Molecular Mechanisms of Functional Food E-Book
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MOLECULAR MECHANISMS OF FUNCTIONAL FOOD Comprehensive resource for understanding state-of-the-art mechanisms behind food health effects This book provides information on the development and validation of functional foods towards their market and industrial application. It covers the available information on developments, efficacy, and testing and safety, while demonstrating the proven or potential effects of food on health and disease. With contributions from the foremost experts in the field, this book will bring readers up to speed on the state of the art in the mechanisms behind food health effects, from their physiological bases to their conception, current uses, and future developments. Sample topics covered by the authors include: * The molecular mechanisms of action of antioxidant fibers, prebiotics, ginger, and cinnamon * Saffron, a functional food with potential molecular effects * Pseudocereals, ancestral grains that can serve as a source of bioactive compounds for functional foods * Molecular effects of future functional foods - psychobiotics, chronobiotics, hempseed, opuntia, common and carioca beans, coffee and cocoa by-products Food industry professionals, government workers involved in projects related to food, and students in programs of study related to food can use this book as an up-to-date reference to fully understand the effects that many common and uncommon foods have on humans.
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Table of Contents
Cover
Title Page
Copyright Page
List of Contributors
Preface
Part I: Functional Food Bioactives
1 Polyphenolic Compounds Mechanisms as Inhibitors of Advanced Glycation End Products and Their Relationship to Health and Disease
1.1 Introduction
1.2 Glycation Reaction and Formation of Advanced Glycation End Products Formation
1.3 Current and Future Perspectives
1.4 Conclusion
References
2 Psychobiotics, a Special Type of Probiotics, and Their Potential Molecular Mechanisms to Ameliorate Symptoms of Stress and Anxiety
2.1 Stress, Anxiety, and Depression, a Public Health Concern
2.2 Physiological Response to Stress: The HPA Axis
2.3 Psychobiotics for the Treatment of Stress‐Related Conditions
2.4 Potential Mechanisms of Psychobiotic Activity
2.5 Limitations of Psychobiotic Research
2.6 Current and Future Perspectives of Psychobiotics Market
2.7 Conclusion
References
3 Molecular Mechanisms of Chronobiotics as Functional Foods
3.1 Introduction
3.2 Circadian Clock and Diseases
3.3 Regulation of Circadian Clocks
3.4 Chronobiotics as Functional Foods
3.5 Current Trends and Perspectives
References
Part II: Functional Food
4 Common Beans Bioactive Components and Their Potential to Modulate Molecular Markers of Obesity and Type 2 Diabetes
4.1 Introduction
4.2 Conclusion
References
5 Benefits of Carioca Beans (
Phaseolus vulgaris
)
5.1 Introduction
5.2 Health Benefits of Compounds in Carioca Beans
5.3 Bioactive Compounds in Carioca Beans
5.4 Potential Benefits of Compounds in Carioca Beans in The Modulation of The Gut Microbiota
5.5 Potential Functional Foods/Industry Products
References
6 Molecular Effects of Bioactive Compounds from Semi‐Desert Plants and Their Uses as Potential Ingredient in Food Products
6.1 Introduction
6.2 Traditional Uses of Semi‐Desert Plants
6.3 Semi‐Desert Plants and Bioactive Compounds
6.4 Antioxidants from Semi‐Desert Plants and Health Effects
6.5 Carotenoids from Semi‐Desert Plants and Health Effects
6.6 Polyphenols from Semi‐Desert Plants and Health Effects
6.7 Vitamins from Semi‐Desert Plants and Health Effects
6.8 Flavonoids from Semi‐Desert Plants and Health Effects
6.9 Bioactive Compounds as Potential Ingredient in Food Products
6.10 Future Trends
6.11 Conclusions
References
7
Opuntia, ficus‐indica
[L.] Mill. and Other Species
7.1 Introduction
7.2 Bioactive Compounds in the
Opuntia
Genus
7.3 Biological Activities of
Opuntia
7.4 Effect of
Opuntia
spp. Extracts Against Several Diseases and Mechanisms of Action
7.5 Current and Potential Applications for Functional Food
7.6 Conclusions
References
8 Molecular Mechanisms of Edible Macro‐ and Microalgae as Functional Foods or Sources of Nutraceuticals
8.1 Introduction
8.2 Cardioprotective Effects of Selected Macroalgae
8.3 Antidiabetic Effects of Selected Macroalgae
8.4 Anticarcinogenic Effects of Selected Macro‐ and Microalgae
8.5 Antiviral Effects of Selected Macro‐ and Microalgae
8.6 Current and Future Perspectives
Acknowledgments
References
9 Hempseed
9.1 Introduction
9.2 Hempseed Characteristics
9.3 Hempseed Oil and Fatty Acid Composition
9.4 Proteins
9.5 Carbohydrates
9.6 Phenolics
9.7 Minor Components
9.8 Molecular Mechanism of Action
9.9 Current Trends and Perspectives
References
10 Phytochemicals and Functional Properties of Coffee: Molecular Mechanism of Action
10.1 Introduction
10.2 Classification of Nutraceuticals
10.3 Regulation of Nutraceuticals
10.4 Current Landscape on Nutraceuticals
10.5 Nutraceuticals and Health
10.6 Bioactive Compounds from Coffee
10.7 Extraction of Bioactive Compounds from Coffee
10.8 New Coffee‐based Food Products, Nutraceuticals, and Supplements Commercialized, Patented, and in Progress
10.9 Conclusion
10.10 Acknowledgments
References
Web References
11 Coffee Proteins
11.1 Introduction
11.2 Coffee as an Alternative Protein Source
11.3 Protein Extraction from Coffee and Coffee By‐products
11.4 Nutritional Value of Coffee Proteins
11.5 Food Safety of Coffee Proteins
11.6 Biological Properties of Coffee Proteins and Their Derivatives
11.7 Conclusions
Acknowledgments
References
12 Coffee, Ginger and Cinnamon
12.1 Introduction
12.2 Bioactive Compounds in Coffee, Ginger, and Cinnamon
12.3 Molecular Mechanisms of Bioactive Compounds in Coffee, Ginger, and Cinnamon for Preventive Noncommunicable Chronic Diseases
12.4 Conclusions
References
13 Chontaduro (
Bactris gasipaes
Kunth)
13.1 Introduction
13.2 Agronomical Description and Cultural Aspects
13.3 Bioactive Compounds
13.4
In vitro
and
in vivo
Studies Featuring the Biological Potential of Chontaduro
13.5 Conclusions and Final Remarks
References
14 Saffron
14.1 Introduction
14.2 Botanical Review
14.3 Chemistry of Saffron
14.4 Bioavailability of Saffron
14.5 Bioactivity of
C. sativus
L. Compounds
14.6 Metabolism of Saffron
14.7 Analytical Methods for Saffron
14.8 Antioxidant Properties of Saffron
14.9 Health Benefits of Saffron
14.10 Conclusion and Future Perspectives
References
15 Cocoa Shell
15.1 Introduction
15.2 Cocoa Shell: From Field to Functional Foods Industry
15.3 Molecular Mechanisms of Bioactive Compounds from Cocoa Shell in Preventing Cardiometabolic Diseases
15.4 Future Perspectives on the Preventive Effects of Cocoa Shell on Cardiometabolic Diseases
15.5 Concluding Remarks
References
16 Pseudocereals
16.1 Introduction
16.2 Pseudocereals Bioactive Compounds
16.3
In Vitro
,
In Vivo
, and Human Bioactivity of Pseudocereals
16.4 Biomarkers
16.5 Conclusions and Perspectives
References
17 Berries as Functional Foods
17.1 Introduction
17.2 Bioactives in Berries and Mechanism of Action
17.3 Conclusion and Outlook
Acknowledgments
References
Index
End User License Agreement
List of Tables
Chapter 1
Table 1.1 Mechanisms of antiglycant action of extracts rich in phenolic comp...
