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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.
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.
Preface7
About the authors9
Table of contents11
Abbreviations17
Chapter 1 A search for ideal diets, the case of polyphenols27
âAbstract27
âKeywords28
â1.1âIntroduction28
â1.2âWhat are ideal diets?28
â1.3âWhat are polyphenols?34
â1.4âAntioxidant activities of polyphenols35
â1.5âPro-oxidant properties of polyphenols39
â1.6âPolyphenol effects in poultry and farm animals41
â1.7âPolyphenols vs vitamin E46
â1.8âDetrimental effects of polyphenols51
â1.9âConclusions53
âReferences55
Chapter 2 From milk thistle to silymarin: chemical and pharmacological properties67
âAbstract67
âKeywords68
â2.1âIntroduction68
â2.2âHistory of milk thistle/SM investigation68
â2.3âChemical composition and structure73
â2.4âPharmacokinetics75
â2.5âSilymarin toxicity78
â2.6âSilymarin applications79
â2.7âConclusions79
âReferences80
Chapter 3 Antioxidant defence systems in health and diseases85
âAbstract85
âKeywords86
â3.1âIntroduction86
â3.2âFree radicals and reactive oxygen and nitrogen species86
â3.3âThree levels of antioxidant defence89
â3.4âAntioxidant defence network92
â3.5âOxidative stress and redox biology95
â3.6âStress-response pathways95
â3.7âConclusions99
âReferences101
Chapter 4 Antioxidant properties of silymarin105
âAbstract105
âKeywords105
â4.1âIntroduction106
â4.2âDirect free radical scavenging106
â4.3âInhibition of free-radical producing enzymes by silybin107
â4.4âProtective effects of silybin on mitochondria, a main source of free radical production in the cell108
â4.5âIs effective silybin concentration in vitro achievable in vivo?117
â4.6âOxidability and pro-oxidant properties of silymarin118
â4.7âConclusions119
âReferences120
Chapter 5 Silymarin and Nrf2127
âAbstract127
âKeywords127
â5.1âIntroduction128
â5.2âTranscription factor Nrf2128
â5.3âPharmacological/nutritional Nrf2 activation135
â5.4âNrf2 and inflammation140
â5.5âNrf2 activation as a clinical strategy141
â5.6âSilymarin and Nrf2 regulation141
â5.7âConclusions143
âReferences144
Chapter 6 Silymarin and NF-κB151
âAbstract151
âKeywords152
â6.1âIntroduction152
â6.2âTranscription factor NF-κB152
â6.3âNF-κB and oxidative stress158
â6.4âNutritional modulation of NF-κB159
â6.5âSilymarin and NF-κB regulation161
â6.6âNrf2 and NF-ĸB interplay in oxidative stress163
â6.7âConclusions167
âReferences168
Chapter 7 Silymarin and vitagenes179
âAbstract179
âKeywords179
â7.1âIntroduction180
â7.2âVitagene family180
â7.3âEffect of silymarin on vitagene expression182
â7.4âConclusions189
âReferences190
Chapter 8 Antitoxic properties of silymarin199
âAbstract199
âKeywords200
â8.1âIntroduction200
â8.2âVarious compounds with toxic effects200
â8.3âOxidative stress-related conditions218
â8.4âConclusions225
âReferences227
Chapter 9 Silymarin and immunity251
âAbstract251
âKeywords251
â9.1âIntroduction252
â9.2âNatural immunity252
â9.3âAdaptive immunity252
â9.4âSilymarin and phagocyte functions262
â9.5âSilymarin and dendrites264
â9.6âSilymarin and mast cells265
â9.7âSilymarin and lymphocyte functions267
â9.8âMolecular mechanisms of silymarin immunomodulation270
â9.9âRONS, redox homeostasis and immunocommunication272
â9.10âVitagene-immunity interactions and silymarin275
â9.11âConclusions278
âReferences279
Chapter 10 Silymarin and inflammation: from understanding molecular mechanisms to practical applications287
âAbstract287
âKeywords288
â10.1âIntroduction288
â10.2âMolecular mechanisms of inflammation288
â10.3âSilymarin and inflammation: In vitro studies291
â10.4âSilymarin and inflammation: In vivo studies296
â10.5âConclusions305
âReferences307
Chapter 11 Silymarin and gut health319
âAbstract319
âKeywords319
â11.1âIntroduction320
â11.2âVitagenes in gut defence321
â11.3âGut redox balance and microbiota338
â11.4âProtective effects of silymarin in the gut341
â11.5âConclusions345
âReferences346
Chapter 12 Hepatoprotective properties of silymarin363
âAbstract363
âKeywords363
â12.1âIntroduction364
â12.2âSilymarin and non-alcoholic fatty liver disease364
â12.3âAntiviral hepatoprotective activity of silymarin375
â12.4âConclusions377
âReferences378
Chapter 13 Neuroprotective properties of silymarin387
âAbstract387
âKeywords387
â13.1âIntroduction388
â13.2âSilymarin and Alzheimerâs disease388
â13.3âSilymarin and Parkinsonâs disease396
