Book Volume 2
Page: i-i (1)
Author: Philip C. Calder
Page: ii-iv (3)
Author: Cristina Otero
Page: v-v (1)
Author: Victorina Aguilar
Page: vi-vii (2)
Author: M. Victorina Aguilar and Cristina Otero
From Pharma to Food: Mechanistic Target Identification for Bioactive Compounds Using Nutritional Systems Biology
Page: 3-23 (21)
Author: Erfan Younesi
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Advancements in molecular biology and the advent of high-throughput technologies for characterization of biological processes across multiple biological scales from cells and tissues to the whole organism have provided exciting opportunities to investigate and evaluate the influence of foods and their bioactive ingredients on the human health and disease. These advances, mainly developed by pharmaceutical stakeholders, are going to transform the way nutrition is addressed in relation to human health by the nutraceutical industry. Consumers now demand healthier food products and regulatory agencies have raised the bars for approval of health claims associated with functional foods. To tackle these issues, a knowledgebased, integrated systems biology strategy is required for successful production of functional foods, which can be adopted from experiences of pharmaceutical industry in this area. This strategy benefits from integrative mechanistic modeling of health and disease processes, which can support the process of health claim substantiation for bioactive food ingredients in new product development. Currently, there are thousands of natural compounds or functional food ingredients whose mode-of-action and their final impact on the human health or disease are unknown. Thus, identification of biological targets for thousands of bioactive compounds in food and their mode-ofaction in the human body is of high priority. This chapter discusses how fundamentals of systems biology and in silico target identification, as is done in the pharmaceutical industry, can be applied to the field of nutrition in support of developing novel functional foods. The author foresees that identification of mechanistic targets for bioactive compounds extracted from foods and natural resources, and explanations for their pharmacological mode-of-action will play a crucial role in the future of healthcare and preventive medicine.
Page: 24-53 (30)
Author: Patrycja Puchalska, Maria Concepción García and Maria Luisa Marina
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Several studies have shown that food is an important source of many bioactive compounds that may have a beneficial health impact on human body. Among them, bioactive peptides have extensively been studied and have proved to possess a variety of activities such as antihypertensive, antioxidant, anti-inflammatory, antimicrobial, and many others. These peptides can be natural constituents of foods but they can also be released from a parent protein present in a food during gastrointestinal digestion or by an enzyme or microorganism during food processing. The analysis of bioactive peptides in food samples is a very challenging task due to their wide concentration dynamic range and the complexity of these samples. The general workflow usually employed in the investigation of the presence of bioactive peptides in foods is presented in this chapter. Some important characteristics of bioactive peptides that need to be taken into account during their analysis are highlighted. Additionally, an overview of novel strategies to obtain bioactive peptides from food protein hydrolysates is presented. A separate section is devoted to describe chromatographic and electrophoretic approaches successfully used for the analysis of food bioactive peptides. Mass spectrometric techniques dominate in the identification of bioactive peptides in complex food matrices. Some alternatives to tentatively assign a signal to a peptide sequence are displayed. In addition, a recent ‘hot topic’ such as the quantitation of bioactive peptides in complex matrices is included. Information given in this chapter is based on the most recent literature.
Page: 54-98 (45)
Author: Antonio Cilla, Reyes Barberá and Amparo Alegría
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The knowledge of bioavailability, i.e. the fraction of bioactive compound that can be absorbed and utilized, is a very relevant topic of food and nutraceutical research. The present review sheds light to the concepts of bioavailability, bioaccessibility, bioactivity, bioefficiency and bioconversion. Besides, it reviews the main in vivo methods such as balance techniques (chemical balances and isotopes methods), plasma biomarkers and animal models. Several in vitro methods that simulate physiological conditions of the human gastrointestinal digestion (static or dynamic models) and the usefulness of Caco2 culture cells for evaluating bioactive compounds bioavailability in foods are also reviewed. The advantages and disadvantages of these methods are discussed, beside specific conditions applied for several bioactive compounds (minerals, carotenoids, α-tocopherols, folic acid, plant sterols and polyphenols) from recent studies. Human studies are the method of choice, and data obtained from these assays represent the gold reference because they provide the most accurate results and the highest scientific evidence regarding the bioavailability of a bioactive compound. In vitro models are reproducible, rapid and simple, due to the fact they allow tight control of the experimental variables than animal or human studies. These methods are particularly useful to check the impact of digestion conditions and to undertake studies on the positive or negative effects of food structure, food composition, dietetic factors and food processing. Furthermore, it is mandatory to promote more research into in vivo-in vitro correlations using well harmonized and standardized systems, so that more valid in vitro models can be designed to evaluate the bioavailability of bioactive food compounds.
