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Johnson W. McRorie Jr.
3.2 Prebiotics: Traveler’s Diarrhea, Antibiotic-Associated Diarrhea, and Clostridium difficile–Associated Diarrhea
3.3 Fermented Fibers/Prebiotics and Enteral Nutrition–Induced Diarrhea
3.4 Mixed Fibers and Enteral Nutrition–Induced Diarrhea
Zeinab
1.
4. The Gastrointestinal System and Obesity
5. Constipation: A Symptom of Chronic
Intolerance?
I. Kearsey, Y.I. Yik, B.R. Southwell and J.M. Hutson
6. Food, Nutrients, and Dietary Supplements in Management of Disorders
Sharma and Jigar Bhagatwala
7. Vitamin D and Quality of Life of Patients With Irritable Bowel Syndrome
Abbasnezhad and Razieh Choghakhori
1.
4.
5.
8. Sealing the Leaky Gut Represents a Beneficial Mechanism of Zinc Intervention for Alcoholic Liver Disease
9. Exclusive Enteral Nutrition in Children With Crohn’s Disease: A Focused Nutritional Intervention Andrew S.
10. Gut Microbes in Liver Diseases: Dietary Intervention for Promoting Hepatic Health
Aryashree Arunima, Jugal Kishore Das and Mrutyunjay Suar
1. Introduction
2. Gut Microbiota
2.1 Gut Homeostasis
2.2 Gut Dysbiosis
3. Gut Microbiota and Liver
3.1 Liver as Vascular Sentinel of the Immune System
3.2 Gut-Liver Axis
3.3 Factors Affecting the Gut Microbiota in Liver Disease
4. Liver Diseases and Role of
4.1
4.2
4.3 Hepatic Fibrogenesis
4.4 Hepatic Encephalopathy
4.5 Viral Hepatitis
4.6 Hepatocellular Carcinoma
4.7 Liver Cirrhosis
4.8 Inflammatory Bowel Diseases
5. Dietary Intervention Strategies for Liver Diseases
5.1
5.2
5.3
6.
Feasible Options to Control Colonization of
Mengfei Peng, Puja Patel, Vinod Nagarajan, Cassandra Bernhardt, Michael Carrion and Debabrata Biswas
12. The Role of Prebiotics in Disease Prevention and Health Promotion
Rabin Gyawali, Nwadiuto Nwamaioha, Rita Fiagbor, Tahl Zimmerman, Robert H. Newman and Salam A. Ibrahim
3.5 Type II Diabetes and Glycemic Control 157
3.6 Weight Management 157
3.7 Immune Function 158
4. Synbiotic Approach 158
5. Insight Into Prebiotics Effect on the Growth of Harmful Bacteria 161
6. Conclusions and Future Directions 163 Acknowledgments 163 References 163
13. Probiotics From Food Products and Gastrointestinal Health
Murat Doğan, İsmail Hakkı Tekiner and Hilal DemirkesenBiçak
1. Introduction 169
2. Probiotic Concept 169
3. Mechanisms of Action of Probiotics 170
3.1 Antimicrobial Effects 170
3.2 Enhancement of Mucosal Barrier Integrity 171
3.3 Immune Modulation 171
4. Dietary Interventions of Probiotics in Gastrointestinal Disorders 171
5. Probiotic Functional Foods, Status, and Claims 172
6. Conclusions 173 List of Abbreviations 173 References 174
14. Prebiotics for Gastrointestinal Infections and Acute Diarrhea
Ignasi Azagra-Boronat, Maria José Rodríguez-Lagunas, Margarida Castell and Francisco J. Pérez-Cano
1. Introduction 179
2. Gastrointestinal Infections 179
3. Prebiotics: Types and Mechanisms of Action 181
3.1 Definition and Types of Prebiotics 181
3.2 Mechanisms of Action in the Protection of Gastrointestinal Infections 181
3.3 Microbiota-Dependent Mechanisms 181
3.4 Microbiota-Independent Mechanisms 183
4. Prebiotics in Gastrointestinal Diseases 183
4.1 In Vitro Evidences 183
4.2 Evidences in Animal Models of Infection 183
4.3 Prebiotics in Human Infections of the Gastrointestinal Tract 186
5. Conclusions
of Abbreviations 187 References 188
15. Probiotics and Applications to Constipation
Elena Scarpato, Vincenzo Coppola and Annamaria Staiano
1. The Role of Microbiota in Gut Motility 193
2. Gut Microbiota and Gastrointestinal Health 193
3. Microbiota Alterations in Functional Constipation 194
4. Probiotics in the Management of Functional Constipation 194
5. Conclusions 195 References 195
16. New Functional Properties of Fermented Rice Bran in Food Processing and Inflammatory Bowel Disease Model Mice
Takashi Kuda
1. Introduction 197
2. Preparation of Fermented Rice Bran for Ammonia Reduction in Shark Meat 198
