nanotechnology in nutraceuticals - taylor & francis ebooks

PRODUCTION TO CONSUMPTION

NANOTECHNOLOGYIN NUTRACEUTICALS

Nanotechnology in Nutraceuticals: Production to ConsumptionShampa Sen and Yashwant Pathak

Herbal Bioactives and Food Fortification: Extraction and FormulationD. Suresh Kumar

Handbook of MetallonutraceuticalsYashwant V. Pathak and Jayant N. Lokhande

Nutraceuticals and Health: Review of Human Evidence Somdat Mahabir and Yashwant V. Pathak

Marine Nutraceuticals: Prospects and Perspectives Se-Kwon Kim

Nutraceuticals: Basic Research/Clinical ApplicationsSeries Editor: Yashwant Pathak, PhD

CRC Press is an imprint of theTaylor & Francis Group, an informa business

Boca Raton London New York

NUTRACEUTICALS Basic Research/Clinical Applications

Edited byShampa Sen • Yashwant Pathak

PRODUCTION TO CONSUMPTION

NANOTECHNOLOGYIN NUTRACEUTICALS

CRC PressTaylor & Francis Group6000 Broken Sound Parkway NW, Suite 300Boca Raton, FL 33487-2742

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Library of Congress Cataloging‑in‑Publication Data

Names: Sen, Shampa, editor. | Pathak, Yashwant, editor.Title: Nanotechnology in nutraceuticals : production to consumption / edited by Shampa Sen and Yashwant Pathak.Description: Boca Raton : Taylor & Francis, 2017. | Series: Nutraceuticals. Basic research/clinical applications ; 4 | “A CRC title.” | Includes bibliographical references and index.Identifiers: LCCN 2016012964 | ISBN 9781498721882Subjects: LCSH: Functional foods. | Nanotechnology.Classification: LCC QP144.F85 N36 2017 | DDC 613.2--dc23LC record available at http://lccn.loc.gov/2016012964

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I profoundly thankAlmightyMy familyMy friends

My students andEveryone

Who have inspired and helped me to complete this book

Shampa Sen

Our adoration to the Rishi-s, the forefathers, the pioneers and the pathfinders

Rig veda (10–14–15)

Yashwant V. Pathak

http://taylorandfrancis.com

vii

Contents

Series Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . xi

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv

Editors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii

Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . xix

1 Recent Trends in Nutraceutical Research and Development: From Concept to Applications . . . . . . . . . . . . . . . . . . . . . . . 1Avipsha Sarkar, Alok Prakash, Yashwant V. Pathak, and Shampa Sen

2 Nanofood Materials Characteristics and Evaluations . . . . . . . . . . . . . . . . . . . . . . 23Harsh Chauhan and Dev Prasad

3 Principles for the Oversight of Nanotechnologies and Nanomaterials in Nutraceuticals and Functional Foods . . . . . 39Stanley Jean-Charles, Shampa Sen, and Yashwant V. Pathak

viii Contents

4 Metallic Nanoparticles in the Food Industry: Advantages and Limitations . . . . . 57Kumar Rajendran and Shampa Sen

5 Targeted Delivery of Nutraceuticals Using Nanoparticles . . . . . . . . . . . . . . . . . . 87Kumar Rajendran and Shampa Sen

6 Developments and Applications of Silver Nanoparticles in the Nutraceuticals Industry . . . . . . . . . . . 117Shanmuga Sundari I., Vithiya K., and Shampa Sen

7 Nanoemulsions in Food Science and Nutrition . . . . . . . . . . . . . . . . . . . . . . .135Shivendu Ranjan, Nandita Dasgupta, Chidambaram Ramalingam, and Ashutosh Kumar

8 Dietary Fibers and Etiology of Health and Disease: An Emerging Concept of Nanonutraceuticals . . . . . . . . . . . . . . . . .165Avipsha Sarkar and Shampa Sen

9 Nanotechnology in Probiotics and Prebiotics . . . . . . . . . . . . . . . . . . . . 177Kumar Rajendran, Shampa Sen, and P. Latha

10 Modeling and Simulation of Nanobiosystems with Special Reference to Functional Foods and Nutraceuticals . . . . . . . . . . . . . . . . . . . .197Sudharsana Sundarrajan and Mohanapriya Arumugam

11 Nanostructured Lipid Carriers . . . . . . . . . . . . 215Melanie Jameson, Anjali Hirani, and Yashwant V. Pathak

ixContents

12 Challenges in the Development of Functional Foods: Role of Nanotechnology . . . . . . . . . . . . . . . . . . 233Pranav K. Singh and Harjinder Singh

13 Nanotechnology in Nutraceuticals and Functional Foods: Production to Consumption . . . . . . . . . . . . . . . . . . . . . 265Corin Agoris, Muhammad Imam, Aditya Grover, and Yashwant V. Pathak

14 Industrial Production of Nanonutraceuticals . . . . . . . . . . . . . . 275Avipsha Sarkar, Shanmuga Sundari I., and Shampa Sen

15 Nanotechnology in Food Products: Implications in Regulatory Requirements . . . .289Charles Preuss, Abhishek Shah, and Yashwant V. Pathak

16 Nanotechnology-Based Nutraceuticals for Use in Cardiovascular Disease: Toward a Paradigm Shift in Adjuvant Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . 301Ashim Malhotra

17 Nanonutraceuticals: Are They Safe? . . . . . . . 317Nandita Dasgupta, Shivendu Ranjan, Chidambaram Ramalingam, and Ashutosh Kumar

18 Consumer Acceptance of Nanotechnology-Based Foods and Food Innovations . . . . . . . . . . . . . . . . 345Jean Gaibort, Shampa Sen, and Yashwant V. Pathak

x Contents

19 Ethics and Economics of Nanonutraceuticals . . . . . . . . . . . . . . 357Alok Prakash, Shanmuga Sundari I., and Shampa Sen

20 Novel Nanoencapsulation Structures for Functional Foods and Nutraceutical Applications . . . . . . . . . . . . . . . . . . . . . . . .373Laura G. Gómez-Mascaraque, Jesús Ambrosio- Martín, Maria José Fabra, Rocío Pérez- Masiá, and Amparo López-Rubio

21 Mesoporous Silica Particles as Encapsulation and Delivery Systems for Food Ingredients and Nutraceuticals . . . 397Édgar Pérez-Esteve, María Ruiz-Rico, Ramón Martínez-Máñez, and José Manuel Barat

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439

xi

Series Preface

Mother Nature is the best scientist of nanotechnology. There are several nanomaterials created by Mother Nature that even with modern science development we cannot yet replicate. Nanoscience and technologies have been influencing practically every walk of life including computer sciences, electronics, communications, energy production, and medi-cine. The food industry is not lagging behind in application of nano-technology, with significant applications in nutraceuticals and functional food. Food products in today’s world are not only contributing to satisfy the appetite, but they also provide vital nutrients and contribute toward positive health outcomes for consumers.

In the food industry, nanotechnology is applied in many areas including developing nanoparticulate food materials such as micelles, liposomes, nanoemulsions, nanosuspensions, and biopolymeric nanomaterials and cubosomes. On the production side, nanosensors are helping to main-tain a high level of quality in products.

Some interesting applications of nanotechnology include protective effects of nanoparticles from oxidation, controlled release of nutrients, taste masking, delivery of nanocapsulated nutraceuticals, vitamins and flavors, detection of pathogens in food and nutraceuticals, food safety and quality enhancements, improved packaging, shelf-life extension, nanoadditives to enhance the quality of the product, antibacterial and self-cleaning packaging, and monitoring the quality of products during transport, transition, and long-term storage.

The scope of the series Nutraceuticals: Basic Research/Clinical Applications aims at bringing out a range of books edited by distinguished scientists and researchers who have significant experience in scientific pursuit and critical analysis. This series addresses various aspects of nutraceutical

xii Series Preface

products including the historical perspective, traditional knowledge base, analytical evaluations, green food, processing, and applications. The series will be very useful to not only the researchers and academi-cians but will be valuable reference books for personnel in the nutraceu-ticals and food industries.

The purpose of the inclusion of this book, Nanotechnology in Nutraceuticals: Production to Consumption, in the series is to cover the recent trends in the food industry, which has been significantly enhanced with the advent of nanotechnology. The forthcoming titles in the series will cover the topics of seaweed bioactives, nutrigenomics, botanical drug products, antioxidant nutraceuticals, and food powders.

The series has proven to be a very good resource for academicians, industrial scientists, and students in the area of nutraceutical basic research and clinical applications. We invite scientists and academicians working in this field to contribute to the series.

Yashwant V. PathakSeries Editor

xiii

Foreword

Changes in lifestyle, food habits, and other environmental conditions resulted in the emergence of drug-resistant diseases. The existing health care system may not be sufficient to provide the necessities to cure emerging diseases. Besides the rapid rise in technological advance-ments, there is an urgent push toward the development of innovative products in the prevention of diseases. Nutraceuticals are nutritional func-tional foods that are already in existence in the form of natural fruits and vegetables. These resources are given in various forms to man for maintaining body health and in preventing diseases. The best example could be Ayurveda, an Ancient Asian medical system that has provided nutraceuticals for several millennia in the form of Rasayana, proven to be potentially beneficial.

Numerous nutraceutical products are available in the market, and the food science and pharma sectors of competitive nutraceutical industries are developing such products. These products are verified to be expedi-ent, but lack stability, bioavailability, and permeability. Hence with the latest technological advancements, nanonutraceuticals were developed to afford a solution. Nanomaterials are nanosized particles in the range of 1 to 100 nm. Nutraceuticals delivered along with nanoparticles in different combinations have been found to be naturally efficient. This book’s chapters explain nanonutraceuticals in practice from production to consumption. The book specifically addresses concepts, techniques, and production methods of both nutraceuticals and nanoparticles, which are converted into nanonutraceuticals. As nanoparticles are toxic beyond a certain limit, implementing nanotechnology under correct regulations is considered to be more important. Hence, this book also addresses such issues as ethics and economics in nutraceutical production. Production of nutraceuticals has rapidly increased in the global nutraceutical market

xiv Foreword

and still emerges in delivering newer forms of nanonutraceuticals. Although pharma sectors play a major role in curing diseases, there is certainly a great need for developing nutraceuticals by nutraceuti-cal industries. The book conveys a key point about nanonutraceuticals: If nanonutraceuticals are produced following appropriate regulations, they can undeniably change the world in preventing life-threatening dis-eases, saving millions of lives.

I heartily congratulate the editors and contributing authors for their immense efforts in producing this book. The volume will be of great value to students, researchers, and practitioners engaged in the study and production of nanonutraceuticals.

Dr. Anand A. Samuel, BE, MS, PhDVice Chancellor

VIT University

xv

Preface

There has been a drastic breakthrough in the field of nanotechnol-ogy over the past few years. Nanotechnology is the science applying nanoscale materials in different areas that would be beneficial to human kind. Nanosized materials possess excellent properties when compared to their respective bulk forms. Hence, the field started growing rap-idly, from environmental to various medical applications. Such immense potential of nanotechnology has also recently touched the food indus-try. Food spoilage during processing, transport, and packaging can be reduced to a greater extent by applying the concept of nanotechnology. Nutraceuticals are functional foods or dietary supplements to facilitate prevention and cure of diseases. Nutraceuticals are more beneficial and possess no side effects, as mostly they are phytochemical compounds of natural resources. However, nutraceuticals retain less stability, efficacy, and bioavailability when they enter the human body system. Hence, to overcome such problems, nanotechnology was applied in the field of nutraceuticals.