Chapter 2
Table 2.1 Psychobiotic double‐blind randomized placebo‐controlled trials for...
Table 2.2 GABA‐producing bacteria and some fermented food containing gamma‐a...
Table 2.3 Effect of administering fermented food containing GABA or GABA‐pro...
Table 2.4 Probiotic interventions in stress‐related conditions, where the po...
Table 2.5 Patented psychobiotics and their claimed effects on mental health....
Chapter 3
Table 3.1 Advances in scientific publication on chronobiology, chrononutriti...
Chapter 4
Table 4.1 Main commercialized common beans and their health benefits.
Table 4.2 Recommend daily percentage of macro and micronutrients vs. percent...
Table 4.3 Main bioactive components in common beans.
Table 4.4 Antidiabetes and antiobesity potential of common beans.
Chapter 5
Table 5.1 Mineral content (mg kg
−1
) of carioca beans.
Table 5.2 Bioactive peptides of carioca beans and their
in vivo
and
in vitro
Table 5.3 Hydrophobicity of bioactive peptides present in carioca bean.
Table 5.4 Phenolic compounds and antioxidant activity of carioca beans.
Table 5.5 Polyphenolic compounds of Fe‐biofortified and Fe standard carioca ...
Table 5.6 Phylum and genus abundance (%) in the gut microbiota with the Fe‐b...
Chapter 6
Table 6.1 Differences between carotenes and xanthophylls including examples ...
Table 6.2 Semi‐desert plants and their polyphenols.
Table 6.3 Vitamins content in fresh and dry Opuntia fruit.
Table 6.4 Beneficial effects of flavonoids from semi‐desert plant in human h...
Chapter 7
Table 7.1 Bioactive compounds present in different
Opuntia
species.
Table 7.2 Biological activities in different parts of
Opuntia
spp. plant....
Table 7.3 Main studies in human subjects with
Opuntia
spp. cladode consumpti...
Table 7.4 Possible mechanisms of action of
Opuntia
spp. extracts tested in
i
...
Chapter 9
Table 9.1 Hempseed composition (g/kg dry matter).
Table 9.2 Composition (g/kg dry matter) of hempseed and its derivatives.
Table 9.3 Fatty acid contents of hempseed.
Table 9.4 Phytosterol content (mg/kg) of hempseed oil, seed, and cake flour....
Table 9.5 Tocopherol content (mg/kg) of hempseed oil.
Table 9.6 Fatty acid composition (% weight) of total phospholipids and lipid...
Table 9.7 Amino acid profiles of selected hempseed products.
Table 9.8 Amino acid profiles of hempseed proteins.
Table 9.9 Amino acid (%) profile of hempseed protein hydrolysates.
Table 9.10 Unique peptides in tryptic digest of cold‐pressed hempseed oil....
Table 9.11 ACE‐inhibitor peptides.
Table 9.12 Carbohydrate composition (g/kg dry matter) of hempseed products....
Table 9.13 Phenolic content (μg/kg fresh weight) of cold‐pressed “
Finola
” oi...
Table 9.14 Phenolic content (mg/kg) of untreated and roasted hempseed.
Table 9.15 Phenypropionamide content (mg/g) of raw and extruded hempseed hul...
Table 9.16 Mineral contents (mg/kg) of hempseed and its products.
Table 9.17 Effects of hempseed oil at the cellular level.
Table 9.18 Animal studies.
Table 9.19 Human studies.
Table 9.20 Protein studies.
Table 9.21 Benefits of hempseed phytochemicals.
Chapter 10
Table 10.1 Nutraceuticals’ classifications based on the foods available in t...
Table 10.2 Nutraceuticals classifications based on their origin, use, and me...
Table 10.3 Principal methods and techniques to extract bioactive compounds f...
Chapter 11
Table 11.1 Nutrition (Regulation (EC) No. 1924/2006) and health (Commission ...
Table 11.2 Methods used to extract proteins from coffee by‐products.
Table 11.3 Amino acid composition of coffee derivatives and conventional pro...
Table 11.4 Examples of peptides obtained by protease digestion from coffee o...
Table 11.5 Biological parameters of amino acids (g/100 g of total amino acid...
Chapter 12
Table 12.1 Bioactive compounds and health benefits of coffee, ginger, and ci...
Chapter 13
Table 13.1 Proximal composition (%) of whole chontaduro (
B. gasipaes
Kunth) ...
Table 13.2 Amino acid profile (g/100 g protein) of yellow and red chontaduro...
Table 13.3 Fatty acid composition of chontaduro mesocarp (%).
Table 13.4 Bioactive compounds of chontaduro (
B. gasipaes
Kunth) fruit pulp....
Table 13.5 Biological properties of chontaduro (
B. gasipaes
Kunth) bioactive...
Chapter 14
Table 14.1 The plant profile (systematic classification) of
C. Sativus.
Table 14.2 The chemical identity of active components in the
Crocus
genus.
Table 14.3 Summary of the main bioactivity of saffron and its bioactive mole...
Table 14.4 Bioactivities of phenolic compounds of saffron and floral bioresi...
Table 14.5 Analytical techniques for saffron analysis.
Chapter 15
Table 15.1 Nutritional and chemical composition of the cocoa shell.
Chapter 16
Table 16.1 Proximal composition (g/100 g) of the main pseudocereals.
Table 16.2 Major bioactive phytochemicals and their concentrations (mg/kg) i...
Table 16.3 Bioactivity of pseudocereals.
Chapter 17
Table 17.1 Bioactive components of berries responsible for biological activi...
Table 17.2
In vitro
,
in vivo
, and human intervention studies of most common ...
List of Illustrations
Chapter 1
Figure 1.1 Overview of of AGEs formation.
Figure 1.2 Origin of AGEs classification. AGEs with fluorescence properties ...
Chapter 2
Figure 2.1 Fundamental mechanisms of the hypothalamic–pituitary–adrenal (HPA...
Figure 2.2 Publications about psychobiotics according to Pub Med data.
Figure 2.3 Mechanisms of psychobiotic activity that affect the hypothalamic–...
Chapter 3
Figure 3.1 Circadian rythm, endocrine response, and body functions are contr...
Figure 3.2 The molecular clock. Figure created with BioRender.
Figure 3.3 Food bioactive compounds with chronobiotic potential.
Figure 3.4 Food bioactive compounds with chronobiotic potential: molecular m...
Chapter 4
Figure 4.1 Native
Phaseolus vulgaris
L. from Oaxaca, Mexico.
Figure 4.2 Diagram for the extraction, purification, and identification of b...
Figure 4.3 Role of obesity in the pathophysiology of the disease (Gadde et a...
Chapter 5
Figure 5.1 Carioca beans: a and b – freshly harvested; c and d – grains stor...
Figure 5.2 Phaseolin subunits.
Figure 5.3 Potential mechanism of action of bioactive peptides and phenolic ...