3. Effect of Fermented Rice Bran on Ammonia Content and Preference Ranking in Shark and Other Fish Meat 199
4. Dietary and Lifestyle Disease Indices and Cecal Microbiota in High-Fat Diet, Dietary Fiber-Free Diet, or DSS-Induced IBD Models in Closed Colony Mice 199
5. Protective Effects of FRB in DSS-Induced IBD Model ICR Mice 200
5.1 Total Phenolic Content and Antioxidant Properties 201
5.2 Immune Promotion and Antiinflammation Activity in Murine Macrophage RAW264.7 Cells 201
5.3 Protective Effects of FRB-AES in DSS-Induced IBD Model ICR Mice 203
6. Conclusion 204
Section IV
Microbes and GI Tract
17. Zataria multiflora and Gastrointestinal Tract Disorders
T. Shomali
1. Introduction 209
2. Beneficial Effects of ZM on Different Gastrointestinal Tract Diseases 210
2.1 Stomatitis and Intraoral Ulcers 210
2.2 Gastric or Duodenal Ulcers 210
2.3 Irritable Bowel Syndrome and Inflammatory Bowel Disease 210
2.4 Intestinal Infections 211
2.5 Colon Cancer Chemopreventive Effect 211
2.6 Hepatoprotective Effects 211
2.7 Road Mapping for Future Studies and Conclusion 211 References 212
18. Influence of a Cocoa-Enriched Diet on the Intestinal Immune System and Microbiota
Mariona Camps-Bossacoma, Malen Massot-Cladera, Francisco J. Pérez-Cano and Margarida Castell
1. Introduction 213
2. Cocoa Composition 213
3. Cocoa and Gut Microbiota 214
3.1 Role of Cocoa Flavonoids on Cocoa Microbiota Influence 215
3.2 Cocoa Fiber and Microbiota 216
3.3 Cocoa Theobromine and Microbiota 216
4. Cocoa and the Intestinal Immune System 217
4.1 Cocoa and the Intestinal Epithelium 217
4.2 Cocoa and the Intestinal Immunoglobulin A 217
4.3 Cocoa and Gut-Associated Lymphoid Tissue Populations 218
5. Cocoa in Gastrointestinal Disease and Food Hypersensitivity 219
5.1 Influence of Cocoa Intake in Intestinal Inflammation 219
5.2 Food Allergy
6. Conclusions
Section V
Foods and Macro Dietary Materials in GI Function
19. High-Fiber Diets
in Gastrointestinal Tract Diseases
Ana Letícia Malheiros Silveira, Adaliene Versiani Matos Ferreira and Mauro Martins Teixeira 1. Basic Concepts:
20. Dietary Interventions in Fatty Liver
Zahra Yari and Azita Hekmatdoost
21. Rice Bran Usage in Diarrhea
Shaohua Lei and Lijuan Yuan
1. Overall Health Benefits of Rice Bran
2.2 Human Rotavirus–Induced Diarrhea 258
2.3 Human Noroviruses–Induced Diarrhea 259
3. Mechanisms for Rice Bran Usage in Reducing Diarrhea 259
3.1 Antimicrobial and Antiviral Activities 260
3.2 Prebiotic and Microbiota Modulatory Properties
3.3 Effects on Intestinal Immunity and Overall Health 260
4. Future Perspective 261 References
22. Milk Bacteria and Gastrointestinal Tract: Microbial Composition of Milk
Aseel T. Issa and Reza Tahergorabi
1. Introduction
2. Sources of Milk Organisms
3. Contamination in the Mammary Glands
4. Contamination Sources in the External Environment
5. Contamination From Handling and Storage Equipment 266
6. Microbial Composition of Milk From Different Sources 266
6.1 Cow Milk
6.2 Goat Milk
6.3 Sheep Milk
6.4 Buffalo Milk
6.5 Other Types of Milk
7. Important Microorganisms Found in Raw Milk
7.1 Lactococcus
7.2 Bifidobacterium
7.3 Lactobacillus
7.4 Streptococcus
7.5 Propionibacterium
7.6 Leuconostoc 269
7.7 Enterococcus 269
7.8 Gram-Positive Subpopulations
7.9 Gram-Negative Subpopulations
7.10 Fungal Populations
7.11 Psychrotrophic
8. Impact of Storage Conditions and Treatments
Staphylococcus aureus
11.5 Coxiella burnetii
Mycobacterium bovis
23. Polyphenols in the Prevention of Ulcerative Colitis: A Revisit
Elroy Saldanha, Arpit Saxena, Kamaljit Kaur, Faizan Kalekhan, Ponemone Venkatesh, Raja Fayad, Suresh Rao, Thomas George and Manjeshwar Shrinath Baliga
1. Introduction
2. Curcumin, the Active Component of Turmeric
3. Resveratrol
Quercetin
Kaempferol
Ellagic Acid
Rutoside or Rutin
8. Green Tea Polyphenols in Colitis
Grape Seed Polyphenols
Silymarin
Polyphenols of Apple
Cocoa