This book contains the basics about nutraceuticals, nanotechnology, and various approaches and techniques used in nanonutraceutical industries. From this book, readers will gain basic knowledge about different forms of nutraceuticals and why they are important in today’s world. The first chapter gives a detailed review of the basics of nutraceuticals and their prospects in the food industry and human health. Organization of nutra-ceuticals, prior investigations done on nutraceuticals, and their applica-tions as antioxidants, prebiotics, and probiotics, and a few therapeutic applications are also highlighted.

The remaining chapters are framed in a format so that the reader can understand the fundamentals of nanotechnology and the concepts of

xvi Preface

applying nanomaterials in the food industry. Chapters 4 through 6 dis-cuss metallic nanoparticles and their applications in the food industry with specific reference to nutraceuticals. A detailed discussion on poten-tial functional properties of nutraceuticals such as antimicrobial activity, anti-inflammatory activity, and anticancer activity with their applications in targeted delivery are given in Chapter 5. The book covers topics on the current status of nutraceutical products on the commercial market, problems faced by nutraceutical industries, and the need for nanobased approaches.

Nanotechnology has reached the market in various applications, but they are at infancy in the area of nutraceuticals. There are various issues concerning nanomaterial toxicity toward humans and the environment. Hence, safety aspects of nutraceuticals and their applications with nanoparticles are discussed in the next few chapters. Nanoparticle toxic-ity, issues regarding the food industry, environment, ethics, and econom-ics in nutraceutical industries are also discussed. Consumer acceptance of nanotechnology-based food innovations, implications of regulatory requirements on production and marketing of nanonutraceuticals, and the rules and regulations that have to be followed during nanonutraceu-tical synthesizing, characterization, and marketing are discussed.

Though several topics on nutraceuticals and nanotechnology are not covered in this book due to space constraints, the readers would get an overview of nutraceuticals and nanotechnology. We thank and appreci-ate all the reviewers for providing critical comments and valuable sug-gestions to improve this book.

Shampa SenYashwant V. Pathak

xvii

Editors

Dr. Shampa Sen completed her PhD in envi-ronmental biotechnology at the Indian Institute of Technology, Guwahati, India. She is an asso-ciate professor in the School of Bio Sciences and Technology at VIT University, Vellore, India. With extensive experience in academia, she has more than 30 publications in environ-

mental biotechnology, bionanotechnology, and nutraceuticals. She has been actively involved in many professional development activities. Her research interests include biosynthesis of metallic nanoparticles, and nanoparticles in biomedical and environmental applications.

Dr. Yashwant V. Pathak completed his PhD in pharmaceutical technology at Nagpur University, India, and EMBA and MS in conflict manage-ment from Sullivan University, Louisville, Kentucky. He is a professor and associate dean for Faculty Affairs at the College of Pharmacy, University of South Florida, Tampa. With exten-sive experience in academia as well as industry,

he has more than 120 publications and one approved patent and five patent applications, including 15 books in nanotechnology, drug deliv-ery systems, nutraceuticals, conflict management, and cultural studies. He is editor of the Nutraceuticals: Basic Research/Clinical Applications series published by CRC Press. Some of the titles in the series include Handbook of Metallonutraceuticals, Marine Nutraceuticals: Prospects and Perspectives, and Nutraceuticals and Health: Review of Human Evidence. Pathak has a passion for travel, which has taken him to more

xviii Editors

than 80 countries. He has received many awards and scholarships inter-nationally. He is actively involved in much nonprofit organization work. His new research interests include the impact of microgravity/hyper-gravity on the stability of space pharmaceuticals with a special focus on mucoadhesive nanoproducts.

xix

Contributors

Corin AgorisMorsani College of MedicineUniversity of South FloridaTampa, Florida

Jesús Ambrosio-MartínInstitute of Agrochemistry

and Food TechnologyIATA-CSICPaterna (Valencia), Spain

Mohanapriya ArumugamSchool of Bio Sciences

and TechnologyVIT UniversityVellore, Tamil Nadu, India

José Manuel BaratGroup for Research

and Innovation FoodPolytechnic University of ValenciaValencia, Spain

Harsh ChauhanSchool of Pharmacy and Health

ProfessionalsCreighton UniversityOmaha, Nebraska

Nandita DasguptaSchool of Bio Sciences


Maria José FabraInstitute of Agrochemistry


Jean GaibortCollege of PharmacyUniversity of South FloridaTampa, Florida

Laura G. Gómez-MascaraqueInstitute of Agrochemistry


Aditya GroverMorsani College of MedicineUniversity of South FloridaTampa, Florida

xx Contributors

Anjali HiraniCollege of PharmacyUniversity of South FloridaTampa, Florida

Muhammad ImamMorsani College of MedicineUniversity of South FloridaTampa, Florida

Melanie JamesonCollege of PharmacyUniversity of South FloridaTampa, Florida

Stanley Jean-CharlesCollege of PharmacyUniversity of South FloridaTampa, Florida

Vithiya K.School of Bio Sciences


Ashutosh KumarSchool of Science and TechnologyAhmedabad UniversityAhmedabad, Gujarat, India

P. LathaSree Vidyanikethan College

of PharmacyTirupati, Andhra Pradesh, India

Amparo López-RubioInstitute of Agrochemistry

and Food TechnologyIATA-CSIC Paterna (Valencia), Spain

Ashim MalhotraSchool of PharmacyCollege of Health ProfessionsPacific UniversityHillsboro, Oregon

Ramón Martínez-MáñezInstitute of Molecular Recognition

and Technological Development (IDM)

Department of ChemistryPolytechnic University of ValenciaValencia, Spain

Yashwant V. PathakCollege of PharmacyUniversity of South FloridaTampa, Florida

Édgar Pérez-EsteveDepartment of Food TechnologyPolytechnical University

of ValenciaValencia, Spain

Rocío Pérez-MasiáInstitute of Agrochemistry


Alok PrakashSchool of Bio Sciences


Dev PrasadFresenius KabiSkokie, Illinois

xxiContributors

Charles PreussMorsani College of MedicineUniversity of South FloridaTampa, Florida

Kumar RajendranSchool of Bio Sciences


Chidambaram RamalingamSchool of Bio Sciences


Shivendu RanjanSchool of Bio Sciences


María Ruiz-RicoDepartment of Food TechnologyPolytechnic University of ValenciaValencia, Spain

Avipsha SarkarSchool of Bio Sciences


Shampa SenSchool of Bio Sciences


Abhishek ShahMorsani College of MedicineUniversity of South FloridaTampa, Florida

Harjinder SinghRiddet InstituteMassey UniversityPalmerston North, New Zealand

Pranav K. SinghCollege of Dairy Science

and TechnologyGuru Angad Dev Veterinary and

Animal Sciences UniversityLudhiana, India

Shanmuga Sundari I.School of Bio Sciences


Sudharsana SundarrajanSchool of Bio Sciences


1

1Recent Trends in Nutraceutical Research and DevelopmentFrom Concept to Applications

Avipsha Sarkar, Alok Prakash, Yashwant V. Pathak, and Shampa Sen

1.1 Nutraceuticals: Basic concepts

Since ancient times, consuming food from plants has provided immense benefits to human health. To be precise, plants contain various phytochemical compounds, mostly polyphenols. These polyphenols are responsible for the aforementioned beneficial activity, as reported by various research studies. Recently pharmaceutical products that contain nutraceuticals as their active ingredient have appeared in health products. These active ingredients are comprised mainly of phytochemicals with bioactivity (Espín et al. 2007). The

Contents1.1 Nutraceuticals: Basic concepts ...................................................................1

1.1.1 Introduction .....................................................................................31.1.2 Classification of nutraceuticals .......................................................41.1.3 Prior investigation ...........................................................................51.1.4 Contemporary explorations ............................................................6

1.2 Nutraceuticals: Applications .......................................................................71.2.1 Nutraceuticals: A functional food ...................................................71.2.2 Functional food: Definition .............................................................81.2.3 Probiotics and prebiotics ................................................................91.2.4 Nutraceuticals: Antioxidants .........................................................101.2.5 Nutraceuticals: Antiaging ..............................................................131.2.6 Nutraceuticals: Anticancer.............................................................131.2.7 Nutraceuticals from algae: Functions ...........................................151.2.8 Nutraceuticals: Therapeutic applications ......................................161.2.9 Metallonutraceuticals ....................................................................18

1.3 Future research ........................................................................................191.4 Conclusion ................................................................................................19References .........................................................................................................20

2 Nanotechnology in Nutraceuticals

most popular phytochemicals used in the nutraceutical industry are anthocyanins, resveratrol, isoflavones, and polyphenols like ellagic acid, proanthocyanins, and flavanones. The Indian market has also taken the initiative to promote the concept of functional food (see Figure 1.1).

Nutraceuticals are basically diet supplements. They have been made accessible within a nonfood medium and are being used for the delivery of known bioactive agents in the health product industries. This is done to enhance human health by introducing dosages of active compounds from food in a higher amount than the amount that can be introduced by the consumption of normal food products. Figure 1.2 illustrates the research evidence that suggests nutraceuticals are safe as well as efficient as diet supplements and pharmaceuticals.

Indianmarket

Functionalfoods (60%)

Dietarysupplements

(40%)

Fortified fooditemsFunctionalbeverages

Vitamin andmineralsupplement

Chyawanprash

Proteinsupplement

Figure 1.1 The Indian market of nutraceuticals.

Nutraceuticals

Research evidence

Pharmaceuticals Diet supplements

Efficie

ncy Safety

Figure 1.2 Research evidence.

3Recent Trends in Nutraceutical Research and Development

1.1.1 IntroductionThere are several definitions for nutraceuticals, one of them being “food, or parts of food, that provide medical or health benefits, including the prevention and treatment of disease” (from Dr. Stephen DeFelice of the Foundation for Innovation in Medicine).

A nutraceutical, like lycopene, can be found in several forms. It can be obtained as a fraction of an intact food source, which is normally present in a tomato slice, or found from tomatoes as an element of a refined food, or as lycopene supplemented in a fruit juice as an embellished essence of the food, or provided in supplemental form (Wildman 2006).

Any kind of food that is consumed is known to have a direct connection to human health. The term health refers to the physical, physiological, and mental state of a human being. It has been known from various studies that food derived from plants like nuts, spices, wine, fruits, grains, vegetables, and so on are beneficially associated with human health, predominantly being favorable to oldaged humans. The instances of agerelated diseases, such as certain types of cancer (e.g., gastrointestinal cancer), cardiovascular diseases, and type 2 diabetes, are more prevalent with the increase in life expectancy of humans. By escalating the use of food products from plants, development of these chronic diseases can be delayed, as recommended by various health organizations all over the world.