Figure 5.4 Flowchart of carioca bean tempeh preparation and its hamburger....
Chapter 6
Figure 6.1 Health effects from Mexican semi‐desert plants flavonoids and mec...
Chapter 7
Figure 7.1 Number of publications on
Opuntia
according to PubMed.
Figure 7.2 Phenolic compounds identified in
Opuntia
genus. (a) Phenolic acid...
Figure 7.3 Structure of some betalains present in
Opuntia
. (Drawings were do...
Figure 7.4 Mechanisms of hypoglycemic action of
O. ficus‐indica
fruit ...
Figure 7.5 Obesity‐preventing mechanism of isorhamnetin. Isorhamnetin can pr...
Figure 7.6 Prickly pear fruit biological activities and mechanisms of action...
Figure 7.7
Opuntia
cladode biological activities and mechanisms of action.
Chapter 8
Figure 8.1 Phloroglucinol (1,3,5‐trihydroxybenzene) and dieckol phlorotannin...
Figure 8.2 Generalized structures of alginate polymers from brown kelp macro...
Figure 8.3 Structures of fucoidan and sulfated fucan from brown kelp macroal...
Figure 8.4 Xanthophylls found in selected macro‐ and microalgae.
Chapter 9
Figure 9.1 (a) Hempseed stained for lignin with phloroglucinol; hempseed hul...
Figure 9.2 Stereomicroscope image (a) and semi‐thin section stained with PAS...
Figure 9.3 Hempseed proteins, edestin 1, 2, and 3 (
CsEde1
,
CsEde2,
and
CsEde
...
Figure 9.4 SARS‐CoV‐2 main protease complex conformation with (a) cannabisin...
Figure 9.5 The two nor‐lignanamides (Sativamide A and Sativamide B) derived ...
Figure 9.6 Common NF‐κB signaling pathway for hempseed oil, protein, and lig...
Figure 9.7 Molecular mechanisms of hempseed and its components. Upregulated ...
Chapter 10
Figure 10.1 Structure of coffee cherry (1) outer skin (pericarp/exocarp), (2...
Chapter 11
Figure 11.1 Protein content in green coffee beans and coffee by‐products (a)...
Figure 11.2 The 7S globulin‐like (AOA6PWNJ1–1 [LOC113734078])
Coffea arabica
Chapter 12
Figure 12.1 Activation of NrF2 pathway induced by compounds from coffee, gin...
Figure 12.2 Antidiabetic mechanisms induced by phytochemicals of coffee, gin...
Figure 12.3 Cardiovascular protection, hepatoprotective, and immunomodulator...
Chapter 13
Figure 13.1 (a) Chontaduro (
Bactris gasipaes
Kunth) fruits color diversity....
Chapter 14
Figure 14.1 Different parts of
Crocus sativus
L. (Saffron) Plant (Shahi, Ass...
Chapter 15
Figure 15.1 Cocoa processing stages (a) from harvesting to roasting, includi...
Figure 15.2 Biorefinery approach in the revalorization of the cocoa shell th...
Chapter 16
Figure 16.1 Molecular and cellular biomarkers influenced by phytochemicals, ...
Figure 16.2 Systemic biomarkers influenced by phytochemicals, extracts, frac...
Chapter 17
Figure 17.1 Various bioactive components in edible berries.
Figure 17.2 Antioxidant and anti‐inflammatory effect of berries
Figure 17.3 Proposed scheme for anti‐atherogenicity effects of anthocyanins ...
Figure 17.4 Schematic representation summarizing potential mechanisms contri...
Guide
Cover Page
Title Page
Copyright Page
List of Contributors
Preface
Table of Contents
Begin Reading
Index
Wiley End User License Agreement
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Molecular Mechanisms of Functional Food
Edited by
Rocio Campos‐Vega
Postgraduate Program in Food of the Center of the Republic (PROPAC), Research and Graduate Studies in Food Science, School of Chemistry, Universidad Autónoma de Querétaro, Santiago de Querétaro, Mexico
B. Dave Oomah
(Retired) Formerly with Summerland Research and Development Centre, Agriculture and Agri‐Food Canada, Summerland, BC, Canada
This edition first published 2023© 2023 John Wiley & Sons Ltd.
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Library of Congress Cataloging-in-Publication DataNames: Campos-Vega, Rocio, editor. | Oomah, B. D. (B. Dave), editor.Title: Molecular mechanisms of functional food / edited by Rocio Campos-Vega, B. Dave Oomah.Description: Hoboken, NJ : Wiley, 2022. | Includes bibliographical references and index.Identifiers: LCCN 2022033406 (print) | LCCN 2022033407 (ebook) | ISBN 9781119804024 (hardback) | ISBN 9781119804031 (adobe pdf) | ISBN 9781119804048 (epub)Subjects: LCSH: Functional foods. | Bioactive compounds.Classification: LCC QP144.F85 M65 2022 (print) | LCC QP144.F85 (ebook) | DDC 613.2–dc23/eng/20220830LC record available at https://lccn.loc.gov/2022033406LC ebook record available at https://lccn.loc.gov/2022033407
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List of Contributors
Cristóbal N. AguilarFood Research Department School of Chemistry Universidad Autónoma de Coahuila Saltillo, Mexico
Clara AlbanoInstitute of Sciences of Food Production (ISPA), CNR, Lecce, Italy
Priscila Zaczuk BassinelloEmbrapa Rice and Beans Santo Antônio de Goiás, Goiás, Brazil
Juliana Aparecida Correira BentoSchool of Agronomy Federal University of Goiás (UFG)Goiânia, Brazil
Irshad Ul Haq BhatDepartment of Applied Sciences, Chemistry SectionUniversity of Technology and Applied SciencesAl‐Khuwair, Muscat, Oman
Rajeev BhatERA‐Chair for Food (By‐) Products Valorisation Technologies (VALORTECH), Estonian University of Life Sciences, Tartu,Estonia, EU
Federica BlandoInstitute of Sciences of Food Production (ISPA), CNR, Lecce, Italy
Cheyenne BraojosDepartment of Agricultural Chemistry and Food Science Universidad Autónoma de Madrid,Madrid, Spain
Martín Calderón‐JuárezPlan de Estudios Combinados en Medicina, National Autonomous University of Mexico,Faculty of Medicine, Mexico City, Mexico
Pedro de Souza Freitas CamposBioprocess LaboratoryFood Science and Nutrition Department,School of Engineering,University of Campinas,Campinas, SP, Brazil
Rocio Campos‐VegaPrograma de Posgrado en Alimentos del Centro de la Republica (PROPAC),Research and Graduate Studies in Food Science,School of Chemistry,Universidad Autónoma de Queretaro (UAQ),Queretaro, Mexico
Silvia CañasDepartment of Agricultural Chemistry and Food Science,Universidad Autónoma de Madrid,Madrid, Spain
Paz Cano‐MuñozDepartment of Agricultural Chemistry and Food Science,Universidad Autónoma de Madrid,Madrid, Spain
Anaberta Cardador‐MartínezEscuela de Ingenieria y Ciencias,Departamento de Bioingenierias,Tecnologico de Monterrey,Queretaro, Mexico
Eugenia Lugo‐CervantesTecnologia Alimentaria,Centro de Investigación y Asistencia en Technologia y Diseño del Estado de JaliscoA.C., CIATEJ, ZapopanJalisco, Mexico
Mónica L. Chávez‐GonzálezFood Research Department,School of Chemistry,Universidad Autónoma de Coahuila Saltillo, Mexico
Marisol Cruz‐RequenaSchool of ChemistryAutonomous University of CoahuilaSaltillo, Coahuila, Mexico
Behrokh Daei‐HasaniDepartment of BiologyPayame Noor UniversityTehran, Iran
Maria Dolores del CastilloInstituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC‐UAMCalle Nicolás CabreraMadrid, Spain
