Current Advances for Development of

Functional Foods Modulating

Inflammation and Oxidative Stress
Blanca Hernandez-Ledesma
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Current Advances for Development of Functional
Foods Modulating Inflammation and Oxidative
Stress
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Current Advances for
Development of Functional
Foods Modulating
Inflammation and Oxidative
Stress
Edited by
Blanca Hernández-Ledesma
Department of Bioactivity and Food Analysis, Institute of Food Science Research
(CIAL, CSIC-UAM, CEI-UAM+CSIC), Madrid, Spain

Cristina Martı́nez-Villaluenga
Department of Food Characterization, Quality and Safety, Institute of Food Science,
Technology and Nutrition (ICTAN-CSIC), Madrid, Spain
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Contents

List of contributors xv 2.2.1 Dietary polyphenols 17

Preface xxi 2.2.2 Fatty acids 19
2.2.3 Proteins and amino acids 20
1. Bioactive compounds modulating 2.2.4 Dietary fibers 21
inflammation and oxidative stress in 2.3 Fermented foods for better bioavailability
some traditional functional foods and of some nutrients—fighting with
inflammation and oxidative stress 23
beverages 1
2.3.1 Importance of good nutrition in
Ilkay Gok inflammation and oxidative stress 23
2.3.2 Food fermentation 24
1.1 A brief overview of inflammation and
2.3.3 Fermented food
functional foods
oxidative stress 1
and health impact 25
1.2 Food compounds for the control of the
2.4 Conclusion 27
oxidative stress and inflammation 2
Acknowledgments 27
1.2.1 Effect of dietary fiber/prebiotics on
References 27
oxidative stress and inflammation 2
1.2.2 Effect of nutritional antioxidants on 3. Development of functional foods by
oxidative stress and inflammation 3
using 3D printing technologies:
1.2.3 Effect of polyunsaturated fatty acids on
inflammation and oxidative stress 5
application to oxidative stress and
1.3 Traditional diet: effects on oxidative
inflammation-related affections 33
stress and inflammation 6 Ivana M. Cotabarren and Camila A. Palla
1.3.1 Effect of food composition on gut
3.1 Introduction 33
microbiota, oxidative stress, and
3.2 3D food printing technologies 33
inflammation 6
1.3.2 Effect of fermented foods on oxidative 3.2.1 Extrusion 34
stress and inflammation 7 3.2.2 Power binding 35
1.4 Functional traditional foods effect on 3.2.3 Inkjet printing 36
oxidative stress and inflammation with 3.3 The role of diet and nutrients in oxidative
bioactive compounds 9 stress and inflammatory processes 36
1.5 Conclusion 13 3.4 Personalized functional foods through
References 13 3D printing 38
Further reading 16 3.4.1 Incorporation of food components
with antioxidant and/or
2. Health-promoting activities and antiinflammatory action 38
bioavailability of bioactive 3.4.2 Customized health diseases
compounds from functional foods 17 preventive foods 46
3.4.3 New food textures for people with
Sonia A. Socaci, Anca C. Fărcaş, Francisc V. Dulf,
swallowing and chewing
Oana L. Pop, Zoriţa M. Diaconeasa and
difficulties 48
Melinda Fogarasi
3.4.4 New ingredients for functional foods
2.1 Introduction 17 development 49
2.2 The role in modulating inflammation and 3.5 Functional foods through 3D printing:
oxidative stress of food bioactive opportunities, challenges, and
compounds 17 perspectives 50

v
vi Contents

3.6 Conclusions 51 5.4 Physicochemical properties of multiple

Acknowledgments 51 emulsions 77
References 51 5.5 Applications of multiple emulsions in
developing functional foods 81
4. The regulatory aspects of substantiating 5.5.1 Multiple emulsions in improving
health benefits of foods containing the fatty acid profile of foods 81
antioxidants 57 5.5.2 Role of emulsions in developing
low-fat food products 82
Karin G.M. Lenssen and Alie de Boer 5.5.3 Multiple emulsions in developing
4.1 Introduction 57 low-sodium food products 83
4.2 European food law 57 5.5.4 Encapsulation of functional
4.2.1 The regulation of novel foods 58 ingredients 83
4.2.2 The regulation of nutrition and health 5.6 Stability of multiple emulsions 92
claims 59 5.6.1 Characterization of multiple
4.3 Health claims on antioxidants 61 emulsions in assessing their stability 92
4.3.1 The substantiation of antioxidant 5.7 Bioavailability and bioaccessibility of
health claims 61 bioactives encapsulated with multiple
4.4 Biomarkers for oxidative damage to DNA, emulsions 93
proteins, and lipids 62 5.8 Conclusion and future trends 94
4.4.1 General characteristics of References 94
biomarkers 62
4.4.2 Biomarkers for protein oxidation 63 6. A new approach of functional pectin
4.4.3 Biomarkers for DNA oxidation 64 and pectic oligosaccharides: role as
4.4.4 Biomarkers for lipid oxidation 65 antioxidant and antiinflammatory
4.5 Discussion and conclusion 68 compounds 105
References 69
Antonia Montilla, Nerea Muñoz-Almagro and
Mar Villamiel
5. Developing novel foods using multiple
emulsions: insights with reference to 6.1 Pectins 105
bioaccessibility and bioavailability 73 6.1.1 General aspects 105
6.1.2 Pectins as antioxidant agents 107
Hafiz Ubaid ur Rahman, Sadia Aslam, 6.1.3 Antiinflammatory effects 109
Aqsa Akhtar, Waqas Asghar and Nauman Khalid 6.2 Pectic oligosaccharides 111
5.1 Introduction 73 6.2.1 General aspects 111
5.2 Types of multiple emulsions 74 6.2.2 Antioxidant activity 112
5.3 Methods of preparing multiple emulsions 74 6.2.3 Antiinflammatory activity 114
5.3.1 Two-step method of multiple 6.3 Concluding remarks 115
emulsion preparations 74 References 116
5.3.2 Phase inversion techniques 76
5.3.3 Preparation of double emulsion by 7. Fatty acids from natural resources in
solvent evaporation techniques 76 inflammatory gastrointestinal diseases
5.3.4 Preparation of multiple emulsion by with specific focus on inflammatory
microfluidics (one-step formation of bowel disease 121
multiple emulsion) 76
Marcin Talar, Aleksandra Tarasiuk,
5.3.5 Preparation of multiple emulsion by
Maciej Salaga and Jakub Fichna
pressure homogenization 76
5.3.6 Preparation of multiple emulsions by 7.1 Preface 121
ultrasonication 76 7.2 Gastrointestinal diseases and fat
5.3.7 Preparation of double emulsion digestion—the background 121
(W/O/W) by microchannel 7.3 Overview of fatty acids nomenclature,
emulsification process 77 classification, their occurrence, and
5.3.8 Preparation of multiple emulsion by role in IBD 123
layer-by-layer deposition 77 7.3.1 Saturated FAs 124
 Contents vii

7.3.2 Unsaturated FAs 127 9.2.3 Sources of phenolics compounds 169

7.4 Tight junctions, FAs, and inflammation 128 9.3 Phenolic compounds as antioxidants 169
7.5 FFAs and FFAR cross-talk in IBD 129 9.3.1 Mechanism of actions 170
7.6 Summary of the role of FAs in 9.4 Phenolic compounds as antiinflammatory
inflammatory gastrointestinal disease 130 agents 171
Acknowledgments 130 9.4.1 Mechanism of actions 174
Author disclosures 130 9.5 Conclusion and future perspectives 177
Authors’ contributions 130 References 177
Abbreviations 131
References 131 10. Role of micronutrients zinc and
selenium in inflammation and
8. Proteins, peptides, and protein oxidative stress 181
hydrolysates as immunomodulatory
Graziela Biude da Silva Duarte, Bruna Zavarize Reis
and antioxidant agents for the and Marcelo Macedo Rogero
formulation of functional foods 137
10.1 Inflammation, oxidative stress,
Andrea Araiza-Calahorra, Martin Mondor,
and chronic diseases 181
Christine Boesch, Caroline Orfila,
10.2 Selenium 181
Francisco M. Goycoolea and
10.2.1 Biological essentiality 182
Alan Javier Hernández-Álvarez
10.2.2 Recommended intake and
8.1 Introduction 137 bioavailability 182
8.2 Sources of food-derived bioactive 10.2.3 Se, inflammation, and oxidative
hydrolysates and peptides 138 stress 183
8.3 Bioactive peptides as antioxidants 138 10.3 Zinc 184
8.3.1 In vitro studies 138 10.3.1 Biological essentiality 184
8.3.2 Studies using in vitro biological 10.3.2 Recommended intake and
models 154 bioavailability 184
8.3.3 In vivo studies 155 10.3.3 Zn, inflammation, and oxidative
8.4 Antiinflammatory properties of stress 185
bioactive peptides 155 10.4 Conclusions 186
8.4.1 In vitro studies in cultivated cells 155 References 186
8.4.2 In vivo studies 156
8.4.3 Structure
function relationship to 11. Glucosinolates and their bioactive
modulate inflammatory activity 157 metabolites as functional compounds
8.5 Bioactive peptides as ingredients in modulating inflammation 189
functional foods 157
Paula Garcı́a-Ibañez, Oumaima Ben-Romdhane
8.5.1 Market opportunity 157
and Diego A. Moreno
8.5.2 Technical aspects of bioactive
peptide incorporation into foods 158 11.1 Introduction 189
8.5.3 Biomarkers 158 11.1.1 Brassicas and their impact on
8.6 Conclusion and future prospective health 189
studies 158 11.1.2 Diet, Brassicas, and inflammation 190
References 159 11.2 Molecular mechanisms of glucosinolates
and their bioactive form in
9. Anti-inflammatory and antioxidant inflammatory pathways 191
phenolic compounds 165 11.2.1 Aliphatic isothiocyanates and
related metabolites 191
Sirima Puangpraphant, Edith-Oliva Cuevas-
11.2.2 Indoles and related compounds 191
Rodrı́guez and Miguel Oseguera-Toledo
11.2.3 Glucosinolates and inflammatory
9.1 Introduction 165 diseases 192
9.2 Phenolic compounds: definition, 11.3 Concluding remarks 198
classification, and sources 166 Acknowledgments 198
9.2.1 Definition 166 Abbreviations 198
9.2.2 Classification 166 References 199
viii Contents