Plantderived food products show a positive effect on the reduction of chronic diseases due to the presence of phytochemicals. These phytochemicals are nonnutritive secondary metabolites and show a wide range of biological activities. As bioactive compounds, these phytochemicals have low effectiveness in comparison to pharmaceutical products, but a perceptible longterm physiological effect can be seen if they are regularly ingested in the diet.

Dietary supplement is distinguished by the U.S. Dietary Supplement Health and Education Act (DSHEA) of 1994. A dietary supplement

• Is a product that consists of more than one nutritional ingredient like an amino acid, a vitamin, an aromatic plant, or mineral. It is a product (excluding tobacco) that is projected to increase the diet. In order to complement the diet, man escalates the entire daily intake of a nutritional substance like a mixture of several ingredients, an extract, a metabolite, or constituents.

• Is proposed in the form of liquid, capsule, or tablet for eating in medication.

• Incorporates accepted novel drug candidates, antibiotics that are licensed, or a marketed nutritional supplement that is an approved biologic before sanction, certification, or authorization.


1.1.2 Classification of nutraceuticalsNutraceuticals can be classified based on food source (Figure 1.3) and mechanism of action.

Food sources include plants, animals, and microbials.

• Plant sources: betaglucan, ascorbic acid, gammatocotrienol, quercetin, luteolin, cellulose, gallic acid, perillyl alcohol, indole3carbinol, pectin, daidzein, glutathione, potassium, allicin, dlimonene, genestein, lycopene, hemicellulose, lignin, capsaicin, alphatocopherol, zeaxanthin

• Animal sources: conjugated linoleic acid (CLA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), selenium, zinc

• Microbials: yeast, Bifidobacterium, Bacillus, Lactobacillus, Streptococcus

Modes of action include bone protective, anticancer, antiinflammatory, blood lipid profile, and antioxidant.

• Anticancer: ellagic acid, capsaicin, genestein, daidzein, carnosol, alphatocotrienol, gammatocotrienol, CLA, limonene, ajoene, alphatocopherol, glycyrrhizin, curcumin, lutein, diallyl sulfide

• Constructive control on blood lipid profile: monounsaturated fatty acids (MUFAs), betaglucan, delta tocotrienol, quercetin, resveratrol, gammatocotrienol, saponins, beta sitosterol, quercetin, omega3 polyunsaturated fatty acids (PUFAs)

• Ascorbic acid• Quercetin• Luteolin• Cellulose• Lutein• Gallic acid• Daidzein• Allicin• Capsaicin• Lycopene• Zeaxanthin• Minerals• MUFA

• Eicosapentaenoic acid • Choline• Docosahexaenoic acid• Lecithin• Selenium• Zinc• Creatine

• Saccharomyces boulardii• B. longum• Bifidobacterium bifidum• L. acidophilus• Streptococcus salvarius

Plants Animals Microbials

Nutraceuticals from food sources

Figure 1.3 Nutraceuticals according to food source.


• Antioxidants: ascorbic acid, tannins, CLA, tocotrienols, alpha tocotrienols, betacarotene, polyphenols, lutein, catechins, gingerol, tocopherols, glutathione, indole3carbinol, ellagic acid, lycopene, hydroxytyrosol, oleuropein, gingerol, chlorogenic acid

• Antiinflammatory: EPA, capsaicin, linolenic acid, quercetin, curcumin, DHA osteogenic, genistein, CLA, calcium, soy protein, daidzein (Wildman 2006)

1.1.3 Prior investigationWidespread research on nutraceuticals has become popular since obesity, besides being a proinflammatory disease, has also been linked with type 2 diabetes, atherosclerosis, cancer, and other chronic diseases. Certain nutraceuticals work by antioxidant and antiinflammatory mechanisms. The most generally studied among these is curcumin (yellow pigment derived from turmeric) as a cure for obesity and related disorders. By interacting with cells of the muscle and pancreas along with adipocytes and macrophages, curcumin can suppress the proinflammatory factors like NFκB, Wnt/βcatenin, and activators of transcription3. It can activate peroxisome proliferatoractivated receptorγ and Nrf2 cell signaling pathways, thereby decreasing production of interleukin6 as well as leptin, TNFs, and MCP1 (Figure 1.4). Hence, there is an upregulation of adiponectin and other antiinflammatory gene products. Other nutraceuticals, derived from cinnamon, cloves, and ginger, have been shown to be effective against obesity and insulin resistance (Aggarwal 2010).

HDL Antioxidant CPT-1

Leptin Curcumin

Resistin

AMPK PPAR-γ AdipocytesIL-6, IL-3

Hyp

ocho

leste

rem

ia

Figure 1.4 Functions of curcumin.


1.1.4 Contemporary explorationsRecent research on anthocyanins has provided new insight to its health benefits. It has been suggested that the gene alteration due to the consumption of anthocyanins might be the reason. Current development in the research on nutraceuticals and anthocyanins has been possible because of rigorous animal trials and in vitro studies on animals. The current research is also strengthening from increasing the number of human trials. Health benefits include effects on brain cognitive function, visual capacity, ulcer protection, cancer prevention, obesity, and cardiovascular risk. There have been various studies that have shown the anthocyanins as a cause to improve the nocturnal vision in myopic patients. Purified anthocyanoside oligomers have been used for these studies. The patients were given repetitive dosage of anthocyanoside oligomers and it showed a positive effect on nocturnal vision in myopic subjects. Various other studies have shown that the berry extracts and anthocyanins lead to an increment in cognitive performance, enhanced memory and reduction of ischemic damage to the brain. The current research reports have also shown that anthocyanins can lead to prevention of diabetes and obesity. This is because anthocyanins reduce the blood sugar level, adipose tissue and body weight gain. Dietary anthocyanin has been shown to prevent cardiovascular diseases in vitro and in vivo studies. It has been observed that consumption of anthocyanins leads to a reduced level of LDL cholesterol and total plasma cholesterol.

Garlic (Allium sativum L.) is a very important and common plant having both gastronomic and remedial uses coming up from its several biological activities, which include antibiotic, anticancer, antithrombotic, and lipidlowering cardiovascular effects. People have been well aware of the medicinal properties of garlic for centuries, but there was no scientific evidence to support. However, recent research has helped us to understand the pharmacological properties of garlic and the associated products. Garlic is asexually propagated and difficult to grow by conventional means. The involvement of biotechnological processes such as tissue culture and gene transfer may possibly improve this crop. Due to new improvisations in instrumentation and dispensation technologies together with more cautious experimental methods, better harvests can be foreseen in the market (Bhagyalakshmi et al. 2005).

Garlic at a glance

• Garlic oil and benzyl salicylate reduces acetate and enhances propionate and butyrate proportions, which is an antimethanogenic effect.

• It breaks down the dietary protein.• The effects of saponins and tannins on rumen and microbial activ

ity is quiescent.• Garlic is a fatburning substance.


Resveratrol (3,4′,5trihydroxystilbene), a phytopolyphenolic component that belongs to a class of stilbenes (profusely found in several roots, grapes, berries, and peanuts), got renewed interest after it was identified in red wine roughly two decades back. It is thought that resveratrol may be behind the “French paradox” (i.e., French people experience a moderately low frequency of coronary heart disease apparently due to the consumption of red wine). News on the prospect for resveratrol to expand life duration in cell culture as well as in lower model organisms and to prevent the expansion of cancer have prompted to explore the mechanisms and/or the probable benefits invitro as well as in various preclinical disease models. Resveratrol has been shown to inhibit myocardial ischemicreperfusion damage along with atherosclerosis. Figure 1.5 illustrates the functions of resveratrol. It is also known to offer vasoprotection in rodent models of metabolic disorder and in aged mice with no expanding life span. Resveratrol is thought to impersonate the antiaging effects of caloric restraints in rodents. In spite of the mounting evidence that resveratrol confers cardiac and vascular shielding effects in premedical disease models, the accurate molecular and cellular procedures of its action remain vague. From the recent research it appears that resveratrol can evoke complex cellular feedbacks by promoting cell endurance, preserving cellular energetics, and inhibiting proinflammatory phenotypic alterations induced by oxidative stressors (Haskó and Pacher 2010).

1.2 Nutraceuticals: Applications1.2.1 Nutraceuticals: A functional foodNutraceuticals, with their versatile role in health effects, are also considered as a potent functional food. But, sometimes the boundary between the nutraceuticals and functional food is not clear. This is because of the minute

Mitochondrial ROS

Glutathione peroxidase

Mitochondrial biogenesis

SIRT 1

Cellular H2O2 NF-KB Vascularinflammation

Endothelial apoptosis

Resveratrol Nrf2 Heme oxygenase

GSH synthase

Figure 1.5 Functions of resveratrol.


difference in the concept of nutraceuticals and functional food; the difference exists because of the volume or mass of consumption. Nutraceuticals, being concentrated food extracts or products, are usually considered to be consumed in small amounts, whereas functional food may be consumed in large amounts. The amount of bioactive compound might be the same in both nutraceuticals and functional food. This can be understood by the following example. Consider 100 mg of a food extract dissolved in 1 L of fruit juice. This makes a potent functional food. Whereas, the same amount of food extract (100 mg) when incorporated into a capsule or other nonfood matrix, makes it a nutraceutical. It is clear from the example that the amount of bioactive compound is the same in the functional food as well as the nutraceutical, but the concentration of bioactive compound is different. The consumption of functional food and nutraceutical in the example will provide the same dosage of bioactive compound. This leads to various issues in governmental regulations for nutraceuticals.

The consequence of food factors on health status has been acknowledged since ancient times. An ample array of food and other ingredients are being included as serviceable (functional) foods and natural fitness products that have a diverse range of bioactive compounds that are valued because of their role in the improvement of health as well as disease impediment. Phenolic along with polyphenolic components are known to act as antioxidants and LDL cholesterol oxidation inhibitors. They compose a very important class of secondary plant metabolites. Hence, both polyphenolics along with phenolics are known for their role in the circumvention of several forms of cancer and cardiovascular diseases. Additionally, food derived from marine sources has been thought as “heart food” due to omega3. This is specifically known to subjugate blood triacylglycerol as well as lowering cholesterol levels. Therefore, there is a strong belief that food ingredients from both plant as well as animal sources partake equally to improve and enhance human health (Shahidi 2006).

1.2.2 Functional food: DefinitionFunctional foods can be defined as a group of food products that upon regular consumption provide a special effect on the physiological condition of humans that is beyond their nutritional properties. To be clearer, functional food provides a healthier status of the human physiology and a lower risk of occurrence for any disease. The International Food Information Council (IFIC) states functional foods are “foods or dietary components that may provide a health benefit beyond basic nutrition.” Another organization, the International Life Sciences Institute of North America (ILSI), states functional foods are “foods that by virtue of physiologically active food components provide health benefits beyond basic nutrition.” Health Canada says functional food is “similar in appearance to a conventional food, consumed as part of the usual diet, with demonstrated physiological benefits, and/or to reduce


the risk of chronic disease beyond basic nutritional functions” (Wildman and Kelley 2006). According to the Institute of Medicine’s Food and Nutrition Board, functional foods can be defined as “any food or food ingredient that may provide a health benefit beyond the traditional nutrients it contains.” In general there is no exact and precise definition of functional food because of its novelty, but several definitions given by different organizations share various common features.

