studies, we observed that quercetin, a plant flavonoid, inhibited endothelin-1 and stimulated tissue plasminogen activator in vascular endothelial cells. Thus, we hypothesize that flavonoids of Scutellaria baicalensis have significant antioxidant potential, and they regulate the concentration of endothelial vasoactive mediators. Heart disease is a
8
Flavonoids
complex multifactorial disorder with a variety of underlying causes and risk factors. In the development of ischemic heart disease, the site of initial injury is the vascular endothelium. During later stages, ischemic and reperfusion injury to cardiomyocytes lead to loss of contractility and cell death. We propose to investigate in vitro pharmacological effects of Scutellaria baicalensis in two experimental models: embryonic chick cardiomyocytes, and human umbilical vein endothelial cells. In the proposed project, we will identify active flavonoids of Scutellaria baicalensis and investigate their 1) antioxidant action in cardiomyocytes, and 2) pharmacological effects on vasoactive mediators in endothelial cells. We will test whether Scutellaria baicalensis extract and its flavonoids (baicalein and wogonin, skullcapflavone I, and skullcapflavone II) act as antioxidants in cardiomyocytes, and test whether Scutellaria baicalensis extract and its flavonoids change the concentration of thrombin-stimulated endothelin-1, and tissue plasminogen activator in vascular endothelial cells. In addition, antioxidant activity comparison will be made between Scutellaria baicalensis and American ginseng. The results of our project will be used to develop potential new therapeutic agents from active components of Scutellaria baicalensis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMICO-PHYSICAL PROPERTIES OF METAL-FLAVONOID Principal Investigator & Institution: Cheng, Francis I.; Chemistry; University of Idaho Moscow, Id 838443020 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (provided by applicant) Flavonoids are recognized as an important class of nutrient that may be responsible for the chemoprevention of a myriad of degenerative diseases. This action is attributed to their putative antioxidant action. Many investigators have recognized that metal chelation is an important determinate in the prediction of the antioxidant action of flavonoids. However, there is a paucity of data accumulated concerning the chemico-physico properties of metal-flavonoid complexes. A previous investigation from this laboratory has found that four flavonoids, baicilein, luteolin, naringenin, and quercetin, chelate pro-oxidant iron ions into a complex that is not Fenton Reaction active. Another plant-borne product, salicylate has been the subject of previous investigations from this laboratory and found to chelate pro-oxidant iron into a form that is again not Fenton Reaction active. The proposed investigations will study the similarity of action between the four aforementioned flavonoids and salicylate, i.e. the ability to bind pro-oxidant metals both as free ions and in low molecular-weight complexes. The pro-oxidant metals of concern in this study are Fe, Cu, and Mn ions and also in complexed forms with EDTA, ATP/ADP and in porphyrins. The redox potential of each metal complex will predict the antioxidant characteristics in terms of Fenton Reaction activity, other redox-dependent actions such as superoxide dismutase and catalase activity. Metal-flavonoid binding constants will aid in determining if the flavonoids are effective in vivo chelation agents. These data will be derived by potentiometric titrations augmented with UV-vis absorbance. The four flavonoids chosen for this study will give insights into structure-activity relationships. It is hoped that the subject of this investigation will give a new paradigm for the design, and discovery of antioxidants, and anti-inflammatory agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CORE--ANALYTICAL LABORATORY Principal Investigator & Institution: Franke, Adrian; University of Hawaii at Manoa Honolulu, Hi 96822
Studies
9
Timing: Fiscal Year 2002 Summary: (Applicant's Description) The Analytical Laboratory Shared Resource (ALSR) was set up in 1990 to facilitate collaborative cancer research in molecular epidemiology, nutrition, food chemistry, carcinogenesis, and other areas of interest at the Center. The mission of this laboratory continues to be the cost-effective provision of accurate chemical analyses and a base for consultation related to the determination of molecules relevant to research interests of Center investigators. The facility is centrally located on the 5th floor of the CRCH and is equipped with modern, state-of-the-art instrumentation required for analytical chemistry and handling of biologically and chemically hazardous materials. Assays established by the ALSR for services include analysis of micronutrients (carotenoids, vitamins, and others), various clinically relevant analytes (HDL- and LDL-cholesterol, triglycerides, homocysteine, creatinine, total nitrogen, and others), and specific phytochemicals (caffeine and its metabolites and a wide variety of flavonoids, isoflavonoids, and other phenolic agents). These compounds are measured in body fluids, tissues, foods or other matrices. Major equipment of this facility include one fully automated liquid chromatography mass spectrometry (LC/MS) system, two fully automated gas chromatography mass spectrometry (GC/MS) systems, three fully automated high pressure liquid chromatography (HPLC) systems with photo-diode array (PDA), fluorescence, or electrochemical detection systems, and spectrophotometers. This Shared Resource has operated at 100 percent of its capacity and provided instrumental support for projects of eight Investigators with peerreviewed grants. The usage of this facility is expected to increase drastically within the cycle of this proposal due to the availability of the recently obtained LC/MS and GC/MS equipment. These new additions are suitable to be used in current and planned CRCH projects and offer great potential because new analytes can be determined that were not measurable previously, including markers of oxidative damage (isoprostanes, oxidized metabolites of vitamins and other phytochemicals), peptides, proteins, nucleotides, and other molecules. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIET, EXOGENOUS HORMONES AND BREAST CANCER RISK Principal Investigator & Institution: Colditz, Graham A.; Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: Using repeated measures of exposure and the long follow-up in the Nurses' Health Study (1976 to 2004), we propose a series of analyses relating specific aspects of diet, nutritional status, and postmenopausal use to breast cancer incidence and survival among women with breast cancer. DNA samples from cohort numbers will be used to evaluate associations between functional important polymorphisms and risk of breast cancer and potential gene-diet interactions. Specific exposures will also be related to tumor characteristics using pathology blocks that have been collected from incident breast cancer cases. Dietary hypotheses include that low folate intake and blood levels increase breast cancer risk, in particular tumors characterized by negative estrogen receptor status and aberrant methylation of the genes for this receptor and p16; that dietary fiber and specific types and sources of fiber, flavonoids, overall antioxidant intake, conjugated linoleic acid (CLA), and decreases in adiposity each reduce risk. We further hypothesize that high dietary glycemic load and intakes of heterocyclic amines from cooked meat, N-3 fatty acids from fish, and (after a long latent period) total fat each in increase risk. Polymorphisms in genes related to specificity dietary exposures (MTHFR, manganese SOD, and NAT1/2) will be examined in relation to breast cancer
10
Flavonoids
directly and as interactions with the corresponding dietary factors. We also propose to evaluate the type and dose of post-menopausal hormone preparations in relation to overall risk of breast cancer and estrogen receptor status of tumors. Finally, we hypothesize that high intake of dietary fat reduces survival among women with breast cancer, but that high intake of protein, regular physical activity, and avoidance of weight gain each increase survival. Because of the prospective design with repeated measures of exposure, long follow-up, and large numbers of breast cancer cases (over 5,000 cases for most dietary analyses), these analyses will provide important data for women and their health providers attempting to reduce risk of breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DRUG INTERACTIONS AND BIOAVAILABILITY OF CRANBERRY Principal Investigator & Institution: Donovan, Jennifer L.; Psychiatry and Behavioral Scis; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2004; Project Start 06-JAN-2004; Project End 31-DEC-2005 Summary: (provided by applicant): Cranberry (CB) juice and powders are currently being used as complementary and alternative medications. CB products may be used alone or in combination with conventional medications to treat urinary tract infection, or other medications to treat acute or chronic conditions. CB is a rich source of flavonoids, a class of phytochemicals with diverse biological activities. The specific aims of this research are 1) to evaluate the potential for CB-drug interactions and 2) to determine the pharmacokinetics and renal clearance of four major CB flavonoids. A normal volunteer study is proposed to determine the potential of CB to participate in interactions with conventional drugs. The induction/inhibition of the major cytochrome P-450 (CYP) enzymes will be the primary method of evaluation. The CYP isoforms to be studied, CYP3A4, CYP2D6 and CYP1A2, are involved in the metabolism of >80% of marketed prescription and over the counter medications. Single doses of the three safe, probe drugs alprazolam (ALPZ; 3A4 probe), dextromethorphan (DM; CYP2D6 probe), and caffeine (CAF; CYP1A2 probe) will be administered at baseline (before treatment with CB) and after a 14-day treatment period with CB powder. Changes in the pharmacokinetics of these probe drugs will indicate the degree of specific enzyme inhibition or induction. In the same normal volunteers, the key pharmacokinetic parameters for four major CB flavonoids will be estimated by following the plasma concentration versus time course of absorbed flavonoids and their excretion in urine. The area under the plasma concentration versus time curve (AUC), oral clearance (Clo), terminal elimination half-life (T1/2) and renal clearance (Clren) will be determined for: epicatechin, quercetin (total glycosides), procyanidin A2, and cyanidin-3-galactoside. These components represent the major classes of flavonoids in CB and are selected for study due to their abundance in CB and their documented biological activities. The pharmacokinetics and renal clearance of CB flavonoids will be determined first after a single dose of a characterized CB juice prior to administration of any probe drugs. Steady-state plasma levels of flavonoids will be determined at the end of the 14-day treatment period of multiple dosing with the characterized CB powder. This research will provide new, important data on the pharmacokinetics of flavonoids from CB juice and from a CB powder, an area where no data currently exist. This information is essential to elucidate the mechanisms of action of CB flavonoids in the context of specific conditions/diseases and to evaluate CB as a source of dietary flavonoids. These data will also complement NCCAM studies assessing the clinical safety and efficacy of CB and will allow more informed recommendations about the use of CB when combined with conventional medications.
Studies
11
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DRUG-DIETARY INTERACTION
FLAVONOID
INTESTINAL
ABSORPTION
Principal Investigator & Institution: Rodriguez, Rosita J.; None; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2002; Project Start 17-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The opportunity for drug-dietary interaction is an everyday occurrence whether the interaction is with food, juice, or dietary supplements. Moreover, the consumption of flavonoids is being urged because of their multiple health benefits; thus, understanding the possible biological effects of the flavonoids on intestinal drug absorption is essential. Flavonoids may be a particularly important class of modulators due to their ubiquitous occurrence in foods and drinks of plant origin and their known interactions with P-glycoprotein (Pgp) and cytochrome P450 (CYP). These dietary constituents may modulate transport in the intestinal tract and significantly alter the absorption of important therapeutic agents. The increased systemic bioavailability of some drugs, nifedipine and felodipine, associated with ingestion of grapefruit juice represents a couple of widely publicized drug-dietary-interactions. An increase or decrease in drug absorption may be due to (i) alterations in Pgp mediated or non Pgp mediated transport and/or (ii) presystemic intestinal metabolism by CYP and/or the flavin-containing monooxygenases. Furthermore, patents have been filed which incorporate flavonoids as excipients in pharmaceutical formations with the intent to alter drug absorption. Thus, the specific hypothesis of this study is that dietary flavonoids can alter the Pgp-dependent or Pgp-independent transport of certain therapeutic drugs. Studies will be conducted using flavonoids belonging to different subclasses such as isoflavone, flavanone, flavonol, and flavanol (e.g., genistein, naringenin, quercetin, and epigallocatechin gallate, respectively) to gain an insight into structure-activity relationships in the alteration of transport of Pgp-dependent substrates and Pgp-independent substrates by these phytochemicals. The flavonoids will be evaluated using Caco-2 cells, a human intestinal cell line. These cells have been well characterized to express Pgp transporters and non Pgp transporters such as Na+/K+, Na+/H+, amino acids, peptides, bile acid, and vitamin B12. This project will provide new knowledge on how flavonoids affect the dynamic transport mechanisms located in the intestinal mucosa. Thus, the results of this study will increase our understanding of the role of flavonoids found in tea, vegetables, soy, and dietary supplements in the intestinal absorption of therapeutic drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXPOSURE REDUCTION AND PREVENTION Principal Investigator & Institution: Knize, Mark G.; University of Calif-Lawrnc Lvrmr Nat Lab Lawrence Livermore National Lab Livermore, Ca 945509234 Timing: Fiscal Year 2002; Project Start 19-APR-2002; Project End 31-JAN-2007 Summary: (provided by applicant): Recent studies estimate that most human cancers result from modifiable lifestyle factors, including diet. Lowering exposure to heterocyclic amines (HAs), which are formed in cooked meats, is an obtainable goal that may have a real impact on cancer incidence. This proposal addresses: 1) safe cooking methods that reduce HA formation, 2) identifying unknown mutagens and establishing their potency, 3) understanding the influence of other foods on reducing human HA absorption, 4) mechanistic studies of inhibition of flavonoids and 5) establishing the
12
Flavonoids
relationship between dietary questionnaires and HAs in urine. Meat cooking will be investigated to understand the conditions that reduce the formation of heterocyclic amines while using microbiology to monitor food safety. New, unknown mutagens will be isolated from beef and their amounts determined in a survey of well-cooked foods. Additionally, the parameters responsible for high mutagenic potency in new and existing HAs will be investigated as structure/activity relationships. Since there is human exposure to HAs, we can now investigate HA-diet interactions in individuals via the analysis of urinary metabolites. Exploratory studies will determine if parsley, green tea, and fiber, each shown to be preventative in epidemiology studies, can affect the total human uptake and metabolism of one HA, PhIP. Enticing results in reducing mutations with the flavonoid apigenin compel us to investigate structure/inhibition relationships experimentally and with a computational model. To quantify the dietary dose of heterocyclic amines in the population and in individuals, HA biomarkers will be developed and related to dietary questionnaires that account for diverse cooking practices. In all, this interdisciplinary research to reduce exposure combines toxicology with analytical chemistry, computational chemistry and physics to investigate heterocyclic amines and human cancer etiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDIES
FLAVONOID
BIOAVAILABILITY
IN
HUMANS-CELLULAR
Principal Investigator & Institution: Walle, Thomas; Professor; Pharmacology; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-FEB-1998; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term goal of this research program is to increase our understanding of how cellular transport and metabolism influence the oral bioavailability of dietary flavonoids, a large class of compounds that has been implicated to play a major role in the prevention of human diseases, in particular cardiovascular disease and cancer. In Specific Aim 1 we will determine the interrelationships between SGLT1 and MRP2, including mechanisms involved, in the enterocyte absorption of flavonoid glycosides and the tea flavonoids, two main classes of dietary flavonoids. These studies will be undertaken in SGLT1- and MRP2transfected cells and in the human intestinal absorption model Caco-2. The role of the potentially most important transporter, i.e. MRP2, will be directly examined in vivo in the MRP2-deficient Tr- rat. In Specific Aim 2 we will investigate the interrelationships between CYPs, UGTs and SULTs, including the identification of the major isoforms involved, in the hepatic as well as intestinal metabolism of flavonoids. This will be done in microsomes as well as in intact cells, e.g. fresh human hepatocytes. These experiments will allow us to establish the major pathway(s) of metabolism of the flavonoids. In addition, autoinduction of flavonoid metabolism will be examined, mainly focusing on CYPs and UGTs. The importance of the UGT family of enzymes will be directly examined in vivo in the genetically deficient Gunn rat. In Specific Aim 3 we will determine the role and mechanisms of a) bacterial- and b) peroxidase-mediated catabolism of flavonoids, including covalent binding to protein. The experiments in a) will be conducted in gnotobiotic compared to normal rats as well as in samples from an in vivo human study. Complementary in vitro studies will include the identification of the bacterial pathway leading from quercetin to CO2 formation. The experiments in b) will be conducted in vitro, using pure enzymes and subcellular fractions, and then in intact cell systems in which production of reactive oxygen species as well as glutathione levels can be manipulated. Structure identification of metabolites as well as elucidation
Studies
13
of covalent binding will be critical factors. The findings from the proposed studies should help us understand the bioavailability of the flavonoids, facilitating optimization of the chemopreventive utility of these natural or synthetic compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FLAVONOID MODULATION OF EPITHELIAL MIGRATION /SIGNALING Principal Investigator & Institution: Hord, Norman G.; Assistant Professor; Food Science & Human Nutrition; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2003; Project Start 02-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Colorectal cancer, the third leading cause of cancer death in men and women in the U.S., results from the interaction of genetic and dietary susceptibility elements. Since colorectal cancer is caused by failure of terminal cell differentiation, dietary factors that promote cell migration, a required phenotype for cell differentiation, can be expected to decrease colorectal cancer risk. Our long-term goal of this research is to identify mechanisms by which specific dietary compounds mediate the development of phenotypes associated with cell differentiation including migration, cell-cell communication and apoptosis. The objective of this application is to identify the intracellular signaling pathways induced by flavonoids that contribute to cell migration. Our central hypothesis is that specific flavonoids, present in the diet in foods and beverages, will elicit the migratory phenotype in non-tumorigenic colon epithelial cells by activating specific intracellular signaling pathways. Wild-type adenomatous polyposis coil (APC) is a gatekeeper gene for inherited and sporadic colorectal cancer in rodents and humans. The migratory phenotype is dependent upon wild-type APC expression since full length APC protein mediates directed cell migration in the colon. We will use non-tumorigenic colon epithelial cell lines with normal Apc genotype (called YAMC) and mutant Apc genotype (called IMCE) to identify biological determinants of cell migration relevant to the early stages of colon tumorigenesis. To test our hypothesis and achieve our objectives, we propose to address three specific aims. First, we will identify specific flavonoids that induce migration in YAMC and IMCE cells by performing dose-response studies of flavonoid-dependent cell migration using twelve (12) compounds representing five (5) flavonoid families. Second, we will quantify the ability of migration-inducing flavonoids to activate relevant cell signaling pathways associated with cell migration by co-treating YAMC and IMCE cells with flavonoids and receptor- and signaling pathway-specific antagonists or inhibitors. Third, we will quantify the ability of selected migration-inducing flavonoids to modulate gene expression in YAMC and IMCE cells using cDNA microarrays constructed from the 15K mouse set of the National Institute of Aging. These analyses will identify genes and clusters of gene families whose transcription is increased or decreased in response to these flavonoids. The identification of dietary compounds which could stimulate migration, and hence, cell differentiation, in cells expressing mutant Apc (IMCE cells) could define a new strategy for prevention of colon cancer by diet-derived compounds. Ultimately, this research will provide critical information necessary for specific and rational dietary recommendations to decrease colon cancer risk in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
14
•
Flavonoids
Project Title: FLAVONOIDS HYPERTIGLYCERIDEMIA
IN
THE
AMELIORATION
OF
Principal Investigator & Institution: Theriault, Andre G.; None; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-APR-2005 Summary: (provided by applicant): The long term goal of this research project is to examine the influence of complementary and alternative medicine (CAM) bioflavonoidrich extracts (i.e. green tea leaf extracts, citrus bioflavonoids, and rutin) on the regulation of hepatic triglyceride-rich lipoprotein production in a hypertriglyceridemic model. Bioflavonoid-rich extracts have been claimed to protect against cardiovascular disease (CVD), in large part through its inhibitory effect on low density lipoprotein (LDL) oxidation. The potential benefit of these compounds in treating hyperlipidemia has also recently been shown in both animal and human studies. However, the molecular mechanisms for this lipid-lowering action are not fully understood. We have recently shown that a citrus bioflavonoid administered to hypertriglyceridemic-insulin resistant (HIR) hamsters lowered blood triglyceride levels through the inhibition of hepatic microsomal triglyceride transfer protein (MTP) protein expression and diacylglycerol acyltransferase (DGAT) activity. These results are preliminary and need to be confirmed on a larger scale. Nonetheless, these results do unveil a potentially exciting area of research. The role of other lipogenic enzymes in VLDL production needs to be explored. Also, whether or not the assembly and secretion of hepatic apoB100-VLDL is altered need to be addressed. Moreover, it is not known if all bioflavonoids possess a triglyceride-lowering ability. Therefore, the specific aim of this study using both plasma and isolated hepatocytes is to investigate the effect of bioflavonoid-rich extracts on the in vivo and ex vivo VLDL production in HIR hamsters. This will be done by measuring the rate in VLDL secretion in plasma, and by using isolated hepatocytes, the synthesis and secretion of apoB-100 and triglyceride, and lipogenic enzyme expression and activity. By understanding the lipid lowering function of these products, we aimed at providing new information of these commonly used CAM products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FORMULATION OF COMBINATION MICROBICIDES Principal Investigator & Institution: Rohan, Lisa C.; Magee-Womens Hlth Corp Pittsburgh, Pa Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Description (provided by applicant): The overall goal of this proposal is to develop a formulated combination microbicide which will prevent the spread of human immunodeficiency virus (HIV) both vaginally and rectally utilizing multiple protective factors which inactivate the virus at different stages in its replication cycle. Inhibition of HIV attachment to the CD4 cellular receptor will be accomplished by formulating plantderived flavonoids with sulfated polysaccharides (carrageenans). There will therefore be redundancy built into the microbicide to inhibit HIV binding to its cellular receptor. Virucidal compounds, which destroy the viral envelope, will also provide redundant protection from infection. Both the antiviral ether lipid 1-0-octylsn- glycerol and citric acid will destabilize the envelopes of viral particles. Furthermore, the HIV reverse transcriptase will be inactivated by both antiviral flavonoids and a non-nucleoside reverse transcriptase inhibitor (Dr. Parniak, Project 1). Herpes simplex virus (HSV) will also be targeted by flavonoids, carrageenans, 1-0-octyl-sn-glycerol and citric acid to reduce genital ulceration and consequently the transmission of HIV to a greater extent
Studies
15