Laura Guspí DomènechInstituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC‐UAMCalle Nicolás CabreraMadrid, Spain
Elisa Dufoo‐HurtadoPrograma de Posgrado en Alimentos del Centro de la Republica (PROPAC)Research and Graduate Studies in Food ScienceSchool of ChemistryUniversidad Autónoma de Queretaro (UAQ)Queretaro, Mexico
Adriana Carolina Flores‐GallegosSchool of ChemistryAutonomous University of CoahuilaSaltillo, Coahuila, Mexico
Alessandra GamberoBioprocess LaboratoryFood Science and Nutrition DepartmentSchool of EngineeringUniversity of CampinasCampinas, SP, Brazil
Jesus David García‐OrtizSchool of ChemistryAutonomous University of CoahuilaSaltillo, Coahuila, Mexico
Vanize M. GenovaBioprocess LaboratoryFood Science and Nutrition DepartmentSchool of EngineeringUniversity of CampinasCampinas, SP, Brazil
Mariana Juste Contin GomesDepartment of Nutrition and HealthFederal University of Viçosa (UFV)Viçosa, Brazil
Ena GuptaDepartment of Home ScienceUniversity of AllahabadAllahabad, India
David Fonseca‐HernandezTecnologia AlimentariaCentro de Investigación y Asistencia en Technologia y Diseño del Estado de JaliscoA.C., CIATEJ, ZapopanJalisco, Mexico
Alan Javier Hernández‐ÁlvarezSchool of Food Science and NutritionUniversity of LeedsLeeds, UK
Tana Hernandez‐BarruetaDepartment of Food ScienceUniversity of CaliforniaDavis, USA
Amaia Iriondo‐DeHondInstituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC‐UAMCalle Nicolás CabreraMadrid, Spain
Cristian Jiménez‐MartínezEscuela Nacional de Ciencias BiológicasInstituto Politécnica NacionalMexico City, Mexico
Maria Bibiana Zapata LondoñoSchool of Nutrition and DieteticsUniversity of AntioquiaMedellin, Colombia
Ivan Luzardo‐OcampoInstitute of NeurobiologyUniversidad Nacional Autónoma de México (UNAM)Queretaro, Mexico
Gabriela A. MacedoBioprocess LaboratoryFood Science and Nutrition DepartmentSchool of EngineeringUniversity of CampinasCampinas, SP, Brazil
Maria Elena Maldonado‐CelisFaculty of Health SciencesUniversity of QuindioArmenia, Colombia
Maria A. Martín‐CabrejasInstitute of Food Science Research (CIAL) (UAM‐CSIC)Madrid, Spain
Hércia Stampini Duarte MartinoDepartment of Nutrition and HealthFederal University of Viçosa (UFV)Viçosa, Brazil
Guiomar Melgar‐LalanneCentro de Investigaciones BiomédicasUniversidad VeracruzanaXalapa, Mexico
Martin MondorSt‐Hyacinthe Research and Development CentreAgriculture and Agri‐Food CanadaSaint‐Hyacinthe, Quebec CityCanada & Institute of Nutrition and Functional Foods (INAF)Université Laval, Quebec City Canada
Luis MojicaTecnologia Alimentaria, Centro de Investigación y Asistencia en Technologia y Diseño del Estado de JaliscoA.C., CIATEJ, ZapopanJalisco, Mexico
Jose Edgar Zapata MontoyaUniversidad de Antioquin (UdeA)MedellinAntioquia, Colombia
Sendar Daniel Nery FloresSchool of ChemistryAutonomous University of CoahuilaSaltillo, Coahuila, Mexico
Menandes Alves de Souza NetoSchool of AgronomyFederal University of Goiás (UFG)Goiânia, Brazil
B. Dave Oomah(Retired) Formerly with Summerland Research and Development CentreAgriculture and Agri‐Food CanadaSummerland, BC, Canada
Johanny Aguillón OsmaFaculty of Exact and Applied SciencesInstituto Tecnológico MetropolitanoMedellin, Colombia
Sandra Pacios‐MichelenaFood Research DepartmentSchool of ChemistryUniversidad Autónoma de CoahuilaSaltillo, Mexico
A. Sócrates Palacios‐PonceFacultad de Ingenieria en Mecánica y Ciencias de la ProducciónEscuela Superior Politécnica del Litoral (ESPOL)Polytechnic UniversityGuayaquil, Ecuador
Lissethe Palomo‐LigasSchool of ChemistryAutonomous University of CoahuilaSaltillo, Coahuila, Mexico
Shazia ParveenChemistry DepartmentFaculty of ScienceTaibah UniversityYanbu, Saudi Arabia
Claudia Mariana Pérez‐JuárezSchool of ChemistryAutonomous University of CoahuilaSaltillo, Coahuila, Mexico
Yousef RasmiDepartment of BiochemistryFaculty of Medicine & Cellular and Molecular Research CenterUrmia University of Medical Sciences, Urmia, Iran
Miguel Rebollo‐HernanzDepartment of Agricultural Chemistry and Food ScienceUniversidad Autónoma de MadridMadrid, Spain
Mario E. Rodríguez‐GarcíaDepartamento de Nanotechnologia,Centro de Fisica Aplicada y Technologia AvanzadaUniversidad Nacional Autónoma de México (UNAM)‐Campus Juriquilla, Queretaro, Mexico
Raúl Rodriguez‐HerreraSchool of ChemistryAutonomous University of CoahuilaSaltillo, Coahuila, Mexico
Elihud SalazarCentro Universitario de la CostaUniversity of GuadalajaraPuerto Vallarta, Mexico
Maria del Pilar SalazarUniversidad de Antioquin (UdeA) MedellínAntioquia, Colombia
Salvador A. Saldaña‐MendozaFood Research DepartmentSchool of ChemistryUniversidad Autónoma de CoahuilaSaltillo, Mexico
Oscar Abel Sánchez‐VelázquezFacultad de Ciencias Químico‐BiológicasUniversidad Autónoma de SinaloaCuliacan, Mexico
Olga Lucia Torres‐VargasResearch Group on Agroindustrial SciencesInterdisciplinary Science InstituteUniversidad del QuindioArmenia, Colombia
Maria Lilibeth Manzanilla ValdezSchool of Food Science and NutritionUniversity of LeedsLeeds, UK
Leidy Johana Valencia‐HernándezFood Research DepartmentSchool of ChemistryUniversidad Autónoma de CoahuilaSaltillo, Mexico
Montserrat Alcazar‐ValleTecnologia AlimentariaCentro de Investigación y Asistencia en Technologia y Diseño del Estado de JaliscoA.C., CIATEJ, ZapopanJalisco, Mexico
Abraham Wall‐MedranoInstituto de Ciencias BiomédicasUniversidad Autónoma de Ciudad JuárezChihuahua, Mexico
Yvonne V. YuanSchool of NutritionToronto Metropolitan University,Toronto, Ontario, Canada
Diego Fernando Uribe YundaSchool of Nutrition and DieteticsUniversity of AntioquiaMedellín, Colombia
Preface
The global functional food ingredients market valued at US $98.9 billion in 2021 is forecast to reach US $137.1 billion by 2026 due to increased consumption of nutritive convenience and fortified foods according to markets. The key functional food ingredients include amino acids, antioxidants, carotenoids, hydrocolloids, minerals, plant extracts, and prebiotics. However, plant sources of these food ingredients (proteins, omega‐3 fatty acids, fibers, phytochemicals, and plant extracts) is the fastest growing segment because of their low carbon footprint, increasing consumer awareness of their health benefits and industry drive toward complete utilization to reduce by‐product waste. The SARS‐CoV‐2 (COVID‐19) pandemic and current boom in functional foods have led to the development of entirely novel ingredient sectors including probiotic and prebiotic components, foods that enhance immunological tolerance, improve physical and mental well‐being, and protect against oxidative stress and chronic diseases, among other health benefits.