1.2.3 Probiotics and prebioticsProbiotics are defined as live microbial food ingredients that constructively affect the host by recuperating its intestinal microbial balance. The candidate probiotics include

• Lactic acid bacteria, bacilli, yeasts, etc.• Lactobacilli and Bifidobacteria

Prebiotics are nondigestible food ingredients that usefully affect the host by selectively stimulating the growth of beneficial bacteria and/or by suppressing that of harmful bacteria in the colon, which have the potential to progress the host’s health. Prebiotics include oligosaccharides, dietary fiber, and resistant starch. The purpose of probiotics and prebiotics to the maneuvering of the microbial bionetwork of the human colon has in recent times seen many systematic advances. The probiotic genome sequencing has provided assets of original fresh information on these microbes. Along with this, communications of probiotics with individual’s cells and with pathogens can be understood. Another way of modifying the microbial population in the colon is by means of prebiotic oligosaccharides. Advancements in knowledge about the metabolism of prebiotics have allowed people to regard this as a dietary intervention tool for specific populations and disease stages. Table 1.1 illustrates a basic comparative study between the probiotics and prebiotics.

The medical efficiency of prebiotics and probiotics has been proven in various experimental settings. Probiotics are experimentally proven to be responsible for side effects in vulnerable individuals including infections, metabolic

Table 1.1 Comparison of Probiotics and Prebiotics

Characteristic Probiotics Prebiotics

Definition Living active microbes when administered in adequate amount benefits the host

Nonliving, nondigestible special form of fiber

Properties More fragile, vulnerable to heat, over time may be killed

In the powdery form can survive acid, heat, and cold

Role Combat the harmful bacteria that reside in the gut Enrich the bacterial population in the intestines and perform their role


behaviors, too much immune stimulation, and gene transfer. Infections occur less often compared to the other side effects. It generally occurs in patients who are sick and received medication (probiotics) because of rigorous medical circumstances.

Prebiotics apply an osmotic outcome in the intestinal lumen and are fermented in the colon. These might stimulate bloating and gaseousness. Large doses can induce diarrhea and pain in the abdomen, and gastroesophageal reflux has recently been correlated to the same. The tolerance and effectiveness of the drugs highly depends on the received dosage and other individual factors (Marteau and Seksik 2004).

1.2.4 Nutraceuticals: AntioxidantsThe bioactivity of polyphenols and other phytochemical ingredients, which constitute the nutraceutical products, are more or less associated with the antioxidant property of these compounds. The antioxidant property is basically the free radical scavenging capacity of any chemical compound. Many chronic diseases basically arise from the free radical activity in the human physiological system. The scavenging of this free radical in the human physiological system by the antioxidant compound leads to reduction or no onset of the chronic diseases. Nutraceuticals have various attributes of which the antioxidant property is one. The antioxidant property of nutraceuticals is due to various phytochemical compounds present in food products. A few examples of such phytochemical compounds are anthocyanins, proanthocyanidins, flavanones, and resveratrol.

The most important class of nutraceuticals with antioxidant properties are the carotenoids. Photosynthesis and photoprotection are the primary functions of this class of nutraceuticals. Carotenoids are specifically known to produce reactive oxygen species, with a special mention to singlet oxygen, produced by introduction to radiation as well as light. By reacting with free radicals, carotenoids have a tendency to form radicals themselves. The span of the succession of conjugated double bonds along with the various functional groups at the end and their characteristics tend to influence the reactivity. Removal of electrons that are unpaired mainly counterpoise the carotenoid radicals. These unpaired electrons of the molecules are located on top of the polyene string. This delocalization also allows additional reactions to occur at many sites on the radical molecules. Carotenoids are principally dominant in scavenging singlet oxygen obtained from lightinduced lipid oxidation as well as radiation. Astaxanthin, zeaxanthin, and lutein are excellent in scavenging free radicals because of the unique end functional groups. When fixed with a surrounding that is highly oxidative (e.g., the environment of the lungs of smokers), carotenoids in large quantity may be harmful, though in smaller amounts they are beneficial against cancer and chronic diseases. Figure 1.6 illustrates the procarcinogenic and anticarcinogenic effects of carotenoids.


The anthocyaninbased nutraceuticals are known for their high concentration of antioxidant capacity. The antioxidant capacity of these nutraceuticals is usually expressed as their in vitro antioxidant activity derived by the ORAC (oxygen radical antioxidant capacity) assay. There are several other health claims for the berryderived nutraceutical products or anthocyaninrich nutraceutical products (Matough et al. 2012). These claims include:

• “It promotes healthy brain function and mental clarity, healthy vision, cardiovascular health, and healthy blood sugar levels. It also prevents the effects of premature ageing.”

• “It reduces oxidative damage and inflammation in the nervous system; prevents LDL oxidation in blood vessels, reduces the risk of retinopathy and decreases eye fatigue.”

• “It helps maintain healthy brain function.”• “Natural vision enhancer that prevents retinopathy, improves capillary

fragility, and reduces inflammation.”• “Supports vision, improves blood glucose levels and memory.”• “May prevent some effects of premature aging, promotes healthy brain

function and mental clarity, cardiovascular health, healthy vision, relieves joint discomfort, maintain healthy blood glucose levels and reduce some other health risks.”

Flavanones such as naringenin or hesperidin are also used as an ingredient for nutraceuticals, though they are less represented in the current market than anthocyanincontaining and isoflavonecontaining nutraceutical products. Flavanonecontaining nutraceuticals are currently prepared from citrus extracts and are marketed in the name of citrus bioflavonoid complex. They

Enhancement of carcinogenbinding to DNA

Oxidativedamage to DNA

Oxidative stress

Damaging levelsHighdose

Lowdose

Desirable levels

Immunemodulation Induction of cell

differentiation

Antiangiogenesis

Photoprotection

Antioxidant

Prooxidant

CarotenoidsOxidative metabolites andproducts

Figure 1.6 Procarcinogenic and anticarcinogenic functions of carotenoids.


are also mixed with a large quantity of ascorbic acid or vitamin C. The health benefits of flavanonederived nutraceuticals are less clearly stated than for other nutraceuticals and hence some of the benefits are very general such as “for maintaining proper health,” “immunity booster and powerful antioxidant,” “prevents heart diseases,” and “reduces the effects of aging.” For example, cranberry as well as its other constituents have traditionally been connected with inhibiting infections in the urinary tract and other health remunerations. Phenolic phytochemicals of the juice have been related to the aforementioned benefits that are presently identified to have prospective for prevention of chronic cardiovascular problems and development of cancer. Helicobacter pylori is considered to be associated with peptic ulcers along with cardiovascular problems and is one of the main pathogens related to humans. There are several restrictions for the currently accepted and used synthetic antimicrobials for managing the pathogens. This is because of the probable progress of little acquiescence as well as resistance. The scientists consider a mixture of antimicrobials compared to a distinct compound might be potentially more successful in managing H. pylori infections. The extracts of grape seed along with blueberry and cranberry have been investigated, which shows promising activity against infections related to H. pylori. The capability of oregano and blueberry as well as the extract of grape seed in a blend along with cranberry powder to increase the free radical quenching and antibacterial action against H. pylori has been investigated as well. The activity against H. pylori of the cranberry extracts and their alliances are interrelated with free radical scavenging activity and the occurrence of biphenyls along with polyphenolic phytochemicals. The action of the extract of cranberry juice against H. pylori was appreciably enhanced by its coordinated amalgamation with oregano extract along with blueberry and grape seed. The lower efficiency of purified phenolics in prohibiting H. pylori in comparison with fruit powder at similar dosage levels propose a collaborative means of performance of the individual phenolics in the entire food background. Using mixtures of fruit juices with other fruits and herb extracts can produce exclusive functional aspects and may perhaps be an efficient strategy in mounting dietbased administration of H. pylori infections along with other oxidationlinked diseases (Vattem et al. 2010).

Star fruit (Averrhoacarambola L.) is a fine resource of natural free radical scavengers, and their polyphenolics components are the key antioxidants. According to current findings, the remainder of star fruit, that is usually redundant during the processing of juice, has antioxidant activity that is much higher than what was extracted via numerous assays that measure the antioxidant capability. The remains only accounted for 15% of the total weight, but in an optimized environment for extraction these contributed to 70% of the entire antioxidant activity and polyphenolic compounds. Freezedried powdery products, which attributed to around 5% of entire weight, had complete polyphenolic substance of 33.2 ± 3.6 mg gallic acid corresponding (GAE)/g sample and overall free radical scavenging activity of 3490 ± 310 along with


3412 ± 290 mg Lascorbic acid equivalent antioxidant capacity (AEAC) or 5270 ± 468 and 5152 ± 706 mg trolox equivalent antioxidant capacity (TEAC) per 100 g sample produced by 2,20azinobis(3ethylbenzthiazoline6sulfonic acid) free radical (ABTS+) and 1,1diphenyl2picrylhydrazyl (DPPH) scavenging assays, respectively. Moreover observations suggested that it can reduce 510.3 ± 68.1 mol ferric by ferric reducing ability of plasma (FRAP) per gram of the sample. The residue pull out also shows very high antioxidant action in postponing oxidative rancidity of soya bean oil at 110°C. The free radical scavenging activities and polyphenolic outline of residue extracts were compared with extracts of regular standardized pyconogenol. The dissimilarities between star fruit and pyconogenol and its isomers were observed by performing highperformance liquid chromatography together with mass spectrometry. Results have suggested that the powder obtained from the residue may convey health remuneration due to elevated composition of phenol components and a profound antioxidant activity when utilized as a part of functional foods (Shui and Leong 2006).

1.2.5 Nutraceuticals: AntiagingAging is related to mitochondrial dysfunctions that are known to prompt membrane leakage, discharge of reactive oxygen species (ROS) and nitrogen, and successive induction of peroxidative reactions that result in biomolecules’ destruction and releasing of metals with magnification of free radicals release. Free radicals stimulate neuronal cell death enhancing tissue loss, which could be linked with memory damage. These pathological procedures are engaged in cardiovascular, neurodegenerative, and carcinogenic actions. Nutritional components taken from various functional foods that are bioactive (carnitine, ubiquinone, ginseng, antioxidant vitamins, ginkgo, phytoestrogens, tomato, curcumin, soy, melatonin, carnosine, polyphenols, etc.) can upgrade or even avert diseases. Fortification from persistent diseases of aging includes antioxidant actions, mitochondrial stabilizing functions, metal chelating processes, prevention of apoptosis of important cells, and initiation of cancer cell apoptosis. Functional foods and nutraceuticals offer a great promise to improve health and avert agingrelated diseases (Ferrari 2004).