than inactivating HIV only. Methods will be developed to quantify antiviral agents at each step in the pre-formulation and formulation process and physical and chemical pre-formulation data including solubility, stability, partitioning, and permeability data will be developed as part of these studies. Once active agents have been selected, their compatibility and toxicity with normal vaginal microflora and local tissues in both the isolated and formulated state will be determined. Following the initial formulation and development of a combination microbicide product, the microbicide will be optimized to maximize each antiviral mechanism and minimize toxicity in an iterative manner. The final formulated product will undergo stability testing, and product assessments will be made to ensure that the product has appropriate physical, chemical, microbiological, and antiviral properties during its shelf life. This project contributes to the program by producing new combinations of formulated microbicides based upon inhibition of viral replication using multiple and redundant antiviral mechanisms. Formulated combination microbicides produced in this project will be evaluated in vitro against HIV (Dr. Parniak, Project 1; Dr. Gupta, Project 2) and normal vaginal flora (Microbiology Core, Dr. Hillier), and as well as in humans (Dr. Landers, Project 4). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION OF HYDROXYLASES AND OTHER OXIDATIVE ENZYMES Principal Investigator & Institution: Coon, Minor J.; Biological Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-APR-1976; Project End 31-MAR-2004 Summary: Of the known biological catalysts, cytochrome P450 is unmatched in its multiplicity of isoforms, inducers, substrates, and types of chemical reactions catalyzed. Rapid progress in recent years as revealed a P450 gene superfamily with numerous members in bacteria, fungi, plants, invertebrates, and vertebrates, including the human. These enzymes are of great interest from a fundamental point of view because of their remarkable versatility and reaction mechanisms involving the generation of a powerful oxidant from molecular oxygen, and also from the viewpoint of their biomedical relevance. Because the substrates include physiologically important compounds such as steroids, bile acids, fatty acids, prostaglandins, retinoids, biogenic amines, and lipid hydroperoxides, as well as a host of "environmental chemicals," it is no exaggeration to say that improved knowledge of P450 function will contribute to progress in drug metabolism and design, as well as to better insights into chemical carcinogenesis, alcoholism, endocrine disorders, and oxidative stress. Our main objectives are: 1. To obtain detailed evidence on the important question of whether multiple oxygenating species contribute to substrate oxidation by cytochrome P450. Mutant P450s blocked in proton delivery to the active site will be examined for their rates of oxidation of various substrates as an indication of the role of peroxo-hydroperoxo- and oxenoid-iron as discrete oxidants. Attempts will be made to characterize these labile species by chemical and physical methods in order to correlate the apparent steady state level of a particular oxidant with the catalytic rates. In addition, the possibility will be examined that the levels of the oxidants are subject to regulation by effectors, including cytochrome b5 and flavonoids. 2. To continue our attempts to obtain one or more mammalian P450s in a crystalline form suitable for structure determination by x-ray diffraction. Various fulllength and truncated P450s will be studied for this purpose. 3. To determine the role of phospholipids and other membrane components in influencing the formation of binary and ternary complexes of P450, NADPH-P450 reductase, and cytochrome b5, and in altering the rates and specificities of substrate oxidation in lipid bilayers. The effect of
16
Flavonoids
lipid composition in membrane bilayers. The effect of lipid composition in membrane bilayers will be examined with respect to single-phase fluid membranes with co-existing solid-phase obstacles to protein diffusion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENES, DIET AND CARCINOGEN ACTIVATION IN SMOKERS Principal Investigator & Institution: Le Marchand, Loic; Professor; None; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2002; Project Start 20-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the Applicant's Abstract): This research will investigate genetic and dietary influences on the Phase I metabolism of tobacco smoke carcinogens and on lung cancer risk. Based on recent findings, we hypothesize that, in smokers: 1) polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke are the primary cause of squamous cell carcinoma of the lung, whereas nitrosamines in tobacco are the primary cause of lung adenocarcinoma; 2) the metabolic activation of PAHs is mainly carried out by CYPIA1, with more minor roles for CYP3A4 and CYP1B 1, and the activation of tobacco-specific nitrosamines (TSNAs) is mainly carried out by CYP2E1, CYPlA2 and CYP2A6; and 3) the activation of these carcinogens is modified by polymorphic genes and dietary inhibitors/inducers. We will use genomic DNA samples from a completed case-control study of lung cancer among Japanese, Caucasians and Hawaiians (341 cases, 456 controls) to test the independent and joint associations of these polymorphisms with lung cancer risk. We will also conduct a cross-sectional study (n=600) among Japanese, Hawaiian and Caucasian smokers participating in our Multiethnic Cohort Study to test associations of: 1) urinary NNAL (the main metabolite of NNK) and TSNA globin adducts with the high activity genotypes for CYP2E1, CYIA2 and/or CYP2A6; 2) urinary total 1-hydroxypyrene and levels of PAH DNA adducts in circulating lymphocytes with the high activity genotypes for CYPIAI, AhR and CYPIBI; and 3) intake and urinary levels of phytochemicals (specific flavonoids, total isothiocyanates) and plasma levels of micronutrients with these markers of activation. Finally, two feeding studies (n=50 each) will use a randomized cross-over design to test the effect of selected foods on markers of PAH or TSNA metabolism and on metabolizing enzymes in smokers with high and low activity genotypes. The elucidation of the main enzymes responsible for carcinogen activation and of the impact of dietary factors on these enzymes would have important implications for cancer prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: GENISTEIN AS MODULATOR OF ANTIOXIDANT PROTEIN EXPRESSION Principal Investigator & Institution: Kuo, Shiu-Ming; Exercise and Nutritional Sciences; State University of New York at Buffalo Suite 211 Ub Commons Buffalo, Ny 14228 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Flavonoids represent a family of phytochemicals found in many human food items. Among them, genistein (Gn) is found especially at high concentration in soybeans, an important element of Oriental diet. Epidemiological studies, in vivo animal studies and in vitro cell studies all suggested that Gn could play a role in the prevention of cancer. More work at the molecular level is needed to define the mechanism. This proposal addresses one potential mechanism: the ability of Gn to increase the expression of an antioxidant protein, metallothionein (MT). We have found that Gn increased the levels of MT protein and mRNA in human intestinal cells, Caco-2. The induction was
Studies
17
synergistic with the stimulatory effect of zinc. Based on these observations, the proposal is designed to determine the physiological significance of MT induction; and the mode of Gn-MT gene interaction. We will compare the level of oxidative byproduct after tertbutylhydroperoxide challenge in cells with and without Gn treatment. In addition, animal study will be conducted to show that Gn feeding leads to an increase in the organ MT level and a decrease in the organ oxidative byproduct level. The mode of GnMT gene interaction will be investigated indirectly through the combination treatment of cells with Gn and other inducers of MT expression like copper, cadmium or cytokines. We will also perform nuclear run-on experiment and mRNA stability analysis in cells to directly confirm the effect of Gn at the transcriptional level. Reporter gene assays will then be conducted to determine the site of Gn-MT gene interaction on the cloned sequence of human MTIIA promoter. The results from the proposed studies will help to assess the essentiality of Gn in the human diet for reduction of cancer risk. These studies may also lead to the identification of a previous unknown pathway for Gn to regulate mammalian genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INFLUENCE OF CRANBERRY ON PLAQUE-RELATED DISEASES Principal Investigator & Institution: Koo, Hyun; Eastman Dentistry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 30-NOV-2006 Summary: (provided by applicant): Dental caries is the most common oral infectious disease that afflicts humans. More than 95% of all adults have experienced this disease. It is more common than asthma, hay fever or chronic bronchitis in 5-17 year old children. The American public spends close to $40 billion per year to treat this disease or its consequences. Dental caries results from the interaction of specific bacteria with constituents of the diet on a susceptible tooth surface. Dental plaque accumulation is the first clinical evidence of this interaction; dental plaque is a biofilm which is comprised of a population of bacteria growing on the tooth surface enmeshed in a polysaccharide matrix. Acid can be formed rapidly by acidogenic bacteria, such as Streptococcus mutans, within the matrix and its persistence results in dissolution of the tooth. Furthermore, plaque is also the major aetiological factor in gingivitis. Cranberries, like other natural products, harbor a plethora of biological compounds such as flavonoids (e.g. quercetin and myricetin), phenolic acids (benzoic acid), anthocyanins, condensed tannins, and others. We have shown that many of these substances can: (i) inhibit enzymes associated with the formation of the plaque polysaccharide matrix, (ii) block adherence of bacteria to surfaces, (iii) prevent acid formation, and (iv) reduce acid tolerance of cariogenic organisms. For example, quercetin and myricetin are effective inhibitors of glucosyltransferases (GTFs), enzymes responsible for the synthesis of glucans; glucans synthesized by GTFs mediate the adherence and accumulation of cariogenic streptococci on the tooth surface. Weak acids, such as benzoate (benzoic acid), affect the acid production by S. mutans and have been shown to reduce dental caries in rats. We propose a comprehensive plan to explore the influence of cranberry on many of the biological aspects involved in the pathogenesis of dental plaque formation and caries. We also propose to examine the ability of cranberry to prevent or reduce caries in our well-proven rodent model and to investigate the effects of cranberry on plaque formation and gingivitis in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
18
•
Flavonoids
Project Title: INFLUENCE OF DIETARY FLAVONOIDS ON THE EXPRESSION OF AT* Principal Investigator & Institution: Keen, Carl L.; Professor and Chairman; Nutrition; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2002; Project Start 15-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Oxidative stress is characterized by excessive concentrations of reactive oxygen and reactive nitrogen species (ROS and RNS). Excessive oxidative damage has been implicated in the pathogenesis of numerous degenerative diseases including coronary vascular diseases (CVD). A current hypothesis suggests that ROS, RNS and oxidized LDL (ox-LDL) induce the expression of atherogenic genes via redox-sensitive signaling pathways. The oxidative stress-induced gene expression has been shown to be mediated via the activation of redox sensitive transcription factors such as nuclear factor- kappaBeta (NFkB), and redox-sensitive transduction pathways such as those involving members of the mitogen activated protein kinase (MAPK) family as well as members of the Src family. Genes regulated by NFkB activation encode for proteins implicated in acute phase and inflammatory responses including certain cytokines and chemokines, cell adhesion molecules and inflammatory enzymes; several of these molecules are involved in the pathogenesis of atherosclerosis. Similarly, studies have shown that JNK, BMK-1 and cSrc are involved in signaling events stimulated by ROS that contribute to atherosclerosis such as smooth muscle cell proliferation. It is well known that diet plays a important role in a large number of chronic diseases. The investigators suggest that this is due in part to an effect of diet on a individual's antioxidant status. Vitamins and minerals contribute to the oxidative defense system because: (1) they are antioxidants (vitamins E, C and Bcarotene); (2) they are essential for the function of enzyme antioxidants (Zn, Cu, Fe, Mn, Se and riboflavin); or (3) they act to maintain low levels of potentially pro-oxidant molecules (vitamins B12, B6 and folate). On the other hand, the cardio-protective effects of flavonoids result in part from their antioxidant properties, and their ability to modulate the activity of a wide spectrum of enzymes. The researchers propose to investigate the hypothesis that diet may influence vascular redox-mediated signaling and transcriptional activities. Using the mouse model, they will test the hypothesis that a diet marginal in select micronutrients will induce a pro-oxidative state that will worsen the pathophysiological state of atherosclerosis. Finally, they will test the hypothesis that addition of flavonoids to diets marginal in antioxidants will attenuate the atherogenic effect of the pro-oxidative effect of micronutrient deficiency and hypercholesterolemia. These issues will be addressed using mutant mice in which the LDL receptor (LDLr) has been inactivated. The researchers will measure the progression of atherosclerosis in LDLr +/+ and -/- mice fed a high fat-micronutrient adequate diet, or a high fat-micronutrient marginal diet, supplemented or not with the flavonoids, quercetin and catechin. They will use biochemical markers and immunohistochemistry to evaluate antioxidant capacity and redox status in the LDLr mice, and correlate these with the severity of atherosclerosis determined by lesion progression and atherogenic gene expression. Finally, they will examine the effects of the diets on the activation of NFkB and cell signaling pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
Project Title: INTERACTION FLAVONOIDS
BETWEEN
IRINOTECAN
AND
19
DIETARY
Principal Investigator & Institution: Iyer, Lalitha V.; Sri International 333 Ravenswood Ave Menlo Park, Ca 940253493 Timing: Fiscal Year 2003; Project Start 18-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Over 50% of cancer patients use alternative medicines regularly while undergoing chemotherapy. These products, though derived from natural sources, may contain active ingredients that may influence the disposition and/or therapeutic outcome of concomitantly administered chemotherapeutics. This application will address the issue of drug/botanical interaction between the anticancer agent irinotecan (used against colorectal cancer) and the popular dietary flavonoids from soy (genistein and daidzein) and fruits and vegetables (chrysin and quercetin). Irinotecan has complex dispositional characteristics, with sequential metabolic activation and inactivation steps, biliary and urinary excretion. The PI has studied some of these pathways extensively and has shown that the enzyme UGT1A1 glucuronidates its active metabolite, SN-38, and that the multidrug resistance transporter, pglycoprotein (P-gp), plays a major role in irinotecan's biliary excretion. Flavonoids such as chrysin and quercetin are known inducers of UGT1A1. Our hypothesis are that (i) the selected dietary flavonoids will influence the disposition and toxicity of irinotecan via induction of the glucuronidation (by UGT1A1) of its active metabolite, SN-38; and (ii) induction of UGT1A1 by dietary flavonoids is influenced by genetic differences in the promoter region of the UGT1A1 gene. The specific aims are to (1) investigate the in vivo interaction of soy isoflavones, chrysin and quercetin with irinotecan in rats, (2) determine whether hepatic UGT1A1 induction by flavonoids is responsible for their interaction with irinotecan, and (3) investigate the influence of the TATA polymorphism in the promoter region of UGT1A1 on inducibility by these flavonoids. Aim 1 will involve in vivo pharmacokinetic, biliary, and urinary excretion studies with irinotecan after chronic pretreatment of rats with the selected dietary flavonoids. The potential induction of UGT1A1 will be studied in Aim 2 by measuring SN-38 glucuronidation in hepatocytes and liver microsomes from flavonoid treated rats, as well as by measuring UGT1A1 protein levels. In Aim 3, luciferase reporter assays will be performed to investigate UGT1A1 activity after pretreatment with flavonoids in Hep G2 cells transfected with known polymorphic forms (TA5,TA6,TA7,TA8) of the TATA sequence of UGT1A1. As irinotecan has a narrow therapeutic index, minor changes in its disposition can significantly modify the therapeutic outcome, so this investigation will have major potential benefits to cancer patients and oncologists. This pilot/developmental project will generate significant preliminary results to propose larger (R01) grants being planned by the PI and colleagues on the interaction between natural medications & dietary supplements and conventional chemotherapy, and its pharmacogenetic implications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTIETHNIC COHORT STUDY OF DIET AND CANCER Principal Investigator & Institution: Kolonel, Laurence N.; Deputy Director; None; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2003; Project Start 01-JAN-1983; Project End 29-FEB-2008 Summary: (provided by applicant): This application requests funding for continued support of the Multiethnic Cohort Study which was established in Hawaii and Los Angeles in 1993-96 to explore the relationship of diet and other lifestyle factors to cancer.
20
Flavonoids
The cohort is comprised of more than 215,000 men and women primarily of African American, Japanese, Latino, Native Hawaiian and Caucasian origin, and is unique among existing cohort studies in its ethnic diversity and representation of minority populations. At entry, each participant completed a 26-page mail questionnaire that included an extensive quantitative diet history, as well as other demographic, medical, and lifestyle information. Multiple 24-hour diet recalls were collected on more than 2,000 of the participants in a calibration study designed to permit correction of nutrient intake estimates for measurement error. In the current cycle (1998-2003), a brief followup questionnaire to update selected dietary and non-dietary baseline information was completed by more than 80 percent of the participants; in the next cycle, the baseline dietary questionnaire will be repeated. Out-migration rates after 7 years were low (< 5 percent), supporting the use of computer linkage with the population-based cancer registries in Hawaii and California to identify incident cases; more than 25,000 cases of breast, prostate, colorectum and lung cancer are expected by the year 2007. Based on an average 4 years of follow-up, some preliminary dietary findings included: positive association of alcohol with breast cancer, dairy products with prostate cancer, and saturated fat with lung cancer; and inverse association of legumes with breast cancer, carotenoids and certain vegetables with lung cancer, and dietary fiber and folate with colorectal cancer. In the next cycle, the larger numbers of incident cases will enable us to further examine these dietary relationships by ethnicity and stage of disease, to examine other cancer sites (pancreas, bladder, ovary, endometrium), and to contribute to analyses of gene-diet interactions. In addition, new information from the follow-up questionnaire and enhancements to the food composition database will be used to directly test the relationship of flavonoids and heterocyclic amines to colorectal, lung, bladder and other cancers. We will also test hypotheses related to use of exogenous hormones and cancers of the breast, ovary and colorectum; and use of NSAIDs and cancers oft he colorectum, lung, breast and ovary. A methodological aim, utilizing biochemical measurements on 750 members of the cohort, will develop new dietary exposure variables to improve testing of etiologic hypotheses. Findings from the Multiethnic Cohort Study should help not only to identify dietary and other risk factors for cancer, but also to better understand the basis for ethnic variations in cancer incidence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BILOBALIDE
NEUROMODULATORY
EFFECTS
OF
GINKGOLIDES
AND
Principal Investigator & Institution: Nakanishi, Koji; Centennial Professor of Chemistry; Chemistry; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2003; Project Start 12-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This proposal is focused on the mode of action of the ginkgolides and bilobalide (terpenoid trilactones) from the tree Ginkgo biloba. The crude extract of G. biloba, a complex mixture composed of many different compounds, have shown effects on the diseased as well as healthy state of the mammalian brain. Clinical studies, animal studies, and various in vitro studies of the extracts have demonstrated beneficial effects against various neurodegenerative diseases, particularly Alzheimer's disease, as well as memory enhancing effects in the normal brain. However, very little is known about effects of individual constituents, especially at the molecular structural level. In this proposal, we will focus on the most unique constituents of the Ginkgo biloba extract, the ginkgolides and bilobalide, but not on the action of the crude
Studies
21
extract which clearly involves synergistic effects, e.g., between the flavonoids (a major component) and the terpenoid trilactones. Some ginkgolides are antagonists of the platelet-activating factor receptor (PAFR), and appear to have antioxidant and neuroprotective properties. We have also found that ginkgolide B is a glycine receptor antagonist, while bilobalide is a potent GABAA receptor antagonist. Our goal is to determine the neuromodulatory effects of terpene trilactones on the mammalian central nervous system, using bioorganic and spectroscopic methods, including those under development in our laboratory on a molecular level. The specific topics to be studied include synthesis of radiotracers for positron emission tomography (PET) and ex vivo autoradiography studies, design and preparation of novel photolabile and fluorescent terpene trilactones analogs to be used to elucidate the interactions of terpene trilactones and PAFR. During these studies we will develop and apply novel methodologies such as ultra-microscale photolabeling and sequencing using unconventional mass spectrometric and circular dichroic techniques, as well as "membrane scissors". Using radioligand binding and microphysiometry, we will initiate studies on the effects of terpene trilactones on the cloned PAFR, using PAFR expressed in Chinese hamster ovary cells. The effects of terpene trilactones on long-term potentiation will be examined in vitro as well as in animal models. These studies can potentially provide new targets for terpene trilactones in the central nervous system that require the synthesis of new ginkgolide and bilobalide ligands. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROSTATE CANCER CHEMOPREVENTION BY APIGENIN Principal Investigator & Institution: Gupta, Sanjay; Assistant Professor; Urology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2004 Summary: (provided by applicant): The marked difference in the incidence of prostate cancer (CaP) among several regions of the world suggest that dietary factors may influence the biological process related to prostate carcinogenesis. Because CaP is the most common and one of the leading causes of cancer-related deaths in American males, to reduce the incidence of this disease, chemoprevention through dietary intervention appears to be a practical and encouraging approach. CaP is known to undergo a transition from an early 'androgen-sensitive' form of cancer to a late (metastatic) 'androgen-insensitive' cancer, and at the time of clinical diagnosis most CaP's represent a mixture of androgen-sensitive and androgen-insensitive cells. Therefore, the key to the control of CaP appears to lie in the elimination of both types of cells through mechanism-based intervention approaches. Epidemiological studies suggest that high consumption of fruits and vegetables is associated with a reduced risk of CaP. These studies are consistent with the observations that Asian men who consume low fat, highfiber diet rich in flavonoids have lowest CaP incidence in the world. Laboratory studies in cell culture systems have demonstrated that apigenin, a plant flavonoid abundantly present in fruits and vegetables afford protection against many types of human cancers. Consistent with this notion in our preliminary studies we demonstrated that apigenin results in I) selective response of normal versus prostate carcinoma cells, ii) inhibition of cell growth, iii) induction of apoptosis, and iii) GO-Gl-phase arrest of cell cycle, in both androgen-dependent LNCaP and androgen- independent DU145 human prostate carcinoma cells. The present proposal capitalizes on these novel findings and is designed to investigate the effect of oral consumption of apigenin on the prostate tumorigenesis under in viva situations. To accomplish this goal, we will employ the well-accepted model of athymic nude mice implanted with androgen-independent PC-3
22
Flavonoids
and androgen-dependent 22Rvl human prostate tumor cells. The hypothesis to be tested in this proposal is that apigenin will impart cancer-preventive and possibly cancertherapeutic effects by modulating cell cycle- and apoptotic- machinery of CaP cells irrespective of their androgen association. A corollary to this hypothesis that will be tested in this proposal is that oral consumption of apigenin will reduce the levels of serum prostate specific antigen (PSA), possibly by modulating the androgen receptor in athymic nude mice transplanted with androgen-sensitive human prostate carcinoma cells. These studies could be considered as a starting point for an expanded program for the development of apigenin as a promising agent against CaP in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF FIBROGENESIS BY THE DIETARY FLAVONOIDS Principal Investigator & Institution: Ricupero, Dennis A.; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 15-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Excess deposition of type I collagen is characteristic of a number of fibrotic disorders including idiopathic pulmonary fibrosis, asthma, and scleroderma. Many fibrotic diseases have features of chronic inflammation. Reactive oxygen species (ROS) are abundant in inflammatory events, although the roles of ROS are not completely understood. TGF-Beta (TGF-B), considered to be the major profibrotic effector, stimulates hydrogen peroxide (H202) production in myofibroblasts. The data presented here demonstrate, for the first time, that in myofibroblasts, H202 stimulates an increase in alpha1(I) collagen mRNA. Apigenin, a common dietary flavonoid with anti-inflammatory and anti-oxidant properties, blocks the TGF-Bstimulated increase of alpha1(I) collagen mRNA and the TGF-stimulated production of H202. The mechanism by which apigenin blocks the TGF-B-stimulated production of H202 remains unclear. Steady-state levels of alpha1(I) collagen mRNA are regulated by the rate of transcription of the alpha1(I) collagen gene and by the stability of the message. The investigators previously reported that inhibition of phosphatidylinositol 3kinase (PI3K) decreased the stability of alpha1(I) collagen mRNA. They found that apigenin blocked the TGF-B-stimulated transcription of the alpha1(I)collagen gene and reduced the stability of the message. Most importantly, they found that in transgenic mice expressing the chloramphenicol acetyl transferase (CAT) reporter construct driven by the alpha1(I)collagen promoter, topically-applied apigenin blocked the CAT activity of skin samples. Thus, it appears that apigenin is a potent downregulator of alpha1(I) collagen expression both in vitro and in vivo. This proposal will (Aim 1) test the hypothesis that an apigenin-rich diet will attenuate the development of fibrosis and (Aim 2) identify the apigenin-sensitive mechanism by which TGF-B stimulates production of H202 and test the hypothesis that alpha1(I) collagen mRNA stability is modulated through PI3K activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SPECIES DIFFERENCE IN THE BIOTRANSFORMATION OF AFLATOXIN Principal Investigator & Institution: Eaton, David L.; Associate Dean for Research; Environmental and Occupational Health Studies; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-MAY-1991; Project End 31-JUL-2004
Studies
23
