Silymarin Puzzle

From basic science to practical applications in human and veterinary medicine and nutrition

For the last 30 years, polyphenols were in the centre of research work worldwide. Silymarin, an extract from a medicinal plant Silybum marianum, also known as milk thistle, has a special place in this group, having been used in human medicine for the management of liver diseases since ancient times. Accumulating scientific evidence indicates that silymarin is characterised by a wide range of protective pharmacological activities and this topic has received tremendous attention in recent years. However, until now there has been no single monograph addressing major questions related to silymarin chemistry, biochemistry and practical applications.
The goal of this book is to provide up to date information about silymarin chemistry, biochemistry and molecular mechanisms of protective actions of this phytochemical with a special emphasis to its vitagene- and transcription factor-modulating properties. Silymarin applications in human diseases, including hepatoprotection, neuroprotection, anti-diabetic, anti-arthritis and other protective activities are reviewed. Immunomodulating, anti-inflammatory, anti-toxic protective activities of silymarin are characterised in detail. Practical applications of silymarin in poultry and animal industry with a special emphasis on its protective roles in gut health maintenance are also presented.
This book will be of practical importance to medical and pharmaceutical scientists, including medical doctors, pharmacists, consultants, etc. as well as to poultry/animal scientists, poultry producers, nutritionists and vets, as well as to students of medical, biological and agricultural backgrounds. It can also be of interest for researchers in areas related to physiology, biochemistry, nutrition and veterinary medicine.

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About the authors9
Table of contents11

Chapter 1 A search for ideal diets, the case of polyphenols27
 1.1 Introduction28
 1.2 What are ideal diets?28
 1.3 What are polyphenols?34
 1.4 Antioxidant activities of polyphenols35
 1.5 Pro-oxidant properties of polyphenols39
 1.6 Polyphenol effects in poultry and farm animals41
 1.7 Polyphenols vs vitamin E46
 1.8 Detrimental effects of polyphenols51
 1.9 Conclusions53

Chapter 2 From milk thistle to silymarin: chemical and pharmacological properties67
 2.1 Introduction68
 2.2 History of milk thistle/SM investigation68
 2.3 Chemical composition and structure73
 2.4 Pharmacokinetics75
 2.5 Silymarin toxicity78
 2.6 Silymarin applications79
 2.7 Conclusions79

Chapter 3 Antioxidant defence systems in health and diseases85
 3.1 Introduction86
 3.2 Free radicals and reactive oxygen and nitrogen species86
 3.3 Three levels of antioxidant defence89
 3.4 Antioxidant defence network92
 3.5 Oxidative stress and redox biology95
 3.6 Stress-response pathways95
 3.7 Conclusions99

Chapter 4 Antioxidant properties of silymarin105
 4.1 Introduction106
 4.2 Direct free radical scavenging106
 4.3 Inhibition of free-radical producing enzymes by silybin107
 4.4 Protective effects of silybin on mitochondria, a main source of free radical production in the cell108
 4.5 Is effective silybin concentration in vitro achievable in vivo?117
 4.6 Oxidability and pro-oxidant properties of silymarin118
 4.7 Conclusions119

Chapter 5 Silymarin and Nrf2127
 5.1 Introduction128
 5.2 Transcription factor Nrf2128
 5.3 Pharmacological/nutritional Nrf2 activation135
 5.4 Nrf2 and inflammation140
 5.5 Nrf2 activation as a clinical strategy141
 5.6 Silymarin and Nrf2 regulation141
 5.7 Conclusions143

Chapter 6 Silymarin and NF-κB151
 6.1 Introduction152
 6.2 Transcription factor NF-κB152
 6.3 NF-κB and oxidative stress158
 6.4 Nutritional modulation of NF-κB159
 6.5 Silymarin and NF-κB regulation161
 6.6 Nrf2 and NF-ĸB interplay in oxidative stress163
 6.7 Conclusions167

Chapter 7 Silymarin and vitagenes179
 7.1 Introduction180
 7.2 Vitagene family180
 7.3 Effect of silymarin on vitagene expression182
 7.4 Conclusions189