â13.4âConclusions341
âReferences402
Chapter 14 Anti-diabetic properties of silymarin409
âAbstract409
âKeywords409
â14.1âIntroduction409
â14.2âSilymarin and diabetes410
â14.3âSilymarin and diabetic complications417
â14.4âConclusions419
âReferences420
Chapter 15 Protective actions of silymarin in arthritis and cardiovascular diseases427
âAbstract427
âKeywords428
â15.1âIntroduction428
â15.2âSilymarin and arthritis428
â15.3âSilymarin and cardiovascular diseases430
â15.4âAnticancer activities of silymarin434
â15.5âConclusions435
âReferences436
Chapter 16 Other beneficial effects of silymarin441
âAbstract441
âKeywords441
â16.1âIntroduction442
â16.2âSM and amatoxin-containing mushrooms poisoning442
â16.3âSilymarin in exercising and stress443
â16.4âSilymarin and burn recovery445
â16.5âAnti-aging effects of silymarin445
â16.6âSilymarin and multidrug resistance446
â16.7âCombined protective effects of silymarin and other antioxidants448
â16.8âSilymarin-drug interactions449
â16.9âConclusions453
âReferences453
Chapter 17 Silymarin in poultry and farm animal nutrition and health463
âAbstract463
âKeywords463
â17.1âIntroduction464
â17.2âSilymarin in poultry464
â17.3âSilymarin in farm animals469
â17.4âConclusions474
âReferences475
Chapter 18 From hepatoprotection to general health of poultry479
âAbstract479
âKeywords480
â18.1âIntroduction480
â18.2âUsage of drinking systems for vitagene-activating nutrient mixture delivery480
â18.3âVitaTonic concept development483
â18.4âShellBone concept development491
â18.5âThe development of multi-nutrient mixture for vitagene activation and increasing stress resistance of poultry499
â18.6âEffect of the vitagene-regulating anti-stress composition on rearing birds, layer and broiler breeders505
â18.7âEffects of the vitagene-regulating anti-stress composition on broilers510
â18.8âVitagene activation as an important strategy in stress prevention/ alleviation516
â18.9âConclusions516
âReferences517
Chapter 19 Looking ahead: silymarin and health535
âAbstract535
âKeywords535
â19.1âIntroduction536
â19.2âSilymarin and oestrogen receptor regulation536
â19.3âSilymarin and transcription factors PPARs539
â19.4âIncreasing silymarin availability is a way forward545
â19.5âConclusions546
âReferences548
About the authors9
Table of contents11
Abbreviations17
Chapter 1 A search for ideal diets, the case of polyphenols27
âAbstract27
âKeywords28
â1.1âIntroduction28
â1.2âWhat are ideal diets?28
â1.3âWhat are polyphenols?34
â1.4âAntioxidant activities of polyphenols35
â1.5âPro-oxidant properties of polyphenols39
â1.6âPolyphenol effects in poultry and farm animals41
â1.7âPolyphenols vs vitamin E46
â1.8âDetrimental effects of polyphenols51
â1.9âConclusions53
âReferences55
Chapter 2 From milk thistle to silymarin: chemical and pharmacological properties67
âAbstract67
âKeywords68
â2.1âIntroduction68
â2.2âHistory of milk thistle/SM investigation68
â2.3âChemical composition and structure73
â2.4âPharmacokinetics75
â2.5âSilymarin toxicity78
â2.6âSilymarin applications79
â2.7âConclusions79
âReferences80
Chapter 3 Antioxidant defence systems in health and diseases85
âAbstract85
âKeywords86
â3.1âIntroduction86
â3.2âFree radicals and reactive oxygen and nitrogen species86
â3.3âThree levels of antioxidant defence89
â3.4âAntioxidant defence network92
â3.5âOxidative stress and redox biology95
â3.6âStress-response pathways95
â3.7âConclusions99
âReferences101
Chapter 4 Antioxidant properties of silymarin105
âAbstract105
âKeywords105
â4.1âIntroduction106
â4.2âDirect free radical scavenging106
â4.3âInhibition of free-radical producing enzymes by silybin107
â4.4âProtective effects of silybin on mitochondria, a main source of free radical production in the cell108
â4.5âIs effective silybin concentration in vitro achievable in vivo?117
â4.6âOxidability and pro-oxidant properties of silymarin118
â4.7âConclusions119
âReferences120
Chapter 5 Silymarin and Nrf2127
âAbstract127
âKeywords127
â5.1âIntroduction128
â5.2âTranscription factor Nrf2128
â5.3âPharmacological/nutritional Nrf2 activation135
â5.4âNrf2 and inflammation140
â5.5âNrf2 activation as a clinical strategy141
â5.6âSilymarin and Nrf2 regulation141
â5.7âConclusions143
âReferences144
Chapter 6 Silymarin and NF-κB151
âAbstract151
âKeywords152
â6.1âIntroduction152
â6.2âTranscription factor NF-κB152
â6.3âNF-κB and oxidative stress158