12. Microalgal bioactive components as 14.1.1 Health implications of aging and

antiinflammatory and antioxidant antiaging interventions 247
agents for health promotion 205 14.1.2 Cereal bioactive compounds and
their potential to counteract
Javier Ávila-Román, Elena Talero, Azahara age-related diseases 247
Rodrı́guez-Luna, Sara Garcı́a-Gil, Marı́a Dolores 14.2 Molecular antiaging mechanisms of
Jiménez-Gordillo and Virginia Motilva bioactive compounds in cereals 261
12.1 Potential scope of microalgae and 14.2.1 Mechanisms behind the
biotechnological implications 205 suppression of oxidative stress 261
12.2 Biotechnology of microalgae in the 14.2.2 Mechanisms behind the
food industry 206 suppression of low-grade chronic
12.3 Biological compounds from microalgae inflammation 262
with properties of interest in 14.2.3 Mechanisms behind the suppression
inflammatory processes 207 of cellular senescence 263
12.4 Main pathological mechanisms of 14.2.4 Mechanisms behind changes in
inflammation, including mediators and microbiota composition and
molecular pathways involved 207 activity 264
12.5 Microalgae-derived products 210 14.3 Health effects of wholegrain cereals 265
12.5.1 Carotenoids 210 14.3.1 Risk factors for T2DM 265
12.6 Conclusions 220 14.3.2 Weight gain, satiety, and food
References 220 intake 274
14.3.3 Risk factors for CVD 274
13. Polysaccharides from macroalgae: 14.3.4 Cognitive function and risk of
chemical characterization, functional neurodegenerative diseases 276
properties and biological activity 233 14.4 Conclusion 276
Acknowledgments 277
Tarcisio Vieira de Brito, Cynthia Maria Carvalho References 277
Pereira, Jalles Arruda Batista, Diva de Aguiar
Magalhães, Stefany Guimarães Sousa, Fernando 15. Potential role of pulses in the
Mesquita de Sousa de Lima, Antonio Kleiton de development of functional foods
Sousa and André Luiz dos Reis Barbosa modulating inflammation and
13.1 Compounds extracted from macroalgae oxidative stress 287
with biological action 233 Helena Ferreira, Elisabete Pinto,
13.2 Sulfated polysaccharides: structure and Ana M. Gil and Marta W. Vasconcelos
chemical characterization 234
13.3 Functional properties and industrial 15.1 Introduction 287
applications of sulfated polysaccharides 15.2 Pulses bioactive compounds,
from seaweed 235 inflammation and oxidative stress 289
13.4 Proven biological activities of sulfated 15.2.1 Proteins and bioactive peptides 289
polysaccharides 238 15.2.2 Carbohydrates 290
13.5 Perspectives for the use of sulfated 15.2.3 Tocopherols and carotenoids 295
polysaccharides 240 15.2.4 Phytosterols 296
13.6 Conclusions 241 15.2.5 Saponins 296
Acknowledgment 241 15.2.6 Polyphenols 297
References 241 15.3 Challenges and opportunities of pulses
in the development of functional foods 298
14. Role of cereal bioactive compounds 15.3.1 Traditional and new uses of
in the prevention of age-related pulses 298
diseases 247 15.3.2 Types of pulses and their
applications 299
Irene Tomé-Sánchez, Elena Peñas, Blanca
15.3.3 Effects of food processing 299
Hernández-Ledesma and Cristina Martı́nez-
15.3.4 Pulse-based new ingredients 300
Villaluenga
15.3.5 Ensuring in vivo biological
14.1 Introduction 247 activity 301
 Contents ix

15.4 Concluding remarks 302 17.7 Gryllodes sigillatus 352

Conflicts of interest 302 17.7.1 Antioxidant activity 356
Acknowledgments 302 17.7.2 Antiinflammatory activity 356
References 302 17.7.3 Antidiabetic activity 356
17.7.4 Antihypertensive activity 357
16. Probiotics and postbiotics: focus on 17.8 Alphitobius diaperinus 357
metabolic syndrome 311 17.9 Conclusion 357
References 358
Paola Gauffin-Cano, Antonela Marquez,
Matı́as Russo, Estefanı́a Andrada,
Claudia Abeijón-Mukdsi and Roxana Medina 18. Advances in production and
properties validation of multifunctional
16.1 Introduction 311 ingredients from Argentine food fruits
16.1.1 Metabolic syndrome, a
to modulate oxidative stress and
noncommunicable disease 311
16.2 Probiotics as nutritional approaches for
inflammation 365
the prevention or treatment of Iris Catiana Zampini and Marı́a Inés Isla
metabolic syndrome 315
18.1 Introduction 365
16.2.1 Short-chain fatty acids 317
18.2 Argentine food fruits and their
16.2.2 Polyunsaturated fatty acids 319
antioxidant and antiinflammatory
16.2.3 Phenolic compounds 320
properties 367
16.3 Conclusion and future directions 322
18.2.1 Solanum betaceum 367
Acknowledgments 322
18.2.2 Ziziphus mistol 367
Conflict of interest 323
18.2.3 Geoffroea decorticans 368
References 323
18.2.4 Prosopis alba 369
17. Potential of edible insects as a new 18.2.5 Prosopis nigra 370
18.3 Use of Northwestern Argentine fruits in
source of bioactive compounds
oxidative stress and inflammatory
against metabolic syndrome 331 processes related to metabolic
Joaquı́n Navarro del Hierro, syndrome 371
Blanca Hernández-Ledesma and Diana Martin 18.4 Development of multifunctional
ingredients from Argentine food fruits 372
17.1 Introduction 331
18.5 Conclusion 374
17.2 Composition of edible insects in
Acknowledgments 374
relation to their health properties and
References 374
metabolic syndrome 332
17.3 Tenebrio molitor 333
17.3.1 Antioxidant activity 333 19. Bioactive compounds from Moringa
17.3.2 Antiinflammatory activity 335 oleifera as promising protectors of
17.3.3 Antidiabetic activity 335 in vivo inflammation and oxidative
17.3.4 Antihypertensive activity 336 stress processes 379
17.3.5 Antilipidemic activity 336
Jaime González-Romero, Eduardo Jesús
17.4 Hermetia illucens 337
Guerra-Hernández and Celia Rodrı́guez-Pérez
17.4.1 Antioxidant activity 337
17.4.2 Antiinflammatory activity 342 19.1 Introduction 379
17.4.3 Antilipidemic activity 342 19.1.1 Chemical composition and
17.5 Musca domestica 343 traditional uses of Moringa
17.5.1 Antioxidant activity 343 oleifera 379
17.5.2 Antiinflammatory activity 346 19.1.2 Principal bioactive compounds
17.5.3 Antidiabetic activity 347 from Moringa oleifera 379
17.5.4 Antihypertensive activity 347 19.2 In vivo antioxidative effect of Moringa
17.5.5 Antilipidemic activity 347 oleifera 386
17.6 Acheta domesticus 348 19.2.1 Antioxidative effect in liver 386
17.6.1 Antioxidant activity 348 19.2.2 Antioxidative effect in other
17.6.2 Antilipidemic activity 352 organs 389
x Contents

