Ginkgo biloba extract (EGb 761): from chemistry to the clinic
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| Main Author: | |
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| Format: | Book |
| Language: | English |
| Published: |
Wiesbaden
Ullstein Med.
1998
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XXII, 401 S. Ill., graph. Darst. |
| ISBN: | 3861261731 |
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MARC
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| 100 | 1 | |a DeFeudis, Francis Vincent |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Ginkgo biloba extract (EGb 761) |b from chemistry to the clinic |c Francis V. DeFeudis |
| 264 | 1 | |a Wiesbaden |b Ullstein Med. |c 1998 | |
| 300 | |a XXII, 401 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
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| adam_text | Contents
Prologue V
list of Abbreviations VII
Table of Contents XIII
Chapter I
- Introduction i
A. The Ginkgo Tree I
B. History of the Medicinal Properties of Ginkgo biloba 2
C. Polyvalent Mechanism of Action of EGb 761 3
D. Some Problems Inherent to Pharmacological Studies of EGb 761.. 4
E. Primary Clinical Indications for EGb 761 4
F. Scope and Target Audience of This Volume 6
Chapter II
- Chemical Composition of Ginkgo biloba Extract (EGb 761):
Methods of Standardization of the Extract 7
A. Introductory Comments 7
B. Cultivation of the Trees, Harvesting of the Leaves, and
Extraction/Standardization of EGb 761 7
1. Cultivation, harvesting and production of EGb 761 7
2. Patenting, extraction and standardization of EGb 761 9
C. Details Concerning the Chemical Constituents of EGb 761 11
1. Flavonoids 11
2. Terpenoids 12
a. Ginkgolides 13
b. Bilobalide 13
3. Proanthocyanidins (prodelphinidins) 14
4. Organic acids 14
5. Constituents of Ginkgo biloba leaves that are not present
in EGb 761 14
6. A note on the quality of plant extracts 15
D. Concluding Comments 15
Chapter III
- Biosynthetic Mechanisms and Pharmacokinetic Studies of EGb 761
and its Constituents 17
A. Biosynthesis of Components of EGb 761 17
1. Flavonoids 17
2. Ginkgolides and bilobalide 17
XIV J
B. Pharmacokinetic Studies 18
1. Introductory comments 18
2. Studies with experimental animals 18
a. Radiolabelled EGb 761 18
b. Flavonoids 19
c. Ginkgolides and bilobalide 20
3. Studies with humans 20
a. Flavonol glycosides 20
b. Ginkgolides and bilobalide 21
C. Concluding Comments 22
Chapter IV
- Effects of EGb 761 on the Central Nervous System: Basic Studies . 25
A. Introductory Remarks 25
B. In Vitro CNS Preparations 25
1. Experiments with CNS subcellular particles 25
a. Lipid peroxidation in brain homogenates 25
b. Uptake of biogenic amines by synaptosome-enriched
preparations 25
c. Excitatory amino acid receptors in
synaptosome-enriched preparations 26
d. Synaptosomal uptake of DA and 5-HT following
prolonged incubation 27
e. Synaptosomal membrane fluidity 27
f. Protein kinase C 28
2. Experiments with cell cultures 29
a. Enzymes of energy metabolism 29
b. Hydroxyl radical-induced neuronal damage 29
c. Excitotoxic neuronal damage 30
C. In Vivo and Ex Vivo Studies of the CNS 30
1. Cerebral blood flow and glucose utilization under
normal conditions 30
2. Cerebral ischaemia and hypoxia 32
a. Hypobaric hypoxia and hypoxic hypoxia 32
b. Focal and global cerebral ischaemia 33
3. Lipid-derived second messengers, phospholipases
and cerebral ischaemia 34
4. Cerebral edema 35
a. Triethyltin- and hexachlorophene-induced cerebral edema .. 35
b. Bromethalin-induced cerebral edema 38
c. Vasogenic cerebral edema 38
5. EGb 761 and blood-brain-barrier permeability 38
6. Vasoconstriction of pial arteries 39
7. Neurotransmitter systems 39
a. Ageing and central neurotransmitter receptors 39 i
b. Effect of EGb 761 on brain muscarinic receptors 40 j
c. Effect of EGb 761 on high-affinity choline uptake 40 f
1
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d. EGb 761 and brain noradrenergic receptors 40
e. EGb 761 and brain dopaminergic systems 41
f. EGb 761 and brain serotoninergic (5-HT) receptors 41
8. Age-associated impairment of rat brain mitochondria 41
D. Concluding Comments 42
Chapter V
- Effects of EGb 761 on Behavior, Learning and Memory,
and Recovery from Traumatic Brain Injury: Evidence for an
Involvement of Neuronal Plasticity 45
A. Introductory Comments 45
B. Acquisition and Retention -- Learning and Memory 45
1. Acquisition and retention 45
2. Scopolamine-induced amnesia 46
3. Cognitive dysfunction induced by brain irradiation 47
C. Behavior in Relation to Recovery from Brain Injury 47