Novel Nutrigenomics Avenues in Nutraceuticals Use: The Current Status of Fermented Papaya Preparation
Page: 99-123 (25)
Author: Amelie Mantello, Roberto Catanzaro, Fang He, Biagio Cuffari, Laura Bissi, Michele Milazzo, Aldo Lorenzetti and Francesco Marotta
Functional foods present a constantly growing research field, interrelating genomics, epidemiology and clinical investigations, followed by increased interest from the public and food supplement industry. As a matter of fact, the outcome of the implementation of functional foods is now amenable to be assessed by employing many of the most recent diagnostic tools.
Nutrigenomics is a relatively new discipline, which studies the genetic and epigenetic interplay with a nutrient or its functional component(s) in order to bring about a phenotypic modification of key cellular functions, such as, cell metabolism, differentiation or apoptosis. This represents one of the most expanding fields of research to unveil the health benefits of functional foods and their bioactive moieties which cannot be differentiated, as it happens in synthetic molecules devised by pharmaceutical industries.
Within this scenario, a specific functional food, i.e. fermented papaya preparation, coming from a controlled bio-fermentation process of papaya, is herewith reported and scientifically backed up by several experimental models and properly-designed clinical protocols.
The promising clinical health benefits provided by fermented papaya preparation are also discussed under the viewpoint of nutrigenomic mechanism understanding, and a significant antioxidant and effective transcriptomic property is described while ongoing investigations are warranted.
In general, this specific fermented papaya preparation represents a functional food, which closely meets the novel criteria of the new nutrigenomic-oriented strategic approach of preventive medicine, aimed to reduce the burden of chronic illnesses, while also offering potential adjuvant benefits within drugs regimens.
Page: 124-145 (22)
Author: Ran Ye and Douglas G. Hayes
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Sugar fatty acid esters are biodegradable and biocompatible nonionic biobased surfactants or emulsifiers, obtained from abundant renewable resources. They have a dozen of applications in food, cosmetic and pharmaceutical industries. In this book chapter, we briefly reviewed the enzymatic synthesis of sugar fatty acid esters in solvent-free system and their bioactive characteristics, including antimicrobial activity, anti-tumor activity and anti-insect activity. In addition, we compared the antimicrobial and antitumor properties of sugar fatty acid esters synthesized from enzyme with commercial sugar fatty acid ester produced and purified from a chemical reaction.
Page: 146-164 (19)
Author: Weili Li, Zhengxiao Zhang and Christopher Smith
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Arabinoxylans are a group of compounds with a basic structure consisting of a xylose backbone with arabinose side chains. Variations in structure occur as a result of variations in the xylose chain length, the ratio of arabinose to xylose and the introduction of alternative side-chains. This allows for an enormous potential range of structures. Arabinoxylans are major components of the cell walls of cereals. They have been reported to have numerous health benefits. This chapter presents a systematic description of the molecular features of arabinoxylans and relates these to the different extraction technologies used to obtain them. The proposal, that their immune modulation activity is related to their molecular weight and structure, is presented. Results demonstrating the effects of various arabinoxylans in various in vitro immunological tests are discussed.