19.2.3 Antidiabetic effect of Moringa oleifera 21.3 Emerging technologies for the
associated to its antioxidant extraction of bioactives 429
activity 389 21.3.1 Pressurized liquid extraction 429
19.3 In vivo antiinflammatory activity of 21.3.2 Microwave-assisted extraction 434
Moringa oleifera 393 21.3.3 Ultrasonic-assisted extraction 435
19.4 Conclusion and future prospects 395 21.3.4 Enzyme-assisted extraction 436
References 395 21.3.5 Supercritical CO2 extraction 437
21.3.6 High voltage electrical
discharge 438
20. Cruciferous vegetables: a mine of 21.3.7 Pulsed electric field 439
phytonutrients for functional and 21.4 Comparative performance 439
nutraceutical enrichment 401 21.5 Combinations 440
Satish Kumar, Shweta Sharma, Vikas Kumar, 21.6 Challenges and future trends 440
Rakesh Sharma, Anamika Minhas and References 441
Revathi Boddu
22. Encapsulation technologies
20.1 Introduction 401 applied to bioactive phenolic
20.2 Cruciferous vegetables and their compounds and probiotics with
significance 402 potential application on chronic
20.3 Crucifer phytochemicals and their
inflammation 447
activity 404
20.4 Nutraceutical significance of the Miriam Ferrer-Sierra, Paloma Rodrı́guez-López,
crucifers 405 Francisco Javier Leyva-Jiménez,
20.4.1 Cabbage 405 Isabel Borras-Linares, Daniela Giacomazza,
20.4.2 Cauliflower 405 Carolina Fredes, Paz Soledad Robert Canales,
20.4.3 Broccoli 408 Antonio Segura-Carretero and
20.4.4 Horseradish 408 Jesús Lozano-Sánchez
20.4.5 Mustard green 408
22.1 Methods 447
20.4.6 Kale 409
22.1.1 Search strategy 447
20.4.7 Arugula 409
22.1.2 Inclusion criteria 447
20.4.8 Kohlrabi 409
22.2 Importance of phenolic encapsulation:
20.4.9 Radish 410
stability, digestion, and absorption 448
20.5 Crucifers their processing and
22.2.1 Stability of phenolic compounds 448
antioxidant potential 410
22.2.2 Digestion and absorption 448
20.6 Recent trends for nutritional
22.2.3 In vitro, in vivo and clinical
improvement of the crucifers 414
trials to study polyphenol
20.6.1 Application of biotechnological
metabolism 449
tools 414
22.3 Encapsulation process applied to
20.6.2 Controlled abiotic stresses to
improve the phenolic bioaccesibility/
enhance the nutraceutical
bioavailability 454
properties 416
22.3.1 Encapsulation of phenolic
20.7 Conclusion and future prospects 418
compounds subject to in vitro
Acknowledgments 418
simulated digestion 454
Conflict of interest 418
22.3.2 In vitro gastrointestinal digestion 459
References 418
22.4 Probiotic encapsulation techniques to
improve the cell viability 463
21. Challenges in the extraction of 22.5 Gut microbiota and polyphenols diet
antiinflammatory and antioxidant interactions: synergistic effects against
compounds from new plant inflammation 465
sources 427 22.5.1 In vitro, in vivo and clinical trials
to study polyphenols—gut
Beatriz Dı́az-Reinoso and Herminia Domı́nguez
microbiota interactions 466
21.1 Introduction 427 22.6 Conclusions 470
21.2 Conventional solvent extraction 428 References 470
 Contents xi

23. Fermentation and germination as 24.4.6 Bovine colostrum and fermented

a way to improve cereals milk 507
antioxidant and antiinflammatory 24.5 Concluding remarks 510
properties 477 Acknowledgments 511
Conflict of interest 511
Morena Gabriele and Laura Pucci References 511
23.1 Background 477
23.2 Fermentation technology for enhancing 25. Current evidence on the modulatory
the nutritional and functional properties effects of food proteins and
of postprocessed cereal grains 477 peptides in inflammation and gut
23.2.1 Effects of fermentation on cereal microbiota 517
grains nutritional value 478
Samuel Fernández-Tomé, Lourdes Amigo,
23.2.2 Effects of fermentation on
Cristina Martı́nez-Villaluenga and Blanca
bioactive compounds and
Hernández-Ledesma
functional properties of cereal
grains 481 25.1 Introduction: inflammation and
23.3 Germination technology for enhancing oxidative stress 517
the nutritional and functional properties 25.2 Impact of “gut health” on
of postprocessed cereal grains 484 “general human health” 517
23.3.1 Effects of germination on cereal 25.3 Inflammatory bowel diseases:
grains nutritional value 485 the role of foods and their bioactive
23.3.2 Effects of germination on bioactive compounds 518
compounds and functional 25.4 Role of food proteins and peptides
properties of cereal grains 489 against inflammatory bowel disease 520
23.4 Possible harms and hurdles 491 25.4.1 In vitro evidence on the
23.5 Conclusions and future perspective 492 antioxidant, antiinflammatory,
References 492 and immunomodulatory
effects 520
24. Modulation of inflammation and 25.4.2 In vivo evidence on experimental
oxidative stress in Helicobacter pylori models of inflammatory bowel
infection by bioactive compounds disease 521
from food components 499 25.5 Effects of food peptides on gut
microbiota 525
Jose Manuel Silvan and Adolfo J. Martinez- 25.6 Future prospects 526
Rodriguez Acknowledgments 529
24.1 Brief overview of Helicobacter pylori as Conflict of interest 529
human pathogen 499 References 529
24.2 Inflammatory response and oxidative
stress associated to H. pylori infection 500 26. Immunonutritional agonists in the
24.3 Helicobacter pylori virulence factors neuroimmune response in
and their relationship with gastric AGE-Ing 535
inflammation and oxidative damage 500
Jana Baranda, Juan Antonio Giménez-Bastida,
24.4 Bioactive compounds from food
M. Morante, Aurora Garcı́a-Tejedor and
components as tools against inflammatory
Jose Moises Laparra
and oxidative damage associated to
H. pylori infection 502 26.1 Introduction 535
24.4.1 Probiotics 502 26.2 Neuroinflammation: pathways and
24.4.2 Phenolic compounds 503 biomarkers 536
24.4.3 Fruits, vegetables and their 26.3 Metabolic-induced neuroinflammation:
metabolites 505 from periphery to central nervous
24.4.4 Herbal extracts, spices and system 537
honey 506 26.4 Immunonutritional communication
24.4.5 Fatty acids 507 within the gut
brain axis 539
xii Contents

26.5 Concluding remarks and future 29. Cancer on fire: role of inflammation
perspectives 540 in prevention and treatment 605
Acknowledgements 540
References 540 Manoj K Pandey, Max Von Suskil,
Robert Chitren, Omar Al-Odat,
Subash C. Jonnalagadda and Bharat B. Aggarwal
27. Role of dietary spices in modulating
inflammation and oxidative stress 545 29.1 Introduction 605
29.2 Inflammatory players and their roles in
Ester S. Oh, Kristina S. Petersen,
tumorigenesis 605
Penny M. Kris-Etherton and Connie J. Rogers
29.2.1 Tumor necrosis factor-α 605
27.1 Introduction 545 29.2.2 Interleukins 607
27.2 Methods 547 29.2.3 Chemokines 607
27.3 Results 547 29.2.4 Inflammatory enzymes 608
27.3.1 Capsicum spp 558 29.2.5 Transcription factor 609
27.3.2 Cardamom 558 29.3 Prevention and treatment of cancers
27.3.3 Cinnamon 559 by targeting inflammatory pathways 610
27.3.4 Cumin 560 29.3.1 Curcumin 612
27.3.5 Dill 560 29.3.2 Capsaicin 612
27.3.6 Fenugreek 561 29.3.3 Diallyl sulfide 613
27.3.7 Garlic 561 29.3.4 Cinnamaldehyde 613
27.3.8 Ginger 562 29.3.5 6-Gingerol 613
27.3.9 Onion 563 29.3.6 Eugenol 613
27.3.10 Oregano 564 29.3.7 Diosgenin 614
27.3.11 Parsley 564 29.3.8 Garcinol 614
27.3.12 Sage 564 29.3.9 Thymoquinone 614
27.3.13 Sesame 565 29.3.10 Quercetin 614
27.3.14 Turmeric 565 29.3.11 Sulforaphane 614
27.3.15 Spice blend 566 29.3.12 α-Pinene 615
27.4 Discussion 567 29.3.13 Piperine 615
27.4.1 Antioxidative effect of spices 567 29.3.14 1,8-Cineole 615
27.4.2 Antiinflammatory effect of spices 568 29.4 Conclusion and future perspective 615
27.5 Conclusion 569 Acknowledgement 616
References 569 Conflict of interest 616
References 616
28. Functional foods, hormesis, and
oxidative stress 581 30. The effects of soya consumption
on glycemic parameters of type 2
Mohammad Alizadeh and Sevana Daneghian
diabetes: potential for functional
28.1 Introduction 581 foods 627
28.2 What is hormesis? 581
Longli Zhou, Alan Javier Hernández-Álvarez,
28.3 Stressor-mediated pathways and
Christine Boesch and Caroline Orfila
disease 582
28.3.1 Endoplasmic reticulum stress 582 30.1 Introduction 627
28.3.2 Mitochondria and oxidative stress 582 30.1.1 Glycemic markers of type 2
28.3.3 KEAP1/NRF2/ARE pathway 583 diabetes mellitus 627
28.3.4 NF-kB signal pathway 584 30.1.2 Dietary approaches in type 2
28.3.5 Heat shock proteins 584 diabetes mellitus 627
28.3.6 Autophagy 585 30.1.3 Soya: an ancient food for
28.4 Antioxidants and related food sources modern times 628
(prooxidants or antioxidants) 586 30.2 Soya intake and type 2 diabetes
28.4.1 Hormetins 586 mellitus 630
28.5 Conclusion and future prospects 595 30.2.1 Evidence from epidemiological
References 595 studies 630
 Contents xiii