Summary: Numerous studies have demonstrated that biologically active, natural components of the diet may confer resistance to chemical carcinogens via induction and/or inhibition of biotransformation enzymes. In particular, specific chemical components of the diet, such as flavonoids, isocyanates, glucosinolates, indoles, dithiolthiones, and polyphenols have been identified as effective inducers and/or inhibitors of carcinogen activation/detoxification pathways in animal models. There is much supporting data from human epidemiological studies on the important relationship between diet and cancer in humans, although the diversity and complexity of the diet, and uncertainty of specific exposures, in such studies makes identification of specific active components nearly impossible. Although animal models are useful for "hypothesis testing", species differences in carcinogen activation and detoxification pathways, as well as differences in gene regulation and expression in response to inducers, make extrapolation of animal data to the human situation tentative, at best. Thus, there is a need to develop model systems that utilize human cells/tissues to determine the efficacy of specific dietary components and/or putative chemoprotectant drugs to favorably modify the biotransformation of human carcinogens. One such model human carcinogen is aflatoxin B1. Aflatoxins are mycotoxins produced by the common fungal molds, Aspergillus flavus and Aspergillus parasiticus. Worldwide, aflatoxins are considered a major public health problem because of their potent carcinogenic effects. Human epidemiological data has documented that humans are susceptible to AFB-induced hepatocarcinogenesis, especially in combination with hepatitis B virus infection. However, there are large species differences in the susceptibility to aflatoxin carcinogenesis. Rats are highly sensitive, whereas mice are very resistant. The mechanism for this difference is associated with the expression of a specific enzyme, glutathione S-transferase A3-3 (mGSTA3-3), which is present in the livers of mice, but not rats. Treatment of rats with the drug, oltipraz, or the food additive, ethoxyquin, protects rats from aflatoxin-induced liver cancer. The mechanism for this protection is due to the ability of these chemicals to "turn on" a gene for a glutathione S-transferase, rGSTA5-5, that is normally not expressed in rat liver, but which efficiently detoxifies aflatoxin. Human liver tissue has very low ability to detoxify aflatoxin -- in fact, worse than the poor ability of rats. There has been considerable interest in devising a dietary or chemointervention strategy for humans that increases resistance to AFB by induction of GSTs. The long range goals of this proposal are to: 1) establish in vitro models that utilize isolated human hepatocytes in culture and human cDNA expressing yeast, to assess the efficacy of specific dietary components as putative chemoprotectors against AFB and other chemical carcinogens, and 2) complete the characterization of species differences in glutathione S-transferases with activity toward AFB-epoxide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNTHESIS AND ELABORATION OF DIVERSE SCAFFOLDS Principal Investigator & Institution: Porco, John A.; Assistant Professor; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: The goal of this project of four unique heterocyclic scaffolds for library development, each displaying a minimum of three orthogonal diversification points for derivatization which can be moved positionally within the scaffold structure. Each scaffold also bears stereocenters which can be constructed with high degrees of selectivity to allow for additional stereochemical diversity. The four parent scaffolds are: (1), 1,7-dioxaspiro[5,5]undecane spiroketals; (2) pipecolic acids; (3) flavonoids; (4)
24
Flavonoids
1,2,3,4-tetrahydro-1,5-naphthyridines, thus representing two oxygen heterocycles and two nitrogen heterocycles. The goal is to produce a variety of libraries with a limited number of members, rather than fewer libraries with a large numbers of structurally repetitive members. Two libraries will be produced using the spiroketal scaffold, three libraries from the pipecolic acid core structure, and four libraries each from the flavonoid and naphthyridine heterocycles. The emphasis within this project will also be on the development of new methodologies for use in chemical library construction. Thus within each subproject defined by the four unique scaffolds, new resin-bound reagents, scavenger resins for reaction work-up, and new capture-and-release strategies are proposed for development. The individual library constructions stress original synthetic strategies that lead to conformationally biased heterocycles that expand stereochemical and positional diversity as they probe three dimensional space. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TASTE PSYCHOPHYSICS OF BITTER PHYTOCHEMICALS Principal Investigator & Institution: Linschoten, Miriam R.; Instructor; Otolaryngology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Diets rich in vegetables and fruit lower the risk of cancer and other systemic diseases. Phytochemicals such as phenols, flavonoids, isoflavones, terpenes and glucosinolates have anti-oxidant and anti-carcinogenic properties and demonstrate a wide spectrum of tumor-blocking activities. Many of these phytochemicals have a bitter taste, which could lead to avoidance of the foods containing them. Taste also is the most important factor in food choice; it is more important than nutritional value, cost, convenience and weight control. The ability, however, to perceive some bitter substances is genetically mediated; about 25% of the population is unable to perceive the bitterness of 6-n-propylthiouracil (PROP), 50% can taste it, and 25% are considered supertasters. It has been shown that PROP tasters have a lower acceptance of bitter vegetables and salad greens. PROP tasters might therefore be less likely to adopt a diet for cancer prevention that emphasizes consumption of bitter vegetables. Very little is known about threshold and suprathreshold bitter perception of the phytochemicals naringin, limonin, quercetin, sinigrin and genistein. The purpose of this study is to determine how these bitter phytochemicals are perceived by (super) tasters and non-tasters of PROP. The knowledge gained through the proposed experiments will provide insight into the role genetic taste sensitivity plays in food preference and food choice. Detection thresholds for the five phytochemicals and sodium chloride and PROP will be determined with a maximum likelihood adaptive staircase method. Psychophysical functions for all seven substances will be measured with the Labeled Magnitude Scale. Subjects will also rate how much they like each of five concentrations of the seven substances. Furthermore, food preference data will be gathered. It is anticipated that this study will result in safe and usable ranges of stimulation for each of the phytochemicals, so that in the future data from children can be obtained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: THE UCLA CLINICAL NUTRITION RESEARCH UNIT Principal Investigator & Institution: Heber, David; Professor/Chief; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024
Studies
25
Timing: Fiscal Year 2002; Project Start 30-SEP-1985; Project End 30-APR-2007 Summary: (provided by applicant) The UCLA Clinical Nutrition Research Unit (CNRU) supports the development of new interdisciplinary research in nutrition and cancer prevention which would not otherwise occur through provision of specialized core research services, pilot/feasibility study funds and a New Investigator Award. The Administrative and Nutrition Education Core has creatively expanded the influence of the CNRU at UCLA. We have established the UCLA Center for Human Nutrition as the focus of nutrition research, education and patient care at UCLA. Our NIH T32 Nutrition and Obesity Training Program has developed new junior faculty and we have recruited many new faculty to the CNRU. An NIH P50 Center for Botanical Dietary Supplements Research was funded in 1999 and led to collaboration with plant molecular biologists and funding of the UCLA Research Growth Center. The Gene-Nutrient Core has established new facilities with private funds for high throughput genotyping, and microarray analysis of gene expression and this has led to new funding. The Molecular Oncology Core provides expertise in studies of the multistep pathway of carcinogenesis. The Nutritional Biomarker Core has supported research with high quality lipid, hormone, and carotenoid measurement and established methods for quantitating dietary flavonoids and assessing oxidant stress supporting new funded research. The Stable Isotope Core has established methods for metabolic phenotyping of cancer cells, and supported phytochemical measurement by LCMS. The Dietary Intervention, Assessment and Body Composition Core has supported dietary intervention research, community-based diet assessment research, and body composition research. The Statistical Coordinating Unit Core has established new methods for analysis of national and local dietary intervention trials, analysis of data from gene-nutrient interaction studies and provided training in translational research. The UCLA CNRU is serving as a regional and national resource at the cutting edge of nutrition and cancer prevention research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THEAFLAVINS AND GALLIC ACID IN TEA Principal Investigator & Institution: Warden, Beverly A.; Senior Research Scientist; Florida International University Division of Sponsored Research and Training Miami, Fl 33199 Timing: Fiscal Year 2002 Summary: Flavonoids are a class of nutrients found in a large number of foods, particularly fruits and vegetables. There is a large number of flavonoid subclasses, most of which have been associated with antioxidant properties important in preventing chronic diseases. Epidemiological studies have demonstrated a protective effect of flavonoids in preventing cardiovascular disease in some populations. However, there is conflicting evidence as to their efficacy in preventing cancer. The long term goal of this research is to study the bioavailability and metabolism of specific subclasses of flavonoids so that future cohort and case controlled studies can be designed to produce more definitive results regarding the link between tea consumption and improve health through prevention of chronic disease. The objective of this proposal is to study the absorptive, metabolic, and excretory processes in humans associated with the intake of gallic acid (GA) and theaflavins (TF) found in regular black tea. The results of this study will help researchers to more fully understand the metabolism of one subclass of flavonoids which is highly consumed by humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
26
•
Flavonoids
Project Title: TOXICOLOGICAL CONTROL MECHANISMS OF HUMAN CYP1A2 Principal Investigator & Institution: Quattrochi, Linda C.; Associate Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-MAR-2005 Summary: (Adapted from the Applicant's Abstract): Cytochrome P450 (CYP) enzymes play an important role in the metabolism of endogenous compounds and such exogenous substrates as drugs and various chemical carcinogens. CYP 1 A, one of the CYP subfamilies in vertebrates consisting of two members, CYP1A1 and CYP1A2, catalyzes the metabolism of such environmental chemicals as polycyclic aromatic hydrocarbons and arylamines as well as numerous drugs. Several factors appear to modulate the expression of CYP1A enzymes including chemicals (e.g. polycyclic aromatic hydrocarbons and halogenated hydrocarbons), dietary constituents (e.g. heterocyclic amines, flavones, indoles) and genetic factors. In the present research proposal, we will examine the hypothesis that the molecular mechanisms involved in the regulation of human CYP1A2 involves complex interactions of trans-acting factors at multiple and redundant regulatory elements, and that naturally-occurring dietary flavonoids alter the expression of both CYP 1 A2 and CYP IA 1. Our goals for the forthcoming grant period are to focus on the fundamental mechanistic events defining CYP1A2 basal and cell type-specific expression, and to define the role of naturally occurring dietary flavonoids in modulating CYP1A gene expression through the interactions of these agents with transcription factors (e.g. arylhydrocarbon receptor, other basic helix-loop-helix proteins) that potentially mediate human CYP1A gene expression. To this end, we will use various cell lines for in vitro studies, and we will develop models to study the molecular mechanisms involved in the in vivo regulation of human CYP1A gene expression. In vivo studies will utilize genome-integrated reporter gene constructs and a transgenic mouse line containing a bacterial artificial chromosome expressing the human CYP1A1 and CYP1A2. The long-term goals are to understand at the cellular and molecular level the mechanisms controlling the expression of CYP1A2 and the mechanisms that affect both CYP1A1 and CYP1A2 in relation to the chemoprotective properties of naturally occurring flavonoids. Additionally, understanding the molecular events associated with altered CYP1A gene expression due to interactions of such "natural" pharmaceuticals as flavonoids and other plant-derived products should lead to an awareness of possible adverse effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: V(D)J RECOMBINASE MEDIATED TRANSPOSITION IN VIVO Principal Investigator & Institution: Murray, Janet M.; Pediatrics; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 01-MAY-2002 Summary: (provided by the applicant): V(D)J recombination is normally associated with immunoglobulin and T cell receptor rearrangements. Aberrant genomic V(D)Jrecombinase-mediated events are potential sources of oncogenic rearrangements. Many aspects of V(D)J recombination are shared by transposons, and V(D)J-mediated transposition has been demonstrated in vitro. Our hypothesis is that V(D)J-mediated transposition occurs in vivo and that genotoxic agents associated with tobacco smoke and dietary flavonoids lead to an increase in aberrant V(D)J recombination and transposition. Specific Aim #1 To determine whether V(D)J-mediated transposition occurs in vivo. We will utilize a plasmid-based assay in an attempt to capture V(D)J-
Studies
27
mediated transposition into the HPRTlocus. Secondly, clones from pediatric patients containing V(D)J-mediated deletion of HPRT exons 2 and 3 will be analyzed for exon 2 and 3 transposition. Specific Aim #2 Using the plasmid-based assay above cells will be treated with genotoxic agents found in tobacco smoke and dietary flavonoids. This assay will allow us to assess the effects of genotoxic exposure on transpositional events as well as V(D)J-mediated aberrant recombination within the HPRT gene. Specific Aim #3 Mechanistic studies will be initiated to examine the expression of known proteins associated with V(D)J recombination including Rag1, Rag2 and DNAPK. Altogether these experiments will help us correlate environmental exposure and the level of aberrant V(D)J recombination to the expression of known V(D)J components. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “flavonoids” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for flavonoids in the PubMed Central database: •
A Cluster of Genes Encodes the Two Types of Chalcone Isomerase Involved in the Biosynthesis of General Flavonoids and Legume-Specific 5-Deoxy(iso)flavonoids in Lotus japonicus. by Shimada N, Aoki T, Sato S, Nakamura Y, Tabata S, Ayabe SI.; 2003 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166860
•
A cytochrome b 5 is required for full activity of flavonoid 3[prime prime or minute],5[prime prime or minute]-hydroxylase, a cytochrome P450 involved in the formation of blue flower colors. by de Vetten N, ter Horst J, van Schaik HP, de Boer A, Mol J, Koes R.; 1999 Jan 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15213
•
A null mutation in the first enzyme of flavonoid biosynthesis does not affect male fertility in Arabidopsis. by Burbulis IE, Iacobucci M, Shirley BW.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=161155
•
Accumulation of a nod gene inducer, the flavonoid naringenin, in the cytoplasmic membrane of Rhizobium leguminosarum biovar viciae is caused by the pHdependent hydrophobicity of naringenin. by Recourt K, van Brussel AA, Driessen AJ, Lugtenberg BJ.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210214
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
28
Flavonoids
•
Alfalfa Root Flavonoid Production Is Nitrogen Regulated. by Coronado C, Zuanazzi J, Sallaud C, Quirion JC, Esnault R, Husson HP, Kondorosi A, Ratet P.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157372
•
An Arabidopsis Mutant Tolerant to Lethal Ultraviolet-B Levels Shows Constitutively Elevated Accumulation of Flavonoids and Other Phenolics. by Bieza K, Lois R.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116467
•
Anaerobic Degradation of Flavonoids by Clostridium orbiscindens. by Schoefer L, Mohan R, Schwiertz A, Braune A, Blaut M.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201214
•
Antisense inhibition of flavonoid biosynthesis in petunia anthers results in male sterility. by van der Meer IM, Stam ME, van Tunen AJ, Mol JN, Stuitje AR.; 1992 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=160126
•
Arabidopsis Flavonoid Mutants Are Hypersensitive to UV-B Irradiation. by Li J, OuLee TM, Raba R, Amundson RG, Last RL.; 1993 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=160260
•
Arabidopsis ICX1 Is a Negative Regulator of Several Pathways Regulating Flavonoid Biosynthesis Genes. by Wade HK, Sohal AK, Jenkins GI.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166846
•
C-ring cleavage of flavonoids by human intestinal bacteria. by Winter J, Moore LH, Dowell VR Jr, Bokkenheuser VD.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184277
•
Degradation of the plant flavonoid phellamurin by Aspergillus niger. by Sakai S.; 1977 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=242690
•
Dietary flavonoids and the MLL gene: A pathway to infant leukemia? by Ross JA.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34309
•
Effects of alfalfa nod gene-inducing flavonoids on nodABC transcription in Rhizobium meliloti strains containing different nodD genes. by Hartwig UA, Maxwell CA, Joseph CM, Phillips DA.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208924
•
Effects of Glucosinolates and Flavonoids on Colonization of the Roots of Brassica napus by Azorhizobium caulinodans ORS571. by O'Callaghan KJ, Stone PJ, Hu X, Griffiths DW, Davey MR, Cocking EC.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101471
•
Elucidation of the Flavonoid Catabolism Pathway in Pseudomonas putida PML2 by Comparative Metabolic Profiling. by Pillai BV, Swarup S.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126565
Studies
29
•
Functional Conservation of Plant Secondary Metabolic Enzymes Revealed by Complementation of Arabidopsis Flavonoid Mutants with Maize Genes. by Dong X, Braun EL, Grotewold E.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117961
•
Gene Expression Profiling in Response to Ultraviolet Radiation in Maize Genotypes with Varying Flavonoid Content. by Casati P, Walbot V.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=181262
•
Inhibition of Prostate Cancer Cell Colony Formation by the Flavonoid Quercetin Correlates with Modulation of Specific Regulatory Genes. by Nair HK, Rao KV, Aalinkeel R, Mahajan S, Chawda R, Schwartz SA.; 2004 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=321331
•
Interactions among enzymes of the Arabidopsis flavonoid biosynthetic pathway. by Burbulis IE, Winkel-Shirley B.; 1999 Oct 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23169
•
Isoliquiritigenin, a strong nod gene- and glyceollin resistance-inducing flavonoid from soybean root exudate. by Kape R, Parniske M, Brandt S, Werner D.; 1992 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=195661
•
Juvenile-Specific Localization and Accumulation of a Rhamnosyltransferase and Its Bitter Flavonoid in Foliage, Flowers, and Young Citrus Fruits. by Bar-Peled M, Fluhr R, Gressel J.; 1993 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=159129
•
NodV and NodW, a second flavonoid recognition system regulating nod gene expression in Bradyrhizobium japonicum. by Loh J, Garcia M, Stacey G.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179067
•
Release of Flavonoids by the Soybean Cultivars McCall and Peking and Their Perception as Signals by the Nitrogen-Fixing Symbiont Sinorhizobium fredii. by Pueppke SG, Bolanos-Vasquez MC, Werner D, Bec-Ferte MP, Prome JC, Krishnan HB.; 1998 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34980
•
Rhizobia catabolize nod gene-inducing flavonoids via C-ring fission mechanisms. by Rao JR, Cooper JE.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=196728
•
Some observations on the effect of Daflon (micronized purified flavonoid fraction of Rutaceae aurantiae) in bancroftian filarial lymphoedema. by Das LK, Subramanyam Reddy G, Pani SP.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153483
•
Strain-Specific Inhibition of nod Gene Induction in Bradyrhizobium japonicum by Flavonoid Compounds. by Kosslak RM, Joshi RS, Bowen BA, Paaren HE, Appelbaum ER.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184405
30
Flavonoids
•
Suppression of nitric oxide production in mouse macrophages by soybean flavonoids accumulated in response to nitroprusside and fungal elicitation. by Scuro LS, Simioni PU, Grabriel DL, Saviani EE, Modolo LV, Tamashiro WM, Salgado I.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=408346
•
The Origin of Novel Flavonoids in Phlox Allotetraploids. by Levy M, Levin DA.; 1971 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=389255
•
The TRANSPARENT TESTA12 Gene of Arabidopsis Encodes a Multidrug Secondary Transporter-like Protein Required for Flavonoid Sequestration in Vacuoles of the Seed Coat Endothelium. by Debeaujon I, Peeters AJ, Leon-Kloosterziel KM, Koornneef M.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135529
•
UV light selectively coinduces supply pathways from primary metabolism and flavonoid secondary product formation in parsley. by Logemann E, Tavernaro A, Schulz W, Somssich IE, Hahlbrock K.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26534
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with flavonoids, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “flavonoids” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for flavonoids (hyperlinks lead to article summaries): •
6
A benzoquinone and flavonoids from Cyperus alopecuroides. Author(s): Nassar MI, Abdel-Razik AF, El-Khrisy Eel-D, Dawidar AA, Bystrom A, Mabry TJ. Source: Phytochemistry. 2002 June; 60(4): 385-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12031430
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
Studies
31
•
Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perused rat intestinal model. Author(s): Liu Y, Hu M. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 April; 30(4): 370-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11901089
•
Activity of plant flavonoids against antibiotic-resistant bacteria. Author(s): Xu HX, Lee SF. Source: Phytotherapy Research : Ptr. 2001 February; 15(1): 39-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11180521
•
Anaerobic degradation of flavonoids by Clostridium orbiscindens. Author(s): Schoefer L, Mohan R, Schwiertz A, Braune A, Blaut M. Source: Applied and Environmental Microbiology. 2003 October; 69(10): 5849-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532034
•
Analysis of flavonoids in tablets and urine by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. Author(s): Watson DG, Pitt AR. Source: Rapid Communications in Mass Spectrometry : Rcm. 1998; 12(4): 153-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9493410
•
Anti-AIDS agents 54. A potent anti-HIV chalcone and flavonoids from genus Desmos. Author(s): Wu JH, Wang XH, Yi YH, Lee KH. Source: Bioorganic & Medicinal Chemistry Letters. 2003 May 19; 13(10): 1813-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729671
•
Antibacterial activity of flavonoids against methicillin-resistant Staphylococcus aureus strains. Author(s): Alcaraz LE, Blanco SE, Puig ON, Tomas F, Ferretti FH. Source: Journal of Theoretical Biology. 2000 July 21; 205(2): 231-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10873434
•
Anticoagulant effect and action mechanism of sulphated flavonoids from Flaveria bidentis. Author(s): Guglielmone HA, Agnese AM, Nunez Montoya SC, Cabrera JL. Source: Thrombosis Research. 2002 January 15; 105(2): 183-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11958811
32
Flavonoids
•
Antihypertensive effect and end-organ protection of flavonoids: some insights, more questions. Author(s): Cosentino F, Volpe M. Source: Journal of Hypertension. 2002 September; 20(9): 1721-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195110
•
Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus. Author(s): Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T. Source: Fitoterapia. 2002 October; 73(6): 536-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12385884
•
Antimicrobial effects of Finnish plant extracts containing flavonoids and other phenolic compounds. Author(s): Rauha JP, Remes S, Heinonen M, Hopia A, Kahkonen M, Kujala T, Pihlaja K, Vuorela H, Vuorela P. Source: International Journal of Food Microbiology. 2000 May 25; 56(1): 3-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10857921
•
Antimicrobial evaluation of coumarins and flavonoids from the stems of Daphne gnidium L. Author(s): Cottiglia F, Loy G, Garau D, Floris C, Casu M, Pompei R, Bonsignore L. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2001 July; 8(4): 302-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11515721
•
Antimutagenic activity of flavonoids from Pogostemon cablin. Author(s): Miyazawa M, Okuno Y, Nakamura S, Kosaka H. Source: Journal of Agricultural and Food Chemistry. 2000 March; 48(3): 642-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10725128
•
Antioxidant ability of various flavonoids against DPPH radicals and LDL oxidation. Author(s): Hirano R, Sasamoto W, Matsumoto A, Itakura H, Igarashi O, Kondo K. Source: J Nutr Sci Vitaminol (Tokyo). 2001 October; 47(5): 357-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11814152
•
Antioxidant and photoprotective activity of a crude extract of Culcitium reflexum H.B.K. leaves and their major flavonoids. Author(s): Aquino R, Morelli S, Tomaino A, Pellegrino M, Saija A, Grumetto L, Puglia C, Ventura D, Bonina F. Source: Journal of Ethnopharmacology. 2002 February; 79(2): 183-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11801380
Studies
33
•
Antioxidant effect of flavonoids on DCF production in HL-60 cells. Author(s): Takamatsu S, Galal AM, Ross SA, Ferreira D, ElSohly MA, Ibrahim AR, ElFeraly FS. Source: Phytotherapy Research : Ptr. 2003 September; 17(8): 963-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13680836
•
Anti-oxidant effect of flavonoids on hemoglobin glycosylation. Author(s): Asgary S, Naderi G, Sarrafzadegan N, Ghassemi N, Boshtam M, Rafie M, Arefian A. Source: Pharmaceutica Acta Helvetiae. 1999 February; 73(5): 223-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10085787
•
Anti-oxidant effect of flavonoids on the susceptibility of LDL oxidation. Author(s): Naderi GA, Asgary S, Sarraf-Zadegan N, Shirvany H. Source: Molecular and Cellular Biochemistry. 2003 April; 246(1-2): 193-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841362
•
Antioxidant flavonoids and phenolic acids from leaves of Leea guineense G Don (Leeaceae). Author(s): Op de Beck P, Cartier G, David B, Dijoux-Franca MG, Mariotte AM. Source: Phytotherapy Research : Ptr. 2003 April; 17(4): 345-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12722137
•
Antioxidant properties of di-tert-butylhydroxylated flavonoids. Author(s): Lebeau J, Furman C, Bernier JL, Duriez P, Teissier E, Cotelle N. Source: Free Radical Biology & Medicine. 2000 November 1; 29(9): 900-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11063915
•
Antioxidative activity of flavonoids in stimulated human neutrophils. Author(s): Zielinska M, Kostrzewa A, Ignatowicz E. Source: Folia Histochem Cytobiol. 2000; 38(1): 25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10763121
•
Antiproliferative activities of citrus flavonoids against six human cancer cell lines. Author(s): Manthey JA, Guthrie N. Source: Journal of Agricultural and Food Chemistry. 2002 October 9; 50(21): 5837-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12358447
•