The first chapter illustrates the importance of phenolic compounds in improving human health by exerting considerable antiglycation potential to reduce disease progression (particularly diabetes and ageing) by different mechanisms. Many antiglycating phenolic compounds can be recovered from industrial by‐products (e.g. citrus residues or other fruit pulps, grape marc, and peanut processing), millets, algaes, cinnamon, and herbal plants, providing a roadmap for further large‐scale development of natural products to reduce the risk and/or prevent various pathologies.
In a global consumer survey, ‘mental wellbeing’ ranked top of health concerns according to Euromonitor market analysis. The survey also revealed that 57% of global respondents suffer at least ‘moderate’ levels of stress, suggesting an opportunity for innovation. Psychobiotics can be considered one of the potential consumer products that can alleviate stress. Psychobiotics are a class of probiotics that, when ingested in adequate amounts, induce health benefits in patients with psychiatric illness. Some psychobiotics, for example, Lactobacillus plantarum PS128™, reduce anxiety and depression and improve visceral hypersensitivity, exerting their psychotropic effects by altering monoamine neurotransmitter levels and by modulating glucocorticoid, anti‐inflammatory and antioxidative responses, and sleep structure among highly stressed individuals. Chapter 2 highlights two main mechanisms of action for potential psychobiotic activity. The first is the production of gamma‐aminobutyric acid (GABA), the major inhibitory neurotransmitter in the human central nervous system, and the second is modulation of host serotonin production. The benefits of psychobiotic interventions are also discussed, along with limitations in this research area. The South Korean Health Functional Food has commercialized a probiotic mixture NV‐1703 (Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98) representing an example of a good psychobiotic. NV‐1703 improved sleep quality (significant insomnia reduction) and gut microbiota and decreased depressive and anxiety symptoms in healthy adults in a recent randomized, double‐blind, placebo‐controlled trial.
Sleep disturbances are a common concern that has been further accelerated with the COVID‐19 pandemic. Natural circadian rhythm is adversely impacted by chronic sleep disturbances, particularly in the world’s most sleep‐deprived countries, Japan and China, where 41% of adults surveyed were unsatisfied with their sleep quality. Impaired sleep has been associated with several health consequences, including cardiovascular disease, chronic pain, neurodegenerative and cognitive disorders, depression, obesity, and all‐cause mortality. Sleep quality is influenced by eating patterns, diets, and food components (amino acids, fiber, polyphenolics, lipids, and alkaloids) that affect circadian rhythm. Chronobiotics (Chapter 3) is an emerging discipline with clinical and therapeutic potential to regulate circadian rhythm, modify dietary patterns, and promote chronobiotics intake. The chapter explores chronobiotics as functional foods, particularly natural products/compounds that synchronize and restore the circadian clocks and mechanisms that control clock‐controlled genes preventing circadian misalignment and associated disorders. Ongoing research shows that in vitro gastrointestinal digestion of pistachio increases phyto‐melatonin bio‐accessibility and colonic metabolites (i.e. short‐chain fatty acids [SCFAs]) biosynthesis with chronobiotic potential to mitigate chronodisruption associated diseases.
The common bean (Phaseolus vulgaris L.), one of the most widely cultivated legumes, forms part of the human daily diet in the Americas, Europe, Africa, and Asia. Two consecutive chapters (Chapters 4 and 5) demonstrate its health benefits; the first is related to bioactive components that modulate markers of noncommunicable diseases, particularly type 2 diabetes and obesity. These bioactive compounds (carbohydrates, carotenoids, dietary fiber, phytosterols, polyphenolics, proteins and peptides, saponins, and tocopherols) are associated with the antidiabetic and antiobesity potential of common beans. Carioca is the most favored bean type by consumers and growers in Brazil due to indigenous influence and early cultivation by Brazilian natives. Its evolution in the late 1960s restructured the Brazilian bean market due to its high productivity in low fertility soils, disease resistance, and fast cooking time, dominating the market to date. This is, to our knowledge, the first chapter focusing on carioca beans as functional foods and/ingredients. Chapter 5 describes the multitude of bioactive compounds present in carioca beans (peptides, phenolic compounds including anthocyanins, phytate, saponins, complex carbohydrates with resistant starch as prebiotics, minerals, and vitamins) responsible for its myriad health benefits. Carioca bean peptides, previously known only for their antioxidant and dipeptidyl peptidase‐IV inhibition, are now considered multifunctional (i.e. stomach mucosal membrane regulation, ubiquitin‐mediated proteolysis, neuroprotection, and memory enhancement and satiety [appropriate for weight management]). The modulation of gut bacteria by carioca bean is of prime importance, particularly in regard to studies demonstrating increased in vitro iron bioavailability of Fe‐biofortified compared to Fe‐standard carioca beans. These gut microbiome changes are primarily due to increased abundance of bacteria associated with phenolic catabolism and beneficial SCFAs‐producing bacteria. The first Brazilian plant‐based product uses carioca bean as an ingredient in vegetable chicken (shredded, strips, and cubes) extruded together with soy and pea proteins. Carioca beans as a cost‐competitive abundant raw material has a small environmental footprint with regional socioeconomic impact. Current research is aimed at producing carioca bean protein isolates and concentrates to formulate alternative “meat‐like” convenience products (e.g. hamburgers and meatballs) and promote further meat reduction consumption (~50%) in Brazil. Plant‐based products made with carioca bean protein are expected to provide quality, diversity, and accessibility of alternative protein sources to the Brazilian consumer.
The pandemic exacerbated food insecurity, highlighting the natural susceptibility to conventional farming that promoted local production by fostering geographical diversification. Sustainable, regenerative, and resilient farming systems and practices require biodiversity restoration simultaneously limiting water use. The investment in climate‐smart plants to integrate them and their products in the functional food sector is illustrated in two subsequent chapters. The bioactive compounds of the Mexican semi‐desert area endemic plants such as Agave, Opuntia, Prosopis, Jatropha, and others (Chapter 6) are described along with their physiological benefits, which can be exploited for functional food and nutraceutical ingredients. In addition to their traditional use, these plants and their bioactives offer health benefits such as antibacterial, anticancer, antioxidant, antiparasitic, hepatoprotective, and neurological effects, and vasodilator activities. Opuntia, one of these endemic plants, and its physiological health benefits is the focus of Chapter 7, since it grows either wild or cultivated in many countries. The antidiabetic activity of Opuntia cladode is of special interest to functional foods and nutraceuticals development based on results from clinical trials as well as its prebiotic effects in improving gut health. Recent studies have demonstrated the wound‐healing, hypocholesterolemic, and anti‐inflammatory effects of Opuntia, with potential applications in functional foods and other health‐related industries. Interestingly, many Opuntia‐derived products are already in the market.