1.2.6 Nutraceuticals: AnticancerAmong U.S. adults one of the most dreaded diseases is pancreatic cancer. Investigational research has established that pancreatic carcinoma can be shielded by the antioxidants that lower DNA damage due to oxidative changes. Numerous epidemiologic research has shown the inverse relation of antioxidant intake and pancreatic cancer, which also suggests that they possess free radical scavenging properties that can inhibit pancreatic cancer. Cancer reducing agents other than plants and food have been established to reduce the development and evolution of pancreatic cancer by regulating


the cellular signaling pathways. The miRNAs and their expression that suppresses tumors are predominantly enhanced by nutraceuticals that also lower the appearance of oncogenic microRNAs, which primarily lead to the inhibition of growth and development of cancer cells. The selfrevival or renewal of pancreatic cancer stem cell is also inhibited through alteration of cellular signaling arrangement. In addition, nutraceuticals can also control miRNAs and DNAs by epigenetically deregulating them, which in turn causes the normalization of the signaling pathways that were initially altered. Therefore, nutraceuticals might have a great deal of broader use in the avoidance and/or management of pancreatic cancer in amalgamation with conventional chemotherapeutics. Figure 1.6 illustrates the challenges and promises faced by the nutraceutical industry in cancer research. Nevertheless, more research including in vitro mechanistic observations, clinical trials, and in vivo experiments with animals are used to comprehend the importance of nutraceuticals in the hindrance and/or management of pancreatic cancer (Li et al. 2015). (See Figure 1.7.)

Epigallocatechin gallate (EGCG) along with genistein is considered to be the most important foodderived phytochemical due to its chemotherapeutic as well as chemopreventive functions. The vascular endothelial growth factor (VEFG) has a lowered expression via transcription, which in turn inhibits the instigation and progression of tumors due to the antiangiogenic activity of EGCG. The tumor progression is inhibited by downregulating several signaling pathways by PI3KAkt kinaseNFκB, and prohibiting

Cancer research and nutraceuticals

Promises Challenges

Targets NF-KB, EGFR, Akt

Deregulates epigeneticprogramming

Well tolerated

Pleiotropic activity

Insufficient preclinical datato advance combinatorialtherapy

Less prioritized

High systemicconcentrations difficult toachieve

Figure 1.7 Cancer and nutraceuticals.


the phosphorylation of EGFR and the receptor of Her2 in breast cancer cells where Her 2/neu is continuously expressed, which suggests apoptotic behavior in breast cancer cells that is independent of estrogen receptor. It also causes antimetastatic activity, and inhibits proteasome formation, insulinlike growth factor, and glucoseregulated protein (GRP78) action. The invasive property of tumors is critically dependent on Wnt signaling, which is inhibited by a transcriptional repressor HMG box transcription factor 1. The expression of this repressor is enhanced by EGCG, which in turn prevents incursion of tumors.

The anticancer criteria that influence most of the experiments regarding EGCG are premedical. For further understanding of precise EGCG effects, clinical trials should be vigilantly planned to take in certain criteria that control the effectiveness of EGCG. EGCG has diverse activities in ERdependent and ERindependent receptors. Consequently, in order to understand the variety of food desired to copy doses that are in vitro, the clinical trials and pharmacokinetics of doses in normal healthy breast cancer patients needs to be thoroughly understood (Saldanha and Tollefsbol 2012).

1.2.7 Nutraceuticals from algae: FunctionsFor many years diet and several beauty products have used numerous algal build up. This especially includes Haematococcus, Chlorella, Spirulina, and Dunaliella. Nonetheless, the path to acceptance and utilization of arrangements from novel species is long, and there are several barriers to surmount. Certain things are needed to achieve approval from the point of view of a large marketer and manufacturer of a large variety of products. The considerations and views of associations were taken into account: merchandise formulators with efficiency as their point of focus; mechanistic properties and assistance that is needed by regulatory staffs to ensure the product is good enough; quality guarantee of ingredients to ensure uniformity and dependability; promotion requirements as well as competition in terms of price; and trustworthy service to the customer by maintaining sufficient delivery (Gellenbeck 2012).

Functional sulfated polysaccharides present in red microalgae contain zeaxanthin, dietary fibers, minerals, PUFAs, vitamins, and proteins. Experiments in rat models sustain the therapeutic activities of algae and the isolated polysaccharides. Algal products integrated into rat diets were initiated to significantly improve serum cholesterol, serum triglycerides, hepatic cholesterol, ratios of HDL/LADL, and enhanced fecal flow of neutral sterols as well as bile acids. Morphological and metabolic alterations were induced by utilization of algal food. These results recommend that red microalgae can be utilized as effective hypocholesterolemic agents, and they also support the budding utilization of red microalgae as innovative nutraceuticals. Figure 1.8 illustrates the health benefits of algae (Dvir et al. 2009).


1.2.8 Nutraceuticals: Therapeutic applicationsSickle cell anemia is a genetically acquired disease where the “SS” (diseased) individual consists of an atypical beta globin gene. A single base replacement in the βglobin subunit results in substitution of β6 glutamic acid by valine that leads to the overwhelming medical manifestations of the syndrome. This changeover causes radical decline in the solubility of sickle cell hemoglobin (HbS) while deoxygenated. Under such conditions, the HbS molecules polymerize to form an elongated intracellular mass of fibers that is accountable for the deformation of the biconcave disc red blood cells into a sickleshaped structure. Initialline clinical supervision of the disease is comprised of the use of hydroxyurea, amino acids supplements, penicillin, and antimalarial prophylaxis to administer the state and blood transfusions for the stabilization of the patient’s hemoglobin level. These are relatively costly and have associated risk factors. But, there is still a flicker of hope that concerns research of antisickling mechanisms of curative plants. This alternative phytotherapy has proven to not only reduce crisis but also reverse sickling (Imaga 2013).

Metabolic disorder represents a network of hazard factors associated with an increased risk of cardiovascular problems as well as type 2 diabetes. Incidence of diabetes and metabolic disorders along with the associated complications has various features that include reversed oxidative state and continuous platelet activation. Regardless of the accessibility of several interventions to neutralize the metabolic changes, which include proper diet, customary exercise, and weight management, epidemiological data are showing rapid increase in the problem, which in turn reflects the multifactorial properties of the disease along with the inadequate fulfillment of

Healthbenefits

of algae

Anticoagulating

Antimicrobial Anticancer

Reducescholesterol

Figure 1.8 Benefits of algae.


patients to already recognized strategies. Several diseases like diabetes mellitus and metabolic disorders can be targeted using nutraceuticals and to modify biochemical endpoints. These involve compounds like vitamins C, D, and E; omega3 fatty acids; nutritional fibers; and phytoestrogens. Quite a few areas of concern subsists regarding the use of nutritional supplements as well as nutraceuticals together with merchandise standardization, description of optimal dosage, and the probable side effects (Davì, Santilli, and Patrono 2010).

From curbing cancer or subjugating the aging process, elementary science thrives with ingredients that promise to curtail many diseases. But, human trials are mostly impossible. Here, resveratrol has been used as an example to reveal the massive difficulties in perceiving the endowing mechanistic behavior, pharmacokinetics, and concluding side effects of a natural component. Very little is known about resveratrol and its effects despite wideranging interest and endeavors and the hopeful results from research. The inability to appeal for natural products to highfunded, hefty companies that are associated with clinical trials pose a certain amount of difficulty because developing their own molecules provides better claim over intellectual property. Small companies face a different scientific dilemma: by trading goods that are unpatentable and producing their own mixes makes comparison of their findings with the others and academic labs difficult. Resveratrol and most other natural components tend to possess several appropriate targets having diverse dose reaction profiles, tissue distribution, and modifiers. New approaches as well as prototypes are necessary to handle these challenges and address the various molecules that claim to be beneficial. Better formation of the available data, voluntary use of supplement tracking, and screening for potential side effects in a large scale along with legislation in order to increase the release of trial results are included as examples. The beneficial effects of resveratrol and its evidence are too sparse to be convincing; yet, the mounting list of studies on animals and other limited information provide strong justification for further study (Smoliga, Vang, and Baur 2012).

This meticulous exploration aims at the preformulation and advancement in the field of intraarticular drug delivery systems by increasing the release of curcumin from curcuminconjugated magnetic nanoparticles for curing rheumatoid arthritis. The studies involved in preformulation procedures like solubility; mismatched studies of drugs; magnetite (Fe3O4); and polymers with diverse stress surroundings, limit of detection (LOD), size of the nanoparticle, hygroscopicity, and thermal nature have been done.

Mohamed, Bharathidasan, and Raffick (2012) provided confirmation that for the successful preparation of magnetic nanosuspension, curcumin is appropriate. Magnetite (Fe3O4) as well as methyl cellulose was utilized for the formulation magnetic nanosuspension by means of the solvent displacement procedure. To acquire data about mass, drug loading, morphology, particle


size, sedimentation rate, pH, and drug release, physical as well as chemical categorization was done by means of dissolution studies that were in vitro with hydrochloric acid (0.01N), 0.8% SLS at 370°C ± 0.50°C. Six formulations (F1–F6) were prepared, out of which curcumin release was maximum in the F6 formulation compared to the others. Figure 1.9 illustrates the nanoformulation that includes the core that is passivated with polymer to surface functionalize it.

1.2.9 MetallonutraceuticalsMetallonutraceuticals include calcium, iodine, iron, boron, chromium, copper, cobalt, magnesium, manganese, potassium, phosphorous, zinc, sodium chloride, and selenium (see Table 1.2).

Polymer

Functional coating

Nanoparticles

Figure 1.9 Formulation of nanosuspension.

Table 1.2 Daily Sources of Metallonutraceuticals

Metal Source Daily Requirement

Calcium Milk, cheese, dairy products, cabbage, soybeans, bread, nuts, fish (sardines, pilchard)

Men: 700 mg; women: 700 mg

Iodine Ocean fish, shellfish, grains, cereals Men: 0.14 mg; women: 0.14 mg

Iron Liver, meat, beans, nuts, dried fruits, apricots, brown rice Men: 8.7 mg; women: 14.8 mg

Boron Green vegetables, fruits, nuts Men: <6 mg; women: <6 mg

Chromium Meat, whole grains, oats, lentils, spices Men: 0.025 mg; women: 0.025 mg

Cobalt Fish, nuts, spinach, green leafy vegetables, broccoli, oats Men: 0.0015 mg; women: 0.0015 mg

Copper Nuts, shellfish Men: 1.2 mg; women: 1.2 mg

Magnesium Fish, nuts, spinach, bread, meat, dairy foods Men: 300 mg; women: 270 mg

Potassium Banana, vegetables, lentils, nuts, seeds, milk, bread, fish, beef, chicken

Men: 3500 mg; women: 3500 mg

Selenium Bread, fish, meat, eggs Men: 0.075 mg; women: 0.06 mg

Sodium chloride Bacon, breakfast cereals, cheese, bread, savory snacks, tinned vegetables

Men: <6 gm; women: <6 gm

Zinc Meat, shellfish, milk, bread, cereal products, wheat germ Men: 9 mg; women: 7 mg

Source: Pathak YV, Lokhande JN, 2014, Handbook of Metallonutraceuticals, Boca Raton, FL: CRC Press.


1.3 Future research

The future research in the field of nutraceuticals needs to include more human trials that can validate the health benefits derived during animal trials and in vitro experiments.

