Natural Products Interactions on Genomes, 1st Edition

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 Clinical Pharmacognosy Series

NATURAL PRODUCTS
INTERACTIONS
ON GENOMES

Edited by
Siva G. Somasundaram, PhD
University of Houston - Victoria
Sugar Land, Texas, USA

Boca Raton London New York

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Taylor & Francis Group, an informa business
CRC Press
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 Dedication

I dedicate to my beloved sons, Dr. Aswin, MD,

and Mr. Alwin for their support.
Contents
Series Preface.............................................................................................................ix
Preface.......................................................................................................................xi
Acknowledgments................................................................................................... xiii
Editor........................................................................................................................ xv
Contributors............................................................................................................xvii

Chapter 1 Genomics Is an Evolving Science due to the Interactions

of Natural Products...............................................................................1
Siva G. Somasundaram

Chapter 2 Interactions of Natural Products with Selected Genes

of Mammalian Chromosomes............................................................. 11
Siva G. Somasundaram

Chapter 3 Interaction of Citrus Natural Products with Genomes........................ 89

Siva G. Somasundaram, Janet Price, G. K. Jayaprakasha,
and Bhimanagouda S. Patil

Chapter 4 Combinatorial Effect of Natural Products and Chemotherapy

Interactions in Cancer....................................................................... 113
Siva G. Somasundaram, Janet Price, G. K. Jayaprakasha,
Richard S. Gunasekera, and Bhimanagouda S. Patil

Chapter 5 Interactions of Natural Products with Microbial Genomes.............. 131

Chandra Somasundaram

Chapter 6 Interactions of Natural Products with Genomes:

Future Challenges............................................................................183
Siva G. Somasundaram
Appendix I............................................................................................................. 199
Index.......................................................................................................................205

vii
Series Preface
Botanical medicines are rapidly increasing in global recognition with significant
­public health and economic implications. For instance, in developing countries, a vast
majority of indigenous populations use medicinal plants as a major form of health
care. Also, in industrialized nations, including those in Europe and North America,
consumers are increasingly using herbs and botanical dietary supplements as part
of integrative health and complementary and alternative therapies. Moreover, the
paradigm shifts occurring in modern medicine, from mono-drug to multi-drug and
poly-pharmaceutical therapies, have led to renewed interest in botanical medicines
and botanical drugs. This is due, in part, to the basic underpinnings of botanical
medicines, according to which a complex matrix of multiple compounds within an
extract elicits multiple biological actions and the activity of a major compound may
be potentiated by multiple minor constituents. In short, the whole is greater than the
sum of its parts. However, the widespread use and resurgence in the popularity of
herbal medicines raises concerns about clinical efficacy, quality, safety, dosing, and
the potential for herb–herb, herb–food, and herb–drug interactions. Pharmacognosy,
the study of drugs from natural sources, plays a critical role in the process of ensur-
ing the authenticity, purity, and consistency of botanicals and also for developing
tools and models for determining their mechanisms and modes of action, doses,
toxicity, and safety. The cross-fertilization of classical pharmacognosy with mod-
ern chemical and biological approaches, and their applications in a clinical setting,
has led to the Clinical Pharmacognosy series, which seeks to disseminate emerging
research and discuss challenges and opportunities on the aforementioned issues.