Chapter 8 is dedicated to edible algae due to its chronic disease risk reduction in Asia and the Pacific where it is part of the daily diet that has spread (or taken root) in Western cultures. Several studies indicate the bioactive roles of edible macro‐ and microalgal constituents as functional foods and nutraceuticals. The biological and molecular mechanisms ascribed to these bioactives include anticarcinogenic, antidiabetic, antioxidant, antiviral, and cardioprotective effects as well as modulation of blood glucose and lipoprotein profiles. The food industry has benefited from algal research and introduced several products such as the docosahexaenoic acid (DHA)‐enriched European Union approved algal oil, protein with meat‐like properties, and antiviral products.
Hempseed (Chapter 9), an old world crop, is being recognized as “green, sustainable and environmentally friendly” due to its agronomic characteristics. However, regulation regarding cannabidiol (CBD) limits its production in many parts of the world, although industrial hempseed is distinct from other Cannabis (marihuana or drug type hemp). New regulation now enables production of industrial hemp (low tetrahydrocannabinol [THC]) that is already being considered for animal feed. In spite of this setback, research on industrial hemp has revealed its potential for human health benefits due to the high quality of its oil and the multifunctionality of its protein and peptides, as well as the lignanamides present in only a few crops. The chapter delves into detailed description of the composition of hempseed and its products (industrial coproducts), followed by extensive cellular, animal, and human studies of hempseed and/or its components. Interestingly, hempseed oil, protein, and lignanamides share a common mechanism of action in providing human health benefits. Notable are the convergence of studies demonstrating that several hempseed constituents can suppress or alleviate severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2).
We have dedicated three chapters to coffee, one of the highest globally traded food commodities. Chapter 10 reviews coffee’s bioactive compounds (cafestol, caffeine, chlorogenic acids, kahweol, sterols, and trigonelline), their extraction, bioactivity, and mechanisms of their physiological health benefits. The chapter also describes commercial new coffee‐based food products, nutraceuticals, and supplements particularly from by‐products and coproducts for complete circular sustainability of the coffee industry. Chapter 11 deals exclusively with coffee as an alternative protein source to diversify, upcycle, reduce environmental impact, and enhance sustainability of the coffee industry. Therefore, characteristics, quality, and peptides and biological parameters have been reviewed for proteins extracted from coffee by‐products, including cascara, green and defective coffee beans, silverskin, and spent coffee grounds. Some coffee protein products are already commercially available to formulate foods for human consumption. Previous studies and reviews have focused on coffee proteins mostly based on their association with coffee flavor, aroma, and quality. Chapter 12 reviews the molecular mechanisms of action of coffee on human health along with those of ginger and cinnamon. These mechanisms involve the prevention and/or regulation of chronic noncommunicable diseases associated with the antidiabetic, anti‐inflammatory, antioxidant, cardioprotective, and hepatoprotective effects of coffee and the abovementioned spices. The regulation and/or modulation of these mechanisms are ascribed to the major bioactive compounds of these natural products: caffeine and gallic acid from coffee; gingerols, shogaols, and paradols from ginger; and cinnamaldehyde, cinnamate, and cinnamic acid from cinnamon.
The last section of this book is dedicated to emerging (chontaduro, saffron, and cocoa shell) or established (pseudocereals and berries) crops or products. These emerging natural products, although elevating/promoting regional biodiversity, have previously not been considered as functional foods, presumably due to lack of investigations and/or interest. Chontaduro (Bactris gasipaes Kunth) or peach palm (Chapter 13), consumed mostly in Latin America, is a rich source of bioactive compounds (dietary fiber, carotenoids, and vitamins): like many Amazonian fruits, exhibiting antioxidant activity with health benefits. Chontaduro polysaccharides have high bifidogenic effect and its protein is highly digestible; the antioxidant and therapeutic effects are ascribed to bioavailable carotenoids with high retinol activity equivalents. Interest in saffron bioactives has increased recently because of their potential preventive and therapeutic applications due to their numerous and varied activities (antioxidant, anti‐inflammatory, anticarcinogenic, antigenotoxic, antimutagenic, antitumoural, cytotoxic, antihypertensive, antiatherogenic, antidiabetic, antihyperlipidemic, anticonvulsive, antidepressive, and neuroprotective). Chapter 14 describes the bioactivity of the three main saffron compounds: crocetin/crocins, picrocrocin, and safranal; saffron’s beneficial effects have been demonstrated in attenuating depression by regulating the endocannabinoid system in adults with major depressive disorders. Furthermore, clinical trials demonstrate the neuroprotective effects of saffron. The phenolic‐rich tepals, saffron’s main by‐product, exert hepatoprotective effects and improve renal function. Another industrial by‐product, cocoa shell (Chapter 15) is reviewed in regard to its biological activity and molecular mechanisms associated with the prevention of obesity, diabetes, and cardiovascular disease. These cardiometabolic disorders are attenuated by methylxanthines (theobromine and caffeine), phenolic compounds, and dietary fibers acting interactively or synergistically, thereby modulating various signaling pathways. Consumption of cocoa shell has potential human health benefits including cognitive and anticancer effects mediated by colonic‐derived metabolites from its bioactive compounds, according to ongoing research. Cocoa shells are already being used in snacks and its flour for production of muffins and biscuits. Moreover, cocoa shells are a source material for the production of extracts rich in fibers, polyphenols, and antioxidants for extensive applications in the functional food industry.
Pseudocereals (amaranth, buckwheat, chia, and quinoa) fostering regional crop biodiversity are regarded as “super‐foods” or alternative grains for celiac patients and/or gluten‐free diets. These ancient grains are increasingly popular in Western countries, form part of many diverse food products, and can be used to develop products and/or formulations to treat dysbiosis, celiac disease, lactose intolerance, inflammatory bowel diseases, and inflammation‐mediated disorders. Chapter 16 reviews pseudocereals bioactives in regard to in vitro, in vivo, and clinical data associating biological markers of diseases (cancer, cardiovascular diseases, diabetes, inflammation, and kidney diseases) at the subcellular, cellular, organ, and biological system levels. Berries have been the most valuable produce category in Europe due to increased consumption and research promoting the positive and profound impact of its intake on human health. It is interesting to note that two Latin American countries (Peru and Chile) are now major exporters of blueberries to Europe and other countries. The wide range of berry phytochemicals regulates the activities of metabolizing enzymes, modulates gene expression and signaling pathways, and repairs DNA oxidative damage. Chapter 17 recapitulates the multimechanistic actions of berry phytochemicals based on their important bioactivities (anti‐inflammatory, antidiabetic, antioxidant, cardioprotective, neuroprotective, anticancer properties). The chapter also includes studies demonstrating human health benefits of berry consumption to those with metabolic diseases and reducing type 2 diabetic risk in older populations.
This book provides useful up‐to‐date information to researchers, nutritionists, health, and industry professionals to advance the field of functional foods based on their mechanism of actions.