List of Contributors
Amir Abbasnezhad Nutritional Health Research Center, Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
Andrés Acosta Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, MN, United States
Aryashree Arunima School of Biotechnology, KIIT University, Bhubaneswar, India
Ignasi Azagra-Boronat Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Santa Coloma de Gramenet, Spain
Manjeshwar Shrinath Baliga Mangalore Institute of Oncology, Mangalore, India
Ayse Gunes Bayir Department of Nutrition and Dietetics, Faculty of Health Sciences, Bezmialem Vakif University, Istanbul, Turkey
Cassandra Bernhardt Department of Animal and Avian Sciences, University of Maryland, College Park, MD, United States
Jigar Bhagatwala Section of Gastroenterology and Hepatology, Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, United States
Debabrata Biswas Department of Animal and Avian Sciences, University of Maryland, College Park, MD, United States; Biological Sciences Program - Molecular and Cellular Biology, University of Maryland, College Park, MD, United States; Center for Food Safety and Security Systems, University of Maryland, College Park, MD, United States
Gerardo Calderón Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, MN, United States
Mariona Camps-Bossacoma Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Santa Coloma de Gramenet, Spain
Michael Carrion Biological Sciences Program - Molecular and Cellular Biology, University of Maryland, College Park, MD, United States
Margarida Castell Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Santa Coloma de Gramenet, Spain
Razieh Choghakhori Nutritional Health Research Center, Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
Vincenzo Coppola Department of Translational Medical Sciences – Section of Paediatrics, University of Naples “Federico II”, Naples, Italy
Jugal Kishore Das School of Biotechnology, KIIT University, Bhubaneswar, India
Andrew S. Day Cure Kids Chair Paediatric Research, Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
Hilal DemirkesenBiçak Istanbul Yeni Yüzy ı l University, Department of Nutrition and Dietetics, Istanbul, Turkey
Murat Doğan Istanbul Gelişim University, Department of Gastronomy and Culinary Arts, Istanbul, Turkey
Raja Fayad Department of General Surgery, Father Muller Medical College, Mangalore, India
Adaliene Versiani Matos Ferreira Department of Nutrition, Nursing School, Federal University of Minas Gerais, Belo Horizonte, Brazil
Rita Fiagbor Food and Nutritional Sciences Program, North Carolina A&T State University, Greensboro, NC, United States
Thomas George MBBS Student, Father Muller Medical College, Mangalore, India
Rabin Gyawali Food and Nutritional Sciences Program, North Carolina A&T State University, Greensboro, NC, United States
Azita Hekmatdoost Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
J.M. Hutson Surgical Research Group, Murdoch Children’s Research Institute, Melbourne, Australia; Urology Department, The Royal Children’s Hospital, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia
Salam A. Ibrahim Food and Nutritional Sciences Program, North Carolina A&T State University, Greensboro, NC, United States
Aseel T. Issa High Point Clinical Trials Center, High Point, NC, United States
Faizan Kalekhan Mangalore Institute of Oncology, Mangalore, India
Kamaljit Kaur Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
I. Kearsey Surgical Research Group, Murdoch Children’s Research Institute, Melbourne, Australia; Urology Department, The Royal Children’s Hospital, Melbourne, Australia
Huriye Senay Kiziltan Department of Radiation Oncology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Abdurrahim Kocyigit Department of Medical Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
Takashi Kuda Department of Food Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan
Shaohua Lei Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