Page: 165-185 (21)
Author: Sanjeet Kumar
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Food security and effective medicines continue to be challenging issues for the third world. Functional plants give us some bio-resources having food and medicinal values. Several species of the genus Dioscorea available in tribal Odisha in India are parochially used as food and medicines for various diseases and disorders. Dioscorea is a monocot having starchy tuberous root. Some tubers are sweet and some are bitter in taste, due to their high content of phenolic compounds and other antinutritional factors. These vines have diverse bioactive compounds including steroidal saponin, diosgenin etc. Keeping this in mind, the ethnobotanical values and contents of bioactive compounds of these vines were collected from field and literature survey. The analysis of the obtained data permits to justify its consideration as a future functional food. The present investigation also highlights the importance of wild edible plants as functional foods and their potentials for the formulation of new drugs.
Page: 186-199 (14)
Author: Yuriy G. Shckorbatov
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Saponins are biologically active components of many medicinal plants. From ancient times till our days the saponins containing medicinal plants are used in medicine with different purposes, in particular as anti-cancer agents in the folk (traditional) medicine. Therefore, many investigations are focused on the proapoptotic, toxic and proliferation suppressing properties of saponins. Publications from 2000 to 2014 dealing with medical applications of plant-derived saponins and saponincontaining herbs are reviewed.
Page: 200-229 (30)
Author: Miriam Román Menacho, Domingo Ly Pen and Antonio Becerra Fernández
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Diabetes mellitus (DM) is the most common endocrine disorder, and with a very high development rate. There are two main groups of DM: type 1 DM (basically due to an insulin deficiency), and type 2 DM (basically due to insulin resistance, i.e.: there is plenty of insulin, but actually the cells are resistant to its action). Both types lead to both abnormal glucose and lipids metabolism, sub-clinical inflammation and higher oxidative stress. We will speak mainly about type 2 DM. Its genesis is multifactorial, but we can ascertain that the diet is the principal modifiable factor. The benefits of a healthy diet are not limited to its nutrient content, must also provide other protective factors against oxidative stress, metabolic syndrome, diabetes and carcinogenesis content especially in plant foods, called compounds bioactive, serving in the body that can promote good health. A diet with high intake of phytochemicals and rich in antioxidant capacity with polyphenolic compounds (as the Mediterranean Diet), is related to a decreased risk of DM.
Page: 230-263 (34)
Author: Antonio Becerra-Fernández, Miriam Menacho Román and Domingo Ly Pen
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Cardiovascular diseases are the main cause of death worldwide and therefore, the most important public health problem. Many factors play a role in the development of cardiovascular diseases, among others: obesity, hypertension, diabetes mellitus, hyperlipidemia, inadequate diet, sedentary life and smoking. Cardiovascular disease incidence can be improved increasing the intake of fruits and vegetables. Cohort studies and randomized controlled trials have shown that intake of dietary antioxidants (vitamins E, A, C, and poliphenols), antioxidant supplements or dietary patterns (Mediterranean diet) influence differently in the occurrence of cardiovascular events or death. This review examines relevant clinical reports on dietary compounds, supplements or dietary patterns to analyze what kind of patients (if any) with increased cardiovascular risk factors will get any benefit for these therapeutic options.
Page: 264-292 (29)
Author: Domingo Ly Pen, Antonio Becerra and Miriam Menacho
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Metabolic syndrome is defined as a set of coexisting metabolic disorders that increase an individual’s likelihood of developing type 2 diabetes, cardiovascular disease and stroke, among other chronic diseases.
In Chapter 9 of this same book, we have already explained in detail, the main concepts about Mediterranean diet and bioactive compounds and diabetes.
In this chapter, we update the evidence about dietary bioactive compounds with potential in preventing / treating the Metabolic Syndrome. We will only focus on the studies where the evidence is relevant, not on the multiple studies in vivo, very interesting indeed, but with no current clinical relevance.
Bioactive compounds should be of the greatest interest because of their multiple positive effects on health, prevention of Metabolic Syndrome related diseases or lowering their complications.