30.2.2 Evidence from clinical trials: soya 30.3.2 Isoflavones 633

protein and isoflavones 630 30.4 Conclusion 633
30.3 Mechanistic effects and potential for References 634
formulation of functional foods 632
30.3.1 Protein and bioactive peptides 632 Index 639
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List of contributors
Claudia Abeijón-Mukdsi Center of Reference for
Lactobacilli (CERELA) -CONICET, San Miguel de
Tucumán, Tucumán, Argentina
Bharat B. Aggarwal Inflammation Research Center, San
Diego, CA, United States
Aqsa Akhtar School of Food and Agricultural Sciences,
University of Management and Technology, Lahore,
Pakistan
Mohammad Alizadeh Food and Beverages Safety
Research Center, Urmia University of Medical
Sciences, Urmia, Iran
Omar Al-Odat Department of Biomedical Sciences,
Cooper Medical School of Rowan University,
Camden, NJ, United States; Department of Chemistry
and Biochemistry, Rowan University, Glassboro, NJ,
United States
Lourdes Amigo Institute of Food Science Research
(CIAL, CSIC-UAM, CEI UAM+CSIC), Department
of Bioactivity and Food Analysis, Madrid, Spain
Estefanı́a Andrada Center of Reference for Lactobacilli
(CERELA) -CONICET, San Miguel de Tucumán,
Tucumán, Argentina; Faculty of Agronomy and
Zootechnics, National University of Tucumán,
Tucumán, Argentina
Andrea Araiza-Calahorra School of Food Science &
Nutrition, University of Leeds, Leeds, United Kingdom
Waqas Asghar School of Food and Agricultural
Sciences, University of Management and Technology,
Lahore, Pakistan
Sadia Aslam School of Food and Agricultural Sciences,
University of Management and Technology, Lahore,
Pakistan
Javier Ávila-Román Department of Biochemistry and
Biotechnology, Universitat Rovira i Virgili,
Tarragona, Spain
Jana Baranda Molecular Immunonutrition Group,
Madrid Institute for Advanced Studies in Food
(IMDEA-Food), Madrid, Spain
Jalles Arruda Batista Laboratory of Experimental
Physiopharmacology, LAFFEX—Parnaiba Delta
Federal University, Parnaiba, PI, Brazil
Oumaima Ben-Romdhane Unit of “Related Risks to
Environmental Stresses, Control and Prevention”
Department of Biology, Faculty of Sciences of
Bizerte, University of Cartage, Zarzouna, Tunisia
Revathi Boddu Department of Food Technology and
Nutrition, School of Agriculture, Lovely Professional
University, Phagwara, Punjab, India
Christine Boesch Nutritional Sciences and Epidemiology
Group, School of Food Science and Nutrition, University
of Leeds, Leeds, United Kingdom
Isabel Borras-Linares Center of Research and
Development of Functional Food, Health Science
Technological Park, Granada, Spain
Paz Soledad Robert Canales Department of Food
Science, Technology and Chemistry, Faculty of
Chemical and Pharmaceutical Sciences, University of
Chile, Santiago de Chile, Chile
Robert Chitren Department of Biomedical Sciences,
Cooper Medical School of Rowan University,
Camden, NJ, United States; Department of Chemistry
and Biochemistry, Rowan University, Glassboro, NJ,
United States
Ivana M. Cotabarren Chemical Engineering
Department—National University of the South, Bahı́a
Blanca, Argentina; Pilot Plant of Chemical
Engineering (PLAPIQUI, UNS-CONICET), Bahı́a
Blanca, Argentina
Edith-Oliva Cuevas-Rodrı́guez Faculty of Chemistry
and Biological Sciences, Autonomous University of
Sinaloa, Culiacán, Sinaloa, Mexico
Graziela Biude da Silva Duarte Faculty of
Pharmaceutical Science, University of São Paulo, São
Paulo, SP, Brazil
Sevana Daneghian Food and Beverages Safety Research
Center, Urmia University of Medical Sciences, Urmia,
Iran
xv
xvi List of contributors
Diva de Aguiar Magalhães Laboratory of Experimental
Physiopharmacology, LAFFEX—Parnaiba Delta
Federal University, Parnaiba, PI, Brazil
Alie de Boer Food Claims Centre Venlo, Campus Venlo,
Maastricht University, Venlo, The Netherlands
Tarcisio Vieira de Brito Laboratory of Experimental
Physiopharmacology, LAFFEX—Parnaiba Delta
Federal University, Parnaiba, PI, Brazil
Antonio Kleiton de Sousa Laboratory of Experimental
Physiopharmacology, LAFFEX—Parnaiba Delta
Federal University, Parnaiba, PI, Brazil
Fernando Mesquita de Sousa de Lima Laboratory of
Experimental Physiopharmacology, LAFFEX—
Parnaiba Delta Federal University, Parnaiba, PI, Brazil
Zoriţa M. Diaconeasa Faculty of Food Science and
Technology, University of Agricultural Sciences and
Veterinary Medicine Cluj-Napoca, Cluj-Napoca,
Romania
Beatriz Dı́az-Reinoso CITI-University of Vigo, Galician
Technological Park, Ourense, Spain
Herminia Domı́nguez Department of Chemical
Engineering, University of Vigo, Faculty of Science,
Campus Ourense, Ourense, Spain
André Luiz dos Reis Barbosa Laboratory of
Experimental Physiopharmacology, LAFFEX—
Parnaiba Delta Federal University, Parnaiba, PI,
Brazil
Francisc V. Dulf Faculty of Agriculture, University of
Agricultural Sciences and Veterinary Medicine Cluj-
Napoca, Cluj-Napoca, Romania
Samuel Fernández-Tomé Health Research Institute of
the University Hospital La Princesa (IIS-IP), CIBER
of Hepatic and Digestive Diseases (CIBEREHD),
Autonomous University of Madrid (UAM), Madrid,
Spain
Helena Ferreira Universidade Católica Portuguesa,
CBQF - Centro de Biotecnologia e Quı́mica Fina –
Laboratório Associado, Escola Superior de
Biotecnologia, Porto, Portugal
Miriam Ferrer-Sierra Department of Food Science and
Nutrition, University of Granada, Campus
Universitario Granada, Spain
Jakub Fichna Department of Biochemistry, Faculty of
Medicine, Medical University of Lodz, Lodz, Poland
Melinda Fogarasi Faculty of Food Science and
Technology, University of Agricultural Sciences and
Veterinary Medicine Cluj-Napoca, Cluj-Napoca,
Romania
Carolina Fredes Department of Health Sciences,
Nutrition and Dietetics Career, Faculty of Medicine,
Pontificia Universidad Católica de Chile, Santiago,
Chile
Anca C. Fărcaş Faculty of Food Science and
Technology, University of Agricultural Sciences and
Veterinary Medicine Cluj-Napoca, Cluj-Napoca,
Romania
Morena Gabriele Institute of Agricultural Biology and
Biotechnology, National Research Council, Pisa, Italy
Sara Garcı́a-Gil Department of Pharmacology,
Universidad de Seville, Seville, Spain
Paula Garcı́a-Ibañez Aquaporins Research Group, Plant
Nutrition Department, CEBAS-CSIC, University
Campus of Espinardo, Murcia, Spain
Aurora Garcı́a-Tejedor Valencian International
University (VIU), Valencia, Spain
Paola Gauffin-Cano Center of Reference for
Lactobacilli (CERELA) -CONICET, San Miguel de
Tucumán, Tucumán, Argentina
Daniela Giacomazza Biophysic Institute, National
Research Council, Palermo, Italy
Ana M. Gil Department of Chemistry and CICECO-
Aveiro Institute of Materials, University of Aveiro,
Campus Universitário de Santiago, Aveiro, Portugal
Juan Antonio Giménez-Bastida Laboratory of Food and
Health, Research Group on Quality, Safety and
Bioactivity of Plant Foods, Department of Food
Science and Technology, CEBAS-CSIC, Murcia,
Spain
Ilkay Gok Faculty of Applied Sciences, Istanbul Okan
University, Istanbul, Turkey
Jaime González-Romero University of Granada,
Departmen of Nutrition and Food Science, Campus of
Cartuja, Granada, Spain
Francisco M. Goycoolea School of Food Science &
Nutrition, University of Leeds, Leeds, United
Kingdom
Eduardo Jesús Guerra-Hernández University of
Granada, Departmen of Nutrition and Food Science,
Campus of Cartuja, Granada, Spain
Alan Javier Hernández-Álvarez Nutritional Sciences
and Epidemiology Group, School of Food Science and
Nutrition, University of Leeds, Leeds, United
Kingdom
Blanca Hernández-Ledesma Department of Bioactivity
and Food Analysis, Institute of Food Science Research
(CIAL, CSIC-UAM, CEI-UAM+CSIC), Madrid, Spain