Malen Massot-Cladera Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Santa Coloma de Gramenet, Spain
Johnson W. McRorie Jr. Procter & Gamble, Mason, OH, United States
Zeinab Mokhtari Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Vinod Nagarajan Department of Animal and Avian Sciences, University of Maryland, College Park, MD, United States
Robert H. Newman Department of Biology, North Carolina A&T State University, Greensboro, NC, United States
Nwadiuto Nwamaioha Food and Nutritional Sciences Program, North Carolina A&T State University, Greensboro, NC, United States
Puja Patel Biological Sciences Program - Molecular and Cellular Biology, University of Maryland, College Park, MD, United States
Mengfei Peng Department of Animal and Avian Sciences, University of Maryland, College Park, MD, United States; Biological Sciences Program - Molecular and Cellular Biology, University of Maryland, College Park, MD, United States
Francisco J. Pérez-Cano Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Santa Coloma de Gramenet, Spain
Suresh Rao Mangalore Institute of Oncology, Mangalore, India
Maria José Rodríguez-Lagunas Secció de Fisiologia, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB), Santa Coloma de Gramenet, Spain
Elroy Saldanha Department of General Surgery, Father Muller Medical College, Mangalore, India
Arpit Saxena Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
Elena Scarpato Department of Translational Medical Sciences – Section of Paediatrics, University of Naples “Federico II”, Naples, Italy
Amol Sharma Section of Gastroenterology and Hepatology, Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, United States
T. Shomali Division of Pharmacology and Toxicology, Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
Ana Letícia Malheiros Silveira Department of Nutrition, Nursing School, Federal University of Minas Gerais, Belo Horizonte, Brazil
B.R. Southwell Surgical Research Group, Murdoch Children’s Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia
Annamaria Staiano Department of Translational Medical Sciences – Section of Paediatrics, University of Naples “Federico II”, Naples, Italy
Mrutyunjay Suar School of Biotechnology, KIIT University, Bhubaneswar, India
Reza Tahergorabi Food and Nutritional Sciences Program, College of Agriculture and Environmental Sciences, North Carolina Agricultural and Technical State University, Greensboro, NC, United States
Mauro Martins Teixeira Department of Biochemistry and Immunology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil
İsmail Hakkı Tekiner Istanbul Gelişim University, Department of Gastronomy, Istanbul, Turkey
Ponemone Venkatesh Mangalore Institute of Oncology, Mangalore, India
Zahra Yari Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Y.I. Yik Department of Pediatric surgery, University of Malaya, Kuala Lumpur, Malaysia
Lijuan Yuan Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
Wei Zhong Center for Translational Biomedical Research, Department of Nutrition, School of Health and Human Sciences, University of North Carolina at Greensboro, Kannapolis, NC, United States
Zhanxiang Zhou Center for Translational Biomedical Research, Department of Nutrition, School of Health and Human Sciences, University of North Carolina at Greensboro, Kannapolis, NC, United States
Tahl Zimmerman Food and Nutritional Sciences Program, North Carolina A&T State University, Greensboro, NC, United States
Biography
Ronald R. Watson, PhD, attended the University of Idaho but graduated from Brigham Young University in Provo, Utah, with a degree in chemistry in 1966. He earned his PhD in biochemistry from Michigan State University in 1971. His postdoctoral schooling in nutrition and microbiology was completed at the Harvard School of Public Health, where he gained 2 years of postdoctoral research experience in immunology and nutrition.