The composition and dosage of various nutraceutical products are still to be established and standardized. Future works should focus on the establishment of proper composition of nutraceutical product taking into consideration a particular health benefit.

The connection between health claims of the product, the sources of these health claims and the functional delivery of compounds are still the underresearched area in nutraceutical science (Hailu et al. 2015). There are several market surveys being done on the relationship between the health claims displayed by the nutraceutical manufacturer and the consumer demand. To provide these marketing surveys with a scientific approach, there is a need for research in molecular identification of nutraceutical compounds and their physiological effect on the human body. This requires expertise in analytical biology, chemistry, animal physiology, human behavior, market research, and many more scientific tools including statistical analysis.

The correlation of nutrition with infection has only been recently affirmed by scientists. Many scientists were initially skeptical, considered nutrition studies as naïve, and didn’t believe the information from a huge number of food enthusiasts who have long boasted about the correlation between vitamins and nutrients in preventing many diseases. Food marketers now recognize nutraceuticals as a means of advertising for improving diets. However, some people view functional foods as just a marketing trick. Civic authorities should take a stand, so as to reveal the fact that their obligation lies with the health of people and not with the profit of the pharmaceutical, food, and other chemical companies.

1.4 Conclusion

Nutraceuticals are present in almost all food ingredients in different concentrations. The factors that affect human health are concentration and duration of supply. Diets rich in nutraceuticals along with regular exercise can reduce the risk of many diseases, manage stress, and maintain body weight.

Nutraceuticals may be beneficial to our health, but we are still in the learning process about the possible damaging effects. Nutraceuticals are a set of new products that lie between foods and drugs, and, because of this, governmental bodies also face many challenges. Experts, including nutritionists and health professionals, should work collectively to plan appropriate guidelines to offer health and curative benefits to mankind.


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6 6: Developments and Applications ofSilver Nanoparticles in theNutraceuticals Industry

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Ashkarran, Ali Akbar. 2010. “A Novel Method for Synthesisof Colloidal Silver Nanoparticles by Arc Discharge inLiquid.” Current Applied Physics 10(6): 1442–1447.doi:10.1016 /j.cap.2010.05.010.

Aslan, Kadir, Zoya Leonenko, Joseph R. Lakowicz, and ChrisD. Geddes. 2005. “Fast and Slow Deposition of SilverNanorods on Planar Surfaces: Application to Metal-EnhancedFluorescence.” The Journal of Physical Chemistry B 109(8):3157–3162. doi:10.1021 / jp045186t.

Chaudhry, Qasim, Michael Scotter, James Blackburn, BryonyRoss, Alistair Boxall, Laurence Castle, Robert Aitken, andRichard Watkins. 2008. “Applications and Implications ofNanotechnologies for the Food Sector.” Food Additives &Contaminants: Part A 25(3): 241–258.doi:10.1080/02652030701744538.

Chauhan, Baby, Gopal Kumar, Nazia Kalam, and Shahid H.Ansari. 2013. “Current Concepts and Prospects of HerbalNutraceutical: A Review.” Journal of AdvancedPharmaceutical Technology & Research 4(1): 4–8.doi:10.4103/2231-4040.107494.

Chopra, Ian. 2007. “The Increasing Use of Silver-BasedProducts as Antimicrobial Agents: A Useful Development ora Cause for Concern?” Journal of Antimicrobial Chemotherapy59(4): 587–90. doi:10.1093/jac/dkm006.

Dash, Siddhartha Shrivastava, Tanmay Bera, Arnab Roy,Gajendra Singh, P. Ramachandrarao, and Debabrata Dash.2007. “Characterization of Enhanced Antibacterial Effectsof Novel Silver Nanoparticles.” Nanotechnology 18(22):225103. http://stacks.iop.org /0957-4484/18/i=22/a=225103.

Devi, Lamabam Sophiya, and S. R. Joshi. 2014.“Ultrastructures of Silver Nanoparticles BiosynthesizedUsing Endophytic Fungi.” Journal of Microscopy andUltrastructure 3(1): 29–37.doi:10.1016/j.jmau.2014.10.004.

Duncan, Timothy V. 2011. “Applications of Nanotechnology inFood Packaging and Food Safety: Barrier Materials,Antimicrobials and Sensors.” Journal of Colloid andInterface Science 363(1): 1–24.doi:10.1016/j.jcis.2011.07.017.

Duraipandy, N., Rachita Lakra, Srivatsan KunnavakkamVinjimur, Debasis Samanta, Purna Sai K., and ManikantanSyamala Kiran. 2014. “Caging of Plumbagin on SilverNanoparticles Imparts Selectivity and Sensitivity toPlumbagin for Targeted Cancer Cell Apoptosis.” Metallomics6(11): 2025–33. doi:10.1039/C4MT00165F.

Farias, Charles B. B., Aline Ferreira Silva, Raquel DinizRufino, Juliana Moura Luna, José Edson Gomes Souza, andLeonie Asfora Sarubbo. 2014. “Synthesis of SilverNanoparticles Using a Biosurfactant Produced in Low-CostMedium as Stabilizing Agent.” Electronic Journal ofBiotechnology 17(3): 122–125.doi:10.1016/j.ejbt.2014.04.003.

Fung, M. C., and D. L. Bowen. 1996. “Silver Products forMedical Indications: Risk-Benefit Assessment.” Journal ofToxicology Clinical Toxicology 34: 119–126. doi:10.3109/15563659609020246.

Gulbranson, Scott H., Joseph A. Hud, and Ronald C. Hansen.2000. “Argyria Following the Use of Dietary SupplementsContaining Colloidal Silver Protein.” Cutis 66(5): 373–374.

Gupta, Subash C., JiHye Kim, Sahdeo Prasad, and Bharat B.Aggarwal. 2010. “Regulation of Survival, Proliferation,Invasion, Angiogenesis, and Metastasis of Tumor Cellsthrough Modulation of Inflammatory Pathways byNutraceuticals.” Cancer and Metastasis Reviews 29(3):405–434. doi:10.1007/s10555-010-9235-2.

Hatchett, David W., and Henry S. White. 1996.

“Electrochemistry of Sulfur Adlayers on the Low-IndexFaces of Silver.” The Journal of Physical Chemistry100(23): 9854–9859. doi:10.1021/jp953757z.

Hathcock, J. 2001. “Dietary Supplements: How They Are Usedand Regulated.” Journal of Nutrition 131: 1114–17.

Huang, Ling, Maolin L. Zhai, Dewu W. Long, Jing Peng, LingXu, Guozhong Z. Wu, Jiuqiang Q. Li, and Genshuan S. Wei.2008. “UV-Induced Synthesis, Characterization and FormationMechanism of Silver Nanoparticles in AlkalicCarboxymethylated Chitosan Solution.” Journal ofNanoparticle Research 10(7): 1193–1202.doi:10.1007/s11051-007-9353-0.

Jeevanandam, P., Chamarthi K. Srikanth, and Suchi Dixit.2010. “Synthesis of Monodisperse Silver Nanoparticles andTheir Self-Assembly through Simple Thermal DecompositionApproach.” Materials Chemistry and Physics 122(2–3):402–407. doi:10.1016 /j.matchemphys.2010.03.015.

Khalil, Mostafa M. H., Eman H. Ismail, Khaled Z.El-Baghdady, and Doaa Mohamed. 2014. “Green Synthesis ofSilver Nanoparticles Using Olive Leaf Extract and ItsAntibacterial Activity.” Arabian Journal of Chemistry7(6): 1131–1139. doi:10.1016/j.arabjc.2013.04.007.

Kim, Jun Sung, Eunye Kuk, Kyeong Nam Yu, Jong-Ho Kim, SungJin Park, Hu Jang Lee, So Hyun Kim et al. 2007.“Antimicrobial Effects of Silver Nanoparticles.”Nanomedicine: Nanotechnology, Biology, and Medicine 3:95–101. doi:10.1016/j.nano.2006.12.001.

Laban, Geoff, Loring F. Nies, Ronald F. Turco, John W.Bickham, and Maria S. Sepúlveda. 2010. “The Effects ofSilver Nanoparticles on Fathead Minnow (PimephalesPromelas) Embryos.” Ecotoxicology 19(1): 185–195.doi:10.1007/s10646-009-0404-4.

Lankveld, D. P. K., A. G. Oomen, P. Krystek, A. Neigh, A.Troost-de Jong, C. W. Noorlander, J. C. H. Van Eijkeren,R. E. Geertsma, and W. H. De Jong. 2010. “The Kinetics ofthe Tissue Distribution of Silver Nanoparticles ofDifferent Sizes.” Biomaterials 31(32): 8350–8361.doi:10.1016/j.biomaterials.2010.07.045.

Lansdown, A. B. G. 2007. “Critical Observations on theNeurotoxicity of Silver.” Critical Reviews in Toxicology37(3): 237–250. doi:10.1080/10408440601177665.

Lee, K. J., Prakash D. Nallathamby, Lauren M. Browning,Christopher J. Osgood, and XiaoHong Nancy Xu. 2007. “InVivo Imaging of Transport and Biocompatibility of SingleSilver Nanoparticles in Early Development of ZebrafishEmbryos.” ACS Nano 1(2): 133–143. doi:10.1021/nn700048y.

Lee, Yong-Ju, Jiwon Kim, Jeehyun Oh, Sujin Bae, SungkyuLee, In Seok Hong, and Sang-Ho Kim. 2012. “Ion-ReleaseKinetics and Ecotoxicity Effects of Silver Nanoparticles.”Environmental Toxicology and Chemistry 31(1): 155–159.doi:10.1002/etc.717.

Li, Chia Chen, Shinn Jen Chang, Fan Jun Su, Shu Wei Lin,and Yi Chun Chou. 2013. “Effects of Capping Agents on theDispersion of Silver Nanoparticles.” Colloids and SurfacesA: Physicochemical and Engineering Aspects 419: 209–215.doi:10.1016 /j.colsurfa.2012.11.077.

Li, Kai, Xiaotong Jia, Aiwei Tang, Xibin Zhu, Huan Meng,and Yingfeng Wang. 2012. “Preparation of Spherical andTriangular Silver Nanoparticles by a Convenient Method.”Integrated Ferroelectrics 136(1): 9–14.doi:10.1080/10584587.2012.686405.

Li, Y., P. Leung, L. Yao et al. 2007. “Green Synthesis ofSilver Nanoparticles Using Capsicum Annuum Leaf Extract.”Green Chemistry 9: 852–858.

Lu, Liang, and Xueqin An. 2015. “Silver NanoparticlesSynthesis Using H2 as Reducing Agent inToluene–supercritical CO2 Microemulsion.” Journal ofSupercritical Fluids 99: 29–37.doi:10.1016/j.supflu.2014.12.024.

Miao, A. J., Z. Luo, C. S. Chen, W. C. Chin, P. H.Santschi, and A. Quigg. 2010. “Intracellular Uptake: APossible Mechanism for Silver Engineered NanoparticleToxicity to a Freshwater Alga Ochromonas Danica.” PLoS ONE5(12): e15196.