Antiproliferative activity of flavonoids on several cancer cell lines. Author(s): Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M. Source: Bioscience, Biotechnology, and Biochemistry. 1999 May; 63(5): 896-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10380632
34
Flavonoids
•
Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines. Author(s): Miranda CL, Stevens JF, Helmrich A, Henderson MC, Rodriguez RJ, Yang YH, Deinzer ML, Barnes DW, Buhler DR. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 1999 April; 37(4): 271-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10418944
•
Antithrombogenic and antiatherogenic effects of citrus flavonoids. Contributions of Ralph C. Robbins. Author(s): Attaway JA, Buslig BS. Source: Advances in Experimental Medicine and Biology. 1998; 439: 165-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781302
•
Anti-ulcer potential of flavonoids. Author(s): Parmar NS, Parmar S. Source: Indian J Physiol Pharmacol. 1998 July; 42(3): 343-51. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9741648
•
Antiviral activities of flavonoids and organic acid from Trollius chinensis Bunge. Author(s): Li YL, Ma SC, Yang YT, Ye SM, But PP. Source: Journal of Ethnopharmacology. 2002 March; 79(3): 365-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11849843
•
Aromatase and 17beta-hydroxysteroid dehydrogenase inhibition by flavonoids. Author(s): Le Bail JC, Laroche T, Marre-Fournier F, Habrioux G. Source: Cancer Letters. 1998 November 13; 133(1): 101-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9929167
•
Artelastocarpin and carpelastofuran, two new flavones, and cytotoxicities of prenyl flavonoids from Artocarpus elasticus against three cancer cell lines. Author(s): Cidade HM, Nacimento MS, Pinto MM, Kijjoa A, Silva AM, Herz W. Source: Planta Medica. 2001 December; 67(9): 867-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11745028
•
Assessment of the antibacterial activity of selected flavonoids and consideration of discrepancies between previous reports. Author(s): Cushnie TP, Hamilton VE, Lamb AJ. Source: Microbiological Research. 2003; 158(4): 281-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717448
Studies
35
•
Bioactive prenylated flavonoids from the stem bark of Artocarpus kemando. Author(s): Seo EK, Lee D, Shin YG, Chai HB, Navarro HA, Kardono LB, Rahman I, Cordell GA, Farnsworth NR, Pezzuto JM, Kinghorn AD, Wani MC, Wall ME. Source: Arch Pharm Res. 2003 February; 26(2): 124-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12643587
•
Bioactivity of flavonoids. Author(s): Robak J, Gryglewski RJ. Source: Polish Journal of Pharmacology. 1996 November-December; 48(6): 555-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9112694
•
Bioavailability of flavonoids and potential bioactive forms in vivo. Author(s): Rice-Evans C, Spencer JP, Schroeter H, Rechner AR. Source: Drug Metabol Drug Interact. 2000; 17(1-4): 291-310. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11201300
•
Bioavailability of flavonoids from tea. Author(s): Hollman PC, Tijburg LB, Yang CS. Source: Critical Reviews in Food Science and Nutrition. 1997 December; 37(8): 719-38. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9447272
•
Bioavailability of flavonoids. Author(s): Hollman PC. Source: European Journal of Clinical Nutrition. 1997 January; 51 Suppl 1: S66-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9023486
•
Biological effects of epicuticular flavonoids from Primula denticulata on human leukemia cells. Author(s): Tokalov SV, Kind B, Wollenweber E, Gutzeit HO. Source: Journal of Agricultural and Food Chemistry. 2004 January 28; 52(2): 239-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14733502
•
Biological properties of citrus flavonoids pertaining to cancer and inflammation. Author(s): Manthey JA, Grohmann K, Guthrie N. Source: Current Medicinal Chemistry. 2001 February; 8(2): 135-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11172671
36
Flavonoids
•
Biological properties of flavonoids pertaining to inflammation. Author(s): Manthey JA. Source: Microcirculation (New York, N.Y. : 1994). 2000; 7(6 Pt 2): S29-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11151968
•
Biologically active flavonoids and terpenoids from Egletes viscosa. Author(s): Lima MA, Silveira ER, Marques MS, Santos RH, Gambardela MT. Source: Phytochemistry. 1996 January; 41(1): 217-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8588867
•
Biomarkers for exposure to dietary flavonoids: a review of the current evidence for identification of quercetin glycosides in plasma. Author(s): Day AJ, Williamson G. Source: The British Journal of Nutrition. 2001 August; 86 Suppl 1: S105-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11520427
•
Biphasic stimulo-inhibitory effect of flavonoids on cell proliferation in vitro. Author(s): Huot J, Hubbes M, Nosal G, Radouco-Thomas C. Source: Arch Int Pharmacodyn Ther. 1974 May; 209(1): 49-65. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4212971
•
Cancer preventive effects of flavonoids--a review. Author(s): Le Marchand L. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2002 August; 56(6): 296-301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12224601
•
Catechol- and pyrogallol-type flavonoids. Analysis of tea catechins in plasma. Author(s): Umegaki K, Sano M, Tomita I. Source: Methods in Molecular Biology (Clifton, N.J.). 2002; 186: 247-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12013773
•
Cellular uptake and metabolism of flavonoids and their metabolites: implications for their bioactivity. Author(s): Spencer JP, Abd-el-Mohsen MM, Rice-Evans C. Source: Archives of Biochemistry and Biophysics. 2004 March 1; 423(1): 148-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14989269
Studies
37
•
Characteristics of delayed excretion of flavonoids in human urine after administration of Shosaiko-to, a herbal medicine. Author(s): Li C, Homma M, Oka K. Source: Biological & Pharmaceutical Bulletin. 1998 December; 21(12): 1251-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9881633
•
Chemotaxonomic features associated with flavonoids of cannabinoid-free cannabis (Cannabis sativa subsp. sativa L.) in relation to hops (Humulus lupulus L.). Author(s): Vanhoenacker G, Van Rompaey P, De Keukeleire D, Sandra P. Source: Natural Product Letters. 2002 February; 16(1): 57-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11942684
•
Chocolate as a source of tea flavonoids. Author(s): Arts IC, Hollman PC, Kromhout D. Source: Lancet. 1999 August 7; 354(9177): 488. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10465183
•
Chocolate contains additional flavonoids not found in tea. Author(s): Lazarus SA, Hammerstone JF, Schmitz HH. Source: Lancet. 1999 November 20; 354(9192): 1825. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10577676
•
Chronic venous insufficiency: worldwide results of the RELIEF study. Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids. Author(s): Jantet G. Source: Angiology. 2002 May-June; 53(3): 245-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12025911
•
C-Isoprenylation of flavonoids enhances binding affinity toward P-glycoprotein and modulation of cancer cell chemoresistance. Author(s): Comte G, Daskiewicz JB, Bayet C, Conseil G, Viornery-Vanier A, Dumontet C, Di Pietro A, Barron D. Source: Journal of Medicinal Chemistry. 2001 March 1; 44(5): 763-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11262086
•
Cocoa and chocolate flavonoids: implications for cardiovascular health. Author(s): Steinberg FM, Bearden MM, Keen CL. Source: Journal of the American Dietetic Association. 2003 February; 103(2): 215-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589329
38
Flavonoids
•
Combined effects of flavonoids and acyclovir against herpesviruses in cell cultures. Author(s): Mucsi I, Gyulai Z, Beladi I. Source: Acta Microbiol Hung. 1992; 39(2): 137-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1339152
•
Commentary: effect of flavonoids on normal and leukemic cells. Author(s): Faderl S, Estrov Z. Source: Leukemia Research. 2003 June; 27(6): 471-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12648504
•
Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. Author(s): Kuntz S, Wenzel U, Daniel H. Source: European Journal of Nutrition. 1999 June; 38(3): 133-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10443335
•
Comparative inhibition of human cytochromes P450 1A1 and 1A2 by flavonoids. Author(s): Zhai S, Dai R, Friedman FK, Vestal RE. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1998 October; 26(10): 989-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9763404
•
Comparative quantitative structure toxicity relationships for flavonoids evaluated in isolated rat hepatocytes and HeLa tumor cells. Author(s): Moridani MY, Galati G, O'Brien PJ. Source: Chemico-Biological Interactions. 2002 March 20; 139(3): 251-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11879815
•
Comparison of the antioxidant effects of Concord grape juice flavonoids alphatocopherol on markers of oxidative stress in healthy adults. Author(s): O'Byrne DJ, Devaraj S, Grundy SM, Jialal I. Source: The American Journal of Clinical Nutrition. 2002 December; 76(6): 1367-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12450905
•
Comparison of the growth-inhibitory effect of Hypericum perforatum L. extracts, differing in the concentration of phloroglucinols and flavonoids, on leukaemia cells. Author(s): Hostanska K, Bommer S, Weber M, Krasniqi B, Saller R. Source: The Journal of Pharmacy and Pharmacology. 2003 July; 55(7): 973-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12906754
Studies
39
•
Comparison of the protective effect of various flavonoids against lipid peroxidation of erythrocyte membranes (induced by cumene hydroperoxide). Author(s): Affany A, Salvayre R, Douste-Blazy L. Source: Fundamental & Clinical Pharmacology. 1987; 1(6): 451-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3447932
•
Consumption of flavonoids in onions and black tea: lack of effect on F2-isoprostanes and autoantibodies to oxidized LDL in healthy humans. Author(s): O'Reilly JD, Mallet AI, McAnlis GT, Young IS, Halliwell B, Sanders TA, Wiseman H. Source: The American Journal of Clinical Nutrition. 2001 June; 73(6): 1040-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11382657
•
Correlation of antiviral and histamine release-inhibitory activity of several synthetic flavonoids. Author(s): Middleton E Jr, Faden H, Drzewiecki G, Perrissoud D. Source: Prog Clin Biol Res. 1986; 213: 541-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2424032
•
Cranberry flavonoids, atherosclerosis and cardiovascular health. Author(s): Reed J. Source: Critical Reviews in Food Science and Nutrition. 2002; 42(3 Suppl): 301-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12058989
•
C-ring cleavage of flavonoids by human intestinal bacteria. Author(s): Winter J, Moore LH, Dowell VR Jr, Bokkenheuser VD. Source: Applied and Environmental Microbiology. 1989 May; 55(5): 1203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2757380
•
Cytotoxic activity of flavonoids and extracts from Retama sphaerocarpa Boissier. Author(s): Lopez-Lazaro M, Martin-Cordero C, Cortes F, Pinero J, Ayuso MJ. Source: Z Naturforsch [c]. 2000 January-February; 55(1-2): 40-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10739098
•
Cytotoxic flavonoids from the stem bark of Lonchocarpus aff. fluvialis. Author(s): Blatt CT, Chavez D, Chai H, Graham JG, Cabieses F, Farnsworth NR, Cordell GA, Pezzuto JM, Kinghorn AD. Source: Phytotherapy Research : Ptr. 2002 June; 16(4): 320-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12112286
40
Flavonoids
•
Cytotoxic flavonoids with isoprenoid groups from Morus mongolica. Author(s): Shi YQ, Fukai T, Sakagami H, Chang WJ, Yang PQ, Wang FP, Nomura T. Source: Journal of Natural Products. 2001 February; 64(2): 181-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11429996
•
Cytotoxicity against human leukemic cell lines, and the activity on the expression of resistance genes of flavonoids from Platanus orientalis. Author(s): Mitrocotsa D, Bosch S, Mitaku S, Dimas C, Skaltsounis AL, Harvala C, Briand G, Roussakis C. Source: Anticancer Res. 1999 May-June; 19(3A): 2085-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10470152
•
Cytotoxicity and lipid peroxidation-inhibiting activity of flavonoids. Author(s): Cos P, Calomme M, Sindambiwe JB, De Bruyne T, Cimanga K, Pieters L, Vlietinck AJ, Vanden Berghe D. Source: Planta Medica. 2001 August; 67(6): 515-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11509970
•
Detecting and measuring bioavailability of phenolics and flavonoids in humans: pharmacokinetics of urinary excretion of dietary ferulic acid. Author(s): Bourne LC, Rice-Evans CA. Source: Methods Enzymol. 1999; 299: 91-106. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9916200
•
Detection of weak estrogenic flavonoids using a recombinant yeast strain and a modified MCF7 cell proliferation assay. Author(s): Breinholt V, Larsen JC. Source: Chemical Research in Toxicology. 1998 June; 11(6): 622-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9625730
•
Dietary agents in cancer prevention: flavonoids and isoflavonoids. Author(s): Birt DF, Hendrich S, Wang W. Source: Pharmacology & Therapeutics. 2001 May-June; 90(2-3): 157-77. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11578656
•
Dietary antioxidant flavonoids and coronary heart disease. Author(s): Nair S, Gupta R. Source: J Assoc Physicians India. 1996 October; 44(10): 699-702. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9251343
Studies
41
•
Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Author(s): Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Source: Lancet. 1993 October 23; 342(8878): 1007-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8105262
•
Dietary flavonoids and cancer risk in the Zutphen Elderly Study. Author(s): Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Source: Nutrition and Cancer. 1994; 22(2): 175-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14502846
•
Dietary flavonoids and hypertension: is there a link? Author(s): Moline J, Bukharovich IF, Wolff MS, Phillips R. Source: Medical Hypotheses. 2000 October; 55(4): 306-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11000057
•
Dietary flavonoids and iodine metabolism. Author(s): Schroder-van der Elst JP, Smit JW, Romijn HA, van der Heide D. Source: Biofactors (Oxford, England). 2003; 19(3-4): 171-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757968
•
Dietary flavonoids and risk of coronary heart disease. Author(s): Mojzisova G, Kuchta M. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2001; 50(6): 529-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11829313
•
Dietary flavonoids and the MLL gene: A pathway to infant leukemia? Author(s): Ross JA. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 April 25; 97(9): 4411-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10781030
•
Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Author(s): Knekt P, Jarvinen R, Seppanen R, Hellovaara M, Teppo L, Pukkala E, Aromaa A. Source: American Journal of Epidemiology. 1997 August 1; 146(3): 223-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9247006
42
Flavonoids
•
Dietary flavonoids as antioxidants in vivo: conjugated metabolites of (-)-epicatechin and quercetin participate in antioxidative defense in blood plasma. Author(s): Terao J. Source: J Med Invest. 1999 August; 46(3-4): 159-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10687310
•
Dietary flavonoids as potential neuroprotectants. Author(s): Youdim KA, Spencer JP, Schroeter H, Rice-Evans C. Source: Biological Chemistry. 2002 March-April; 383(3-4): 503-19. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12033439
•
Dietary flavonoids in atherosclerosis prevention. Author(s): Wedworth SM, Lynch S. Source: The Annals of Pharmacotherapy. 1995 June; 29(6): 627-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7663037
•
Dietary flavonoids interact with trace metals and affect metallothionein level in human intestinal cells. Author(s): Kuo SM, Leavitt PS, Lin CP. Source: Biological Trace Element Research. 1998 June; 62(3): 135-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9676879
•
Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro. Author(s): Duthie SJ, Dobson VL. Source: European Journal of Nutrition. 1999 February; 38(1): 28-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10338685
•
Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study. Author(s): Keli SO, Hertog MG, Feskens EJ, Kromhout D. Source: Archives of Internal Medicine. 1996 March 25; 156(6): 637-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8629875
•
Dietary flavonoids: bioavailability, metabolic effects, and safety. Author(s): Ross JA, Kasum CM. Source: Annual Review of Nutrition. 2002; 22: 19-34. Epub 2002 January 04. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12055336
Studies
43
•
Dietary flavonoids: intake, health effects and bioavailability. Author(s): Hollman PC, Katan MB. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 1999 September-October; 37(9-10): 937-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10541448
•
Differences in the serum levels of acetaldehyde and cytotoxic acetaldehyde-albumin complexes after the consumption of red and white wine: in vitro effects of flavonoids, vitamin E, and other dietary antioxidants on cytotoxic complexes. Author(s): Wickramasinghe SN, Hasan R, Khalpey Z. Source: Alcoholism, Clinical and Experimental Research. 1996 August; 20(5): 799-803. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8865951
•
Differential effects of flavonoids as inhibitors of tyrosine protein kinases and serine/threonine protein kinases. Author(s): Hagiwara M, Inoue S, Tanaka T, Nunoki K, Ito M, Hidaka H. Source: Biochemical Pharmacology. 1988 August 1; 37(15): 2987-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3164998
•
Differential inhibition of proliferation of human squamous cell carcinoma, gliosarcoma and embryonic fibroblast-like lung cells in culture by plant flavonoids. Author(s): Kandaswami C, Perkins E, Drzewiecki G, Soloniuk DS, Middleton E Jr. Source: Anti-Cancer Drugs. 1992 October; 3(5): 525-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1450447
•
Di-tert-butylhydroxylated flavonoids protect endothelial cells against oxidized LDLinduced cytotoxicity. Author(s): Furman C, Lebeau J, Fruchart J, Bernier J, Duriez P, Cotelle N, Teissier E. Source: Journal of Biochemical and Molecular Toxicology. 2001; 15(5): 270-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11835624
•
Effect of an extract of the root of Scutellaria baicalensis and its flavonoids on aflatoxin B1 oxidizing cytochrome P450 enzymes. Author(s): Kim BR, Kim DH, Park R, Kwon KB, Ryu DG, Kim YC, Kim NY, Jeong S, Kang BK, Kim KS. Source: Planta Medica. 2001 July; 67(5): 396-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11488450
44
Flavonoids
•
Effect of antioxidant flavonoids and a food mutagen on lymphocytes of a thalassemia patient without chelation therapy in the Comet assay. Author(s): Anderson D, Dhawan A, Yardley-Jones A, Ioannides C, Webb J. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 2001; 21(2): 165-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11223893
•
Effect of antiproliferative flavonoids on ascorbic acid accumulation in human colon adenocarcinoma cells. Author(s): Kuo SM, Morehouse HF Jr, Lin CP. Source: Cancer Letters. 1997 June 24; 116(2): 131-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9215855
•
Effect of citrus flavonoids on HL-60 cell differentiation. Author(s): Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M. Source: Anticancer Res. 1999 March-April; 19(2A): 1261-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10368686
•
Effect of diets based on foods from conventional versus organic production on intake and excretion of flavonoids and markers of antioxidative defense in humans. Author(s): Grinder-Pedersen L, Rasmussen SE, Bugel S, Jorgensen LV, Dragsted LO, Gundersen V, Sandstrom B. Source: Journal of Agricultural and Food Chemistry. 2003 September 10; 51(19): 5671-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952417
•
Effect of flavonoids on cell cycle progression in prostate cancer cells. Author(s): Kobayashi T, Nakata T, Kuzumaki T. Source: Cancer Letters. 2002 February 8; 176(1): 17-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11790449
•
Effect of flavonoids on MRP1-mediated transport in Panc-1 cells. Author(s): Nguyen H, Zhang S, Morris ME. Source: Journal of Pharmaceutical Sciences. 2003 February; 92(2): 250-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12532374
•
Effect of flavonoids on protease activities in human skeletal muscle tissue in vitro. Author(s): Mantle D, Falkous G, Perry EK. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1999 July; 285(1-2): 13-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10481919
Studies
45
•
Effect of plant flavonoids on immune and inflammatory cell function. Author(s): Middleton E Jr. Source: Advances in Experimental Medicine and Biology. 1998; 439: 175-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781303
•
Effect of the flavonoids biochanin A and silymarin on the P-glycoprotein-mediated transport of digoxin and vinblastine in human intestinal Caco-2 cells. Author(s): Zhang S, Morris ME. Source: Pharmaceutical Research. 2003 August; 20(8): 1184-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948016
•
Effect of three flavonoids, 5,7,3',4'-tetrahydroxy-3-methoxy flavone, luteolin, and quercetin, on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophil. Author(s): Lu HW, Sugahara K, Sagara Y, Masuoka N, Asaka Y, Manabe M, Kodama H. Source: Archives of Biochemistry and Biophysics. 2001 September 1; 393(1): 73-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11516163
•
Effects of dietary flavonoids on major signal transduction pathways in human epithelial cells. Author(s): O'Prey J, Brown J, Fleming J, Harrison PR. Source: Biochemical Pharmacology. 2003 December 1; 66(11): 2075-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609732
•
Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes. Author(s): Noroozi M, Angerson WJ, Lean ME. Source: The American Journal of Clinical Nutrition. 1998 June; 67(6): 1210-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9625095
•
Effects of flavonoids isolated from Scutellariae radix on cytochrome P-450 activities in human liver microsomes. Author(s): Kim JY, Lee S, Kim DH, Kim BR, Park R, Lee BM. Source: Journal of Toxicology and Environmental Health. Part A. 2002 March; 65(5-6): 373-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11936218
46
Flavonoids
•
Effects of flavonoids isolated from scutellariae radix on the production of tissue-type plasminogen activator and plasminogen activator inhibitor-1 induced by thrombin and thrombin receptor agonist peptide in cultured human umbilical vein endothelial cells. Author(s): Kimura Y, Yokoi K, Matsushita N, Okuda H. Source: The Journal of Pharmacy and Pharmacology. 1997 August; 49(8): 816-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9379363
•
Effects of flavonoids of Ginkgo biloba on proliferation of human skin fibroblast. Author(s): Kim SJ, Lim MH, Chun IK, Won YH. Source: Skin Pharmacol. 1997; 10(4): 200-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9413894
•
Effects of flavonoids on cisplatin-induced apoptosis of HL-60 and L1210 leukemia cells. Author(s): Cipak L, Rauko P, Miadokova E, Cipakova I, Novotny L. Source: Leukemia Research. 2003 January; 27(1): 65-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479854
•
Effects of flavonoids on the growth and cell cycle of cancer cells. Author(s): Choi SU, Ryu SY, Yoon SK, Jung NP, Park SH, Kim KH, Choi EJ, Lee CO. Source: Anticancer Res. 1999 November-December; 19(6B): 5229-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10697540
•
Effects of flavonoids on the susceptibility of low-density lipoprotein to oxidative modification. Author(s): Safari MR, Sheikh N. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2003 July; 69(1): 73-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878454
•
Effects of selected flavonoids and caffeic acid derivatives on hypoxanthine-xanthine oxidase-induced toxicity in cultivated human cells. Author(s): Beyer G, Melzig MF. Source: Planta Medica. 2003 December; 69(12): 1125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14750029
•
Effects of selected flavonoids on deformability, osmotic fragility and aggregation of human erythrocytes. Author(s): Bilto YY, Abdalla SS. Source: Clinical Hemorheology and Microcirculation. 1998 July; 18(2-3): 165-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9699038
Studies
47
•
Effects of several flavonoids on the growth of B16F10 and SK-MEL-1 melanoma cell lines: relationship between structure and activity. Author(s): Rodriguez J, Yanez J, Vicente V, Alcaraz M, Benavente-Garcia O, Castillo J, Lorente J, Lozano JA. Source: Melanoma Research. 2002 April; 12(2): 99-107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11930105
•
Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1. Author(s): Casagrande F, Darbon JM. Source: Biochemical Pharmacology. 2001 May 15; 61(10): 1205-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11322924
•
Effects of the flavonoids biochanin A, morin, phloretin, and silymarin on Pglycoprotein-mediated transport. Author(s): Zhang S, Morris ME. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 March; 304(3): 1258-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12604704
•
Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. Author(s): Janssen K, Mensink RP, Cox FJ, Harryvan JL, Hovenier R, Hollman PC, Katan MB. Source: The American Journal of Clinical Nutrition. 1998 February; 67(2): 255-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9459373
•
Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids. Author(s): Le Bail JC, Varnat F, Nicolas JC, Habrioux G. Source: Cancer Letters. 1998 August 14; 130(1-2): 209-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9751276
•
Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Author(s): Kris-Etherton PM, Keen CL. Source: Current Opinion in Lipidology. 2002 February; 13(1): 41-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11790962
48
Flavonoids
•
Expression of antioxidant proteins in human intestinal Caco-2 cells treated with dietary flavonoids. Author(s): Kameoka S, Leavitt P, Chang C, Kuo SM. Source: Cancer Letters. 1999 November 15; 146(2): 161-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10656621
•
Fasting plasma concentrations of selected flavonoids as markers of their ordinary dietary intake. Author(s): Radtke J, Linseisen J, Wolfram G. Source: European Journal of Nutrition. 2002 October; 41(5): 203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395214
•
Flavonoids and gene expression in mammalian cells. Author(s): Kuo SM. Source: Advances in Experimental Medicine and Biology. 2002; 505: 191-200. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12083463
•
Flavonoids and the risk of cardiovascular disease in women. Author(s): Donovan JL. Source: The American Journal of Clinical Nutrition. 2004 March; 79(3): 522-3; Author Reply 523. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985231
•
Flavonoids and thyroid disease. Author(s): van der Heide D, Kastelijn J, Schroder-van der Elst JP. Source: Biofactors (Oxford, England). 2003; 19(3-4): 113-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757961
•
Flavonoids as anticancer agents: structure-activity relationship study. Author(s): Lopez-Lazaro M. Source: Current Medicinal Chemistry. Anti-Cancer Agents. 2002 November; 2(6): 691714. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12678721
•
Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context. Author(s): Zhang S, Qin C, Safe SH. Source: Environmental Health Perspectives. 2003 December; 111(16): 1877-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644660
Studies
49
•
Flavonoids as DNA topoisomerase I poisons. Author(s): Lopez-Lazaro M, Martin-Cordero C, Toro MV, Ayuso MJ. Source: Journal of Enzyme Inhibition and Medicinal Chemistry. 2002 February; 17(1): 259. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12365457