From 1973 to 1974, Dr. Watson served as an assistant professor of immunology and performed research at the University of Mississippi Medical Center in Jackson. He was an assistant professor of microbiology and immunology at the Indiana University Medical School from 1974 to 1978 and associate professor at Purdue University in the Department of Food and Nutrition from 1978 to 1982. In 1982, Dr. Watson joined the faculty at the University of Arizona Health Sciences Center in the Department of Family and Community Medicine of the School of Medicine. He is currently professor of health promotion sciences in the Mel and Enid Zuckerman Arizona College of Public Health. Dr. Watson joined the faculty at the University of Arizona Health Sciences Center in the Department of Family and Community Medicine of the School of Medicine. His primary appointment now is professor of health promotion sciences in the Mel and Enid Zuckerman Arizona College of Public Health. He has 14 patents on dietary supplement and health promotion. He continues to do research in animals and in clinical trials on dietary supplements and health.
Dr. Watson is a member of national and international nutrition, immunology, cancer, and alcoholism research societies. His patents are for antioxidant polyphenols in several dietary supplements including passion fruit peel extract, with more pending. This results from more than 10 years of polyphenol research in animal models and human clinical trials. He had done research on mouse AIDS and immune function for 20 years. For 30 years, he was funded by the NIH and foundations to study dietary supplements in health promotion. Dr. Watson has edited more than 120 books on nutrition, dietary supplements and over-the-counter agents, and drugs of abuse as scientific reference books. He has published more than 500 research and review articles.
Victor R. Preedy, BSc, PhD, DSc, FSB, FRCPath, FRSPH is attached to both the Diabetes and Nutritional Sciences Division and the Department of Nutrition and Dietetics. He is professor of Nutritional Biochemistry (Kings College London) and professor of Clinical Biochemistry (Hon: Kings College Hospital). He is also director of the Genomics Center and a member of the School of Medicine. Professor Preedy graduated in 1974 with an honours degree in Biology and Physiology with Pharmacology. He gained his University of London PhD in 1981. In 1992, he received his Membership of the Royal College of Pathologists and in 1993 he gained his second doctoral degree for his outstanding contribution to protein metabolism in health and disease. Professor Preedy was elected as a Fellow to the Institute of Biology in 1995
and to the Royal College of Pathologists in 2000. Since then, he has been elected as a Fellow to the Royal Society for the Promotion of Health (2004) and the Royal Institute of Public Health (2004). In 2009, Professor Preedy became a Fellow of the Royal Society for Public Health. In his career, Professor Preedy has carried out research at the National Heart Hospital (part of Imperial College London) and the MRC Centre at Northwick Park Hospital. He has collaborated with research groups in Finland, Japan, Australia, USA, and Germany. Professor Preedy has a wide interest in diet–tissue interactions and especially micronutrients. He has lectured nationally and internationally. To his credit, Professor Preedy has published over 570 articles, which includes 165 peer-reviewed manuscripts based on original research, 90 reviews, and over 40 books and volumes.
Acknowledgments
The work of Dr. Watson’s editorial assistant, Bethany L. Stevens, in communicating with authors and editors and working on the manuscripts was critical to the successful completion of the book. It is very much appreciated. Support for Ms. Stevens’ and Dr. Watson’ editing was graciously provided by the Natural Health Research Institute (www.naturalhealthresearch.org) and Southwest Scientific Editing & Consulting, LLC. The encouragement and support of Elwood Richard and Dr. Richard Sharpee was vital. Direction and guidance from Elsevier’s staff Pat Gonzalez was critical. Finally, the work of the librarian at the Arizona Health Science Library, Mari Stoddard, was vital and very helpful in identifying key researchers who participated in the book.