Navindra P. Seeram
University of Rhode Island

ix
Preface
The mechanistic roles of natural products and genomes are included in the six chap-
ters of this book. The Dictionary of Natural Products reported 210,000 compounds
in their database. There are around 20,000 genes in human chromosomes that code
for the proteins. If we want to study the impact of 210,000 compounds for each gene,
then it is an endless process and a huge task. Here, the authors try to present the tip
of the iceberg to understand the methods of study of the natural products and their
effects on genomes. To achieve our objective, we selected major natural products
and studied their interactions with randomly selected genes for each chromosome.
Then we focused on genes that are involved in specific disease and presented the
natural product interactions. For example, natural products and their extracts modu-
late mechanisms of inflammation. Inflammation is the basic pathogenesis of any
chronic illness, including cancer. Most of the natural products generally inhibit acute
inflammation inducing genes. For example, they fail to inhibit carcinogenesis if the
inflammation becomes chronic. If we have comprehensive knowledge of the genomic
interactions for all the chromosomes related to a specific natural product, it is easy
to formulate a tailor-made therapy for individuals depending on their genomic pro-
file. This approach eventually enables formulation of personalized medical therapy
through clinical pharmacognosy using available natural products.
In addition, there are several reports available on the negative effects of the inter-
actions of natural products with regular therapy. As the natural products supple-
ments are not regulated by FDA, and available from over the counter, it is possible
that the patients are using their own choice of selecting dietary supplements and
mixing up their own medications without the knowledge of the side effects of drug–
natural product interactions.
Here, we provide two specific studies on breast cancer and prostate cancer to
address this important issue. Next, we focus on the effect of natural products on
microbial growth and finally provide future perspectives on the interaction of natural
products with genomes.
Throughout this volume, there are figures whose captions contain URLs to the
PubMed websites, where they will find an updated literature for the respective natu-
ral products for the selected genes. In this way, this book is automatically updating
the relevant bibliographical details when it is published in the PubMed and keeping
abreast of the latest knowledge regarding content of interest. This will reduce the
time and search for the readers and remain useful beyond the date of the publication
of the book as long as the PubMed websites are active.

Siva G. Somasundaram
University of Houston-Victoria

xi
Acknowledgments
The work of editorial assistants Ashley Weinstein and Hilary LaFoe was helpful;
CRC Press was also helpful in the completion of the book. Their cooperation is
much appreciated. I thank them for their daily responses to queries and collection of
manuscripts and documents.

xiii
Editor
Dr. Somasundaram is the Director of Biological Sciences for Undergraduate
Studies and Professor of Biology at University of Houston-Victoria, where he teaches
genome sciences as part of the MS biomedical science program. He has accumulated
33 years of research experience and published 45 peer-reviewed research articles.
He has been teaching biology and biochemistry for 22 years. Dr. Somasundaram
received the Hari Ohm Ashram gold medals for his clinical research on diabetes and
arthritis in India. He received the Enron Teaching Excellence Award 2013 and the
Research Excellence Award 2010 from the University of Houston-Victoria, Sugar
Land, Texas.
Dr. Somasundaram was a visiting scientist at MRC-Clinical Research Center,
Harrow, United Kingdom, from 1990 to 1992. He then moved to King’s College
Hospital, London, as an associate clinical biochemist (1992–1997) and researched
pathogenesis and prevention of intestinal inflammation induced by nonsteroidal
anti-inflammatory drugs. There he has applied a novel noninvasive method to study
small-intestinal permeability and absorptive capacity in HIV/AIDS, liver transplan-
tation, cardiopulmonary bypass surgery, and inflammatory bowel disease patients.
Dr. Somasundaram moved to the University of Washington, Seattle, as a senior
fellow (1997–2000) and carried out research on the transcriptional regulation and
function of ileal bile acid transporter gene in human, hamster, CFTR mice, and
rats by RT-PCR and immunofluorescent histochemistry. He has served as a research
associate in the Lineberger Comprehensive Cancer Center, University of North
Carolina, Chapel Hill, North Carolina (2000–2002) and contributed to the study of
molecular signal transduction in apoptosis, mainly the inhibition of chemotherapy-
induced apoptosis of human breast cancer cell lines by in vitro and in vivo xeno-
graft animal models using dietary antioxidant supplements. He was selected as an
NIH-sponsored regional fellow to conduct Inside Cancer Workshops in 2009–2010.
He received USDA grants in 2006 for studying the effect of citrus limonin on the
transcriptomic profiling metastasis breast cancer genome.

xv