Mittal, Amit Kumar, Sanjay Kumar, and Uttam Chand Banerjee.2014. “Quercetin and Gallic Acid Mediated Synthesis ofBimetallic (Silver and Selenium) Nanoparticles and TheirAntitumor and Antimicrobial Potential.” Journal of Colloidand Interface Science 431: 194–199.doi:10.1016/j.jcis.2014.06.030.

Mukherjee, Priyabrata, Absar Ahmad, Deendayal Mandal,Satyajyoti Senapati, Sudhakar R. Sainkar, Mohammad I Khan,Renu Parishcha et al. 2001. “Fungus-Mediated Synthesis of

Silver Nanoparticles and Their Immobilization in theMycelial Matrix: A Novel Biological Approach toNanoparticle Synthesis.” Nano Letters 1(10). AmericanChemical Society: 515–19. doi:10.1021/nl0155274.

Park, Jason Y., Sam F. Y. Li, and Larry J. Kricka. 2006.“Letter to the Editor.” Clinical Chemistry 52(2).

Paul, Sanjeeta, and Archana Chugh. 2011. “Assessing theRole of Ayurvedic ‘Bhasms’ as Ethno-Nanomedicine in theMetal Based Nanomedicine Patent Regime.” Journal ofIntellectual Property Rights 16: 509–515.

Poinern, G. E. J., P. Chapman, M. Shah, and D. Fawcett.2013. “Green Biosynthesis of Silver Nanocubes Using theLeaf Extracts from Eucalyptus Macrocarpa.” Nano Bulletin2(1): 130101.

Prabhu, Sukumaran, and Eldho K. Poulose. 2012. “SilverNanoparticles: Mechanism of Antimicrobial Action,Synthesis, Medical Applications, and Toxicity Effects.”International Nano Letters 2(1): 1–10.doi:10.1186/2228-5326-2-32.

Project on Emerging Nanotechnologies. 2013.http://www.nanotechproject.org/cpi.

Raab, Christina, Myrtill Simkó, André Gazsó, UlrichFiedeler, and Michael Nentwich. 2011. “What Are SyntheticNanoparticles?” Nano Trust Dossiers. http://epub.oeaw.ac.at/0xc1aa500e0x00254418.pdf.

Ravindra, Sakey, Antoine F. Mulaba-Bafubiandi, V.Rajinikanth, K. Varaprasad, N. Narayana Reddy, and K.Mohana Raju. 2012. “Development and Characterization ofCurcumin Loaded Silver Nanoparticle Hydrogels forAntibacterial and Drug Delivery Applications.” Journal ofInorganic and Organometallic Polymers and Materials 22(6):1254–1262. doi:10.1007/s10904-012-9734-4.

Remita, S., P. Fontaine, E. Lacaze, Y. Borensztein, H.Sellame, R. Farha, C. Rochas, M. Goldmann. 2007. “X-RayRadiolysis Induced Formation of Silver Nano-Particles: ASAXS and UV– visible Absorption Spectroscopy Study.”Nuclear Instruments and Methods in Physics ResearchSection B 263(2): 436–440.

Rhim, Jong-Whan, Long-Feng Wang, Yonghoon Lee, and Seok-InHong. 2014. “Preparation and Characterization ofBio-Nanocomposite Films of Agar and Silver Nanoparticles:

Laser Ablation Method.” Carbohydrate Polymers 103: 456–465.doi:10.1016/j.carbpol .2013.12.075.

Rishi, R. K. 2006. “Nutraceuticals: Borderline between Foodand Drug?” Pharma Review, 51–53.

Royal Commission on Environmental Pollution (RCEP). 2008.“Novel Materials in the Environment: The Case ofNanotechnology.” http://www.rcep.org.uk/.

Salari, Zeinab, Firoozeh Danafar, Shima Dabaghi, and SayedAhmad Ataei. 2014. “Sustainable Synthesis of SilverNanoparticles Using Macroalgae Spirogyra Varians andAnalysis of Their Antibacterial Activity.” Journal ofSaudi Chemical Society. doi:10.1016 /j.jscs.2014.10.004.

Schultz, W. B., and L. Barclay. 2009. “A Hard Pill ToSwallow: Barriers to Effective FDA Regulation ofNanotechnology-Based Dietary Supplements.”http://www.nanotechproject.org/process/assets/files/7056/pen17_final.pdf.

Senjen, Rye. 2009. “Nano and Biocidal Silver: Extreme GermKillers Present a Growing Threat to Public Health.”Friends of the Earth.

Shivaji, S., S. Madhu, and Shashi Singh. 2011.“Extracellular Synthesis of Antibacterial SilverNanoparticles Using Psychrophilic Bacteria.” ProcessBiochemistry 46(9): 1800–1807.doi:10.1016/j.procbio.2011.06.008.

Sivakumar, P., P. Karthika, P. Sivakumar, N. G.Muralidharan, S. Renganathan, and P. Devendran. 2013.“Bio-Synthesis of Silver Nano Cubes from Active CompoundQuercetin-3-O-Β-DD-Galactopyranoside Containing PlantExtract and Its Antifungal Application.” Asian Journal ofPharmaceutial and Clinical Research 6: 76–79.

Sondi, Ivan, and Branka Salopek-Sondi. 2004. “SilverNanoparticles as Antimicrobial Agent: A Case Study on E.Coli as a Model for Gram-Negative Bacteria.” Journal ofColloid and Interface Science 275(1): 177–182.doi:10.1016/j.jcis.2004.02.012.

Soutter, Will. 2012.

Srivatsan, Kunnavakkam Vinjimur, N. Duraipandy, ShajithaBegum, Rachita Lakra, Usha Ramamurthy, Purna SaiKorrapati, and Manikantan Syamala Kiran. 2015. “Effect of

Curcumin Caged Silver Nanoparticle on CollagenStabilization for Biomedical Applications.” InternationalJournal of Biological Macromolecules 75: 306–315.doi:10.1016/j.ijbiomac.2015.01.050.

Syed, Asad, Supriya Saraswati, Gopal C. Kundu, and AbsarAhmad. 2013. “Biological Synthesis of Silver NanoparticlesUsing the Fungus Humicola Sp. and Evaluation of TheirCytoxicity Using Normal and Cancer Cell Lines.”Spectrochimica Acta. Part A, Molecular and BiomolecularSpectroscopy 114: 144–147. doi:10.1016/j.saa.2013.05.030.

Varaprasad, K., Y. Murali Mohan, K. Vimala, and K. MohanaRaju. 2011. “Synthesis and Characterization ofHydrogel-Silver Nanoparticle-Curcumin Composites for WoundDressing and Antibacterial Application.” Journal of AppliedPolymer Science 121(2): 784–796. doi:10.1002/app.33508.

Wiley, Benjamin J., Yeechi Chen, Joseph M. McLellan, YujieXiong, Zhi-Yuan Li, David Ginger, and Younan Xia. 2007.“Synthesis and Optical Properties of Silver Nanobars andNanorice.” Nano Letters 7(4): 1032–1036.doi:10.1021/nl070214f.

Wong, Kenneth K. Y., Stephanie O. F. Cheung, Liuming Huang,Jun Niu, Chang Tao, Chi Ming Ho, Chi Ming Che, and Paul K.H. Tam. 2009. “Further Evidence of the Anti-InflammatoryEffects of Silver Nanoparticles.” ChemMedChem 4: 1129–1135.doi:10.1002/cmdc.200900049.

Xiu, Zong-Ming, Qing-Bo Zhang, Hema L. Puppala, Vicki L.Colvin, and Pedro J. J. Alvarez. 2012. “NegligibleParticle-Specific Antibacterial Activity of SilverNanoparticles.” Nano Letters 12(8): 4271–4275.doi:10.1021/nl301934w.

Yacaman, Jose Ruben Morones, Jose Luis Elechiguerra,Alejandra Camacho, Katherine Holt, Juan B. Kouri, JoseTapia Ramírez, and Miguel Jose. 2005. “The BactericidalEffect of Silver Nanoparticles.” Nanotechnology 16(10):2346. http://stacks.iop .org /0957-4484/16/i=10/a=059.

Yan, Yang, Ke-Bin Chen, Hao-Ran Li, Wei Hong, Xiao-bin Hu,and Zhou Xu. 2014. “Capping Effect of Reducing Agents andSurfactants in Synthesizing Silver Nanoplates.”Transactions of Nonferrous Metals Society of China 24(11):3732–3738. doi:10.1016 / S1003-6326(14)63522-6.

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7 7: Nanoemulsions in Food Science andNutrition

Abbas, Shabbar, Mohanad Bashari, Waseem Akhtar, Wei Wei Li,and Xiaoming Zhang. 2014. “Process Optimization ofUltrasound-Assisted Curcumin Nanoemulsions Stabilized byOSA-Modified Starch.” Ultrasonics Sonochemistry 21(4):1265–1274.

Abbas, Shabbar, Eric Karangwa, Mohanad Bashari, KhizarHayat, Xiao Hong, Hafiz Rizwan Sharif, and Xiaoming Zhang.2015. “Fabrication of Polymeric Nanocapsules fromCurcumin-Loaded Nanoemulsion Templates by Self-Assembly.”Ultrasonics Sonochemistry 23: 81–92.

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Sultana, K., G. Godward, N. Reynolds, R. Arumugaswamy, andP. Peiris. 2000. Encapsulation of probiotic bacteria withalginate–starch and evaluation of survival in simulatedgastrointestinal conditions and in yogurt. InternationalJournal of Food Microbiology 62(1–2): 47–55.

Sun, W., and M. W. Griffiths. 2000. Survival ofbifidobacteria in yogurt and simulated gastric juicefollowing immobilization in gellan–xanthan beads.International Journal of Food Microbiology 61(1): 17–25.

Szajewska, H., and J. Z. Mrukowicz. 2005. Use of probioticsin children with acute diarrhea. Pediatric drugs 7(2):111–122.

Ten Bruggencate, S. J., I. M. Bovee-Oudenhoven, M. L.Lettink-Wissink, and R. Van der Meer. 2005. Dietaryfructooligosaccharides increase intestinal permeability inrats. Journal of Nutrition 135: 837–842.

Truelstrup-Hansen, L., P. M. Allan-Wojotas, Y. L. Jin, andA. T. Paulson. 2002. Survival of Ca-alginatemicroencapsulated Bifidobacterium spp. in milk andsimulated gastrointestinal conditions. Food Microbiology19(1): 35–45.

Vázquez, M. J., J. L. Alonso, H. Domínguez, and J. C.

Parajo. 2000. Xylooligosaccharides: Manufacture andapplications. Trends in Food Science and Technology 11:387–393.

Vicariotto, F., M. Del Piano, L. Mogna, and G. Mogna. 2012.Effectiveness of the association of 2 probiotic strainsformulated in a slow release vaginal product, in womenaffected by vulvovaginal candidiasis: A pilot study.Journal of Clinical Gastroenterology 46: S73–S80.

Villamiel, M., N. Corzo, M. I. Foda, F. Montes, and A.Olano. 2002. Lactulose formation catalysed byalkaline-substituted sepiolites in milk permeate. FoodChemistry 76: 7–11.