•
Flavonoids as inhibitors of MRP1-like efflux activity in human erythrocytes. A structure-activity relationship study. Author(s): Bobrowska-Hagerstrand M, Wrobel A, Mrowczynska L, Soderstrom T, Shirataki Y, Motohashi N, Molnar J, Michalak K, Hagerstrand H. Source: Oncology Research. 2003; 13(11): 463-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812360
•
Flavonoids differentially regulate IFN gamma-induced ICAM-1 expression in human keratinocytes: molecular mechanisms of action. Author(s): Bito T, Roy S, Sen CK, Shirakawa T, Gotoh A, Ueda M, Ichihashi M, Packer L. Source: Febs Letters. 2002 June 5; 520(1-3): 145-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12044887
•
Flavonoids from Artocarpus lanceifolius. Author(s): Cao S, Butler MS, Buss AD. Source: Natural Product Research. 2003 April; 17(2): 79-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12713118
•
Flavonoids from Calicotome villosa. Author(s): Pistelli L, Fiumi C, Morelli I, Giachi I. Source: Fitoterapia. 2003 June; 74(4): 417-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12781819
•
Flavonoids in cell function. Author(s): Manthey JA, Buslig BS, Baker ME. Source: Advances in Experimental Medicine and Biology. 2002; 505: 1-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12083454
•
Flavonoids in food. Author(s): Adler T. Source: Environmental Health Perspectives. 2003 December; 111(16): A897. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674395
50
Flavonoids
•
Flavonoids inhibit VEGF/bFGF-induced angiogenesis in vitro by inhibiting the matrix-degrading proteases. Author(s): Kim MH. Source: Journal of Cellular Biochemistry. 2003 June 1; 89(3): 529-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12761886
•
Flavonoids of cocoa inhibit recombinant human 5-lipoxygenase. Author(s): Schewe T, Kuhn H, Sies H. Source: The Journal of Nutrition. 2002 July; 132(7): 1825-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12097654
•
Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2). Author(s): Salucci M, Stivala LA, Maiani G, Bugianesi R, Vannini V. Source: British Journal of Cancer. 2002 May 20; 86(10): 1645-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12085217
•
Flavonoids. Nature's paintbox and medicine cabinet. Author(s): Gottlieb SH. Source: Diabetes Forecast. 2004 June; 57(6): 31, 33-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15195624
•
Flavonoids: promising anticancer agents. Author(s): Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Source: Medicinal Research Reviews. 2003 July; 23(4): 519-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12710022
•
GC-MS determination of flavonoids and phenolic and benzoic acids in human plasma after consumption of cranberry juice. Author(s): Zhang K, Zuo Y. Source: Journal of Agricultural and Food Chemistry. 2004 January 28; 52(2): 222-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14733499
•
Genetic and carcinogenic effects of plant flavonoids: an overview. Author(s): MacGregor JT. Source: Advances in Experimental Medicine and Biology. 1984; 177: 497-526. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6388266
Studies
51
•
Genetic toxicology of flavonoids: the role of metabolic conditions in the induction of reverse mutation, SOS functions and sister-chromatid exchanges. Author(s): Rueff J, Laires A, Borba H, Chaveca T, Gomes MI, Halpern M. Source: Mutagenesis. 1986 May; 1(3): 179-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3331657
•
Genotoxic flavonoids and red wine: a possible role in stomach carcinogenesis. Author(s): Gaspar J, Laires A, Rueff J. Source: European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (Ecp). 1994 December; 3 Suppl 2: 13-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7735040
•
Glycosyl flavonoids from the roots and rhizomes of Asarum longerhizomatosum. Author(s): Zhang SX, Tani T, Yamaji S, Ma CM, Wang MC, Cai- SQ, Zhao YY. Source: Journal of Asian Natural Products Research. 2003 March; 5(1): 25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12608635
•
Glycosylation, esterification and polymerization of flavonoids and hydroxycinnamates: effects on antioxidant properties. Author(s): Williamson G, Plumb GW, Garcia-Conesa MT. Source: Basic Life Sci. 1999; 66: 483-94. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10800458
•
Grapefruit juice and its flavonoids inhibit 11 beta-hydroxysteroid dehydrogenase. Author(s): Lee YS, Lorenzo BJ, Koufis T, Reidenberg MM. Source: Clinical Pharmacology and Therapeutics. 1996 January; 59(1): 62-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8549035
•
Growth inhibitory effects of flavonoids in human thyroid cancer cell lines. Author(s): Yin F, Giuliano AE, Van Herle AJ. Source: Thyroid : Official Journal of the American Thyroid Association. 1999 April; 9(4): 369-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10319943
•
Haemolytic complement consumption by Parietaria pollen extracts in relation to peptide-bound flavonoids. Author(s): Berrens L, de la Cuadra Lopez B. Source: Cellular and Molecular Life Sciences : Cmls. 1997 March; 53(3): 275-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9104492
52
Flavonoids
•
Heterogeneous effect of flavonoids on K+ loss and lipid peroxidation induced by oxygen-free radicals in human red cells. Author(s): Maridonneau-Parini I, Braquet P, Garay RP. Source: Pharmacol Res Commun. 1986 January; 18(1): 61-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3006093
•
Heterogenous effects of natural flavonoids on monooxygenase activities in human and rat liver microsomes. Author(s): Siess MH, Leclerc J, Canivenc-Lavier MC, Rat P, Suschetet M. Source: Toxicology and Applied Pharmacology. 1995 January; 130(1): 73-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7839372
•
High intake of specific carotenoids and flavonoids does not reduce the risk of bladder cancer. Author(s): Garcia R, Gonzalez CA, Agudo A, Riboli E. Source: Nutrition and Cancer. 1999; 35(2): 212-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10693178
•
How flavonoids inhibit the generation of luminol-dependent chemiluminescence by activated human neutrophils. Author(s): 'T Hart BA, Ip Via Ching TR, Van Dijk H, Labadie RP. Source: Chemico-Biological Interactions. 1990; 73(2-3): 323-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2155715
•
Human 17beta-hydroxysteroid dehydrogenase type 5 is inhibited by dietary flavonoids. Author(s): Krazeisen A, Breitling R, Moller G, Adamski J. Source: Advances in Experimental Medicine and Biology. 2002; 505: 151-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12083459
•
Human absorption and excretion of flavonoids after broccoli consumption. Author(s): Nielsen SE, Kall M, Justesen U, Schou A, Dragsted LO. Source: Cancer Letters. 1997 March 19; 114(1-2): 173-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9103283
•
Human metabolic pathways of dietary flavonoids and cinnamates. Author(s): Williamson G, Day AJ, Plumb GW, Couteau D. Source: Biochemical Society Transactions. 2000 February; 28(2): 16-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10816092
Studies
53
•
Human metabolism of dietary flavonoids: identification of plasma metabolites of quercetin. Author(s): Day AJ, Mellon F, Barron D, Sarrazin G, Morgan MR, Williamson G. Source: Free Radical Research. 2001 December; 35(6): 941-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11811545
•
Hydrolysis of flavonoids by human intestinal bacteria. Author(s): Bokkenheuser VD, Winter J. Source: Prog Clin Biol Res. 1988; 280: 143-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3174689
•
Identification and determination of ecdysones and flavonoids in Serratula strangulata by micellar electrokinetic capillary chromatography. Author(s): Wang S, Dai J, Chen X, Hu Z. Source: Planta Medica. 2002 November; 68(11): 1029-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451496
•
Immunomodulatory activities of flavonoids, monoterpenoids, triterpenoids, iridoid glycosides and phenolic compounds of Plantago species. Author(s): Chiang LC, Ng LT, Chiang W, Chang MY, Lin CC. Source: Planta Medica. 2003 July; 69(7): 600-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898413
•
In vitro anti-mycotic activity of some medicinal plants containing flavonoids. Author(s): Trovato A, Monforte MT, Forestieri AM, Pizzimenti F. Source: Boll Chim Farm. 2000 September-October; 139(5): 225-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11213443
•
In vitro antiprotozoal and cytotoxic activities of some alkaloids, quinones, flavonoids, and coumarins. Author(s): del Rayo Camacho M, Phillipson JD, Croft SL, Yardley V, Solis PN. Source: Planta Medica. 2004 January; 70(1): 70-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765298
•
In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids. Author(s): Chiang LC, Chiang W, Liu MC, Lin CC. Source: The Journal of Antimicrobial Chemotherapy. 2003 August; 52(2): 194-8. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837746
54
Flavonoids
•
In vitro availability of flavonoids and other phenolics in orange juice. Author(s): Gil-Izquierdo A, Gil MI, Ferreres F, Tomas-Barberan FA. Source: Journal of Agricultural and Food Chemistry. 2001 February; 49(2): 1035-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11262068
•
In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Author(s): Breinholt VM, Offord EA, Brouwer C, Nielsen SE, Brosen K, Friedberg T. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2002 May; 40(5): 609-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11955666
•
Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements. Author(s): Walle UK, Walle T. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 May; 30(5): 564-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11950788
•
Influence of flavonoids and vitamins on the MMP- and TIMP-expression of human dermal fibroblasts after UVA irradiation. Author(s): Hantke B, Lahmann C, Venzke K, Fischer T, Kocourek A, Windsor LJ, Bergemann J, Stab F, Tschesche H. Source: Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology. 2002 October; 1(10): 826-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656486
•
Inhibition of environmental estrogen-induced proliferation of human breast carcinoma MCF-7 cells by flavonoids. Author(s): Han D, Tachibana H, Yamada K. Source: In Vitro Cellular & Developmental Biology. Animal. 2001 May; 37(5): 275-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11513082
•
Inhibition of human CYP3A4 activity by grapefruit flavonoids, furanocoumarins and related compounds. Author(s): Ho PC, Saville DJ, Wanwimolruk S. Source: Journal of Pharmacy & Pharmaceutical Sciences [electronic Resource] : a Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques. 2001 September-December; 4(3): 217-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11737987
Studies
55
•
Inhibition of LDL oxidation by flavonoids in relation to their structure and calculated enthalpy. Author(s): Vaya J, Mahmood S, Goldblum A, Aviram M, Volkova N, Shaalan A, Musa R, Tamir S. Source: Phytochemistry. 2003 January; 62(1): 89-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475624
•
Inhibition of peroxynitrite-mediated LDL oxidation by prenylated flavonoids: the alpha,beta-unsaturated keto functionality of 2'-hydroxychalcones as a novel antioxidant pharmacophore. Author(s): Stevens JF, Miranda CL, Frei B, Buhler DR. Source: Chemical Research in Toxicology. 2003 October; 16(10): 1277-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14565769
•
Inhibition of the PDGF receptor by red wine flavonoids provides a molecular explanation for the "French paradox". Author(s): Rosenkranz S, Knirel D, Dietrich H, Flesch M, Erdmann E, Bohm M. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2002 December; 16(14): 1958-60. Epub 2002 October 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397093
•
Inhibitory effect of flavonoids on low-density lipoprotein peroxidation catalyzed by mammalian 15-lipoxygenase. Author(s): da Silva EL, Abdalla DS, Terao J. Source: Iubmb Life. 2000 April; 49(4): 289-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10995031
•
Inhibitory effects of several flavonoids on E-selectin expression on human umbilical vein endothelial cells stimulated by tumor necrosis factor-alpha. Author(s): Takano-Ishikawa Y, Goto M, Yamaki K. Source: Phytotherapy Research : Ptr. 2003 December; 17(10): 1224-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14669262
•
Intake of flavonoids, carotenoids, vitamins C and E, and risk of stroke in male smokers. Author(s): Hirvonen T, Virtamo J, Korhonen P, Albanes D, Pietinen P. Source: Stroke; a Journal of Cerebral Circulation. 2000 October; 31(10): 2301-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11022054
56
Flavonoids
•
Interaction between cultured endothelial cells and macrophages: in vitro model for studying flavonoids in redox-dependent gene expression. Author(s): Rimbach G, Saliou C, Canali R, Virgili F. Source: Methods Enzymol. 2001; 335: 387-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11400388
•
Intracellular flavonoids as electron donors for extracellular ferricyanide reduction in human erythrocytes. Author(s): Fiorani M, De Sanctis R, De Bellis R, Dacha M. Source: Free Radical Biology & Medicine. 2002 January 1; 32(1): 64-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11755318
•
Introduction to the proceedings of the Third International Scientific Symposium on Tea and Human Health: Role of Flavonoids in the Diet. Author(s): Blumberg J. Source: The Journal of Nutrition. 2003 October; 133(10): 3244S-3246S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519820
•
Japanese intake of flavonoids and isoflavonoids from foods. Author(s): Kimira M, Arai Y, Shimoi K, Watanabe S. Source: J Epidemiol. 1998 August; 8(3): 168-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9782673
•
Lack of effect of the flavonoids, myricetin, quercetin, and rutin, on repair of H2O2induced DNA single-strand breaks in Caco-2, Hep G2, and V79 cells. Author(s): Aherne SA, O'Brien NM. Source: Nutrition and Cancer. 2000; 38(1): 106-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11341035
•
Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes. Author(s): Wang C, Makela T, Hase T, Adlercreutz H, Kurzer MS. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1994 August; 50(34): 205-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8049151
•
Main flavonoids in the root of Scutellaria baicalensis cultivated in Europe and their comparative antiradical properties. Author(s): Bochorakova H, Paulova H, Slanina J, Musil P, Taborska E. Source: Phytotherapy Research : Ptr. 2003 June; 17(6): 640-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820232
Studies
57
•
MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide. Author(s): Schroeter H, Boyd C, Spencer JP, Williams RJ, Cadenas E, Rice-Evans C. Source: Neurobiology of Aging. 2002 September-October; 23(5): 861-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12392791
•
Masking of antioxidant capacity by the interaction of flavonoids with protein. Author(s): Arts MJ, Haenen GR, Voss HP, Bast A. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2001 August; 39(8): 787-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11434985
•
Measurement of food flavonoids by high-performance liquid chromatography: A review. Author(s): Merken HM, Beecher GR. Source: Journal of Agricultural and Food Chemistry. 2000 March; 48(3): 577-99. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10725120
•
Mechanism of protection by the flavonoids, quercetin and rutin, against tertbutylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Author(s): Aherne SA, O'Brien NM. Source: Free Radical Biology & Medicine. 2000 September 15; 29(6): 507-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11025194
•
Metabolic engineering and applications of flavonoids. Author(s): Forkmann G, Martens S. Source: Current Opinion in Biotechnology. 2001 April; 12(2): 155-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11287230
•
Metabolism of flavonoids via enteric recycling: mechanistic studies of disposition of apigenin in the Caco-2 cell culture model. Author(s): Hu M, Chen J, Lin H. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 October; 307(1): 314-21. Epub 2003 July 31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12893842
•
Metabolism of flavonoids via enteric recycling: role of intestinal disposition. Author(s): Chen J, Lin H, Hu M. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 March; 304(3): 1228-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12604700
58
Flavonoids
•
Metabolism of food-derived heterocyclic amines in human and rabbit tissues by P4503A proteins in the presence of flavonoids. Author(s): McKinnon RA, Burgess WM, Hall PM, Abdul-Aziz Z, McManus ME. Source: Cancer Research. 1992 April 1; 52(7 Suppl): 2108S-2113S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1544149
•
Metabolism of tea flavonoids in the gastrointestinal tract. Author(s): Spencer JP. Source: The Journal of Nutrition. 2003 October; 133(10): 3255S-3261S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519823
•
Methylation of quercetin and fisetin, flavonoids widely distributed in edible vegetables, fruits and wine, by human liver. Author(s): De Santi C, Pietrabissa A, Mosca F, Pacifici GM. Source: Int J Clin Pharmacol Ther. 2002 May; 40(5): 207-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12051572
•
Micronized flavonoids in pain control after hemorrhoidectomy: a prospective randomized controlled study. Author(s): Colak T, Akca T, Dirlik M, Kanik A, Dag A, Aydin S. Source: Surgery Today. 2003; 33(11): 828-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605954
•
Modification of low-density lipoproteins by flavonoids. Author(s): de Whalley CV, Rankin SM, Hoult JR, Jessup W, Wilkins GM, Collard J, Leake DS. Source: Biochemical Society Transactions. 1990 December; 18(6): 1172-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2088842
•
Modulating effects of flavonoids on food mutagens in human blood and sperm samples in the comet assay. Author(s): Anderson D, Basaran N, Dobrzynska MM, Basaran AA, Yu TW. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 1997; 17(2): 45-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9261919
•
Modulation by (iso)flavonoids of the ATPase activity of the multidrug resistance protein. Author(s): Hooijberg JH, Broxterman HJ, Heijn M, Fles DL, Lankelma J, Pinedo HM. Source: Febs Letters. 1997 August 18; 413(2): 344-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9280310
Studies
59
•
Modulation by flavonoids of cell multidrug resistance mediated by P-glycoprotein and related ABC transporters. Author(s): Di Pietro A, Conseil G, Perez-Victoria JM, Dayan G, Baubichon-Cortay H, Trompier D, Steinfels E, Jault JM, de Wet H, Maitrejean M, Comte G, Boumendjel A, Mariotte AM, Dumontet C, McIntosh DB, Goffeau A, Castanys S, Gamarro F, Barron D. Source: Cellular and Molecular Life Sciences : Cmls. 2002 February; 59(2): 307-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11915946
•
Modulation of AAPH-induced oxidative stress in cell culture by flavonoids. Author(s): Plumb GW, Dupont MS, Williamson G. Source: Biochemical Society Transactions. 1997 November; 25(4): S560. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9449988
•
Modulation of multidrug resistance protein 1 (MRP1/ABCC1) transport and atpase activities by interaction with dietary flavonoids. Author(s): Leslie EM, Mao Q, Oleschuk CJ, Deeley RG, Cole SP. Source: Molecular Pharmacology. 2001 May; 59(5): 1171-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11306701
•
Molecular modeling of flavonoids that inhibits xanthine oxidase. Author(s): Lin CM, Chen CS, Chen CT, Liang YC, Lin JK. Source: Biochemical and Biophysical Research Communications. 2002 May 31; 294(1): 167-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12054758
•
Myeloperoxidase/nitrite-mediated lipid peroxidation of low-density lipoprotein as modulated by flavonoids. Author(s): Kostyuk VA, Kraemer T, Sies H, Schewe T. Source: Febs Letters. 2003 February 27; 537(1-3): 146-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12606047
•
Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells. Author(s): Hirano T, Gotoh M, Oka K. Source: Life Sciences. 1994; 55(13): 1061-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8084211
•
Naturally occurring flavonoids and human basophil histamine release. Author(s): Middleton E Jr, Drzewiecki G. Source: Int Arch Allergy Appl Immunol. 1985; 77(1-2): 155-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2409013
60
Flavonoids
•
Neuroprotection by flavonoids. Author(s): Dajas F, Rivera-Megret F, Blasina F, Arredondo F, Abin-Carriquiry JA, Costa G, Echeverry C, Lafon L, Heizen H, Ferreira M, Morquio A. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2003 December; 36(12): 1613-20. Epub 2003 November 17. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14666245
•
New bioactive flavonoids and stilbenes in cube resin insecticide. Author(s): Fang N, Casida JE. Source: Journal of Natural Products. 1999 February; 62(2): 205-10. Erratum In: J Nat Prod 2000 Feb; 63(2): 293. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10075742
•
New flavonoids from Avicennia marina. Author(s): Sharaf M, El-Ansari MA, Saleh NA. Source: Fitoterapia. 2000 June; 71(3): 274-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10844167
•
Nitric oxide radical scavenging of flavonoids. Author(s): Haenen GR, Bast A. Source: Methods Enzymol. 1999; 301: 490-503. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9919597
•
No evidence for the in vivo activity of aromatase-inhibiting flavonoids. Author(s): Saarinen N, Joshi SC, Ahotupa M, Li X, Ammala J, Makela S, Santti R. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2001 September; 78(3): 231-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11595503
•
Non-nutritive bioactive food constituents of plants: bioavailability of flavonoids. Author(s): Rasmussen SE, Breinholt VM. Source: Int J Vitam Nutr Res. 2003 March; 73(2): 101-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12747217
•
Osteoblastic proliferation stimulating activity of Psoralea corylifolia extracts and two of its flavonoids. Author(s): Wang D, Li F, Jiang Z. Source: Planta Medica. 2001 November; 67(8): 748-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731919
Studies
61
•
Overview of dietary flavonoids: nomenclature, occurrence and intake. Author(s): Beecher GR. Source: The Journal of Nutrition. 2003 October; 133(10): 3248S-3254S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519822
•
Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2, and CYP2C9. Author(s): Otake Y, Walle T. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 February; 30(2): 103-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11792676
•
Permeability characteristics and membrane affinity of flavonoids and alkyl gallates in Caco-2 cells and in phospholipid vesicles. Author(s): Tammela P, Laitinen L, Galkin A, Wennberg T, Heczko R, Vuorela H, Slotte JP, Vuorela P. Source: Archives of Biochemistry and Biophysics. 2004 May 15; 425(2): 193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15111127
•
Permeability of the flavonoids liquiritigenin and its glycosides in licorice roots and davidigenin, a hydrogenated metabolite of liquiritigenin, using human intestinal cell line Caco-2. Author(s): Asano T, Ishihara K, Morota T, Takeda S, Aburada M. Source: Journal of Ethnopharmacology. 2003 December; 89(2-3): 285-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14611893
•
P-glycoprotein (Pgp) does not affect the cytotoxicity of flavonoids from Sophora flavescens, which also have no effects on Pgp action. Author(s): Choi SU, Kim KH, Choi EJ, Park SH, Lee CO, Jung NP, Yoon SK, Ryu SY. Source: Anticancer Res. 1999 May-June; 19(3A): 2035-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10470145
•
Phenols and flavonoids in Aleppo pine needles as bioindicators of air pollution. Author(s): Robles C, Greff S, Pasqualini V, Garzino S, Bousquet-Melou A, Fernandez C, Korboulewsky N, Bonin G. Source: J Environ Qual. 2003 November-December; 32(6): 2265-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674550
62
Flavonoids
•
Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables. Author(s): Erlund I, Silaste ML, Alfthan G, Rantala M, Kesaniemi YA, Aro A. Source: European Journal of Clinical Nutrition. 2002 September; 56(9): 891-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12209378
•
Polyphenolic flavonoids differ in their antiapoptotic efficacy in hydrogen peroxidetreated human vascular endothelial cells. Author(s): Choi YJ, Kang JS, Park JH, Lee YJ, Choi JS, Kang YH. Source: The Journal of Nutrition. 2003 April; 133(4): 985-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12672908
•
Polyphenolic flavonoids inhibit macrophage-mediated oxidation of LDL and attenuate atherogenesis. Author(s): Aviram M, Fuhrman B. Source: Atherosclerosis. 1998 April; 137 Suppl: S45-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9694541
•
Polyphenols, flavonoids, food constituents and oils attenuate neurodegenerative process. Author(s): Soliman KF. Source: Ethn Dis. 2001 Winter; 11(1): 165-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11289242
•
Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans. Author(s): Aviram M, Dornfeld L, Kaplan M, Coleman R, Gaitini D, Nitecki S, Hofman A, Rosenblat M, Volkova N, Presser D, Attias J, Hayek T, Fuhrman B. Source: Drugs Exp Clin Res. 2002; 28(2-3): 49-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12224378
•
Potent antioxidant properties of novel apple-derived flavonoids with commercial potential as food additives. Author(s): Ridgway T, O'Reilly J, West G, Tucker G, Wiseman H. Source: Biochemical Society Transactions. 1996 August; 24(3): 391S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8878935
•
Potential health benefits from the flavonoids in grape products on vascular disease. Author(s): Folts JD. Source: Advances in Experimental Medicine and Biology. 2002; 505: 95-111. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12083471
Studies
63
•
Prenylated flavonoids from the roots of Sophora flavescens with tyrosinase inhibitory activity. Author(s): Son JK, Park JS, Kim JA, Kim Y, Chung SR, Lee SH. Source: Planta Medica. 2003 June; 69(6): 559-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865979
•
Prevention of cellular ROS damage by isovitexin and related flavonoids. Author(s): Lin CM, Chen CT, Lee HH, Lin JK. Source: Planta Medica. 2002 April; 68(4): 365-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11988866
•
Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics. Author(s): Galati G, Sabzevari O, Wilson JX, O'Brien PJ. Source: Toxicology. 2002 August 1; 177(1): 91-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126798
•
Pro-oxidative properties of flavonoids in human lymphocytes. Author(s): Yen GC, Duh PD, Tsai HL, Huang SL. Source: Bioscience, Biotechnology, and Biochemistry. 2003 June; 67(6): 1215-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843645
•
Protection by the flavonoids myricetin, quercetin, and rutin against hydrogen peroxide-induced DNA damage in Caco-2 and Hep G2 cells. Author(s): Aherne SA, O'Brien NM. Source: Nutrition and Cancer. 1999; 34(2): 160-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10578483
•
Protective effect of flavonoids on endothelial cells against linoleic acid hydroperoxide-induced toxicity. Author(s): Kaneko T, Baba N. Source: Bioscience, Biotechnology, and Biochemistry. 1999 February; 63(2): 323-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10192914
•
Protective effects of flavonoids contained in the red vine leaf on venular endothelium against the attack of activated blood components in vitro. Author(s): Nees S, Weiss DR, Reichenbach-Klinke E, Rampp F, Heilmeier B, Kanbach J, Esperester A. Source: Arzneimittel-Forschung. 2003; 53(5): 330-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12854360
64
Flavonoids
•