Rocio Campos‐Vega
B. Dave Oomah
Part IFunctional Food Bioactives
1Polyphenolic Compounds Mechanisms as Inhibitors of Advanced Glycation End Products and Their Relationship to Health and Disease
Vanize Martins Genova, Alessandra Gambero, Pedro de Souza Freitas Campos, and Gabriela A. Macedo
Bioprocesses Laboratory, Food Science and Nutrition Department, School of Food Engineering, University of Campinas, UNICAMP, Campinas, SP, Brazil
1.1 Introduction
The glycation reaction occurs when an amino group of a protein reacts with a carbonyl group of a reducing sugar, which through several cascades forms glycated proteins, which can undergo oxidation generating advanced glycation end products (AGEs) (Ahmed, 2005). These highly toxic products can be formed both endogenously and exogenously causing health problems.
Natural products have been used since antiquity by different societies to fight diseases. Currently, this field presents a promising path to develop formulations based on natural products on a large scale, through biotechnology (Sun et al., 2020), in order to provide sources of treatment and/or prevention for various pathologies through a product, as a functional ingredient or as a natural intervention (e.g. supplements). Phenolic compounds are widely studied for their high antioxidant capacity; these compounds are metabolites that have a regulatory role and response to infections in plants. Their structure consists of a benzene ring attached to at least one hydroxyl group (Moreno & Peinado, 2012), and its antiglycant capacity has been based on a possible direct relationship with its chemical structures (Xie & Chen, 2013).
Thus, phenolic compounds have demonstrated to be efficient as different inhibition mechanisms in AGEs formation and have been shown to be an intervention of great importance for health promotion and reducing complications and/or disease progression.
1.2 Glycation Reaction and Formation of Advanced Glycation End Products Formation
1.2.1 Advanced Glycation End Products—AGEs
AGEs are the final components of a reaction that takes place both in vivo (defined as an endogenous glycation reaction) and in food preparation processes (which can be defined as an exogenous Maillard reaction). In the human body, it occurs in the presence of proteins with a sugar reducer during the natural life process, common mostly in people with diabetes mellitus where high blood glucose levels induce this reaction. In foods, they are formed through the Maillard reaction, defined mainly as acrylamides ingested as a component of the diet.
The Maillard reaction, also known as the nonenzymatic browning reaction, consists of a series of reactions that modify color, aroma, and nutritional properties of foods. It begins with the formation of the Schiff base from the condensation via nucleophilic addition of carbonyls of reducing sugars with amino groups of lipids, nucleic acids, free amino acids, or their residues in peptides, aminophospholipids, or proteins (Jakus & Rietbrock, 2004). The Schiff base undergoes dehydration and rearrangements to a more stable and reversible form, called Amadori products. Amadori products, in turn, undergo dehydration, oxidation, and rearrangements, generating AGEs/acrylamides, or oxidize or hydrolyze to form carbonyl compounds. In addition to reducing sugars, other agents and/or processes produce the reactive carbonyl compounds known as α‐dicarbonyls or oxoaldehydes, such as the intermediates of the glycolytic pathway, the oxidation products of lipids, amino acids, and ascorbic acid by fragmenting phosphate trioses and catabolizing threonine and acetone (Monnier, 2003).
The α‐dicarbonyls have potential for glycation and react with ε‐amino groups of lysine, cysteine (cys) thiol (‐SH), arginine guanidino, and N‐terminal amino acids, leading to the formation of AGEs that have high thermal stability and, therefore, constitute the final phase of the Maillard reaction (Akillioglu & Gokmen, 2016; Barbosa, Souza, Santana, & Goulart, 2016; Wu, Huang, Lin, & Yen, 2011). As seen at the figure 1.1.
Figure 1.1 Overview of of AGEs formation.
Source: Adapted from Melo (2018).
AGEs can have harmful health effects when accumulated in the body. These effects arise from their interactions with proteins and/or cellular receptors, which lead to increased expression of inflammatory mediators, morpho‐functional changes, and oxidative stress (Ahmed, 2005; Bierhaus, Hofmann, & Nawroth, 1998). Thus, the glycation process is the main spontaneous cause of damage to cellular and extracellular proteins, mainly of long half‐life, with the loss of essential amino acids and formation of substances potentially harmful to health (Paul & Bailey, 1999; Thornalley et al., 2003).
Studies have shown an association between the formation and accumulation of AGEs with the progression of diseases such as diabetes mellitus, Alzheimer and Parkinson's (Li, Liu, Lu, & Zhang, 2012), atherosclerosis (Wang et al., 2012), renal insufficiency (Kalousova et al., 2006), neuropathy, retinopathy and cataracts (Ahmed, 2005), rheumatoid arthritis (Degroot, 2001), and liver cirrhosis (Sebekova, Kupcová, Schinzel, & Heiland, 2002), in addition to the aging process (Uribarri et al., 2007), development and/or complications related to aging, various metabolic and neoplastic diseases, among others (Ahmed, 2005).
AGEs are, therefore, a heterogeneous class of molecules that can be classified into two large groups based on the fluorescence property and crosslinking structure: (a) AGEs with fluorescence property and crosslinking structure and (b) AGEs without fluorescence property and without crosslinking structure (Wu, Huang, Lin, & Yen, 2011) and in six different classes, according to their origin (Takeuchi & Yamagishi, 2008) (Figure 1.2).
Figure 1.2 Origin of AGEs classification. AGEs with fluorescence properties and crosslinking structure (A); AGEs without fluorescence properties and without crosslinking structure (B); precursors in the formation of AGEs (C). Abbreviations: AGE‐1: glucose‐derived AGEs; AGE‐2: glyceraldehyde derivatives; AGE‐3: alpha‐dicarbonyl derivatives; AGE‐4: methyl glyoxal derivatives; AGE‐5: glyoxal derivatives; AGE‐6: 3‐deoxyglucosone derivatives. AGE: advanced glycation end products; GOLD: glyoxal‐lysine dimer; MOLD: methyl glyoxal‐lysine dimer; DOLD: lysine dimer and 3‐deoxyglucosone; GA: glycoaldehyde; CML: carboxymethyllsine; CEL: carboxyethyllisine; Arg‐Lys: arginine‐lysine; GLAP: pyridinium derived from glyceraldehyde; GO: glyoxal; DG: deoxyglucosone; 3‐DG: 3‐deoxyglucosone.
Source: Adapted from Melo (2018).
The reactive carbonyl compounds precursor to AGEs, called glyoxal (GO), methylglyoxal (MGO), and 3‐deoxyglucosone (3‐DG), are represented in Figure 1.2. GO and MGO present glycation potential around 200 times higher than glucose (Zeng, Dunlop, Rodgers, & Davies, 2006).
As explained, the deleterious effects on health are due to both the endogenous formation and exogenous sources of AGEs, as well as through a diet rich in these products (Koschinsky et al., 1997; Vlassara et al., 2002) and smoking. Studies show that the total AGEs consumed in common Western diet is greater than the amount present in biological systems, such as plasma and tissues (Henle, 2003). The urinary excretion of AGEs also demonstrates that 90% of pyrralin and fructoselysine are from dietary origin (Förster, Kühne, & Henle, 2005). The high chronic consumption of AGEs correlates with oxidative stress markers, which can overlap the body's antioxidant and detoxifying capacity, contributing to the pathophysiology of several diseases.