Chapter 8 Antitoxic properties of silymarin199
 8.1 Introduction200
 8.2 Various compounds with toxic effects200
 8.3 Oxidative stress-related conditions218
 8.4 Conclusions225

Chapter 9 Silymarin and immunity251
 9.1 Introduction252
 9.2 Natural immunity252
 9.3 Adaptive immunity252
 9.4 Silymarin and phagocyte functions262
 9.5 Silymarin and dendrites264
 9.6 Silymarin and mast cells265
 9.7 Silymarin and lymphocyte functions267
 9.8 Molecular mechanisms of silymarin immunomodulation270
 9.9 RONS, redox homeostasis and immunocommunication272
 9.10 Vitagene-immunity interactions and silymarin275
 9.11 Conclusions278

Chapter 10 Silymarin and inflammation: from understanding molecular mechanisms to practical applications287
 10.1 Introduction288
 10.2 Molecular mechanisms of inflammation288
 10.3 Silymarin and inflammation: In vitro studies291
 10.4 Silymarin and inflammation: In vivo studies296
 10.5 Conclusions305

Chapter 11 Silymarin and gut health319
 11.1 Introduction320
 11.2 Vitagenes in gut defence321
 11.3 Gut redox balance and microbiota338
 11.4 Protective effects of silymarin in the gut341
 11.5 Conclusions345

Chapter 12 Hepatoprotective properties of silymarin363
 12.1 Introduction364
 12.2 Silymarin and non-alcoholic fatty liver disease364
 12.3 Antiviral hepatoprotective activity of silymarin375
 12.4 Conclusions377

Chapter 13 Neuroprotective properties of silymarin387
 13.1 Introduction388
 13.2 Silymarin and Alzheimer’s disease388
 13.3 Silymarin and Parkinson’s disease396
 13.4 Conclusions341

Chapter 14 Anti-diabetic properties of silymarin409
 14.1 Introduction409
 14.2 Silymarin and diabetes410
 14.3 Silymarin and diabetic complications417
 14.4 Conclusions419

Chapter 15 Protective actions of silymarin in arthritis and cardiovascular diseases427
 15.1 Introduction428
 15.2 Silymarin and arthritis428
 15.3 Silymarin and cardiovascular diseases430
 15.4 Anticancer activities of silymarin434
 15.5 Conclusions435

Chapter 16 Other beneficial effects of silymarin441
 16.1 Introduction442
 16.2 SM and amatoxin-containing mushrooms poisoning442
 16.3 Silymarin in exercising and stress443
 16.4 Silymarin and burn recovery445
 16.5 Anti-aging effects of silymarin445
 16.6 Silymarin and multidrug resistance446
 16.7 Combined protective effects of silymarin and other antioxidants448
 16.8 Silymarin-drug interactions449
 16.9 Conclusions453

Chapter 17 Silymarin in poultry and farm animal nutrition and health463
 17.1 Introduction464
 17.2 Silymarin in poultry464
 17.3 Silymarin in farm animals469
 17.4 Conclusions474

Chapter 18 From hepatoprotection to general health of poultry479
 18.1 Introduction480
 18.2 Usage of drinking systems for vitagene-activating nutrient mixture delivery480
 18.3 VitaTonic concept development483
 18.4 ShellBone concept development491
 18.5 The development of multi-nutrient mixture for vitagene activation and increasing stress resistance of poultry499
 18.6 Effect of the vitagene-regulating anti-stress composition on rearing birds, layer and broiler breeders505
 18.7 Effects of the vitagene-regulating anti-stress composition on broilers510
 18.8 Vitagene activation as an important strategy in stress prevention/ alleviation516
 18.9 Conclusions516

Chapter 19 Looking ahead: silymarin and health535
 19.1 Introduction536
 19.2 Silymarin and oestrogen receptor regulation536
 19.3 Silymarin and transcription factors PPARs539
 19.4 Increasing silymarin availability is a way forward545
 19.5 Conclusions546
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