Protective effects of flavonoids in the roots of Scutellaria baicalensis Georgi against hydrogen peroxide-induced oxidative stress in HS-SY5Y cells. Author(s): Gao Z, Huang K, Xu H. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2001 February; 43(2): 173-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11243719
•
Protein synthesis inhibition by flavonoids: roles of eukaryotic initiation factor 2alpha kinases. Author(s): Ito T, Warnken SP, May WS. Source: Biochemical and Biophysical Research Communications. 1999 November 19; 265(2): 589-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10558914
•
QSAR aspects of flavonoids as a plentiful source of new drugs. Author(s): Voskresensky ON, Levitsky AP. Source: Current Medicinal Chemistry. 2002 July; 9(14): 1367-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12132993
•
Quantitative structure-activity relationship of flavonoids for inhibition of heterocyclic amine mutagenicity. Author(s): Hatch FT, Lightstone FC, Colvin ME. Source: Environmental and Molecular Mutagenesis. 2000; 35(4): 279-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10861947
•
Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal haemorrhoids. Author(s): Khubchandani IT. Source: Techniques in Coloproctology. 2001 April; 5(1): 57-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11803925
•
Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal haemorrhoids. Author(s): Ho YH, Seow-Choen F. Source: The British Journal of Surgery. 2000 December; 87(12): 1732-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11123161
•
Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal haemorrhoids. Author(s): Misra MC, Parshad R. Source: The British Journal of Surgery. 2000 July; 87(7): 868-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10931020
Studies
65
•
Recent advances in the discovery and development of flavonoids and their analogues as antitumor and anti-HIV agents. Author(s): Wang HK, Xia Y, Yang ZY, Natschke SL, Lee KH. Source: Advances in Experimental Medicine and Biology. 1998; 439: 191-225. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781305
•
Reduction in free-radical-induced DNA strand breaks and base damage through fast chemical repair by flavonoids. Author(s): Anderson RF, Amarasinghe C, Fisher LJ, Mak WB, Packer JE. Source: Free Radical Research. 2000 July; 33(1): 91-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10826925
•
Regulation of lipoprotein metabolism in HepG2 cells by citrus flavonoids. Author(s): Kurowska EM, Manthey JA. Source: Advances in Experimental Medicine and Biology. 2002; 505: 173-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12083461
•
Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Author(s): Rimm EB, Katan MB, Ascherio A, Stampfer MJ, Willett WC. Source: Annals of Internal Medicine. 1996 September 1; 125(5): 384-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8702089
•
Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids. Author(s): Han DH, Denison MS, Tachibana H, Yamada K. Source: Bioscience, Biotechnology, and Biochemistry. 2002 July; 66(7): 1479-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12224631
•
RELIEF study: first consolidated European data. Reflux assEssment and quaLity of lIfe improvement with micronized Flavonoids. Author(s): Jantet G. Source: Angiology. 2000 January; 51(1): 31-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10667641
•
Repair of amino acid radicals of apolipoprotein B100 of low-density lipoproteins by flavonoids. A pulse radiolysis study with quercetin and rutin. Author(s): Filipe P, Morliere P, Patterson LK, Hug GL, Maziere JC, Maziere C, Freitas JP, Fernandes A, Santus R. Source: Biochemistry. 2002 September 10; 41(36): 11057-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12206678
66
Flavonoids
•
Restoration of the cellular thiol status of peritoneal macrophages from CAPD patients by the flavonoids silibinin and silymarin. Author(s): Tager M, Dietzmann J, Thiel U, Hinrich Neumann K, Ansorge S. Source: Free Radical Research. 2001 February; 34(2): 137-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11264891
•
Role of dietary flavonoids in protection against cancer and coronary heart disease. Author(s): Hollman PC, Hertog MG, Katan MB. Source: Biochemical Society Transactions. 1996 August; 24(3): 785-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8878848
•
Role of flavonoids in controlling the phototoxicity of Hypericum perforatum extracts. Author(s): Wilhelm KP, Biel S, Siegers CP. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2001 July; 8(4): 306-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11515722
•
Role of flavonoids in oxidative stress. Author(s): Cotelle N. Source: Current Topics in Medicinal Chemistry. 2001 December; 1(6): 569-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895132
•
Role of flavonoids in suppressing the enhancement of phospholipid metabolism by tumor promoters. Author(s): Nishino H, Nagao M, Fujiki H, Sugimura T. Source: Cancer Letters. 1983 November; 21(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6640509
•
Role of flavonoids in the oxygen-free radical modulation of the immune response. Author(s): Pignol B, Etienne A, Crastes de Paulet A, Deby C, Mencia-Huerta JM, Braquet P. Source: Prog Clin Biol Res. 1988; 280: 173-82. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3140246
•
Rutinoside at C7 attenuates the apoptosis-inducing activity of flavonoids. Author(s): Chen YC, Shen SC, Lin HY. Source: Biochemical Pharmacology. 2003 October 1; 66(7): 1139-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505793
Studies
67
•
Screening of eight alkaloids and ten flavonoids isolated from four species of the genus Boronia (Rutaceae) for antimicrobial activities against seventeen clinical microbial strains. Author(s): Nazrul Islam SK, Gray AI, Waterman PG, Ahasan M. Source: Phytotherapy Research : Ptr. 2002 November; 16(7): 672-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12410551
•
Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP. Author(s): Wilcox LJ, Borradaile NM, de Dreu LE, Huff MW. Source: Journal of Lipid Research. 2001 May; 42(5): 725-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11352979
•
Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Author(s): Freedman JE, Parker C 3rd, Li L, Perlman JA, Frei B, Ivanov V, Deak LR, Iafrati MD, Folts JD. Source: Circulation. 2001 June 12; 103(23): 2792-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11401934
•
Separation of structurally related flavonoids by GC/MS technique and determination of their polarographic parameters and potential carcinogenicity. Author(s): Novotny L, Vachalkova A, Al-Nakib T, Mohanna N, Vesela D, Suchy V. Source: Neoplasma. 1999; 46(4): 231-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10613603
•
Side effects of flavonoids in medical practice. Author(s): Jaeger A, Walti M, Neftel K. Source: Prog Clin Biol Res. 1988; 280: 379-94. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2971975
•
Some biological properties of plant flavonoids. Author(s): Middleton E Jr. Source: Ann Allergy. 1988 December; 61(6 Pt 2): 53-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3061322
•
Specific inhibition of hypoxia-inducible factor (HIF)-1 alpha activation and of vascular endothelial growth factor (VEGF) production by flavonoids. Author(s): Hasebe Y, Egawa K, Yamazaki Y, Kunimoto S, Hirai Y, Ida Y, Nose K. Source: Biological & Pharmaceutical Bulletin. 2003 October; 26(10): 1379-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519939
68
Flavonoids
•
Specific regulation of HSPs in human tumor cell lines by flavonoids. Author(s): Morino M, Tsuzuki T, Ishikawa Y, Shirakami T, Yoshimura M, Kiyosuke Y, Matsunaga K, Yoshikumi C, Saijo N. Source: In Vivo. 1997 May-June; 11(3): 265-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9239522
•
Steroid hormone activity of flavonoids and related compounds. Author(s): Zand RS, Jenkins DJ, Diamandis EP. Source: Breast Cancer Research and Treatment. 2000 July; 62(1): 35-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10989984
•
Structure-activity relationships for the anti-HIV activity of flavonoids. Author(s): Olivero-Verbel J, Pacheco-Londono L. Source: Journal of Chemical Information and Computer Sciences. 2002 SeptemberOctober; 42(5): 1241-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377014
•
Structure-activity relationships of flavonoids and the induction of granulocytic- or monocytic-differentiation in HL60 human myeloid leukemia cells. Author(s): Takahashi T, Kobori M, Shinmoto H, Tsushida T. Source: Bioscience, Biotechnology, and Biochemistry. 1998 November; 62(11): 2199-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9972240
•
Structure-activity studies of flavonoids as inhibitors of hyaluronidase. Author(s): Kuppusamy UR, Khoo HE, Das NP. Source: Biochemical Pharmacology. 1990 July 15; 40(2): 397-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2375774
•
Structure-related inhibition of human hepatic caffeine N3-demethylation by naturally occurring flavonoids. Author(s): Lee H, Yeom H, Kim YG, Yoon CN, Jin C, Choi JS, Kim BR, Kim DH. Source: Biochemical Pharmacology. 1998 May 1; 55(9): 1369-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10076527
•
Studies on inhibitors of skin tumor promotion. XI. Inhibitory effects of flavonoids from Scutellaria baicalensis on Epstein-Barr virus activation and their anti-tumorpromoting activities. Author(s): Konoshima T, Kokumai M, Kozuka M, Iinuma M, Mizuno M, Tanaka T, Tokuda H, Nishino H, Iwashima A. Source: Chemical & Pharmaceutical Bulletin. 1992 February; 40(2): 531-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1318792
Studies
69
•
Sulfation of flavonoids and other phenolic dietary compounds by the human cytosolic sulfotransferases. Author(s): Pai TG, Suiko M, Sakakibara Y, Liu MC. Source: Biochemical and Biophysical Research Communications. 2001 August 3; 285(5): 1175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11478778
•
Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural flavonoids. Author(s): De Santi C, Pietrabissa A, Spisni R, Mosca F, Pacifici GM. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 2000 September; 30(9): 857-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11055264
•
Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: structure-activity relationship. Author(s): Mutoh M, Takahashi M, Fukuda K, Komatsu H, Enya T, Matsushima-Hibiya Y, Mutoh H, Sugimura T, Wakabayashi K. Source: Japanese Journal of Cancer Research : Gann. 2000 July; 91(7): 686-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10920275
•
Suppression of TNFalpha-mediated NFkappaB activity by myricetin and other flavonoids through downregulating the activity of IKK in ECV304 cells. Author(s): Tsai SH, Liang YC, Lin-Shiau SY, Lin JK. Source: Journal of Cellular Biochemistry. 1999 September 15; 74(4): 606-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10440930
•
Synergism among flavonoids in inhibiting platelet aggregation and H2O2 production. Author(s): Violi F, Pignatelli P, Pulcinelli FM. Source: Circulation. 2002 February 26; 105(8): E53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11864937
•
Synthesis and anticancer effect of B-ring trifluoromethylated flavonoids. Author(s): Zheng X, Cao JG, Meng WD, Qing FL. Source: Bioorganic & Medicinal Chemistry Letters. 2003 October 20; 13(20): 3423-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505641
70
Flavonoids
•
t-BOOH-induced oxidative damage in sickle red blood cells and the role of flavonoids. Author(s): Cesquini M, Torsoni MA, Stoppa GR, Ogo SH. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2003 May-June; 57(3-4): 124-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12818473
•
Tea flavonoids and cardiovascular health. Author(s): Riemersma RA, Rice-Evans CA, Tyrrell RM, Clifford MN, Lean ME. Source: Qjm : Monthly Journal of the Association of Physicians. 2001 May; 94(5): 277-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11353103
•
Tea flavonoids: bioavailability in vivo and effects on cell signaling pathways in vitro. Author(s): Wiseman S, Mulder T, Rietveld A. Source: Antioxidants & Redox Signalling. 2001 December; 3(6): 1009-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11813977
•
The biochemistry and medical significance of the flavonoids. Author(s): Havsteen BH. Source: Pharmacology & Therapeutics. 2002 November-December; 96(2-3): 67-202. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453566
•
The effects of flavonoids on human phenolsulphotransferases: potential in drug metabolism and chemoprevention. Author(s): Ghazali RA, Waring RH. Source: Life Sciences. 1999; 65(16): 1625-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10573180
•
The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Author(s): Middleton E Jr, Kandaswami C, Theoharides TC. Source: Pharmacological Reviews. 2000 December; 52(4): 673-751. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11121513
•
The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. Author(s): Milligan SR, Kalita JC, Pocock V, Van De Kauter V, Stevens JF, Deinzer ML, Rong H, De Keukeleire D. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 December; 85(12): 4912-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11134162
Studies
71
•
The flavonoids of leek, Allium porrum. Author(s): Fattorusso E, Lanzotti V, Taglialatela-Scafati O, Cicala C. Source: Phytochemistry. 2001 June; 57(4): 565-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11394858
•
The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide. Author(s): Pignatelli P, Pulcinelli FM, Celestini A, Lenti L, Ghiselli A, Gazzaniga PP, Violi F. Source: The American Journal of Clinical Nutrition. 2000 November; 72(5): 1150-5. Erratum In: Am J Clin Nutr 2001 February; 73(2): 360. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11063442
•
The flavonoids, quercetin and isorhamnetin 3-O-acylglucosides diminish neutrophil oxidative metabolism and lipid peroxidation. Author(s): Zielinska M, Kostrzewa A, Ignatowicz E, Budzianowski J. Source: Acta Biochimica Polonica. 2001; 48(1): 183-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11440168
•
The inhibitory effects of flavonoids and antiestrogens on the Glut1 glucose transporter in human erythrocytes. Author(s): Martin HJ, Kornmann F, Fuhrmann GF. Source: Chemico-Biological Interactions. 2003 December 15; 146(3): 225-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14642735
•
The therapeutic potential of flavonoids. Author(s): Wang HK. Source: Expert Opinion on Investigational Drugs. 2000 September; 9(9): 2103-19. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11060796
•
The use of a high-volume screening procedure to assess the effects of dietary flavonoids on human cyp1a1 expression. Author(s): Allen SW, Mueller L, Williams SN, Quattrochi LC, Raucy J. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 August; 29(8): 1074-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11454723
72
Flavonoids
•
Therapeutic efficacy of flavonoids in oedema following reperfusion on acutely ischaemic legs. Author(s): Filis KA, Georgopoulos SE, Papas SC, Votteas V, Bastounis EA. Source: International Angiology : a Journal of the International Union of Angiology. 1999 December; 18(4): 327-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10811522
•
Thiol-inducing and immunoregulatory effects of flavonoids in peripheral blood mononuclear cells from patients with end-stage diabetic nephropathy. Author(s): Dietzmann J, Thiel U, Ansorge S, Neumann KH, Tager M. Source: Free Radical Biology & Medicine. 2002 November 15; 33(10): 1347-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12419466
•
Transformation of flavonoids by intestinal microorganisms. Author(s): Blaut M, Schoefer L, Braune A. Source: Int J Vitam Nutr Res. 2003 March; 73(2): 79-87. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12747214
•
Two flavonoids from the leaves of Morus alba induce differentiation of the human promyelocytic leukemia (HL-60) cell line. Author(s): Kim SY, Gao JJ, Kang HK. Source: Biological & Pharmaceutical Bulletin. 2000 April; 23(4): 451-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10784426
•
Two new flavonoids from Retama raetam. Author(s): Kassem M, Mosharrafa SA, Saleh NA, Abdel-Wahab SM. Source: Fitoterapia. 2000 December; 71(6): 649-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11077171
•
Unique uptake and transport of isoflavone aglycones by human intestinal caco-2 cells: comparison of isoflavonoids and flavonoids. Author(s): Murota K, Shimizu S, Miyamoto S, Izumi T, Obata A, Kikuchi M, Terao J. Source: The Journal of Nutrition. 2002 July; 132(7): 1956-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12097676
•
Urinary detection of hydroxycinnamates and flavonoids in humans after high dietary intake of fruit. Author(s): Bourne LC, Rice-Evans CA. Source: Free Radical Research. 1998 April; 28(4): 429-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9684988
Studies
73
•
Urinary metabolites of flavonoids and hydroxycinnamic acids in humans after application of a crude extract from Equisetum arvense. Author(s): Graefe EU, Veit M. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 1999 October; 6(4): 239-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10589442
•
Variance of common flavonoids by brand of grapefruit juice. Author(s): Ross SA, Ziska DS, Zhao K, ElSohly MA. Source: Fitoterapia. 2000 April; 71(2): 154-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10727812
•
Vitamins and especially flavonoids in common beverages are powerful in vitro antioxidants which enrich lower density lipoproteins and increase their oxidative resistance after ex vivo spiking in human plasma. Author(s): Vinson JA, Jang J, Yang J, Dabbagh Y, Liang X, Serry M, Proch J, Cai S. Source: Journal of Agricultural and Food Chemistry. 1999 July; 47(7): 2502-4. Erratum In: J Agric Food Chem 2001 September; 49(9): 4520. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10552516
•
Wine flavonoids protect against LDL oxidation and atherosclerosis. Author(s): Aviram M, Fuhrman B. Source: Annals of the New York Academy of Sciences. 2002 May; 957: 146-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12074969
•
Wine, flavonoids, and the "water of life". Author(s): Brust JC. Source: Neurology. 2002 November 12; 59(9): 1300-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12427873
75
CHAPTER 2. NUTRITION AND FLAVONOIDS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and flavonoids.
Finding Nutrition Studies on Flavonoids The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “flavonoids” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
76
Flavonoids
The following information is typical of that found when using the “Full IBIDS Database” to search for “flavonoids” (or a synonym): •
Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perused rat intestinal model. Author(s): Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, Washington 99164-6534, USA. Source: Liu, Yan Hu, Ming Drug-Metab-Dispos. 2002 April; 30(4): 370-7 0090-9556
•
Analysis of flavonoids in Ginkgo biloba L. and its phytopharmaceuticals by capillary electrophoresis with electrochemical detection. Author(s): School of Chemical and Material Engineering, Southern Yangtze University, Wuxi 214036, P R China. Source: Cao, Y Chu, Q Fang, Y Ye, J Anal-Bioanal-Chem. 2002 September; 374(2): 294-9 1618-2642
•
Anticholestatic activity of flavonoids from artichoke (Cynara scolymus L.) and of their metabolites. Author(s): Institut fur Biochemie, Universitatsklinikum Leipzig, Germany.
[email protected] Source: Gebhardt, R Med-Sci-Monit. 2001 May; 7 Suppl 1: 316-20 1234-1010
•
Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus. Author(s): School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
[email protected] Source: Fukai, T Marumo, A Kaitou, K Kanda, T Terada, S Nomura, T Fitoterapia. 2002 October; 73(6): 536-9 0367-326X
•
Antimicrobial and pesticidal activity of partially purified flavonoids of Annona squamosa. Source: Kotkar, H.M. Mendki, P.S. Sadan, S.V.G.S. Jha, S.R. Upasani, S.M. Maheshwari, V.L. Pest-manag-sci. West Sussex, UK : Wiley, c2000-. January 2002. volume 58 (1) page 33-37. 1526-498X
•
Antimicrobial flavonoids from Bolusanthus speciosus. Author(s): Department of Chemistry, University of Botswana, Gaborone, Botswana. Source: Bojase, G Majinda, R R Gashe, B A Wanjala, C C Planta-Med. 2002 July; 68(7): 615-20 0032-0943
•
Antioxidant activity of flavonoids from Solenostemon rotundifolius in rats fed normal and high fat diets. Source: Sandhya, C. Vijayalakshmi, N.R. J-nutraceuticals-funct-med-foods. Binghamton, NY : Pharmaceutical Products Press, an imprint of the Haworth Press, Inc., c1997-. 2001. volume 3 (2) page 55-66. 1089-4179
•
Antiviral and antioxidant activity of flavonoids and proanthocyanidins from Crataegus sinaica. Source: Shahat, A.A. Cos, P. Bruyne, T. de. Apers, S. Hammouda, F.M. Ismail, S.I. Azzam, S. Claeys, M. Goovaerts, E. Pieters, L. Planta-med. Stuttgart : Georg Thieme Verlag,. June 2002. volume 68 (6) page 539-541. 0032-0943
•
Behavioral characterisation of the flavonoids apigenin and chrysin. Author(s): Department of Pharmaceutical Sciences, Modena and Reggio Emilia University, Modena, Italy.
[email protected] Source: Zanoli, P Avallone, R Baraldi, M Fitoterapia. 2000 August; 71 Suppl 1: S117-23 0367-326X
Nutrition
77
•
Biosynthesis of flavonoids and effects of stress. Author(s): Department of Biology, Virginia Tech, Blacksburg, Virginia 24061-0406, USA.
[email protected] Source: Winkel Shirley, Brenda Curr-Opin-Plant-Biol. 2002 June; 5(3): 218-23 1369-5266
•
Determination of flavonoids in Hypericum perforatum by HPLC analysis. Author(s): Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, China. Source: Wu, Y Zhou, S D Li, P Yao-Xue-Xue-Bao. 2002 April; 37(4): 280-2 0513-4870
•
Deuterated phytoestrogen flavonoids and isoflavonoids for quantitation. Author(s): Organic Chemistry Laboratory, Department of Chemistry, University of Helsinki, PO Box 55, FIN-00014, Helsinki, Finland.
[email protected] Source: Wahala, K Rasku, S Parikka, K J-Chromatogr-B-Analyt-Technol-Biomed-Life-Sci. 2002 September 25; 777(1-2): 111-22 1570-0232
•
Dietary flavonoids as potential neuroprotectants. Source: Youdim, K.A. Spencer, J.P.E. Schroeter, H. Rice Evans, C. Biol-Chem. Berlin; New York : W. de Gruyter, c1996-. Mar/April 2002. volume 383 (3/4) page 503-519. 1431-6730
•
Di-tert-butylhydroxylated flavonoids protect endothelial cells against oxidized LDLinduced cytotoxicity. Author(s): Departement de Recherches sur les Lipoproteines et l'Atherosclerose, INSERM U325, Institut Pasteur et Faculte de Pharmacie, Universite de Lille 2, 59000 Lille, France. Source: Furman, C Lebeau, J Fruchart, J Bernier, J Duriez, P Cotelle, N Teissier, E JBiochem-Mol-Toxicol. 2001; 15(5): 270-8 1095-6670
•
Effect of total flavonoids of hippophae rhamnoides on contractile mechanics and calcium transfer in stretched myocyte. Author(s): School of Basic Medical Sciences, West China University of Medical Sciences, Chengdu. Source: Wang, Z R Wang, L Yin, H H Yang, F J Gao, Y Q Zhang, Z J Space-Med-MedEng-(Beijing). 2000 February; 13(1): 6-9 1002-0837
•
Effects of flavonoids on cisplatin-induced apoptosis of HL-60 and L1210 leukemia cells. Author(s): Cancer Research Institute, Vlarska 7, 833 91, Bratislava, Slovak Republic. Source: Cipak, L Rauko, P Miadokova, E Cipakova, I Novotny, L Leuk-Res. 2003 January; 27(1): 65-72 0145-2126
•
Effects of several flavonoids on the growth of B16F10 and SK-MEL-1 melanoma cell lines: relationship between structure and activity. Author(s): Department of Pathology, Faculty of Medicine, University of Murcia, Murcia, Spain. Source: Rodriguez, J Yanez, J Vicente, V Alcaraz, M Benavente Garcia, O Castillo, J Lorente, J Lozano, J A Melanoma-Res. 2002 April; 12(2): 99-107 0960-8931
•
Evaluation of variation of acteoside and three major flavonoids in wild and cultivated Scutellaria baicalensis roots by micellar electrokinetic chromatography. Author(s): School of Pharmaceutical Sciences, Peking University, Haidian District, Beijing, People's REpublic of China. Source: Xie, L H Wang, X Basnet, P Matsunaga, N Yamaji, S Yang, D Y Cai, S Q Tani, T Chem-Pharm-Bull-(Tokyo). 2002 July; 50(7): 896-9 0009-2363
78
Flavonoids
•
Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Author(s): Nutrition Department, The Pennsylvania State University, University Park, Pennsylvania, USA. Source: Kris Etherton, Penny M Keen, Carl L Curr-Opin-Lipidol. 2002 February; 13(1): 41-9 0957-9672
•
Identification and determination of ecdysones and flavonoids in Serratula strangulata by micellar electrokinetic capillary chromatography. Author(s): Department of Chemistry, Lanzhou University, Lanzhou, People's Republic of China. Source: Wang, S Dai, J Chen, X Hu, Z Planta-Med. 2002 November; 68(11): 1029-33 00320943
•
Influence of some flavonoids on N-nitrosoproline formation In vitro and In vivo. Author(s): National Fisheries University of Pusan, Pusan (Korea Republic). Department of Nutrition and Food Science Source: Lee, J.H. Choi, J.S. Journal-of-the-Korean-Society-of-Food-and-Nutrition (Korea Republic). (June 1993). volume 22(3) page266-272. 0253-3154
•
Inhibition of the PDGF receptor by red wine flavonoids provides a molecular explanation for the “French paradox”. Author(s): Klinik III fur Innere Medizin, Universitat zu Koln, Germany.
[email protected] Source: Rosenkranz, S Knirel, D Dietrich, H Flesch, M Erdmann, E Bohm, M FASEB-J. 2002 December; 16(14): 1958-60 1530-6860
•
Inhibition of VHR dual-specificity protein tyrosine phosphatase activity by flavonoids isolated from Scutellaria baicalensis: structure-activity relationships. Author(s): Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, South Korea. Source: Lee, M S Oh, W K Kim, B Y Ahn, S C Kang, D O Sohn, C B Osada, H Ahn, J S Planta-Med. 2002 December; 68(12): 1063-5 0032-0943
•
Interactions of different phenolic acids and flavonoids with soy proteins. Source:
•
Kinetic evaluation of the reactivity of flavonoids as radical scavengers. Author(s): Department of Oral Diagnosis, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan.
[email protected] Source: Fujisaw, S Ishihara, M Kadoma, Y SAR-QSAR-Environ-Res. 2002 October; 13(6): 617-27 1062-936X
•
Palm oil tocotrienols and plant flavonoids act synergistically with each other and with Tamoxifen in inhibiting proliferation and growth of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells in culture. Author(s): Departments of Biochemistry, The University of Western Ontario, London, Ontario (Canada) Source: Guthrie, N. Gapor, A. Chambers, A.F. Carroll, K.K. Asia-Pacific-Journal-ofClinical-Nutrition (United Kingdom). (1997). volume 6(1) page 41-45.
•
Preincubation of Mesorhizobium ciceri with flavonoids improves its nodule occupancy. Author(s): Department of Microbiology, Chaudhary Charan Singh Haryana Agricultural University, Hisar 125 004, India.
Nutrition
79
Source: Sharma, P K Upadhyay, K K Kamboj, D V Kukreja, K Folia-Microbiol-(Praha). 2002; 47(5): 541-4 0015-5632 •
Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics. Author(s): Department of Pharmacology, Faculty of Pharmacy, University of Toronto, 19 Russell St., Toronto, Ontario, Canada M5S 2S2. Source: Galati, Giuseppe Sabzevari, Omid Wilson, John X O'Brien, Peter J Toxicology. 2002 August 1; 177(1): 91-104 0300-483X
•
QSAR aspects of flavonoids as a plentiful source of new drugs. Author(s): Faculty of Organic and Medicinal Technologies, Odessa National Polytechnic University, 1, Shevhenko Av., Odessa, 65044, Ukraine.
[email protected] Source: Voskresensky, O N Levitsky, A P Curr-Med-Chem. 2002 July; 9(14): 1367-83 0929-8673
•
Radioprotective Effects In Vivo of Phenolics Extracted from Olea europaea L. Leaves Against X-Ray-Induced Chromosomal Damage: Comparative Study Versus Several Flavonoids and Sulfur-Containing Compounds. Author(s): Research and Development Department, Furfural Espanol S.A., Camino Viejo de Pliego s/n, 80320 Alcantarilla, Murcia, Spain. Source: Benavente Garcia, O Castillo, J Lorente, J Alcaraz, M J-Med-Food. 2002 Fall; 5(3): 125-35 1096-620X
•
Role of flavonoids in oxidative stress. Author(s): Laboratoire de Chimie Organique et Macromoleculaire, UPRESA 8009, Equipe Polyphenols, Universite des Sciences et Technologies de Lille, Villeneuve d'Ascq, France.