Urso-, Glycoursodeoxycholic and Tauroursodeoxycholic Acids: From Basic Research to Clinical Applications in CNS Disorders
Page: 293-325 (33)
Author: Dora Brites
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Tauroursodeoxycholic acid and glycoursodeoxycholic acid are the conjugates of ursodeoxycholic acid, which is largely used in the treatment of hepatobiliary diseases due to its detergent properties. These bile acids exist only in minor quantities in the normal human body. Ursodeoxycholic acid was approved by U.S. Food and Drug Administration (FDA) for cholesterol gallstone dissolution, and as a cytoprotective agent in primary biliary cirrhosis. Orally administered ursodeoxycholic acid is later conjugated with taurine and glycine in the liver and originates the conjugated species that have fewer side effects than the counterpart free species. Because glycoursodeoxycholic acid may represent more than 50% of total bile acids, and tauroursodeoxycholic usually less than 10%, we consider glycoursodeoxycholic acid as the one having the highest clinical relevance in people taking ursodeoxycholic acid. However, its mechanisms of action have been less explored than the free and the taurine conjugated species. In this overview, the biological properties of glycoursodeoxycholic acid are highlighted and their mechanisms of action compared with ursodeoxycholic acid and tauroursodeoxycholic acid. Recent studies have demonstrated that such bile acids have unexpected efficacy in the treatment of certain neurodegenerative diseases, opening up the range of opportunities for their therapeutic use. Therefore, we additionally summarize current knowledge on the potential applications of such bile acids in the prevention and recovery of diseases associated to central nervous system (CNS) dysfunction and pathology. Forthcoming studies will hopefully better elucidate the benefits of glycoursodeoxycholic acid over those of ursodeoxycholic acid and tauroursodeoxycholic acid for the treatment of age-associated neurodegenerative diseases, a major public health issue and a challenge to the health care system.
Page: 326-356 (31)
Author: Sofia M. Yartseva and Yan A. Ivanenkov
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Prostate cancer (PCa) is the most common solid neoplasm and is one of the major causes of cancer mortality among men. Recent studies have shown the beneficial effect of some nutrients in PCa management. Natural phytochemicals often have pleiotropic effects, targeting virtually every molecular signaling pathway, which makes them promising agents for multi-target anti-cancer therapy. Furthermore, they are usually well-tolerated, easily available and cost-efficient. This chapter describes the variety of naturally occurring bioactive compounds used for the treatment and prevention of prostate cancer, especially focusing on dietary polyphenols and their analogs, including green tea polyphenols, resveratrol and curcuminoids, vitamins, organosulfur compounds from onions and garlic (predominantly allyl derivatives) and phytochemicals from cruciferous vegetables. While some of these compounds (e.g. curcumin and sulforaphane) have established anticarcinogenic properties, the others provide contradictory results in preclinical and clinical studies. Selenium and vitamin E supplementation is the most prominent case of such controversy. In this chapter, we cover molecular mechanisms that lead to PCa progression, as well as key mechanisms of antitumor action. Impact of different nutrients on cancer-associated epigenetic modifications is analyzed. Results of epidemiological studies and dietary interventions conducted to date are also provided. Main challenges associated with design and interpretation of such interventions are discussed, together with major issues of developing naturally occurring compounds into clinically used agents. While a promising scientific area, further research is required to completely elucidate the relationship between nutrients and PCa.
Page: 357-382 (26)
Author: Antonio Peña-Fernández, Mark D. Evans and Avninder S. Bhambra
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Methylxanthines, namely caffeine, theobromine and theophylline are found in several beverages and food products such as coffee, cocoa, tea and cola drinks. These substances can provide benefits to humans but also prove harmful mainly when consumed in high amounts. However, the beneficial and deleterious effects of methylxanthines are controversial in research findings, largely because of inconsistencies within research conducted and factors associated within studies. For instance, some authors have reported methylxanthines could have potential antioxidant activity under physiological conditions but opposing studies do not support these claims. Factors that influence the effects of methylxanthines include age, gender and health status of the individual. In addition to these, other factors such as doses, consumption of drugs or pharmaceuticals, alcohol and tobacco habits and diet also play a role in methylxanthine effects and metabolism. Therefore, our review is to provide a clearer understanding of the beneficial/adverse effects of methylxanthines in humans. A description of the physiological and toxicological effects of these methylxanthines is provided.