Section I
Background and Overview of Diet and GI Tract Health
Chapter 1
Plant Family, Carvacrol, and Putative Protection in Gastric Cancer
1Department of Nutrition and Dietetics, Faculty of Health Sciences, Bezmialem Vakif University, Istanbul, Turkey; 2Department of Radiation Oncology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey; 3Department of Medical Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
1. PLANT FAMILY AND PHYTOCHEMICALS
1.1
General Properties of Dietary Phytochemicals
Plant chemicals called as phytochemicals are more than 5000 bioactive nonnutrient compounds in plants, including fruits, vegetables, grains, and other plant foods.1 These compounds in plants are the secondary metabolites within the functions in reproduction, growth, defense mechanisms against pathogens, the taste, smell, and color of plants. They have a role in oxidative stress metabolism, which is important for the development and prevention of a wide range of chronic diseases.2 Therefore, plant foods containing phytochemicals may provide to reduce the risk of chronic diseases.
1.2 Classification of Phytochemicals
Phytochemicals are classified as polyphenols, terpenoids, alkaloids, phytosterols, and organosulfur compounds (Fig. 1.1). The most commonly found and studied phytochemical classes are the polyphenols.3 Until now 8000 polyphenolic compounds are identified, which have antioxidant and prooxidant activities depending on their doses.4 Polyphenols at higher doses have shown to play an important role in induction of apoptosis, suppression of cell proliferation, migration, and invasion of cancer cells, whereas their lower doses scavenge the free radicals in cells. Chemical structure of polyphenols demonstrates one or more aromatic rings with one or more hydroxyl groups.5 They have been classified according to their chemical structure as phenolic acids, flavonoids, stilbenes, and isoflavones.
1.3 Mechanisms of Phytochemicals in Cancer Chemoprevention
The use of many dietary agents, medicinal plants, and their phytochemicals as specific natural or synthetic chemical compounds in cancer prevention gained importance over the past few years.6 However, the cancer preventive effect of these compounds should be tested in in vitro and in vivo before their investigations in clinical studies. Therefore, the mechanism of chemoprevention in cancer encompasses to prevent, suppress, or reverse all of the cancer stages that involve initiation, promotion, and progression.7 Chemopreventive agents are classified into blocking and suppressing agents.8 Phytochemicals can play a role as blocking or suppressing agents in different stages of cancer (Fig. 1.2). On the other hand, some phytochemicals can interact as both blocking and suppressing agents in carcinogenesis. Blocking agents can block or reverse the initiation stage of cancerogenesis and inhibit the reach of procarcinogens into the target cells, the metabolic activation of the procarcinogens, or their, subsequently, interaction with macromolecules such as DNA, RNA, lipids, and proteins. Suppressing agents inhibit the malignant transformation of initiated cells in either the promotion or the progression stages of cancerogenesis. Both agents affect the cancerogenesis at the molecular and cellular levels, which include the activation or detoxification of procarcinogens by metabolizing enzymes, reparation of DNA damage, and progression of cell cycle.9 It was included hormonal and growth factor activity, cell proliferation, cell differentiation, apoptosis, expression and functional activation/inactivation of oncogenes, angiogenesis, and tumor metastasis. On the other hand, two important mechanisms of polyphenols in cancer chemoprevention are the antioxidant and prooxidant activities that occur depending on their concentrations.2 Polyphenols at higher concentrations induce the overgeneration of intracellular reactive oxygen species (ROS) that may cause damage of DNA and
Dietary Interventions in Gastrointestinal Diseases. https://doi.org/10.1016/B978-0-12-814468-8.00001-6
FIGURE 1.1 Classification of phytochemicals
FIGURE 1.2 Roles of blocking and suppressing phytochemical agents.
macromolecules in cells and induce apoptosis of cells. Lower concentrations of polyphenols activate the antioxidant defense system in cells by reducing ROS level, and so the normal cells were prevent from the carcinogenesis. However, the molecular and cellular effects of chemopreventive phytochemicals still remain incomplete. Hence the clinical significance and direct impact on organs and organ functions in patients are also still unknown.