[email protected] Source: Cotelle, N Curr-Top-Med-Chem. 2001 December; 1(6): 569-90 1568-0266
•
Structural requirements of flavonoids and related compounds for aldose reductase inhibitory activity. Author(s): Kyoto Pharmaceutical University, Japan. Source: Matsuda, H Morikawa, T Toguchida, I Yoshikawa, M Chem-Pharm-Bull(Tokyo). 2002 June; 50(6): 788-95 0009-2363
•
Studies on antimutagenic and lipotropic action of flavonoids of buckwheats Desmutagenic activity of buckwheat leaf extracts. Author(s): Kangwon National University, Chuncheon (Korea Republic). Department of Food Science and TechnologyKangwon National University, Chuncheon (Korea Republic). Department of Applied Biology and Technology Source: Ham, S.S. Choi, K.P. Lee, S.Y. Choi, Y.S. Journal-of-The-Korean-Society-of-Foodand-Nutrition (Korea Republic). (August 1994). volume 23(4) page 698-703. 0253-3154
•
Studies on the chemical components and biological activities of edible plants in Korea-(2)-Isolation and quantitative analysis of flavonoids from the leaves of Cedrela sinensis A. juss. by HPLC. Author(s): Sunchon National University, Sunchon (Korea Republic). Department of Oriental Medicine ResourcesSunchon National University, Sunchon (Korea Republic). Department of Food and NutritionPusan National University, Pusan (Korea Republic). College of PharmacyKyongbuk Institute of Health and Environment, Taegu (Korea Republic) Source: Park, J.C. Chon, S.S. Yang, H.S. Kim, S.H. Journal-of-the-Korean-Society-ofFood-and-Nutrition (Korea Republic). (October 1993). volume 22(5) page 581-585. 02533154
80
Flavonoids
•
Tartary buckwheat flavonoid activates caspase 3 and induces HL-60 cell apoptosis. Author(s): Department of Hematology, Shanxi Medical University, Shanxi University, Taiyuan, Shanxi, P.R. China. Source: Ren, W Qiao, Z Wang, H Zhu, L Zhang, L Lu, Y Cui, Y Zhang, Z Wang, Z Methods-Find-Exp-Clin-Pharmacol. 2001 October; 23(8): 427-32 0379-0355
•
The pharmaco-chemical study on the plant of Ixeris spp. - (2) - Flavonoids and free amino acid composition of Ixeris sonchifolia. Author(s): Pusan National University, Pusan (Korea Republic). College of PharmacyNational Fisheries University, Pusan (Korea Republic). Department of Food Science and Nutrition Source: Young, H.S. Im, K.S. Choi, J.S. Journal-of-The-Korean-Society-of-Food-andNutrition (Korea Republic). (June 1992). volume 21(3) page296-301. 0253-3154
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
•
The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
•
The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
•
The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
•
The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
•
Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
•
Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
•
Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
•
Google: http://directory.google.com/Top/Health/Nutrition/
Nutrition
•
Healthnotes: http://www.healthnotes.com/
•
Open Directory Project: http://dmoz.org/Health/Nutrition/
•
Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
•
WebMDHealth: http://my.webmd.com/nutrition
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
81
The following is a specific Web list relating to flavonoids; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Multiple Vitamin-Mineral Supplements Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html Vitamin C and Flavonoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,935,00.html
•
Minerals Bromelain/Quercetin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,941,00.html Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Naproxen/Naproxen Sodium Source: Healthnotes, Inc.; www.healthnotes.com Quercetin Source: Healthnotes, Inc.; www.healthnotes.com
82
Flavonoids
Quercetin Source: Integrative Medicine Communications; www.drkoop.com Quercetin Source: Prima Communications, Inc.www.personalhealthzone.com Quercetin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10053,00.html Stinging Nettle Alternative names: Urtica dioica, Urtica urens, Nettle Source: Integrative Medicine Communications; www.drkoop.com •
Food and Diet Apples Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,44,00.html Artichoke Alternative names: Cynara scolymus Source: Healthnotes, Inc.; www.healthnotes.com Asparagus Source: Healthnotes, Inc.; www.healthnotes.com Avocado Source: Healthnotes, Inc.; www.healthnotes.com Beets Source: Healthnotes, Inc.; www.healthnotes.com Berries Source: Healthnotes, Inc.; www.healthnotes.com Brazil Nuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,115,00.html Broccoflower Source: Healthnotes, Inc.; www.healthnotes.com Broccoli Source: Healthnotes, Inc.; www.healthnotes.com Bruising Source: Healthnotes, Inc.; www.healthnotes.com
Nutrition
Brussels Sprouts Source: Healthnotes, Inc.; www.healthnotes.com Cabbage Source: Healthnotes, Inc.; www.healthnotes.com Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com Carrots Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,14,00.html Cauliflower Source: Healthnotes, Inc.; www.healthnotes.com Cherries Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,49,00.html Chicory Source: Healthnotes, Inc.; www.healthnotes.com Chocolate Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,179,00.html Collards Source: Healthnotes, Inc.; www.healthnotes.com Dandelion Greens Source: Healthnotes, Inc.; www.healthnotes.com Jerusalem Artichoke Source: Healthnotes, Inc.; www.healthnotes.com Jicama Source: Healthnotes, Inc.; www.healthnotes.com Kale Source: Healthnotes, Inc.; www.healthnotes.com Kohlrabi Source: Healthnotes, Inc.; www.healthnotes.com Leeks Source: Healthnotes, Inc.; www.healthnotes.com
83
84
Flavonoids
Mustard Greens Source: Healthnotes, Inc.; www.healthnotes.com Okra Source: Healthnotes, Inc.; www.healthnotes.com Onions Source: Healthnotes, Inc.; www.healthnotes.com Onions Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,27,00.html Parsnips Source: Healthnotes, Inc.; www.healthnotes.com Radishes Source: Healthnotes, Inc.; www.healthnotes.com Romaine Lettuce Source: Healthnotes, Inc.; www.healthnotes.com Rutabagas Source: Healthnotes, Inc.; www.healthnotes.com Snow Peas Source: Healthnotes, Inc.; www.healthnotes.com Soy Source: Healthnotes, Inc.; www.healthnotes.com Strawberries Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,108,00.html Summer Squash Source: Healthnotes, Inc.; www.healthnotes.com Sweet Peppers Source: Healthnotes, Inc.; www.healthnotes.com Sweet Potatoes Source: Healthnotes, Inc.; www.healthnotes.com Tea Source: Healthnotes, Inc.; www.healthnotes.com Tomatoes Source: Healthnotes, Inc.; www.healthnotes.com
Nutrition
Turnips Source: Healthnotes, Inc.; www.healthnotes.com Walnuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,100,00.html Winter Squash Source: Healthnotes, Inc.; www.healthnotes.com Yams Source: Healthnotes, Inc.; www.healthnotes.com Zucchini Source: Healthnotes, Inc.; www.healthnotes.com
85
87
CHAPTER 3. ALTERNATIVE MEDICINE AND FLAVONOIDS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to flavonoids. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to flavonoids and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “flavonoids” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to flavonoids: •
Analysis of flavonoids and other phenolic compounds using high-performance liquid chromatography with coulometric array detection: relationship to antioxidant activity. Author(s): Aaby K, Hvattum E, Skrede G. Source: Journal of Agricultural and Food Chemistry. 2004 July 28; 52(15): 4595-603. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15264888
•
Analytical procedure for the in-vial derivatization--extraction of phenolic acids and flavonoids in methanolic and aqueous plant extracts followed by gas chromatography with mass-selective detection. Author(s): Fiamegos YC, Nanos CG, Vervoort J, Stalikas CD. Source: J Chromatogr A. 2004 July 2; 1041(1-2): 11-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15281249
•
Antibacterial and brine shrimp lethality tests of biflavonoids and derivatives of Rheedia gardneriana.
88
Flavonoids
Author(s): Verdi LG, Pizzolatti MG, Montanher AB, Brighente IM, Smania Junior A, Smania Ed Ede F, Simionatto EL, Monache FD. Source: Fitoterapia. 2004 June; 75(3-4): 360-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15158995 •
Anti-inflammatory flavonoids and pterocarpanoid from Crotalaria pallida and C. assamica. Author(s): Ko HH, Weng JR, Tsao LT, Yen MH, Wang JP, Lin CN. Source: Bioorganic & Medicinal Chemistry Letters. 2004 February 23; 14(4): 1011-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013012
•
Antimicrobial and antioxidant flavonoids from the root wood of Bolusanthus speciosus. Author(s): Erasto P, Bojase-Moleta G, Majinda RR. Source: Phytochemistry. 2004 April; 65(7): 875-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081287
•
Antioxidant properties of complexes of flavonoids with metal ions. Author(s): de Souza RF, De Giovani WF. Source: Redox Report : Communications in Free Radical Research. 2004; 9(2): 97-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15231064
•
Antiprotozoal effect of crude extracts and flavonoids isolated from Chromolaena hirsuta (asteraceae). Author(s): Taleb-Contini SH, Salvador MJ, Balanco JM, Albuquerque S, de Oliveira DC. Source: Phytotherapy Research : Ptr. 2004 March; 18(3): 250-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15103676
•
Antiviral flavonoids from the seeds of Aesculus chinensis. Author(s): Wei F, Ma SC, Ma LY, But PP, Lin RC, Khan IA. Source: Journal of Natural Products. 2004 April; 67(4): 650-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15104496
•
Application of preparative high-speed counter-current chromatography for the separation of flavonoids from the leaves of Byrsonima crassa Niedenzu (IK). Author(s): Sannomiya M, Rodrigues CM, Coelho RG, dos Santos LC, Hiruma-Lima CA, Souza Brito AR, Vilegas W. Source: J Chromatogr A. 2004 April 30; 1035(1): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15117073
•
BIOACTIVE COMPOUNDS IN NUTRITION AND HEALTH-RESEARCH METHODOLOGIES FOR ESTABLISHING BIOLOGICAL FUNCTION: The
Alternative Medicine 89
Antioxidant and Anti-inflammatory Effects of Flavonoids on Atherosclerosis. Author(s): Kris-Etherton PM, Lefevre M, Beecher GR, Gross MD, Keen CL, Etherton TD. Source: Annual Review of Nutrition. 2004 July; 24: 511-538. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15189130 •
Biological activity of five antibacterial flavonoids from Combretum erythrophyllum (Combretaceae). Author(s): Martini ND, Katerere DR, Eloff JN. Source: Journal of Ethnopharmacology. 2004 August; 93(2-3): 207-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15234754
•
Consumption of foods rich in flavonoids is related to a decreased cardiovascular risk in apparently healthy French women. Author(s): Mennen LI, Sapinho D, de Bree A, Arnault N, Bertrais S, Galan P, Hercberg S. Source: The Journal of Nutrition. 2004 April; 134(4): 923-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15051848
•
Cytoprotection by Achyrocline satureioides (Lam) D.C. and some of its main flavonoids against oxidative stress. Author(s): Arredondo MF, Blasina F, Echeverry C, Morquio A, Ferreira M, AbinCarriquiry JA, Lafon L, Dajas F. Source: Journal of Ethnopharmacology. 2004 March; 91(1): 13-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15036461
•
Cytotoxic activities of flavonoids from two Scutellaria plants in Chinese medicine. Author(s): Sonoda M, Nishiyama T, Matsukawa Y, Moriyasu M. Source: Journal of Ethnopharmacology. 2004 March; 91(1): 65-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15036470
•
Cytotoxic flavonoids and alpha-pyrones from Cryptocarya obovata. Author(s): Dumontet V, Van Hung N, Adeline MT, Riche C, Chiaroni A, Sevenet T, Gueritte F. Source: Journal of Natural Products. 2004 May; 67(5): 858-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15165150
•
Differential effects of natural flavonoids on growth and iodide content in a human Na*/I- symporter-transfected follicular thyroid carcinoma cell line. Author(s): Schroder-van der Elst JP, van der Heide D, Romijn JA, Smit JW. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2004 April; 150(4): 557-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15080787
90
Flavonoids
•
Disposition of Flavonoids via Enteric Recycling: Enzyme-Transporter Coupling Affects Metabolism of Biochanin A and Formononetin and Excretion of Their Phase II Conjugates. Author(s): Jia X, Chen J, Lin H, Hu M. Source: The Journal of Pharmacology and Experimental Therapeutics. 2004 May 5 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128864
•
Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription. Author(s): O'Leary KA, de Pascual-Tereasa S, Needs PW, Bao YP, O'Brien NM, Williamson G. Source: Mutation Research. 2004 July 13; 551(1-2): 245-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15225597
•
Effects of betaine, coumarin and flavonoids on mucin release from cultured hamster tracheal surface epithelial cells. Author(s): Lee CJ, Lee JH, Seok JH, Hur GM, Park Js J, Bae S, Lim JH, Park YC. Source: Phytotherapy Research : Ptr. 2004 April; 18(4): 301-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15162365
•
Ether-linked biflavonoids from Quintinia acutifolia. Author(s): Ariyasena J, Baek SH, Perry NB, Weavers RT. Source: Journal of Natural Products. 2004 April; 67(4): 693-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15104507
•
Flavonoids and coumarins from Leaves of Phellodendron chinense. Author(s): Kuo PC, Hsu MY, Damu AG, Su CR, Li CY, Sun HD, Wu TS. Source: Planta Medica. 2004 February; 70(2): 183-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14994201
•
Flavonoids and isoflavones: absorption, metabolism, and bioactivity. Author(s): Rice-Evans C. Source: Free Radical Biology & Medicine. 2004 April 1; 36(7): 827-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15019967
•
Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Author(s): Zhang S, Yang X, Morris ME. Source: Molecular Pharmacology. 2004 May; 65(5): 1208-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15102949
•
Flavonoids from Achyrocline satureioides with relaxant effects on the smooth muscle of Guinea pig corpus cavernosum.
Alternative Medicine 91
Author(s): Hnatyszyn O, Moscatelli V, Rondina R, Costa M, Arranz C, Balaszczuk A, Coussio J, Ferraro G. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2004; 11(4): 366-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15185852 •
Flavonoids from artichoke (Cynara scolymus L.) upregulate eNOS gene expression in human endothelial cells. Author(s): Li H, Xia N, Brausch I, Yao Y, Forstermann U. Source: The Journal of Pharmacology and Experimental Therapeutics. 2004 May 3 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15123766
•
Flavonoids from grape seeds prevent increased alcohol-induced neuronal lipofuscin formation. Author(s): de Freitas V, da Silva Porto P, Assuncao M, Cadete-Leite A, Andrade JP, Paula-Barbosa MM. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 2004 July-August; 39(4): 303-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15208161
•
Flavonoids from Radix Scutellariae as potential stroke therapeutic agents by targeting the second postsynaptic density 95 (PSD-95)/disc large/zonula occludens-1 (PDZ) domain of PSD-95. Author(s): Tang W, Sun X, Fang JS, Zhang M, Sucher NJ. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2004; 11(4): 277-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15185839
•
Flavonoids from Spatholobus suberectus. Author(s): Yoon JS, Sung SH, Park JH, Kim YC. Source: Arch Pharm Res. 2004 June; 27(6): 589-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15283457
•
Flavonoids of an extract of Pterospartum tridentatum showing endothelial protection against oxidative injury. Author(s): Vitor RF, Mota-Filipe H, Teixeira G, Borges C, Rodrigues AI, Teixeira A, Paulo A. Source: Journal of Ethnopharmacology. 2004 August; 93(2-3): 363-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15234778
•
Flavonoids Promote Cell Migration in Nontumorigenic Colon Epithelial Cells Differing in Apc Genotype: Implications of Matrix Metalloproteinase Activity. Author(s): Fenton JI, Hord NG.
92
Flavonoids
Source: Nutrition and Cancer. 2004 March; 48(2): 182-188. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15231453 •
Flavonoids: antioxidants or signalling molecules? Author(s): Williams RJ, Spencer JP, Rice-Evans C. Source: Free Radical Biology & Medicine. 2004 April 1; 36(7): 838-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15019969
•
Hypochlorite scavenging activity of flavonoids. Author(s): Firuzi O, Mladenka P, Petrucci R, Marrosu G, Saso L. Source: The Journal of Pharmacy and Pharmacology. 2004 June; 56(6): 801-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15231046
•
Identification and quantification of caffeoylquinic acids and flavonoids from artichoke (Cynara scolymus L.) heads, juice, and pomace by HPLC-DAD-ESI/MS(n). Author(s): Schutz K, Kammerer D, Carle R, Schieber A. Source: Journal of Agricultural and Food Chemistry. 2004 June 30; 52(13): 4090-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15212452
•
In vitro inhibition of diacylglycerol acyltransferase by prenylflavonoids from Sophora flavescens. Author(s): Chung MY, Rho MC, Ko JS, Ryu SY, Jeune KH, Kim K, Lee HS, Kim YK. Source: Planta Medica. 2004 March; 70(3): 258-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15114505
•
Inhibitory effects of flavonoids from Hypericum perforatum on nitric oxide synthase. Author(s): Luo L, Sun Q, Mao YY, Lu YH, Tan RX. Source: Journal of Ethnopharmacology. 2004 August; 93(2-3): 221-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15234756
•
Investigation of the membrane localization and distribution of flavonoids by highresolution magic angle spinning NMR spectroscopy. Author(s): Scheidt HA, Pampel A, Nissler L, Gebhardt R, Huster D. Source: Biochimica Et Biophysica Acta. 2004 May 27; 1663(1-2): 97-107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15157612
•
Isolation of flavonoids and a cerebroside from the stem bark of Albizzia julibrissin. Author(s): Jung MJ, Kang SS, Jung HA, Kim GJ, Choi JS. Source: Arch Pharm Res. 2004 June; 27(6): 593-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15283458
Alternative Medicine 93
•
Mechanism of action of antiatherogenic and related effects of Ficus bengalensis Linn. flavonoids in experimental animals. Author(s): Daniel RS, Devi KS, Augusti KT, Sudhakaran Nair CR. Source: Indian J Exp Biol. 2003 April; 41(4): 296-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15255637
•
Modulation of DeltaF508 CFTR trafficking and function with 4-PBA and flavonoids. Author(s): Lim M, McKenzie K, Floyd AD, Kwon E, Zeitlin PL. Source: American Journal of Respiratory Cell and Molecular Biology. 2004 June 10 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15191910
•
Monitoring the antioxidant activity of extracts originated from various Serratula species and isolation of flavonoids from Serratula coronata. Author(s): Bathori M, Zupko I, Hunyadi A, Gacsne-Baitz E, Dinya Z, Forgo P. Source: Fitoterapia. 2004 March; 75(2): 162-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030920
•
New evidences of antimalarial activity of Bidens pilosa roots extract correlated with polyacetylene and flavonoids. Author(s): Oliveira FQ, Andrade-Neto V, Krettli AU, Brandao MG. Source: Journal of Ethnopharmacology. 2004 July; 93(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15182902
•
Nutritional flavonoids modulate estrogen receptor alpha signaling. Author(s): Virgili F, Acconcia F, Ambra R, Rinna A, Totta P, Marino M. Source: Iubmb Life. 2004 March; 56(3): 145-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15185748
•
Oral administration of Crataegus flavonoids protects against ischemia/reperfusion brain damage in gerbils. Author(s): Zhang DL, Zhang YT, Yin JJ, Zhao BL. Source: Journal of Neurochemistry. 2004 July; 90(1): 211-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15198680
•
Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Author(s): Imai Y, Tsukahara S, Asada S, Sugimoto Y. Source: Cancer Research. 2004 June 15; 64(12): 4346-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15205350
94
Flavonoids
•
Potent Inhibitory effect of flavonoids in Scutellaria baicalensis on amyloid beta protein-induced neurotoxicity. Author(s): Heo HJ, Kim DO, Choi SJ, Shin DH, Lee CY. Source: Journal of Agricultural and Food Chemistry. 2004 June 30; 52(13): 4128-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15212458
•
Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Author(s): Galati G, O'Brien PJ. Source: Free Radical Biology & Medicine. 2004 August 1; 37(3): 287-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15223063
•
Structural aspects of flavonoids as trypsin inhibitors. Author(s): Maliar T, Jedinak A, Kadrabova J, Sturdik E. Source: European Journal of Medicinal Chemistry. 2004 March; 39(3): 241-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15051172
•
Suppression of nitric oxide production in mouse macrophages by soybean flavonoids accumulated in response to nitroprusside and fungal elicitation. Author(s): Scuro LS, Simioni PU, Grabriel DL, Saviani EE, Modolo LV, Tamashiro WM, Salgado I. Source: Bmc Biochemistry [electronic Resource]. 2004 April 21; 5(1): 5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15102332
•
The increase in human plasma antioxidant capacity after apple consumption is due to the metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids. Author(s): Lotito SB, Frei B. Source: Free Radical Biology & Medicine. 2004 July 15; 37(2): 251-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15203196
•
The induction of human UDP-glucuronosyltransferase 1A1 mediated through a distal enhancer module by flavonoids and xenobiotics. Author(s): Sugatani J, Yamakawa K, Tonda E, Nishitani S, Yoshinari K, Degawa M, Abe I, Noguchi H, Miwa M. Source: Biochemical Pharmacology. 2004 March 1; 67(5): 989-1000. Erratum In: Biochem Pharmacol. 2004 June 15; 67(12): 2991-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15104253
•
The Inhibitory Effects of Pure Flavonoids on in Vitro Protein Glycosylation. Author(s): Asgary S, Naderi GA, Sarraf Zadegan N, Vakili R. Source: J Herb Pharmcother. 2002; 2(2): 47-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15277096
Alternative Medicine 95
•
The relation between the chemical structure of flavonoids and their estrogen-like activities. Author(s): Vaya J, Tamir S. Source: Current Medicinal Chemistry. 2004 May; 11(10): 1333-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15134523
•
The thiol reactivity of the oxidation product of 3,5,7-trihydroxy-4H-chromen-4-one containing flavonoids. Author(s): Michels G, Haenen GR, Watjen W, Rietjens S, Bast A. Source: Toxicology Letters. 2004 June 15; 151(1): 105-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15177646
•
Toward the prediction of the activity of antioxidants: experimental and theoretical study of the gas-phase acidities of flavonoids. Author(s): Martins HF, Leal JP, Fernandez MT, Lopes VH, Cordeiro MN. Source: Journal of the American Society for Mass Spectrometry. 2004 June; 15(6): 848-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15144974
•
Transinactivation of the epidermal growth factor receptor tyrosine kinase and focal adhesion kinase phosphorylation by dietary flavonoids: effect on invasive potential of human carcinoma cells. Author(s): Lee LT, Huang YT, Hwang JJ, Lee AY, Ke FC, Huang CJ, Kandaswami C, Lee PP, Lee MT. Source: Biochemical Pharmacology. 2004 June 1; 67(11): 2103-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15135307
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
•
AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
•
Chinese Medicine: http://www.newcenturynutrition.com/
•
drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
•
Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
•
Google: http://directory.google.com/Top/Health/Alternative/
•
Healthnotes: http://www.healthnotes.com/
•
MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
•
Open Directory Project: http://dmoz.org/Health/Alternative/
96
Flavonoids
•
HealthGate: http://www.tnp.com/
•
WebMDHealth: http://my.webmd.com/drugs_and_herbs
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
•
Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to flavonoids; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Allergic Rhinitis Source: Integrative Medicine Communications; www.drkoop.com Allergies Alternative names: Hay Fever Source: Prima Communications, Inc.www.personalhealthzone.com Allergies and Sensitivities Source: Healthnotes, Inc.; www.healthnotes.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Anaphylaxis Source: Integrative Medicine Communications; www.drkoop.com Angina Source: Healthnotes, Inc.; www.healthnotes.com Angioedema Source: Integrative Medicine Communications; www.drkoop.com Asthma Source: Healthnotes, Inc.; www.healthnotes.com Asthma Source: Prima Communications, Inc.www.personalhealthzone.com Atherosclerosis Source: Healthnotes, Inc.; www.healthnotes.com Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com
Alternative Medicine 97
Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com Bursitis Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Capillary Fragility Source: Healthnotes, Inc.; www.healthnotes.com Cataracts Source: Healthnotes, Inc.; www.healthnotes.com Cataracts (prevention) Source: Prima Communications, Inc.www.personalhealthzone.com Cellulitis Source: Integrative Medicine Communications; www.drkoop.com Chronic Venous Insufficiency Source: Healthnotes, Inc.; www.healthnotes.com Cold Sores Source: Healthnotes, Inc.; www.healthnotes.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Common Cold/Sore Throat Source: Healthnotes, Inc.; www.healthnotes.com Congestive Heart Failure Source: Healthnotes, Inc.; www.healthnotes.com Cough Source: Healthnotes, Inc.; www.healthnotes.com Crohn's Disease Source: Integrative Medicine Communications; www.drkoop.com Dermatitis Source: Integrative Medicine Communications; www.drkoop.com Dysmenorrhea Source: Healthnotes, Inc.; www.healthnotes.com
98
Flavonoids
Eczema Source: Integrative Medicine Communications; www.drkoop.com Edema Source: Healthnotes, Inc.; www.healthnotes.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Gastritis Source: Healthnotes, Inc.; www.healthnotes.com Genital Herpes Source: Healthnotes, Inc.; www.healthnotes.com Gingivitis Source: Healthnotes, Inc.; www.healthnotes.com Glaucoma Source: Healthnotes, Inc.; www.healthnotes.com Glaucoma Source: Integrative Medicine Communications; www.drkoop.com Gout Source: Healthnotes, Inc.; www.healthnotes.com Hay Fever Source: Integrative Medicine Communications; www.drkoop.com Hemorrhoids Source: Healthnotes, Inc.; www.healthnotes.com Hemorrhoids Source: Prima Communications, Inc.www.personalhealthzone.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com Herpes Alternative names: Genital Herpes, Cold Sores Source: Prima Communications, Inc.www.personalhealthzone.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine 99