Marı́a Inés Isla Faculty of Natural Sciences and Miguel
Lillo Institute, National University of Tucumán,
Institute of Bioprospecting and Plant Physiology,
National Council for Scientific and Technical
Research, San Lorenzo, Argentina
Marı́a Dolores Jiménez-Gordillo Department of
Pharmacology, Pediatrics and Radiology, Universidad
de Sevilla, Seville, Spain
Subash C. Jonnalagadda Department of Chemistry and
Biochemistry, Rowan University, Glassboro, NJ,
United States
Nauman Khalid School of Food and Agricultural
Sciences, University of Management and Technology,
Lahore, Pakistan
Penny M. Kris-Etherton Department of Nutritional
Sciences, The Pennsylvania State University,
University Park, PA, United States
Satish Kumar Department of Food Science and
Technology, Dr. Y. S. Parmar University of
Horticulture and Forestry, Nauni, Solan, India
Vikas Kumar Department of Food Technology and
Nutrition, School of Agriculture, Lovely Professional
University, Phagwara, Punjab, India
Jose Moises Laparra Molecular Immunonutrition
Group, Madrid Institute for Advanced Studies in Food
(IMDEA-Food), Madrid, Spain
Karin G.M. Lenssen Food Claims Centre Venlo,
Campus Venlo, Maastricht University, Venlo, The
Netherlands
Francisco Javier Leyva-Jiménez Center of Research
and Development of Functional Food, Health Science
Technological Park, Granada, Spain
Jesús Lozano-Sánchez Department of Food Science and
Nutrition, University of Granada, Campus
Universitario, Granada, Spain; Center of Research and
Development of Functional Food, Health Science
Technological Park, Granada, Spain
Antonela Marquez Center of Reference for Lactobacilli
(CERELA) -CONICET, San Miguel de Tucumán,
Tucumán, Argentina
Diana Martin Department of Production and
Characterization of Novel Foods, Institute of Food
Science Research (CIAL) (CSIC-UAM), Madrid,
Spain; Departmental Section of Food Science, Faculty
of Science, Universidad Autónoma de Madrid (UAM),
Madrid, Spain
Adolfo J. Martinez-Rodriguez Food Microbiology and
Biocatalysis Group (MICROBIO), Department of
List of contributors xvii
Biotechnology and Microbiology, Institute of Food
Science Research (CIAL), CSIC-UAM, Madrid, Spain
Cristina Martı́nez-Villaluenga Institute of Food Science,
Technology and Nutrition (ICTAN-CSIC), Department
of Food Characterization, Quality and Safety, Madrid,
Spain
Roxana Medina Center of Reference for Lactobacilli
(CERELA) -CONICET, San Miguel de Tucumán,
Tucumán, Argentina; Faculty of Agronomy and
Zootechnics, National University of Tucumán,
Tucumán, Argentina
Anamika Minhas Department of Food Technology and
Nutrition, School of Agriculture, Lovely Professional
University, Phagwara, Punjab, India
Martin Mondor Saint-Hyacinthe Research and
Development Centre, Agriculture and Agri-Food
Canada, Quebec, Canada; Institute of Nutrition and
Functional Foods (INAF), Université Laval, Quebec,
Canada
Antonia Montilla Chemistry and Functionality of
Carbohydrates and Derivatives, Institute of Food
Science Research, CIAL (CSIC-UAM), CEI (UAM
+CSIC) Madrid, Spain
M. Morante Molecular Immunonutrition Group, Madrid
Institute for Advanced Studies in Food (IMDEA-
Food), Madrid, Spain
Diego A. Moreno Phytochemistry and Healthy Foods
Lab (LabFAS), Department of Food Science and
Technology, CEBAS-CSIC, University Campus of
Espinardo-25, Murcia, Spain
Virginia Motilva Department of Pharmacology,
Universidad de Seville, Seville, Spain
Nerea Muñoz-Almagro Chemistry and Functionality of
Carbohydrates and Derivatives, Institute of Food
Science Research, CIAL (CSIC-UAM), CEI (UAM
+CSIC) Madrid, Spain
Joaquı́n Navarro del Hierro Department of Production
and Characterization of Novel Foods, Institute of Food
Science Research (CIAL) (CSIC-UAM), Madrid,
Spain; Departmental Section of Food Science, Faculty
of Science, Universidad Autónoma de Madrid (UAM),
Madrid, Spain
Ester S. Oh Department of Nutritional Sciences, The
Pennsylvania State University, University Park, PA,
United States
Caroline Orfila Nutritional Sciences and Epidemiology
Group, School of Food Science and Nutrition,
University of Leeds, Leeds, United Kingdom
xviii List of contributors
Miguel Oseguera-Toledo Department of
Nanotechnology, Center for Applied Physics and
Technology, National Autonomous University of
Mexico, Querétaro, Mexico
Camila A. Palla Chemical Engineering Department—
National University of the South, Bahı́a Blanca,
Argentina; Pilot Plant of Chemical Engineering
(PLAPIQUI, UNS-CONICET), Bahı́a Blanca,
Argentina
Manoj K Pandey Department of Biomedical Sciences,
Cooper Medical School of Rowan University,
Camden, NJ, United States
Elena Peñas Department of Food Characterization, Quality
and Safety, Institute of Food Science, Technology and
Nutrition (ICTAN-CSIC), Madrid, Spain
Cynthia Maria Carvalho Pereira Laboratory of
Experimental Physiopharmacology, LAFFEX—
Parnaiba Delta Federal University, Parnaiba, PI, Brazil
Kristina S. Petersen Department of Nutritional
Sciences, Texas Tech University, Lubbock, TX,
United States
Elisabete Pinto Universidade Católica Portuguesa,
CBQF - Centro de Biotecnologia e Quı́mica Fina –
Laboratório Associado, Escola Superior
Biotecnologia, Porto, Portugal; EPIUnit - Instituto de
Saúde Pública, Universidade do Porto, Porto, Portugal
Oana L. Pop Faculty of Food Science and Technology,
University of Agricultural Sciences and Veterinary
Medicine Cluj-Napoca, Cluj-Napoca, Romania
Sirima Puangpraphant Department of Food
Technology, Faculty of Science, Chulalongkorn
University, Bangkok, Thailand
Laura Pucci Institute of Agricultural Biology and
Biotechnology, National Research Council, Pisa, Italy
Bruna Zavarize Reis Faculty of Pharmaceutical Science,
University of São Paulo, São Paulo, SP, Brazil;
Department of Nutrition, Federal University of Rio
Grande do Norte, Natal, RN, Brazil
Paloma Rodrı́guez-López Department of Food Science
and Nutrition, University of Granada, Campus
Universitario Granada, Spain
Azahara Rodrı́guez-Luna Department of Pharmacology,
Universidad de Seville, Seville, Spain
Celia Rodrı́guez-Pérez University of Granada,
Departmen of Nutrition and Food Science, Campus of
Cartuja, Granada, Spain; Institute of Nutrition and
Food Technology (INYTA) “José Mataix,”
Biomedical Research Centre, University of Granada,
Avenida del Conocimiento s/n, Granada, Spain;
Institute of Biosanitary Research ibs. Avenida de
Madrid, Granada, Spain
Marcelo Macedo Rogero Department of Nutrition,
School of Public Health, University of São Paulo, São
Paulo, SP, Brazil; Food Research Center (FoRC),
CEPID-FAPESP, Research Innovation and
Dissemination Centers São Paulo Research
Foundation, São Paulo, SP, Brazil
Connie J. Rogers Department of Nutritional Sciences,
The Pennsylvania State University, University Park,
PA, United States; Center for Molecular
Immunology and Infectious Disease, The
Pennsylvania State University, University Park, PA,
United States
Matı́as Russo Center of Reference for Lactobacilli
(CERELA) -CONICET, San Miguel de Tucumán,
Tucumán, Argentina
Maciej Salaga Department of Biochemistry, Faculty of
Medicine, Medical University of Lodz, Lodz,
Poland
Antonio Segura-Carretero Department of Analytical
Chemistry, Faculty of Sciences, University of
de
Granada, Granada, Spain,; Center of Research and
Development of Functional Food, Health Science
Technological Park, Granada, Spain
Rakesh Sharma Department of Food Science and
Technology, Dr. Y. S. Parmar University of
Horticulture and Forestry, Nauni, Solan, India
Shweta Sharma MS Swaminathan School of
Agriculture, Shoolini University of Biotechnology and
Management Sciences, Solan (H.P.), India
Jose Manuel Silvan Food Microbiology and Biocatalysis
Group (MICROBIO), Department of Biotechnology
and Microbiology, Institute of Food Science Research
(CIAL), CSIC-UAM, Madrid, Spain
Sonia A. Socaci Faculty of Food Science and
Technology, University of Agricultural Sciences and
Veterinary Medicine Cluj-Napoca, Cluj-Napoca,
Romania
Stefany Guimarães Sousa Laboratory of Experimental
Physiopharmacology, LAFFEX—Parnaiba Delta
Federal University, Parnaiba, PI, Brazil
Marcin Talar Department of Biochemistry, Faculty of
Medicine, Medical University of Lodz, Lodz, Poland
Elena Talero Department of Pharmacology, Universidad
de Seville, Seville, Spain

Aleksandra Tarasiuk Department of Biochemistry,
Faculty of Medicine, Medical University of Lodz,
Lodz, Poland
Irene Tomé-Sánchez Department of Food
Characterization, Quality and Safety, Institute of Food
Science, Technology and Nutrition (ICTAN-CSIC),
Madrid, Spain
Hafiz Ubaid ur Rahman School of Food and
Agricultural Sciences, University of Management and
Technology, Lahore, Pakistan
Marta W. Vasconcelos Universidade Católica
Portuguesa, CBQF - Centro de Biotecnologia e
Quı́mica Fina Laboratório Associado, Escola Superior
de Biotecnologia, Porto, Portugal
Mar Villamiel Chemistry and Functionality of
Carbohydrates and Derivatives, Institute of Food
List of contributors xix
Science Research, CIAL (CSIC-UAM), CEI (UAM
+CSIC) Madrid, Spain
Max Von Suskil Department of Biomedical Sciences,
Cooper Medical School of Rowan University,
Camden, NJ, United States; Department of Chemistry
and Biochemistry, Rowan University, Glassboro, NJ,
United States
Iris Catiana Zampini Faculty of Natural Sciences and
Miguel Lillo Institute, National University of
Tucumán, Institute of Bioprospecting and Plant
Physiology, National Council for Scientific and
Technical Research, San Lorenzo, Argentina
Longli Zhou Nutritional Sciences and Epidemiology
Group, School of Food Science and Nutrition,
University of Leeds, Leeds, United Kingdom
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Preface