2. CARVACROL
2.1 Carvacrol as a Molecule
Carvacrol is a monoterpenoid phenol representing with the chemical formula of C6H3CH3(OH) (C3H7).10 Its formula was described according to International Union of Pure and Applied Chemistry as 2-methyl-5-propan-2-ylphenol. The structural formula of carvacrol is demonstrated in Fig. 1.3
2.2 Carvacrol Sources
Carvacrol is a compound of many aromatic plants that are usually used as spices in culinary and for therapy/prevention purposes in folk medicine. These aromatic plants are including oregano (Origanum vulgare, O. majorana, O. compactum, O. dictamnus, O. microphyllum, O. onites, and O. scabrum), thyme (Thymus vulgaris, T glandulosus, T zygis, and T serpyllum), Spanish origanum (Thymbra capitata), pepperwort (Lepidium flavum), black cumin (Nigella sativa), and summer and winter savory (Satureja hortensis and S montana).10–14 On the other hand, carvacrol can be synthesized by chemical and biotechnological methods.15–18
2.3 Chemical and Physical Properties of Carvacrol
Carvacrol is a liquid and boils at 237–238°C.19 It can be volatile with steam. Its melting point is 1°C. Its highly lipophilic character can allow its solubility in carbon tetrachloride, ethanol, diethyl ether, and acetone. Because of its lipophilic character, carvacrol is insoluble in water. The density of carvacrol differs between 0.97 g/cm3 at 20°C and 0.975 g/cm3 at 25°C.
2.4 Metabolism and Excretion of Carvacrol
A study revealed that carvacrol is the substrate of the UDP-glucuronosyltransferase isoform UGT1A4.20 It was reported that carvacrol can rapidly be metabolized and excreted in rats.21 Its excretion after 24 h was very limited and the molecule was found unchanged. After 48–72 h of carvacrol treatments of rats, no metabolites were observed. Ring hydroxylation of carvacrol molecule is the reason why the metabolism of this compound is very quick. The biological activities of polyhydroxylated compounds generally seem to be dependent on their chemical properties such as structure and lipophilicity, which can also affect their uptake into cells or influence their interaction with proteins and enzymes. Another study showed that oral feeding of carvacrol in pigs was almost completely absorbed in the stomach and proximal small intestine, whereas 29% degradation of carvacrol was observed in cecum.22
2.5 Acute Toxicity of Carvacrol
The median lethal dose (LD50) of carvacrol in rats was reported as 810 mg/kg body weight when it was applied by oral gavage.23 The LD50 for intravenous, intraperitoneal, or subcutaneous applications of carvacrol to mice were 80, 73.3, and 680 mg/kg body weight, respectively.24 In dogs, the LD50 of intravenously administered carvacrol was 0.31 g/kg body weight.
2.6 Biological Activities of Carvacrol
In the past few years, increasing use of carvacrol as food additives for flavoring substance or natural food preservative in the food packaging system and a lot of carvacrol’s biological activities have attracted the attention of researchers for its possible potential in clinical applications. The preventing free radicals and hazardous compounds from interacting with cellular DNA are associated with its wide range of biological activities. Therefore, in vitro and in vivo studies were performed to research its biological activities, which are presented below.
2.6.1 Antioxidant Activity
Antioxidant substances scavenge the ROS namely free radicals, and so they protect the cells against cellular stress. Furthermore, they inhibit prostaglandin synthesis, induce drug-metabolizing enzymes, and show many biological activities such as protecting from DNA damage, enzyme-induced hepatotoxicity, inhibiting/preventing from cancer imitation, etc. The reason for antioxidant activity of carvacrol was the presence of hydroxyl group (OH) that linked to aromatic ring of carvacrol molecule.25 During the reaction of carvacrol molecule with free radicals, it donates hydrogen atoms to an unpaired electron and produces another radical which is generated at a molecule resonance structure. Carvacrol can interact with the phospholipid membrane of cells or low-density lipoprotein and reduce the lipid peroxidation and nitric oxide production, which leads to oxidative destruction of cellular membranes.26,27 Nitric oxide is produced from the spontaneous