The content of AGEs in food is influenced by the distribution of macronutrients, mainly proteins and fats, in addition to numerous factors such as pH, cooking time, and temperature, the relationship between amino acid and carbohydrate, protein origin, carbohydrate reduction properties (mono‐, di‐, oligo‐, and polysaccharides), and glycoconjugate structure (Sanmartin, Arboleya, Villamiel, & Moreno, 2009). The binomial time and temperature of food processing contribute to a greater or lesser AGEs production, since cooking at high temperatures for extended period in limited water enables greater formation of these products (Uribarri et al., 2010). Among the different processing methods, those that showed the highest AGEs formation in decreasing order are grilling (225 °C), frying (177 °C), roasting (177 °C), and boiling (100 °C) (Goldberg et al., 2004).
Glycation also results in physical–chemical modifications of food proteins, directly influencing their functional properties and molecular weight (Liu, Ru, & Ding, 2012). These modifications include increased thermal stability (Sato, Sawabe, & Saeki, 2005), sparkling properties (Chobert, Gaudin, Dalgalarrondo, & Haertlé, 2006), and antioxidant activity (Lertittikul, Benjakul, & Tanaka, 2007), improved texture and emulsifying properties, and antimicrobial or bactericidal activity (Diftis & Kiosseoglou, 2004; Gerrard, Brown, & Fayle, 2003).
AGEs content is generally high in red meats, butter, cheese, margarine, mayonnaise, oils, nuts, tofu, fish, and eggs, but relatively low in carbohydrates‐rich foods particularly processed items, grains, milk, vegetables, starchy vegetables, and breads (Goldberg et al., 2004). Henle (2003) estimated, using chromatographic methods, the ingestion of glucotoxins in a conventional diet (containing heated milk, confectionery, and coffee) at around 1,500–4,000 μmol day−1 of derivatives from the Maillard reaction and around 100 to 300 μmol day−1 of AGEs [such as pyrralin and carboxymethyllysine (CML)]. AGEs consumption has been estimated at approximately 16,000 ± 5,000 kU day−1 based on the analysis of the 3‐day food record of 90 healthy North American individuals. However, information about the quantity and presence of reactive carbonyl compounds in foods is scarce due to the high reactivity and the possible polymerization or formation of adducts with other components during analyses (Uribarri et al., 2015).
Pyrraline and pentosidine AGEs have the highest absorption rate (60–80%). Most of the absorbed AGEs are simple amino acids, low‐molecular‐weight peptides, or high‐molecular‐weight compounds. Nε‐ CML is absorbed by passive diffusion, while pyrraline is absorbed into intestinal tissue via peptide transport. The path of protein digestion is the first step toward AGEs absorption, but the proteins in AGEs are modified and there is an impediment to the natural process to digestion and absorption. After digestion, fructoselysine and CML are associated with low‐molecular‐weight peptides (less than 1000 Da) making them easily absorbed. The absorption and assimilation of Nε‐1‐carboxyethyllysine (CEL) and CML were studied in rats by intravenous administration of these glycated compounds (Bergmann et al., 2001). AGEs reached and accumulated in the liver temporarily.
1.2.2 Detoxification Process
In addition to the metabolism itself, some resources such as drugs and food can also be used to protect cells and systems against glycation damage. Chemically, AGEs are products derived from the condensation reaction between the aldehyde group of sugars and the amino group of proteins. This reaction is more efficient and intense at pH 7.0 (Figure 1.2). The mechanisms of detoxification that begin after the aldimines formed at the initial phase are rearranged in covalent bonds to generate Amadori products. Up to this point, the reactions are reversible, stage when drugs or phytotherapies can act in order to prevent AGEs formation. After this phase, the numerous chemical rearrangements that Amadori compounds undergo to form AGEs are irreversible reactions (Figure 1.2). Several intermediate products are formed in this reaction cascade with different physiological effects. AGEs can be found in food in molecular forms as follows: CML, CEL, pyrraline, GO, MGO, acrylamide, furan, and derivatives of bis(lysyl)imidazolium, such as deoxyglucosone‐derived lysine dimer[1,3‐di(Nε‐lysino)‐4(2,3,4‐trihydroxybutyl)‐imidazolium salt] (DOLD) and GO‐derived lysine dimer[1,3‐di(Nε‐lysino) imidazolium salt] (GOLD).
Inhibitory mechanisms of formation and/or accumulation of advanced glycation products in vivo include reducing AGEs absorption, inhibiting Amadori products formation, decreasing carbonyl stress, preventing the progression of Amadori products to AGEs, and interrupting biochemical pathways and detoxification of dicarbonyl intermediates (Huebschmann, Regensteiner, Vlassara, & Reusch, 2006). The inhibitory mechanisms used are generally based on blocking the attack of proteins by carbonyls, preventing oxidative stress, or breaking crosslinks formed by AGEs (Peng, Ma, Chen, & Wang, 2011).
AGEs formed in tissues can be degraded by proteolysis or phagocytosed by macrophages mediated by scavenger receptors, which release them as small, soluble peptides excreted by the kidneys (Monnier, 2003). In addition, several systems are in place to limit tissue damage caused by glycation, which include reducing agents (glutathione), antioxidant and enzymatic pathways, and detoxifying systems (glyoxalase, aldose reductase, and aldehyde dehydrogenase) (Shinohara et al., 1998). The glyoxalase system present in the cytosol of all mammalian cells acts in the presence of glutathione, converting GO to glycolate and MGO to D‐lactate. This system uses the enzymes glyoxylase I and glyoxylase II, in addition to glutathione (Shangari & O’brien, 2004). Antioxidant pathways possibly act by attenuating oxidative stress by chelating metal ions and reducing free radicals (Peng et al., 2011).
1.2.3 Mechanisms of Detoxification and Intracellular Accumulation
1.2.3.1 Receptor for Advanced Glycation End Products (RAGE)
AGEs are capable of inducing cellular responses through signaling at receptors. The detoxification mechanism is related to receptor for advanced glycation end products (RAGE) initially described in 1992 as a transmembrane protein of the immunoglobulin superfamily (Neeper et al., 1992; Schmidt et al., 1992). Subsequently, numerous splicing variants have been described at mRNA and protein level. The detailed structure of the integral protein (full‐length RAGE protein), the membrane RAGE (mRAGE), is composed of three immunoglobulin domains: the extracellular one that consists of a type V and two types C (C1 and C2), a transmembrane domain, and a short C terminal cytoplasmic domain (Koch et al., 2010; Park, Adsit, & Boyington, 2010). The analysis of the amino acid composition showed that the V region has the unusual characteristic of containing many residues of arginine and lysine, which gives a positive charge on neutral pH on the VC1 surface.
In contrast, the C2 domain has more acidic residues on the surface and is negatively charged. These characteristics indicate that the extracellular domain of RAGE is composed of two subdomains that reflect on the ligand‐binding properties (Fritz, 2011). Most ligands bind to the VC1 domain (Allmen, Koch, Fritz, & Legler, 2008; Ostendorp et al., 2007; Sturchler, Galichet, Weibel, Leclerc, & Heizmann, 2008) with the C1 region as the recognition function of ligand, which has negative charges as standard (Xue et al., 2011), in addition to participating in the stabilization of region V (Dattilo et al., 2007).
The extracellular domain without the cytoplasmic domain and the transmembrane domain is called soluble RAGE (sRAGE), which is found extracellularly in the circulation (Kierdorf & Fritz, 2013), being a product of the cleavage of mRAGE by metalloproteinases ADAM10 (Raucci et al., 2008) and MMP‐9 (Zhang et al., 2008