A growing awareness of the relationship between diet and health has led to an increasing demand for food products that
support health beyond simply providing basic nutrition. Experimental, clinical, and epidemiological studies have
revealed that chronic inflammation contributes to the development of approximately 15%
20% of malignancies world-
wide, included inflammatory bowel disease, Type 2 diabetes, obesity, arthritis, and cardiovascular diseases. Together
with inflammatory process, oxidative stress, resulting from an imbalance between reactive species and antioxidant
endogenous defenses, has been recognized as one of the most critical factors implicated in chronic diseases. Thus
exploiting the antioxidant and antiinflammatory properties of dietary bioactive compounds to be incorporated into func-
tional foods is an area of great interest for the food industry. Moreover, incorporation of bioactives into foods can yield
health benefits in the body that are linked via the immune system. There is, therefore, a considerable demand for a con-
centrated source of information on the development and characterization of new functional foods able to modulate oxi-
dative stress, inflammation, and immune response.
This Book presents the latest international advances in fundamental and applied research into functional foods and
dietary bioactive components centered in the specific fields of oxidative stress and chronic inflammation. It focuses on
nutritional and technological aspects related to the development of functional foods with antiinflammatory and antioxi-
dant effects. Within this context, the reader will find detailed and up-to-date information on (1) analytical approaches
for characterization of antiinflammatory and antioxidant properties of healthy foods and functional constituents; (2)
technological strategies for extraction of compounds and fractions from raw materials for the production of antiinflam-
matory and antioxidant ingredients, (3) molecular mechanisms by which foods and their components are able to modu-
late inflammation, oxidative stress, and immune response, and the link between these effects and disease prevention;
and (4) clinical research dealing with nutritional needs in pathological subjects with inflammatory diseases will be
considered.
The objectives of this book could only be met with the participation of a multidisciplinary board of experts and
invited contributors in different knowledge areas, such as Microbiology, Nutrition, Analytical Chemistry, Molecular
Biology, Biotechnology, and Food Science and Technology. We expect that these contributions will offer the reader a
comprehensive book that provides a comprehensive reference on the naturally occurring antioxidant and antiinflamma-
tory dietary compounds to enable food professionals in selecting and using these components in their products. This
book is intended for nutrition researchers, academics, and scientists working in the research and development sector of
the food industry as well as students focused on related fields.
This book would not have been possible without the excellent effort of our contributors, who we greatly thank for
their time and expertise.

Blanca Hernández-Ledesma
Cristina Martı́nez-Villaluenga

xxi
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Chapter 1

Bioactive compounds modulating

inflammation and oxidative stress in
some traditional functional foods and
beverages
Ilkay Gok
Faculty of Applied Sciences, Istanbul Okan University, Istanbul, Turkey

1.1 A brief overview of inflammation and oxidative stress

Inflammation is a defensive reaction of the immune system against external (microbial) and internal factors (due to cell
lysis) such as pathogens, damaged cells, and irritants. Diseases, such as arthritis, arthrophlogosis, and asthma may cause
inflammation. The vital aim of inflammation is to heal infectious diseases and to restore homeostasis (Battino et al.,
2020; Iddir et al., 2020; Iftikhar et al., 2020).
In early phase of inflammation, macrophages are activated as a response of tissue against the injury and pathogens,
resulting in the release of cytokines, such as interleukin (IL)-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6
which are proinflammatory factors, and IL-10, which acts as antiinflammator (Iftikhar et al., 2020). In the acute phase,
the increase in blood flow and vascular permeability together with accumulation of fluid, leukocytes, and inflammatory
mediators such as cytokines are generated. Inflammation is arbitrated by secreted soluble polypeptides, cytokines and
chemokines that promote the outgrowth of neoplastic cells and the production of the autocrine growth factor by the
tumor cells themselves. If inflammation is uncontrolled, it can turn in a chronic form and lead to transformation of fatal
cells into the surrounding tissue increasing the cancer risk (Landskron et al., 2014). The reaction of numerous immune
and inflammatory cells, chemokines, cytokines, and proinflammatory mediators can result in signals, leading to the pro-
liferation of tumor cells and stimulating cancer (Aranda-Olmedo & Rubio, 2020). In summary, the long-term inflamma-
tion results in higher cancer risk (Reuter et al., 2010).
There is a relationship between oxidation and inflammatory processes by which prolonged oxidative stress can
induce chronic inflammation and ended with chronic illnesses, including cancer, diabetes, cardiovascular, neurological,
and pulmonary diseases. Excess amount of free radical (FR) formation at the infection part by immune cells, especially
macrophages, initiates oxidative stress. Immune system is strongly regulated by oxidative stress and inflammatory pro-
cesses (Battino et al., 2020; Iddir et al., 2020; Reuter et al., 2010).
Reactive oxygen species (ROS) are metabolic by-products of biological systems. When the level of ROS increases
inside cells, they become harmful for cellular structures such as proteins, lipids, and nucleic acids. Increase in intracel-
lular levels of FRs results in many chronic illnesses (Guo et al., 2020; Pizzino et al., 2017). High amount of ROS or
less antioxidant activity may be also the main reason of oxidative stress in obesity. Accumulation of fat in cells causes
oxidative stress that results in the formation of malonaldehyde (MDA), an indicator of lipid oxidation, advanced oxida-
tion products (AOPP), and protein oxidation. These metabolites can react with proteins and induce an inflammatory
response by the initiation of monocytes and/or macrophages (Ambulay et al., 2020). Oxidative stress induced by FRs is
linked to the formation of cancer and tumors. FRs promote DNA damages resulting in mutation. Oxidative damage that
is triggered by FR might be controlled by some foods. Studies showed that bioactive compounds in some foods may
have the ability of cancer prevention (Adebo et al., 2017; Ghosh & Karmakar, 2021; Liu, 2013; Pisoschi et al., 2021).

Current Advances for Development of Functional Foods Modulating Inflammation and Oxidative Stress. DOI: https://doi.org/10.1016/B978-0-12-823482-2.00013-3
© 2022 Elsevier Inc. All rights reserved. 1
2 Current Advances for Development of Functional Foods Modulating Inflammation and Oxidative Stress

Various types of nutrition may be the source of oxidative stress that triggers inflammation. Oxidative stress plays an
important function in aging, obesity, nonalcoholic fatty liver disease, type 2 diabetes mellitus (T2DM), depression, and
neurodegeneration. ROS and reactive nitrogen species (RNS) are produced through oxidative metabolism, mitochon-
drial bioenergetics, and immune function. The basal forms of ROS including superoxide anion, hyphochlorous acid,
hydrogen peroxide, singlet oxygen, hypochlorite, hydroxyl radical, and lipid peroxides are participated in the progres-
sion, growth, death, and differentiation of cells and can connect with nucleic acids, enzymes, membrane lipids, proteins,
and other small molecules. The intracellular redox homeostasis can be prevented by an efficient antioxidant system
(Guo et al., 2020; Tan et al., 2018). Inflammation, which is principally mediated by nuclear factor-kappa B (NF-κB), is
activated by short-term postprandial mitochondrial oxidative stress (Muñoz & Costa, 2013; Tan et al., 2018).
Diets may enhance or diminish oxidative stress and inflammation. High intake of refined carbohydrates and satu-
rated fat intercedes oxidative stress and, afterwards, favors inflammation via NF-κB-mediated cell signaling pathways.
Oxidative stress is connected with the type and quantity of macronutrients consumed that may result in obesity and
related diseases (Satokari, 2020; Tan et al., 2018).
Overconsumption of macronutrients such as simple carbohydrates (glucose and fructose) and lipids (saturated and
omega-6 fatty acids) may prompt chronic levels of inflammation and oxidative stress and result in progression of obe-
sity, cardiovascular disease, diabetes, and cancer (Cheng et al., 2020; Satokari, 2020; Tan et al., 2018).
High intake of macronutrients can boost oxidative stress and generate inflammation via NF-κB-mediated pathways,
likewise through different mechanisms, such as beyond excessive n-6-accelerated inflammation. There are nutritional
options that may prevent oxidation and inflammation. Studies showed that dietary choices such as Mediterranean and
Okinawan diets significantly reduce T2DM, cardiovascular disease, metabolic syndrome, and cancer. Excess consump-
tion of foods results in obesity on the long-term scale with production of white adipose tissue which leads long
stable state of inflammation (Guo et al., 2020; Muñoz & Costa, 2013; Pompili et al., 2020).
Effect of lipid on oxidative stress is found as either lipid accumulation or lipid peroxidation where the lipid accu-
mulation is primary reason with high fat intake in the diet. Highly active ROS produced in mitochondria are the
major parts related with lipid oxidation. High glucose in diet promotes ROS production through nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase generation in different cell types and organs, resulting in mitochondrial dis-
function and loss of antioxidant enzymes activity such as glutathion peroxidase (GPx), superoxide dismutase (SOD),
and catalase (CAT) with antigenicity in human macrophages and can initiate the stimulation of proinflammatory cyto-
kines and chemokine, including NF-κB, causing rise in inflammatory process (Ambulay et al., 2020; Guo et al.,
2020; Pompili et al., 2020). High fat diets may accompany with rise in inflammation and endothelial dysfunction
(Davis et al., 2011).
Inflammation can be improved and eventually treated with some natural compounds present in foods depending
on the cellular and molecular pathways in its development. These compounds have antiinflammatory properties
such as dietary fibers, bioactive peptides, fatty acids, flavonoids and its derivatives, phytosterol, genistein, tocoph-
erol, curcumin, ascorbic acid, triterpenoids, alkaloids, saponins, tannin, and anthraquinones. Research showed that
foods with natural properties and wide range of bioactivities may also possess anticancer, antibacterial, immunomo-
dulating, antimalarial, and antituberculosis activities (Guo et al., 2020; Neri-Numa et al., 2020; Soomro, 2019; Gok,
2021).