â6.4âNutritional modulation of NF-κB159
â6.5âSilymarin and NF-κB regulation161
â6.6âNrf2 and NF-ĸB interplay in oxidative stress163
â6.7âConclusions167
âReferences168
Chapter 7 Silymarin and vitagenes179
âAbstract179
âKeywords179
â7.1âIntroduction180
â7.2âVitagene family180
â7.3âEffect of silymarin on vitagene expression182
â7.4âConclusions189
âReferences190
Chapter 8 Antitoxic properties of silymarin199
âAbstract199
âKeywords200
â8.1âIntroduction200
â8.2âVarious compounds with toxic effects200
â8.3âOxidative stress-related conditions218
â8.4âConclusions225
âReferences227
Chapter 9 Silymarin and immunity251
âAbstract251
âKeywords251
â9.1âIntroduction252
â9.2âNatural immunity252
â9.3âAdaptive immunity252
â9.4âSilymarin and phagocyte functions262
â9.5âSilymarin and dendrites264
â9.6âSilymarin and mast cells265
â9.7âSilymarin and lymphocyte functions267
â9.8âMolecular mechanisms of silymarin immunomodulation270
â9.9âRONS, redox homeostasis and immunocommunication272
â9.10âVitagene-immunity interactions and silymarin275
â9.11âConclusions278
âReferences279
Chapter 10 Silymarin and inflammation: from understanding molecular mechanisms to practical applications287
âAbstract287
âKeywords288
â10.1âIntroduction288
â10.2âMolecular mechanisms of inflammation288
â10.3âSilymarin and inflammation: In vitro studies291
â10.4âSilymarin and inflammation: In vivo studies296
â10.5âConclusions305
âReferences307
Chapter 11 Silymarin and gut health319
âAbstract319
âKeywords319
â11.1âIntroduction320
â11.2âVitagenes in gut defence321
â11.3âGut redox balance and microbiota338
â11.4âProtective effects of silymarin in the gut341
â11.5âConclusions345
âReferences346
Chapter 12 Hepatoprotective properties of silymarin363
âAbstract363
âKeywords363
â12.1âIntroduction364
â12.2âSilymarin and non-alcoholic fatty liver disease364
â12.3âAntiviral hepatoprotective activity of silymarin375
â12.4âConclusions377
âReferences378
Chapter 13 Neuroprotective properties of silymarin387
âAbstract387
âKeywords387
â13.1âIntroduction388
â13.2âSilymarin and Alzheimerâs disease388
â13.3âSilymarin and Parkinsonâs disease396
â13.4âConclusions341
âReferences402
Chapter 14 Anti-diabetic properties of silymarin409
âAbstract409
âKeywords409
â14.1âIntroduction409
â14.2âSilymarin and diabetes410
â14.3âSilymarin and diabetic complications417
â14.4âConclusions419
âReferences420
Chapter 15 Protective actions of silymarin in arthritis and cardiovascular diseases427
âAbstract427
âKeywords428
â15.1âIntroduction428
â15.2âSilymarin and arthritis428
â15.3âSilymarin and cardiovascular diseases430
â15.4âAnticancer activities of silymarin434
â15.5âConclusions435
âReferences436
Chapter 16 Other beneficial effects of silymarin441
âAbstract441
âKeywords441
â16.1âIntroduction442
â16.2âSM and amatoxin-containing mushrooms poisoning442
â16.3âSilymarin in exercising and stress443
â16.4âSilymarin and burn recovery445
â16.5âAnti-aging effects of silymarin445
â16.6âSilymarin and multidrug resistance446
â16.7âCombined protective effects of silymarin and other antioxidants448
â16.8âSilymarin-drug interactions449
â16.9âConclusions453
âReferences453
Chapter 17 Silymarin in poultry and farm animal nutrition and health463
âAbstract463
âKeywords463
â17.1âIntroduction464
â17.2âSilymarin in poultry464
â17.3âSilymarin in farm animals469
â17.4âConclusions474
âReferences475
Chapter 18 From hepatoprotection to general health of poultry479
âAbstract479
âKeywords480
â18.1âIntroduction480
â18.2âUsage of drinking systems for vitagene-activating nutrient mixture delivery480
â18.3âVitaTonic concept development483
â18.4âShellBone concept development491
â18.5âThe development of multi-nutrient mixture for vitagene activation and increasing stress resistance of poultry499
â18.6âEffect of the vitagene-regulating anti-stress composition on rearing birds, layer and broiler breeders505
â18.7âEffects of the vitagene-regulating anti-stress composition on broilers510
â18.8âVitagene activation as an important strategy in stress prevention/ alleviation516
â18.9âConclusions516
âReferences517
Chapter 19 Looking ahead: silymarin and health535
âAbstract535
âKeywords535
â19.1âIntroduction536
â19.2âSilymarin and oestrogen receptor regulation536
â19.3âSilymarin and transcription factors PPARs539
â19.4âIncreasing silymarin availability is a way forward545
â19.5âConclusions546
âReferences548