Vitali, B., F. Cruciani, M. E. Baldassarre et al. 2012.Dietary supplementation with probiotics during latepregnancy: Outcome on vaginal microbiota and cytokinesecretion. BMC Microbiology 12: 236.

Wake Forest University Baptist Medical Center. 2008.Hydrogen peroxide has a complex role in cell health.ScienceDaily. http://www.sciencedaily.com/releases/2008/01/080102134129.htm.

Wang, X., M. Huang, F. Yang, H. Sun, X. Zhou, Y. Guo, X.Wang, and M. Zhang. 2015. Rapeseed polysaccharides asprebiotics on growth and acidifying activity of probioticsin vitro. Carbohydrate Polymers 125: 232–240

Weichselbaum, E. 2009. Probiotics and health: A review ofthe evidence. Nutrition Bulletin 34(4): 340–373.

Yu, Z.-T., C. Chen, D. E. Kling et al. 2012. The principalfucosylated oligosaccharides of human milkoligosaccharides of human milk exhibit prebiotic propertieson cultured infant microbiota. Glycobiology 23: 169–177.

10 10: Modeling and Simulation ofNanobiosystems with Special Reference toFunctional Foods and Nutraceuticals

Andersen, Oyvind M., and Kenneth R. Markham, eds.Flavonoids: Chemistry, Biochemistry and Applications CRCPress, 2005. Accessed August 27, 2015. https://www .crcpress

Aqvist, J., P. Sandblom, T. A. Jones, M. E. Newcomer, W. F.van Gunsteren, and O. Tapia. “Molecular DynamicsSimulations of the Holo and Apo Forms of Retinol BindingProtein. Structural and Dynamical Changes Induced byRetinol Removal.” Journal of Molecular Biology 192, no. 3(December 5, 1986): 593–603.

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Brown, Kenneth L., Xiang Zou, and Helder M. Marques.“NMR-Restrained Molecular Modeling of Cobalt Corrinoids:Cyanocobalamin (Vitamin B12) and Methylcobalt Corrinoids.”Journal of Molecular Structure: THEOCHEM 453, no. 1–3(October 30, 1998): 209–224.doi:10.1016/S0166-1280(98)00206-1.

Cerezo, Javier, José Zúñiga, Adolfo Bastida, AlbertoRequena, and José Pedro Cerón-Carrasco. “ConformationalChanges of β-Carotene and Zeaxanthin Immersed in a ModelMembrane through Atomistic Molecular Dynamics Simulations.”Physical Chemistry Chemical Physics 15, no. 17 (2013):6527. doi:10.1039/c3cp43947j.

Coward, Lori, Neil C. Barnes, Kenneth D. R. Setchell, andStephen Barnes. “Genistein, Daidzein, and TheirBeta-Glycoside Conjugates: Antitumor Isoflavones in SoybeanFoods from American and Asian Diets.” Journal ofAgricultural and Food Chemistry 41, no. 11 (November 1,1993): 1961–1967. doi:10.1021/jf00035a027.

Cui, Fengchao, Kecheng Yang, and Yunqi Li. “Investigate theBinding of Catechins to Trypsin Using Docking andMolecular Dynamics Simulation.” PLOS ONE 10, no. 5 (May 4,2015): e0125848. doi:10.1371/journal.pone.0125848.

Della-Longa, Stefano, and Alessandro Arcovito.“Intermediate States in the Binding Process of Folic Acid

to Folate Receptor α: Insights by Molecular Dynamics andMetadynamics.” Journal of Computer-Aided Molecular Design29, no. 1 ( January 2015): 23–35. doi:10.1007/s10822-014-9801-8.

Furse, Kristina E., Derek A. Pratt, Claus Schneider, AlanR. Brash, Ned A. Porter, and Terry P. Lybrand. “MolecularDynamics Simulations of Arachidonic Acid-DerivedPentadienyl Radical Intermediate Complexes with COX-1 andCOX-2: Insights into Oxygenation Regio- andStereoselectivity.” Biochemistry 45, no. 10 (2006):3206–3218.

Grossfield, Alan, Scott E. Feller, and Michael C. Pitman.“A Role for Direct Interactions in the Modulation ofRhodopsin by Omega-3 Polyunsaturated Lipids.” Proceedingsof the National Academy of Sciences of the United Statesof America 103, no. 13 (2006): 4888–4893.

Jiang, Ping, Weifeng Li, Joan-Emma Shea, and Yuguang Mu.“Resveratrol Inhibits the Formation of Multiple-Layeredβ-Sheet Oligomers of the Human Islet Amyloid PolypeptideSegment 22-27.” Biophysical Journal 100, no. 6 (March 16,2011): 1550– 1558. doi:10.1016/j.bpj.2011.02.010.

Jones, Peter J. H., and Suhad S. AbuMweis. “Phytosterols asFunctional Food Ingredients: Linkages to CardiovascularDisease and Cancer.” Current Opinion in Clinical Nutritionand Metabolic Care 12, no. 2 (March 2009): 147–151.

Karkola, Sampo, and Kristiina Wähälä. “The Binding ofLignans, Flavonoids and Coumestrol to CYP450 Aromatase: AMolecular Modelling Study.” Molecular and CellularEndocrinology 301, no. 1–2 (March 25, 2009): 235–244.doi:10.1016/j.mce.2008.10.003.

Lof, Marie, and Elisabete Weiderpass. “Impact of Diet onBreast Cancer Risk.” Current Opinion in Obstetrics &Gynecology 21, no. 1 (February 2009): 80–85. doi:10.1097 /GCO.0b013e32831d7f22.

MacKay, Dylan S., and Peter J. H. Jones. “Phytosterols inHuman Nutrition: Type, Formulation, Delivery, andPhysiological Function.” European Journal of Lipid Scienceand Technology 113, no. 12 (December 2011): 1427–1432.doi:10.1002/ejlt.201100100.

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Mahaddalkar, Tejashree, Charu Suri, Pradeep Kumar Naik, andManu Lopus. “Biochemical Characterization and MolecularDynamic Simulation of β-Sitosterol as a TubulinBindingAnticancer Agent.” European Journal of Pharmacology 760(August 2015): 154–162. doi:10.1016/j.ejphar.2015.04.014.

Manas, Eric S., Zhang B. Xu, Rayomand J. Unwalla, andWilliam S. Somers. “Understanding the Selectivity ofGenistein for Human Estrogen Receptor-β Using X-RayCrystallography and Computational Methods.” Structure 12,no. 12 (December 2004): 2197–2207.doi:10.1016/j.str.2004.09.015.

Marques, Helder M., Ricky P. Hicks, and Kenneth L. Brown.“Solution Structure of Cyanocobalamin (vitamin B12) byNMR-Restrained Molecular Dynamics and Simulated AnnealingCalculations.” Chemical Communications, no. 12 (January 1,1996): 1427– 1428. doi:10.1039/CC9960001427.

Mascayano, Carolina, Gabriel Núñez, Waldo Acevedo, andMarcos Caroli Rezende. “Binding of Arachidonic Acid andTwo Flavonoid Inhibitors to Human 12- and 15-Lipoxygenases:A Steered Molecular Dynamics Study.” Journal of MolecularModeling 16, no. 5 (May 2010): 1039–1045.doi:10.1007/s00894-009-0616-9.

Neuringer, Martha. “Infant Vision and Retinal Function inStudies of Dietary Long-Chain Polyunsaturated Fatty Acids:Methods, Results, and Implications.” The American Journalof Clinical Nutrition 71, no. 1 (2000): 256S–267S.

Nyberg, Pia, MerjaYlipalosaari, Timo Sorsa, and Tuula Salo.“Trypsins and Their Role in Carcinoma Growth.”Experimental Cell Research 312, no. 8 (May 1, 2006):1219–28. doi:10.1016/j.yexcr.2005.12.024.

Olausson, Bjoern E. S., Alan Grossfield, Michael C. Pitman,Michael F. Brown, Scott E. Feller, and Alexander Vogel.“Molecular Dynamics Simulations Reveal SpecificInteractions of Post-Translational Palmitoyl Modificationswith Rhodopsin in Membranes.” Journal of the AmericanChemical Society 134, no. 9 (March 7, 2012): 4324–31.doi:10.1021 / ja2108382.

Qin, Shan-Shan, Zhi-Wu Yu, and Yang-Xin Yu. “Structural andKinetic Properties of α-Tocopherol in Phospholipid

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Richard, Tristan, Alison D. Pawlus, Marie-Laure Iglésias,Eric Pedrot, Pierre Waffo-Teguo, Jean-Michel Mérillon, andJean-Pierre Monti. “Neuroprotective Properties ofResveratrol and Derivatives.” Annals of the New YorkAcademy of Sciences 1215 (January 2011): 103–108.doi:10.1111/j.1749-6632.2010.05865.x.

Soreide, K., E. A. Janssen, H. Körner, and J. P. A. Baak.“Trypsin in Colorectal Cancer: Molecular BiologicalMechanisms of Proliferation, Invasion, and Metastasis.”The Journal of Pathology 209, no. 2 ( June 2006):147–156. doi:10.1002/path.1999.

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Verma, Sharad, Amit Singh, and Abha Mishra. “Quercetin andTaxifolin Completely Break MDM2–p53 Association: MolecularDynamics Simulation Study.” Medicinal Chemistry Research22, no. 6 ( June 2013): 2778–87.doi:10.1007/s00044-012-0274-9.

Von Fircks, Anne, Stefan Naumann, Rudolf Friedemann, andStephan König. “Molecular Dynamics Simulations on theCoenzyme Thiamin Diphosphate in Apoenzyme Environment.”Molecular Modeling Annual 2, no. 9 (September 27, 1996):312–318. doi:10.1007/s0089460020312.

Yuan, Minggui, Minxian Luo, Yao Song, Qiu Xu, XiaofengWang, Yi Cao, Xianzhang Bu, Yanliang Ren, and Xiaopeng Hu.“Identification of Curcumin Derivatives as HumanGlyoxalase I Inhibitors: A Combination of BiologicalEvaluation, Molecular Docking, 3D-QSAR and MolecularDynamics Simulation Studies.” Bioorganic & MedicinalChemistry 19, no. 3 (February 2011): 1189–1196.doi:10.1016/j.bmc.2010.12.039.

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Zeng, Jianping, Aimin Wang, Xuedong Gong, Jingwen Chen,Song Chen, and Feng Xue. “Molecular Dynamics Simulation ofDiffusion of Vitamin C in Water Solution.” Chinese Journalof Chemistry 30, no. 1 ( January 1, 2012): 115–120.doi:10.1002/cjoc.201180459.

Zhao, Guijun, P. V. Subbaiah, Evan Mintzer, See-Wing Chiu,Eric Jakobsson, and H. L. Scott. “Molecular DynamicSimulation Study of Cholesterol and Conjugated Double Bondsin Lipid Bilayers.” Chemistry and Physics of Lipids 164,no. 8 (November 2011): 811–818.doi:10.1016/j.chemphyslip.2011.09.008.

11 11: Nanostructured Lipid Carriers

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18 18: Consumer Acceptance ofNanotechnology-Based Foods and FoodInnovations

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19 19: Ethics and Economics ofNanonutraceuticals

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