Insect Bites and Stings Source: Integrative Medicine Communications; www.drkoop.com Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com Ménière's Disease Source: Healthnotes, Inc.; www.healthnotes.com Macular Degeneration Source: Healthnotes, Inc.; www.healthnotes.com Macular Degeneration Source: Integrative Medicine Communications; www.drkoop.com Macular Degeneration Source: Prima Communications, Inc.www.personalhealthzone.com Measles Source: Integrative Medicine Communications; www.drkoop.com Menopausal Symptoms (Other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Healthnotes, Inc.; www.healthnotes.com Menorrhagia Source: Healthnotes, Inc.; www.healthnotes.com Migraine Headache Source: Integrative Medicine Communications; www.drkoop.com Night Blindness Source: Healthnotes, Inc.; www.healthnotes.com Osteoporosis Source: Healthnotes, Inc.; www.healthnotes.com Peptic Ulcer Source: Healthnotes, Inc.; www.healthnotes.com Peptic Ulcer Source: Integrative Medicine Communications; www.drkoop.com Prostatitis Source: Healthnotes, Inc.; www.healthnotes.com
100
Flavonoids
Reiter's Syndrome Source: Integrative Medicine Communications; www.drkoop.com Retinopathy Source: Healthnotes, Inc.; www.healthnotes.com Rheumatoid Arthritis Source: Integrative Medicine Communications; www.drkoop.com Sexually Transmitted Diseases Source: Integrative Medicine Communications; www.drkoop.com Skin Infection Source: Integrative Medicine Communications; www.drkoop.com STDs Source: Integrative Medicine Communications; www.drkoop.com Temporomandibular Joint Dysfunction Source: Integrative Medicine Communications; www.drkoop.com Tendinitis Source: Integrative Medicine Communications; www.drkoop.com TMJ Source: Integrative Medicine Communications; www.drkoop.com Ulcers Source: Prima Communications, Inc.www.personalhealthzone.com Uveitis Source: Integrative Medicine Communications; www.drkoop.com Varicose Veins Source: Healthnotes, Inc.; www.healthnotes.com Varicose Veins Source: Integrative Medicine Communications; www.drkoop.com Varicose Veins Source: Prima Communications, Inc.www.personalhealthzone.com •
Alternative Therapy Apitherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,669,00.html Nutrition Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine 101
•
Herbs and Supplements Acetaminophen Source: Healthnotes, Inc.; www.healthnotes.com Achillea Alternative names: Yarrow; Achillea millefolium L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Acyclovir Oral Source: Healthnotes, Inc.; www.healthnotes.com Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Agrimony Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,833,00.html Anthocyanins Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,1026,00.html Antioxidants Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10004,00.html Apium Graveolens Source: Integrative Medicine Communications; www.drkoop.com Arctium Alternative names: Burdock, Gobo; Arctium lappa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aspirin Source: Healthnotes, Inc.; www.healthnotes.com Astragalus Alternative names: Astragalus membranaceus Source: Healthnotes, Inc.; www.healthnotes.com Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Astragalus Sp Alternative names: Vetch, Rattlepod, Locoweed; Astragalus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
102
Flavonoids
Australian Fevertree Source: Integrative Medicine Communications; www.drkoop.com Beta-Carotene Source: Prima Communications, Inc.www.personalhealthzone.com Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Bilberry Alternative names: Vaccinium myrtillus Source: Healthnotes, Inc.; www.healthnotes.com Bilberry Alternative names: Vaccinium myrtillus, European Blueberry, Huckleberry Source: Integrative Medicine Communications; www.drkoop.com Bilberry Source: Prima Communications, Inc.www.personalhealthzone.com Blueberry Alternative names: Vaccinium spp. Source: Healthnotes, Inc.; www.healthnotes.com Boldo Alternative names: Peumus boldus Source: Healthnotes, Inc.; www.healthnotes.com Boneset Alternative names: Eupatorium perfoliatum Source: Healthnotes, Inc.; www.healthnotes.com Bromelain Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,760,00.html Buchu Alternative names: Barosma betulina, Agathosma betulina, Agathosma crenultata Source: Healthnotes, Inc.; www.healthnotes.com Butcher’s Broom Alternative names: Ruscus aculeatus Source: Healthnotes, Inc.; www.healthnotes.com Butcher's Broom Source: Prima Communications, Inc.www.personalhealthzone.com
Alternative Medicine 103
Butcher's Broom Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10010,00.html Calendula Alternative names: Calendula officinalis Source: Healthnotes, Inc.; www.healthnotes.com Catechins Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,1023,00.html Celery Seed Alternative names: Apium graveolens Source: Integrative Medicine Communications; www.drkoop.com Chamomile Alternative names: Matricaria recutita Source: Healthnotes, Inc.; www.healthnotes.com Chamomile Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Chamomile Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,766,00.html Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Cherry Fruit Extract Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10015,00.html Chickweed Alternative names: Stellaria media Source: Healthnotes, Inc.; www.healthnotes.com Chinese Scullcap Alternative names: Scutellaria baicalensis Source: Healthnotes, Inc.; www.healthnotes.com Cleavers Alternative names: Galium aparine Source: Healthnotes, Inc.; www.healthnotes.com
104
Flavonoids
Crataegus Alternative names: Hawthorn; Crataegus oxyacantha L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Crataegus Laevigata Source: Integrative Medicine Communications; www.drkoop.com Crataegus Monogyna Source: Integrative Medicine Communications; www.drkoop.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Cynara Artichoke Alternative names: Artichoke; Cynara scolymus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com Echinacea Alternative names: Echinacea angustifolia, Echinacea pallida, Echinacea purpurea, Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Echinacea angustifolia Source: Integrative Medicine Communications; www.drkoop.com Echinacea pallida Source: Integrative Medicine Communications; www.drkoop.com Echinacea purpurea Source: Integrative Medicine Communications; www.drkoop.com Elderberry Alternative names: Sambucus nigra Source: Healthnotes, Inc.; www.healthnotes.com Elderberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10024,00.html Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
Alternative Medicine 105
Eriodictyon Yerbasanta Alternative names: Yerba Santa; Eriodictyon californicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Estradiol Source: Healthnotes, Inc.; www.healthnotes.com Etodolac Source: Healthnotes, Inc.; www.healthnotes.com Eucalyptus Alternative names: Eucalyptus globulus, Eucalyptus fructicetorum, polybractea, smithii, Australian Fevertree Source: Integrative Medicine Communications; www.drkoop.com Eucalyptus globulus Source: Integrative Medicine Communications; www.drkoop.com European Blueberry Source: Integrative Medicine Communications; www.drkoop.com Felodipine Source: Healthnotes, Inc.; www.healthnotes.com Fennel Source: Healthnotes, Inc.; www.healthnotes.com Flavonoids Source: Healthnotes, Inc.; www.healthnotes.com Flavonoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,782,00.html Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com Foeniculum Alternative names: Fennel; Foeniculum vulgare Mill Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Garcinia Kola Alternative names: Bitter Kola Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Garcinia Sp Alternative names:. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org General Anesthetics Source: Healthnotes, Inc.; www.healthnotes.com
106
Flavonoids
Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Glycyrrhiza glabra Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Grape Seed Extract Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,793,00.html Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc.; www.healthnotes.com Green Tea Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10032,00.html Hawthorn Alternative names: Crataegus laevigata, Crataegus oxyacantha, Crataegus monogyna Source: Healthnotes, Inc.; www.healthnotes.com Hawthorn Alternative names: Crataegus monogyna, Crataegus laevigata Source: Integrative Medicine Communications; www.drkoop.com Hawthorn Source: Prima Communications, Inc.www.personalhealthzone.com Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Horehound Alternative names: Marrubium vulgare Source: Healthnotes, Inc.; www.healthnotes.com Horse Chestnut Alternative names: Aesculus hippocastanum Source: Healthnotes, Inc.; www.healthnotes.com Horsetail Alternative names: Equisetum arvense Source: Healthnotes, Inc.; www.healthnotes.com
Alternative Medicine 107
Huckleberry Source: Integrative Medicine Communications; www.drkoop.com Humulus Alternative names: Hops; Humulus lupulus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hypericum Perforatum Source: Integrative Medicine Communications; www.drkoop.com Ibuprofen Source: Healthnotes, Inc.; www.healthnotes.com Ipriflavone Source: Healthnotes, Inc.; www.healthnotes.com Ipriflavone Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10039,00.html Isoflavones Source: Prima Communications, Inc.www.personalhealthzone.com Juniperus Alternative names: Juniper; Juniperus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Klamathweed Source: Integrative Medicine Communications; www.drkoop.com Lemon Balm Alternative names: Melissa officinalis Source: Healthnotes, Inc.; www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc.; www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Licorice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Linden Alternative names: Tilia spp. Source: Healthnotes, Inc.; www.healthnotes.com
108
Flavonoids
Lipotropic Combination Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,861,00.html Mad-Dog Skullcap Source: Integrative Medicine Communications; www.drkoop.com Matricaria Alternative names: Chamomile; Matricaria chamomilla Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Meadowsweet Alternative names: Filipendula ulmaria Source: Healthnotes, Inc.; www.healthnotes.com Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Alternative names: Silybum marianum, Carduus marianus Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Alternative names: Silybum marianum, St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com Milk Thistle Source: Prima Communications, Inc.www.personalhealthzone.com Musa Banana Alternative names: Plantain, Banana; Musa sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Nabumetone Source: Healthnotes, Inc.; www.healthnotes.com Naringin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10089,00.html Nettle Source: Integrative Medicine Communications; www.drkoop.com Nitrous Oxide Source: Healthnotes, Inc.; www.healthnotes.com Ocimum Alternative names: Basil, Albahaca; Ocimum basilicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
Alternative Medicine 109
Olive Leaf Alternative names: Olea europa Source: Healthnotes, Inc.; www.healthnotes.com OPCS (Oligomeric Proanthocyanidins) Source: Prima Communications, Inc.www.personalhealthzone.com Oregano/Wild Marjoram Alternative names: Origanum vulgare Source: Healthnotes, Inc.; www.healthnotes.com Oxaprozin Source: Healthnotes, Inc.; www.healthnotes.com Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Passiflora Alternative names: Passion Flower; Passiflora alata L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Passiflora Incarnata Source: Integrative Medicine Communications; www.drkoop.com Passion Flower Alternative names: Passiflora incarnata Source: Healthnotes, Inc.; www.healthnotes.com Passion Flower Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Passionflower Alternative names: Passiflora incarnata Source: Integrative Medicine Communications; www.drkoop.com Phyllanthus Alternative names: Phyllanthus niruri Source: Healthnotes, Inc.; www.healthnotes.com Phytolacca Alternative names: Poke root, Endod; Phytolacca dodecandra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Picrorhiza Alternative names: Picrorhiza kurroa Source: Healthnotes, Inc.; www.healthnotes.com Pimpinella Alternative names: Anise; Pimpinella anisum (L) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
110
Flavonoids
Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Proanthocyanidins Source: Healthnotes, Inc.; www.healthnotes.com Pueraria Alternative names: Kudzu; Pueraria lobata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Purple Coneflower Source: Integrative Medicine Communications; www.drkoop.com Red Clover Alternative names: Trifolium pratense , beebread, cow clover, cow grass, meadow clover, purple clover Source: Integrative Medicine Communications; www.drkoop.com Ribes Alternative names: Black Currant; Ribes nigrum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ruta Alternative names: Rue; Ruta graveolens L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sage Alternative names: Salvia officinalis Source: Healthnotes, Inc.; www.healthnotes.com Scutellaria Lateriflora Source: Integrative Medicine Communications; www.drkoop.com Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Silybum Marianum Source: Integrative Medicine Communications; www.drkoop.com Sitosterol Source: Prima Communications, Inc.www.personalhealthzone.com Skullcap Alternative names: Scutellaria lateriflora, Mad-dog Skullcap Source: Integrative Medicine Communications; www.drkoop.com Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine 111
St. John’s Wort Alternative names: Hypericum perforatum Source: Healthnotes, Inc.; www.healthnotes.com St. John's Wort Alternative names: Hypericum perforatum, Klamathweed Source: Integrative Medicine Communications; www.drkoop.com St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com Swertia Alternative names: Swertia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tamoxifen Source: Healthnotes, Inc.; www.healthnotes.com Tanacetum V Alternative names: Tansy; Tanacetum vulgare (L.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thyme Alternative names: Thymus vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Thymus Alternative names: Thyme; Thymus vulgaris Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Trigonella Alternative names: Fenugreek; Trigonella foenum graecum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Uncaria Asian Alternative names: Asian species; Uncaria sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Urtica Dioica Source: Integrative Medicine Communications; www.drkoop.com Urtica Urens Source: Integrative Medicine Communications; www.drkoop.com Vaccinium Myrtillus Source: Integrative Medicine Communications; www.drkoop.com Vacciniumb Alternative names: Bilberry; Vaccinium myrtillus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
112
Flavonoids
Verbascum Alternative names: Mullein; Verbascum thapsus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Viburnum Alternative names: Cramp Bark, Highbush Cranberry; Viburnum sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Vitex Alternative names: Chaste; Vitex agnus-castus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Vitex Alternative names: Vitex agnus-castus Source: Healthnotes, Inc.; www.healthnotes.com Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
113
CHAPTER 4. DISSERTATIONS ON FLAVONOIDS Overview In this chapter, we will give you a bibliography on recent dissertations relating to flavonoids. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “flavonoids” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on flavonoids, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Flavonoids ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to flavonoids. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Alterations in the permeability of cimetidine by dietary flavonoids using an in vitro transport model, Caco-2 cells by Taur, Jan-Shiang, PhD from OREGON STATE UNIVERSITY, 2003, 146 pages http://wwwlib.umi.com/dissertations/fullcit/3103576
•
Bioavailability of the tea flavonoids epicatechin and epicatechin gallate: Role of membrane transport and metabolism by Vaidyanathan, Jayabharathi, PhD from MEDICAL UNIVERSITY OF SOUTH CAROLINA, 2003, 157 pages http://wwwlib.umi.com/dissertations/fullcit/3098199
•
Biologically active substances in birch leaves flavonoids as growth regulators by Baxter, James W; ADVDEG from MCGILL UNIVERSITY (CANADA), 1968 http://wwwlib.umi.com/dissertations/fullcit/NK02607
114
Flavonoids
•
Development and application of LC/MS and MS/MS methods for the structural characterization of flavonoid glycosides by Cuyckens, Filip, Dr from UNIVERSITAIRE INSTELLING ANTWERPEN (BELGIUM), 2003, 182 pages http://wwwlib.umi.com/dissertations/fullcit/3120561
•
Enzymatic aspects of O-glucosylation of anthraquinones and O-methylation of flavonoids in plant tissues by Khouri, Henry; PhD from CONCORDIA UNIVERSITY (CANADA), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL41662
•
Flavone: The molecular and mechanistic study of how a simple flavonoid protects DNA from oxidative damage by Dean, Jennifer D., MS from EAST TENNESSEE STATE UNIVERSITY, 2003, 51 pages http://wwwlib.umi.com/dissertations/fullcit/1418472
•
The effects of cocoa flavonoids on cardiovascular health by Wang, Janice Flora, PhD from UNIVERSITY OF CALIFORNIA, DAVIS, 2003, 115 pages http://wwwlib.umi.com/dissertations/fullcit/3098002
•
Understanding the potential role played by major flavonoid components of apple leaves in plant defense against herbivorous arthropods by Coli, William Michael, PhD from UNIVERSITY OF MASSACHUSETTS AMHERST, 2003, 122 pages http://wwwlib.umi.com/dissertations/fullcit/3078674
•
Wine consumption and breast cancer: An evaluation of the effect of grape wine flavonoids on human mammary cell proliferation by Hakimuddin, Fatima Kamal, MSc from UNIVERSITY OF GUELPH (CANADA), 2003, 124 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76073
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
115
CHAPTER 5. PATENTS ON FLAVONOIDS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “flavonoids” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on flavonoids, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Flavonoids By performing a patent search focusing on flavonoids, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
116
Flavonoids
example of the type of information that you can expect to obtain from a patent search on flavonoids: •
Assay for a new gaucher disease mutation Inventor(s): Beutler; Ernest (La Jolla, CA), Sorge; Joseph A. (Rancho Santa Fe, CA) Assignee(s): The Scripps Research Institute (La Jolla, CA) Patent Number: 5,234,811 Date filed: September 27, 1991 Abstract: A method for detecting a new Gaucher disease mutation in an allele in a human having an insertion mutation of a guanine nucleotide adjacent to nucleotide position 57 in the normal glucocerebrosidase gene exon 2 is provided. Identification of the mutation is accomplished by first amplifying, with a polymerase chain reaction (PCR) primer, a region of human genomic DNA containing nucleotide positions 57 and 58 of glucocerebrosidase gene exon 2 followed by detection of the mutation. Excerpt(s): The present invention relates to a method for detecting a Gaucher disease allele in a human having an insertion mutation of a guanine nucleotide adjacent to nucleotide position 57 in the normal glucocerebrosidase gene exon 2. Gaucher disease is an autosomal recessive disorder caused by a deficiency of glucocerebrosidase, the enzyme that is required for the lysosomal degradation of lipids containing covalently bound sugars (glycolipids). Brady et al., J. Biol. Chem., 240:39-43 (1965). In the absence of glucocerebrosidase, the extremely insoluble glucosylceramide (glucocerebroside) accumulates. The gene for glucocerebrosidase is located on chromosome-1 in the region of q21. See, Shafit-Zagardo et al., Am. J. Hum Genet., 33:564-575 (1981); Ginns et al., Proc. Natl. Acad. Sci., U.S.A., 82:7101-7105 (1985). The fact that a number of different mutations caused Gaucher disease was inferred from clinical observations (Beutler, Genetic Diseases Among Ashkenazi Jews, eds. Boudman et al., Raven Press, NY, pp. 157-169 (1979)) and from differences in the kinetic properties of the residual enzyme in different patients with the disorder. Grabowski et al., Am J. Hum. Genet., 37:499-510 (1985). However, real understanding of the genetics of this disease has had to await the cloning and sequencing of the cDNA (Sorge et al., Proc. Natl. Acad. Sci., U.S.A., 82:72897293 (1985) and Tsuji et al., N. Engl. J. Med., 316:570-621 (1987)) and of the gene (Horowitz et al., Genomics, 4:87-96 (1989)). Analysis of mutations is complicated by the existence of a pseudogene which is approximately 16 kilobases (Kb) downstream from the glucocerebrosidase gene. Zimran et al., J. Clin. Invest., 86:1137-1141 (1990). The pseudogene is about 95% homologous to the functional gene. It is transcribed (Sorge et al., J. Clin. Invest., 86:1137-1141 (1990)), but cannot be translated into glucocerebrosidase because of numerous deletions of coding sequences. Web site: http://www.delphion.com/details?pn=US05234811__
•
Gene therapy for Gaucher disease using retroviral vectors Inventor(s): Bahnson; Alfred B. (Pittsburgh, PA), Barranger; John A. (Gibsonia, PA), Robbins; Paul (Pittsburgh, PA) Assignee(s): University of Pittsburgh (Pittsburgh, PA) Patent Number: 5,911,983 Date filed: June 6, 1995
Patents 117
Abstract: The present invention relates to gene therapy for Gaucher disease using retroviral vectors which express the glucocerebrosidase gene. Methods are provided for transduction of autologous hematopoietic stem cells (e.g., human CD34+ cells) with these vectors and for transplantation of the transduced cells into a Gaucher disease patient to provide therapeutically effective levels of glucocerebrosidase activity. The invention also provides for retroviral vectors that express the glucocerebrosidase gene, and for human hematopoietic cells that contain the retroviral vector. Excerpt(s): Gaucher disease is the name given to a group of lysosomal storage disorders caused by mutations in the gene that codes for an enzyme called glucocerebrosidase ("GC"). Gaucher disease is caused by deficiency of GC as reported by Patrick, A. D., Biochem. J. 97:17C (1965) and Brady, R. O., et al., Biochem. Biophys. Res. Commun. 18:221 (1965). All of the mutations in the gene alter the structure and function of the enzyme which lead to an accumulation of the undegraded glycolipid substrate glucosylceramide, also called glucocerebroside, in cells of the reticuloendothelial system. Each particular mutation of the human GC gene leads to a clinical disease collectively known as Gaucher disease. These disorders are usually classified into three types; type 1 (non-neuronopathic), type 2 (acute neuronopathic) and type 3 (subacute neuronopathic), the type depending on the presence and severity of neurologic involvement. Gaucher disease is the most prevalent Jewish genetic disease and the most common lysosomal storage disease. Human GC cDNA was first cloned as described by Ginns, E. I., et al., Biochem. Biophys. Res. Commun. 123:574 (1984). Subsequent characterizations of other GC cDNA clones by, for example, Sorge, J., et al., Proc. Nat. Acad. Sci. USA 82:7289 (1985) and Tsuji, S., et al., J. Biol. Chem. 261:50 (1986), have led to the elucidation of the complete nucleotide sequence of human GC. As reported by Ginns, E. I., et al., Proc. Nat. Acad. Sci. USA 82:7101 (1985), the GC gene was localized to human chromosome lq21 by in situ hybridization. Tsuji, S., et al., New Enql. J. Med. 316:570 (1987), have shown that the GC gene comprises 11 exons and 10 introns spanning approximately 7 Kb. While more than twenty mutations in the human GC gene are known, only two are common. See, Tsuji, S., et al., Proc. Natl. Acad. Sci. USA 85:2349 (1988). The two common mutations account for approximately 70% of the mutant alleles, as reported by Firon, N., et al., Am. J. Hum. Genet. 46:527 (1990). Mutant GC genes code for aberrant proteins that are either catalytically altered or unstable and rapidly disappear from the cell. Web site: http://www.delphion.com/details?pn=US05911983__ •
Products and methods for gaucher disease therapy Inventor(s): Callahan; John W. (Mississauga, CA), Clarke; Joe T. R. (Toronto, CA), Mahuran; Don J. (Toronto, CA) Assignee(s): HSC Research & Development Limited Partnership (CA) Patent Number: 6,696,272 Date filed: June 2, 2000 Abstract: The invention relates to products and methods for medical treatment of Gaucher disease and, in particular, an improved Gcc DNA for insertion into any applicable expression vector for gene therapy treatment. The invention includes an isolated Gcc DNA molecule, wherein nucleic acid molecules have been modified at cryptic splice sites to prevent or decrease splicing of mRNA produced from the DNA molecule, while preserving the ability of the DNA to express functional Gcc polypeptides.
118
Flavonoids
Excerpt(s): The invention relates to products and methods for medical treatment of Gaucher disease and, in particular, nucleic acid molecules, polypeptides and vectors for polypeptide or gene therapy treatment. Gaucher disease is a lysosomal storage disease caused by the deficiency of functional glucocerebrosidase (Gcc) enzyme. Gcc is present in all cell types. The defective enzyme cannot break down a fatty substance, glucocerebroside, which is an important component of cell membranes. The fat accumulates in macrophages (which are known as the "Gaucher cells"). The fat-laden macrophages are found typically in the liver, spleen, bone marrow and lungs. The amount of the enzyme deficiency varies from person to person as do the symptoms. Some patients may show no clinical symptoms, while others may die from the disease. The symptoms of the disease and mutant forms of Gcc that cause Gaucher disease are described, for example, in U.S. Pat. No. 5,266,459 (Beutler) and U.S. Pat. No. 5,234,811 (Beutler and Sorge). There are therapies for Gaucher disease. Ceredase is a form of the Gcc enzyme from placenta that is able to metabolize the fat in Gaucher cells. The enzyme restores normal function to a Gaucher cell. The amount of enzyme used in treatment varies. As much as 30-60 units per kilogram of bodyweight (U/kg/bw) may be given every other week. Positive results have been reported with 2.3 U/kg/bw given three times a week. Lower doses, such as 1-5 U/kg/bw twice weekly, have also been used with success, but this is less frequent. The intarcellular half life of the enzyme is up to 60 hours. A large number of placentas are needed to make sufficient Ceredase, so this form of therapy is very expensive. It has been almost completely replaced by treatment with a recombinant form of the enzyme, Cerezyme but this therapy is also expensive. Cerezyme is dispensed as a powder whereas Ceredase comes as a liquid. Sterile water must be added to the Cerezyme bottle to dissolve the powder. The shelf life of the drugs is short (