1.2 Food compounds for the control of the oxidative stress and inflammation
1.2.1 Effect of dietary fiber/prebiotics on oxidative stress and inflammation
The prebiotics are a kind of dietary fibers, which are either soluble or insoluble in the intestine, and defined as “a sub-
strate that is selectively utilized by host microorganisms conferring a health benefit” (Cheng et al., 2020; Hurtado-
Romero et al., 2020; Gok, 2021). Inulin, fructooligosaccharides, galactooligosaccharides, and xylooligosaccharides are
the carbohydrate-based prebiotics. Also, some minerals, polyphenols, or polyunsaturated fatty acids (PUFAs) are con-
sidered as prebiotics (Hurtado-Romero et al., 2020). Consumption of prebiotic carbohydrates support the growth of ben-
eficial bacteria such as species of the Lactobacillus and Bifidobacterium genera. Gut microbiota metobilize some
prebiotic carbohydrates and generate microbial metabolites such as short-chain fatty acids and show beneficial effects
on health by inhibition of pathogens and activation of the immune system, reducing blood lipid levels, insulin resis-
tance, inflammation, risk of colon cancer, symptoms of gastrointestinal disorders, and frequency and length of infec-
tious and antibiotic-related diarrhea, and supporting the brain function and energy metabolism (Hurtado-Romero et al.,
2020; Li et al., 2021; Neri-Numa et al., 2020; Li et al., 2020).
 Bioactive compounds modulating inflammation and oxidative stress in some traditional Chapter | 1 3

Brown seaweed, deoiled cumin fiber, mango peel, orange peel, potato peel, papaya peel, passion fruit peel, lemon
peel, wheat bran, bee honey, apple, orange, cranberry, blueberry, and raspberry pomace are the examples of prebiotic
fibers obtained from food sources (Hurtado-Romero et al., 2020). Studies on mice with liver fibrosis showed that die-
tary fiber consumption has potential to decrease systemic inflammation (Li et al., 2021).
The prebiotic dietary polyphenols (catechins, anthocyanins, and proanthocyanidins); flavanols (epigallocatechin
gallate, epigallocatechin, epicatechin gallate, and epicatechin); and phenolic compounds (lignans, phenolic acids, stil-
benes, and vanillin) are used as a substrate for the gut microbiota producing better absorbing metabolites in the colon
(Alves-Santos et al., 2020; Ghosh & Karmakar, 2021). According to the study, consumption of galactooligosacchar-
ides by healthy aged people provided increase in the number of beneficial gut bacteria, especially bifidobacteria, in
phagocytosis, natural killer cell activity, and in the antiinflammatory IL-10, and decrease in proinflammatory cyto-
kines (Ibrahim & El-Sayed, 2016). Research showed that several carbohydrate polymers of different medicinal plants
which have pectic arabinogalactan esterified with phenolic acids in monomeric and dimeric form have strong antioxi-
dant potential, and phenolic polysaccharides may be used as for fighting aging and age-based diseases (Ghosh &
Karmakar, 2021).

1.2.2 Effect of nutritional antioxidants on oxidative stress and inflammation

Oxidative stress is correlated with excessive formation of FRs or ROS in the cells and tissues and decrease in abil-
ity of antioxidant system to control the effect of FR/ROS. In addition, RNS are produced through respiratory chain
reactions which resulted in reactive products such as aldehydes. They may be harmful for cellular molecules such
as DNA, proteins, and lipids. FR/ROS are highly reactive and produced in the body at a certain amount through
continuous metabolic routes and important in regulation of some metabolic reactions. The generation of reactive
products, FR/ROS/RNS for long period may be harmful for cellular structure and their functions, and may result in
somatic mutations and preneoplastic and neoplastic transformations. If excessive production of these reactive pro-
ducts is not controlled in a short time, irreversible damages in cells and tissue may take place and cause cell death
by the necrotic and apoptotic processes. The damage of these products is prevented by antioxidants (Hussain et al.,
2016; Neha et al., 2019).
According to studies, it was found that oxidative stress plays a pathogenic role in chronic inflammatory dis-
eases. Effects of FR and oxidative stress can be controlled by enzymes (such as SOD, CAT, and GPx) and non-
enzymatic antioxidants (e.g., lipoic acid; glutathione; L-arginine; coenzyme Q10; thioredoxin; glutathione; vitamins
A, C, and E; lycopene; lutein; and quercetin). These antioxidants prevent the production of FR by stopping the
chain reaction or can lower the concentration of FR by donating hydrogen and an electron. They also behave as
peroxide decomposer (vitamin E), enzyme inhibitor, singlet oxygen quencher (vitamin E), synergist, and metal
chelating agents (tranferritin) (Neha et al., 2019; Pisoschi et al., 2021; Singh et al., 2014). Natural antioxidants
such as carotenoids, vitamins E, A, and C, natural flavonoids, or different other compounds are tabulated in
Table 1.1.
According to epidemiological, clinical, and nutritional studies, it was found that dietary polyphenols which are natu-
ral antioxidants may lower the catalytic activity of enzymes participated in ROS generation and can protect against oxi-
dative damage across different mechanisms. Vegetables, cereals, beverages, fruits such as grapes, apple, pear, cherries,
berries, and their by-products, red wine, tea or coffee, chocolates, dry legumes, herbs, spices, stems, and flowers are the
examples of nutritional compounds, including polyphenols. Polyphenols are daily consumed as a part of the diet in
most countries (Hussain et al., 2016; Zhang & Tsao, 2016). They provide the adjustment of redox status and immune
response through scavenging of FR, regulating mitochondrial function, and stimulating the activity of SOD, GSH, GPx,
and glutathione S-transferases (Guo et al., 2020).
Phenolic acids are one of the most important groups of bioactive compounds categorized under phenolic com-
pounds. They are found in different plant sources such as fruits, vegetables, spices, grains, and beverages. Phenolic
acids which provide color, flavor, astringency, harshness, and typical organoleptic attributes of the foods are the aro-
matic secondary metabolites and have important functional properties with health benefits such as antioxidant, antiin-
flammatory, immunoregulatory, antiallergenic, antiatherogenic, antimicrobial, antithrombotic, cardioprotective,
anticancer, and antidiabetic properties (Rashmi & Negi, 2020).
Epigallocatechin-3-gallate in green tea, resveratrol in wine, oleuropein (OP) in olive leaves, berberine in Coptis chi-
nensis, and curcumin in turmeric rhizomes are one of the important diet-based examples for natural antioxidant com-
pounds with antioxidative, and antiinflammatory properties (Guo et al., 2020).
4 Current Advances for Development of Functional Foods Modulating Inflammation and Oxidative Stress
TABLE 1.1 Dietary source of antioxidants on oxidative stress and inflammation (Hussain et al., 2016; Inan, 2019;
Pisoschi et al., 2021; Neha et al., 2019; Pizzino et al., 2017).
Antioxidants
Vitamin C (ascorbic acid)
Vitamin E (α-tocopherol)
Carotenoids
Phenolics—flavonoids (flavones,
flavonols, stilbene derivatives, lignans,
flavanols, flavanones, isoflavones,
anthocyanins) and nonflavonoids
(phenolic acids)
Source
Fruits and vegetables (citrus fruits, kiwi,
strawberries, spinach, broccoli, red
pepper, Brussels sprouts)
Vegetable oils
Broccoli
Almonds
Nuts
Seeds
Green leafy vegetables (kale, spinach,
collards, and mustard greens) and colored
fruits (kiwi, tomatoes, apricots, papayas);
most bioavailable when they are
embedded in, or consumed with foods
that also have a lipid base (like the yolks
of eggs) and when preparation (e.g.,
blending and heating) breaks down the
cell walls of the plant
Carrots, palm oil; crude palm oil and red
palm olein
Corn, soybean, and peanut oils
Fruits (berries, grapes, citrus fruits,
apricots, apples, plums, cherries, peaches,
and tropical fruits)
Beverages (herbal teas, fruit juices, cocoa,
coffee, red wine, and beer)
Seeds, grains, and nuts
Effect
Neutralizes free radicals, protects DNA,
proteins, and lipids from oxidative
damages, and hinders carcinogenic
nitrosamine synthesis
Neutralize free radicals and prevent
membrane lipid oxidation
Protects cells from free radical decay
Stop the occurrence of free radicals
within the cells
Alleviate heart disease risk
Prevent lipid peroxidation linked to DNA
damage-induced carcinogenity
Protect against age-related macular
degeneration
Inhibits peroxynitrite-induced lipid
peroxidation and inflammation
Reduce cellular damage
Decrease morbidity in nonsmokers
Prevent cancer
Reduce the risk of prostate cancer
Inhibit cell lipid peroxidation
Show preventative effect against
neurodegenerative diseases
Protect lipids from superoxide and
hydroxyl radical attack
Improve eye health
Filter phototoxic blue light in certain
tissues
Reduce cellular damage
May act by protecting against a series of
diseases linked to oxidative stress, such
as cardiovascular and respiratory
pathology, cancer, and diabetes
Trans-resveratrol is related to
cardiovascular benefits by relaxing
arteries and by lowering oxidative stress
(Continued )
 Bioactive compounds modulating inflammation and oxidative stress in some traditional Chapter | 1 5