Page: 383-411 (29)
Author: Cristina Garcia-Viguera and Cristina Soler-Rivas
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Consumption of vegetables, cereals and fish products are highly recommended by nutritionist pyramidal outliners since they are important for the proper intake of all food nutrients needed for a healthy diet. However, despite the already well known compounds such as vitamins, minerals, essential amino acids etc. which are essential because human body cannot synthetize them by itself, these food also contains bioactive compounds (carotenoids, glucosinolates, flavonoids and other phenolic compounds, dietary fibers, ω3-fatty acids, etc.) showing specific functionalities far more important than the classical nutrition because they reduce the risk of several diseases by showing health beneficial properties such as i.e. antioxidant, immunomodulatory, anticancerogenic, hypocholesterolemic, antimicrobial activities. However, the culinary methods utilized, during the domestic processing of those foods, modify not only their nutritional composition but also the concentration and availability of the bioactive compounds, being cooking one of the most influencing because of the high temperatures utilized. The media and the technology used might also affect positively or negatively, i.e., the lower temperatures used during aqueous cooking are beneficial for carotenoids, dietary fibers and other compounds not soluble in water, but methods such as boiling induce leaching of water soluble compounds such as glucosinolates, phenols etc. Steam-pressure is detrimental for dietary fibers but reduces cooking times and osmotic processes making them suitable for the maintenance of water soluble compounds. Maillard reactions induced during dry heating or cooking using fats or oils as medium protect some compounds from leaching but destroy others because of the high temperatures generated. They also induce cross-linking impairing the proper digestion and absorption of formed complexes. The use of lipid medium during frying also modify the ω3/ ω6 ratio of products containing ω3-polyunsaturared fatty acids.
Page: 412-418 (7)
Author: M. Victorina Aguilar and Cristina Otero
Functional foods (foods with known bioactive properties) have shown potential for preventive and therapeutic treatments. However, this potential must be safely determined before they enter the commercial market. At the same time, nutrition research is transforming into a data driven field with reference to the identification and development of functional food products due to the large number of variables affecting food biochemistry in the human body. This volume presents reviews of recent advances in food chemistry, food technology and nutraceutical research (for diet therapy and cosmetics). Chapters in this volume cover a broad spectrum of topics: - drug discovery and development in the modern nutraceutical industry, - recent developments in the extraction, identification and quantification of bioactive peptides in foods, - concepts of bioavailability, bioaccessibility, bioactivity, bioefficiency and bioconversion of bioactive foods, - synthetic routes for obtaining bioactive compounds, - the role of nutrigenomics to identify key cellular functions by specific genetic and epigenetic interactions with a nutrient, - anti-cancer properties of important bioactive components of medicinal plants, - the effect of a diet based on different bioactive foods on prevention and treatment of diabetes, - antioxidant effects on cardiovascular disease, - beneficial effects of bioactive foods on metabolic syndrome, - the potential of tauroursodeoxycholic acid on prevention and recovery of neurodegenerative diseases, - the effects of natural phytochemicals in prostate cancer, - the effects of methylxanthines (caffeine and others), and culinary methods on physiological and toxicological effects of the bioactive food constituents. The volume is an ideal reference for pharmacy students, nutritionists, healthcare providers and nutraceutical R&D specialists interested in functional foods. [Series Intro] Frontiers in Bioactive Compounds brings edited reviews on the analysis and characterization of natural compounds of medicinal interest. Each volume covers useful information on a variety of natural sources as well as analytical techniques. This series is essential reading for analytical and medicinal chemists as well as professionals involved in natural and pharmaceutical product research and development.