TABLE 1.1 (Continued)

Antioxidants Source Effect

Vegetables (onions, spinach, broccoli,
cauliflower, artichoke, tomato, beans,
soybeans, carrots, capers, and olives)
Spices and herbs (clove bud, turmeric,
celery, parsley, mint, rosemary, thyme,
sage, dill, curry, and ginger)
Table oils
Selenium Shrimp, oysters, and tuna
Meats
Nuts
Pasta
Zinc Shellfish
Meats
Green peas, mushrooms, spinach, beans,
asparagus, broccoli, nuts, and cocoa
Possess antiinflammatory potential
Alleviate oxidative stress-induced
endothelial dysfunction
Antiinflammatory
May reduce mortality
Modulate inflammatory response in
infectious and autoimmune diseases
Acts as antioxidant fighters for thyroid
regulation and male-fertility
improvement
Antiinflammatory and antidiarrhea
Its deficiency induces free radical
damage that eventually can lead to
spleen fibrosis
Its deficiency increases oxidative stress,
mainly in diabetes
Its presence contributes to immune
function improvement

1.2.3 Effect of polyunsaturated fatty acids on inflammation and oxidative stress

Fatty acids are the natural constituents of the diet and several fatty acids have functional roles such as omega-6 (n-6)
and omega-3 (n-3) families. PUFAs can influence inflammatory cell functions and inflammatory processes by various
mechanisms. The n-3 fatty acids are a family of PUFAs which has the last double bond between carbon numbers 3 and
4 in the hydrocarbon (acyl) chain with the terminal methyl carbon as number one. Longer chain n-3 fatty acids consist
of eicosapentaenoic acid (EPA; 20:5n-3), docosapentaenoic acid (DPA; 22:5n-3), and docosahexaenoic acid (DHA;
22:6n-3) (Calder, 2015; Oppedisano et al., 2020).
FR (such as peroxynitrite) boosts the synthesis of proinflammatory cytokines, adjusts the cyclooxygenase (COX)
pathway, and stimulates the synthesis of proinflammatory prostaglandin E2 (PGE2) as well. The n-3 PUFAs behave as
antioxidants which protect endothelial cells and cardiomyocytes from damage and cell death. Maresins, protectins, and
resolvins are known as specialized proresolving mediators which obtained from n-3 show antiinflammatory properties
(Oppedisano et al., 2020; Wawrzyniak et al., 2020). Long-chain n-3 PUFAs also increase microbiome variety in the
gut, boost short-chain fatty acid-producing bacteria, and enhance intestinal barrier function by closing epithelial tight
joints (Wawrzyniak et al., 2020).
The n-3 fatty acids have antiinflammatory and immunomodulatory dietary effects, improve blood pressure, cardiac
function, arterial compliance, endothelial function, vascular reactivity, glucose, lipid, and lipoprotein metabolism, and
decrease neutrophil and monocyte cytokine production (Mori & Beilin, 2004). According to clinical studies, n-3 fatty
acids have beneficial effect on insulin sensitivity, hyperlipidemia, and obesity, suppress adipogenesis, and show antitu-
mor effects (Hussain et al., 2016; Zhang & Tsao, 2016).
Oily fish (e.g., anchovy, sardine, salmon, and cod) and other seafoods have EPA, DPA, and DHA in considerable
amount, and are known as marine n-3 fatty acids. The n-3 fatty acids, in dietary fish and plants, can control inflamma-
tion in acute and critical illness (Calder, 2015; Molfino et al., 2017). The World Health Organization and many
6 Current Advances for Development of Functional Foods Modulating Inflammation and Oxidative Stress

researchers advise oily fish intake once or twice a week for very long-chain n-3 PUFAs to provide health benefits. The
n-3 PUFAs, including alpha-linolenic acid (ALA; 18:3 n-3), is a metabolic precursor of EPA and DHA present in
plants, green plant tissues, some nuts (e.g., walnuts), rapeseed oil (also known as canola oil), soybean oil (in which
ALA contributes 10% of total fatty acids), and flaxseed oil [in which ALA contributes 50% of total fatty acids and
stearidonic acid (SDA; 18:4 n-3)] (Baker et al., 2016).

1.3 Traditional diet: effects on oxidative stress and inflammation

Consumption of high carbohydrate such as sugars and refined carbohydrates increases glycemic index or glycemic load
and may lead in oxidative stress with yielding chronic inflammation via NF-κB-mediated cell signaling pathways and
may activate TNF-α. Westernized high-calorie diet resulting from high amount of carbohydrates and fat consumption
will induce more substrate entrance into mitochondrial respiration (Serafini & Peluso, 2016; Tan et al., 2018) and also
may result in porous intestinal lining, systemic entrance to food antigens, environmental toxins, and structural compo-
nents of microbes, such as lipopolysaccharide (LPS) endotoxin which is related to depressive symptoms and confound
blood glucose control (Selhub et al., 2014).
Traditional diets such as Mediterranean with higher intakes of vegetables, fruits, whole wheat, nuts, yogurts, olive
oil, fermented foods and beverages such as wine provide antiinflammatory potential together with polyphenols, mono-
unsaturated fatty acids, and other bioactive molecules (Fig. 1.1) (Tan et al., 2018; Razquin and Martinez-Gonzalez,
2019; Childs et al., 2019; Fiore et al., 2020; Nagpal et al., 2020). For example, some bioactive polyphenols such as
hydroxytyrosol and tyrosol, oleocanthal, and resveratrol found in red wine and extra-virgin olive oil have antiinflamma-
tory properties. The extra-virgin olive oil with its fatty acid oleic acid and bioactive polyphenols is not only important
for its cardioprotective properties but also for its reducing ability of low-grade inflammation (Fiore et al., 2020;
Hurtado-Romero et al., 2020; Li et al., 2021; Neri-Numa et al., 2020; Razquin and Martinez-Gonzalez, 2019).

1.3.1 Effect of food composition on gut microbiota, oxidative stress, and inflammation
Human-related microbes are called microbiota and the gut microbiota is a complex ecosystem with wide diversities of
species containing bacteria, archaea, fungi, protozoa, and viruses. The human gastrointestinal tract (GIT) has 10 million
genes, including various microbial genus, and all genes may support the health of the host, by regulating homeostasis
of the immune system, producing beneficial components, and protecting against pathogenic microorganisms. The
human gut microbiota consists of both anaerobic and aerobic microbial populations (Cheng et al., 2020; Rajoka et al.,
2017).

FIGURE 1.1 High carbohydrate-,

protein-, and fat-based diet will
finally lead to obesity with other dis-
eases such as CVD, diabetes, and
cancer. Healthy diet includes whole
grains, nuts, fruits and vegetables,
fish, and legumes, and fermented
foods and beverages. They contain
dietary fiber, unsaturated fatty acids
such as MUFA and n-3 PUFA, pro-
tein, vitamins, minerals, and other
health-promoting components which
have antioxidant ability and decrease
oxidative stress. CVD, cardiovascular
diseases; MUFA, monounsaturated
fatty acids; n-3 PUFA, n-3 polyun-
saturated fatty acid. From Tan et al.
(2018).
Another random document with
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 Lábjegyzetek.
1) A ténykérdés és jogkérdésnek megkülönböztetése, habár
némileg hasonlít is, de nem felel meg és nem azonos a római per
in jure es in judicis való eljárásához.
2) A centumvirek (centumviri litibus judicandis) éppen úgy, mint a
judices, arbitri és recuperatores in judicio jártak el.
Ford.
3)

Visszatér az öreg az ősi forrásba,

Változó napokból örök éjszakába.
Lángot látsz lobogni az ifjú szemében
S világosságot az öreg emberében.

4) Szerző ezen szellemes szójátékával a magistrature assise-t,

vagyis az ítélőbíróságot az assisi szent Ferenc-rendhez
hasonlítja.
Ford.
5) Revue des Deux Mondes 1909 november 15.
6) Synergia alatt több szerv együttműködését vagy az összetett
erők együttműködését értjük.
Ford.
 TARTALOM.

A fordító előszava 5
I. A kormányformák alapelvei 9
II. A munkakörök zűrzavara 30
III. A hivatottság menedéke 47
IV. A hivatásos törvényhozó 53
V. Törvények a demokráciában 67
VI. Kontárság a kormányzat körében 75
VII. Kontárság a jogszolgáltatás körében 78
VIII. Egyéb kontárság 101
IX. Közerkölcsök 129
X. Hivatásszerű szokások 135
XI. Megkisérlett gyógyszerek 143
XII. Az álom 175
Fordító magyarázó jegyzetei 190
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