1. Introductory comments 47
2. Recovery of function after bilateral frontal lobotomy 48
3. Recovery of function in animal models of cortical hemiplegia. 48
4. Recovery of function after septohippocampal damage 50
D. Learning and Behavior in Relation to Ageing 50
1. Cage-climbing behavior in mice 50
2. Performance of rats in an eight-arm radial maze 51
3. Studies with genetically different mouse strains 51
4. Related studies 52
F. Effects of EGb 761 on Neuronal Plasticity 52
1. Behavioral recovery and expression of neurotrophins
after lesions to the entorhinal cortex 52
2. Release of apolipoproteins E and J by astrocytes after lipid
peroxidation and apolipoprotein E after entorhinal cortex
lesions 53
3. Plasticity of visual pathways during postnatal development. . 54
4. Apoptosis and regeneration of primary olfactory neurones
following target lesions 54
5. Age-dependent structural changes in mouse hippocampus. . 55
6. Post-lesion neuronal plasticity of rat sympathetic ganglia ... 56
G. Concluding Remarks 57
Chapter VI
- Stress-Alleviating Action of EGb 761: A Basis for
Neuropsychological Adaptation 59
A. Introductory Comments 59
B. Anti-Stress or Stress-Alleviating Activity of EGb 761 59
C. Effects of EGb 761 in Rodent Models of Stress 60
1. Learned helplessness 60
2. Vogel conflict, four-plates, staircase and eating tests,
and ethologically-based models 61
XVI I
3. Stress-induced polydipsia 61
4. Stress, learning ability and circulating stress hormones .... 62
5. Surgical stress and the hypothalamo-pituitary-adrenal axis .. 63
6. Stress and the down-regulation of hippocampal
glucocorticoid Type II receptors 63
7. Social interaction test 64
8. Cold-hypoxia-restraint model:Multiple stress 65
D. Neuroprotective Effects of EGb 761 Under Stressful
Conditions 66
1. Heat stress 66
2. Stress-induced 5-HTj^ receptor desensitization 66
E. Regulation of the Peripheral Benzodiazepine Receptor by
EGb 761 and Ginkgolides: Relation to Stress 68
F. Possible Molecular Mechanisms Mediating the
Stress-Alleviating Effect of EGb 761 69
G. Concluding Comments 7°
Chapter VII I
- Effects of EGb on Neurosensory Systems: Basic Studies 73 ¦
A. Effects of EGb 761 on the Visual System 73 :
1. Introductory comments 73
2. Models of diabetic retinopathy 73
a. Alloxan- or streptozotocin-induced diabetic retinopathy.. 73
b. Chloroquine-induced retinopathy 74
c. Retinal tolerance to glucose 74
3. Reperfusion-induced histologic changes in rat retina 74
4. Tractional retinal detachment 75
5. Susceptibility of retinal cells to proteolytic enzymes 75
6. Retinal lipid peroxidation 75
7. Expression of protooncogene protein Bcl-2 76
8. Related studies 76
B. Effects of EGb 761 on the Vestibular and Auditory Systems 77
1. Vestibular compensation in the rat 77
2. Vestibular compensation in the guinea pig 7%
3. Vestibular compensation in the cat 7
4. Animal model of tinnitus 79
C. Effects of EGb 761 on the Olfactory System 80
D. Concluding Remarks 80
Chapter VIII
- Actions of EGb 761 on the Cardiovascular System 81
A. In Vitro Studies with EGb 761 81
1. Rabbit isolated aorta 81
a. Early studies: Implication of catecholaminergic systems .. 81
b. Papaverine-like effect of EGb 761: Possible involvement
of cyclic-GMP phosphodiesterase 82 ,
c. EGb 761 and the EDRF/nitric oxide (NO) mechanism ... 82 j
d. Rutin does not elicit EDRF/NO-mediated vasorelaxation... 83 I
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2. Rabbit isolated saphenous artery and vein 83
3. Rat isolated aorta 84
4. Rabbit isolated vena cava and portal vein 84
5. Isolated heart preparations 85
a. Guinea pig isolated heart 85
b. Rat isolated heart 85
c. Ischaemic preconditioning in the rat isolated heart 87
6. Cellular preparations 88
a. Exposure of endothelial cells to hypoxia-reoxygenation
or hypoxia 88
b. Exposure of endothelial cells to 02 89
c. Glucose uptake and glycogen storage in vascular
smooth muscle cells 90
d. Glucose uptake and glycogen storage in erythrocytes.... 90
B. In Vivo Studies with EGb 761 90
1. Platelets and thrombosis 90
a. Platelet hyperaggregation in the microcirculation 90
b. White-platelet thrombogenesis in rat mesenteric artery .. 91
2. Myocardial ischaemia and cardiac arrhythmias 91
a. Myocardial ischaemia in the anaesthetized rat 91
b. Myocardial ischaemia and reperfusion injury in the
anaesthetized rabbit 91
c. Myocardial stunning in the anaesthetized pig 92
d. Early arrhythmia in the dog 92
e. Hypoxia-induced changes in myocardial enzyme activities.. 92
f. Protection of the myocardium of old rats against hypoxia .. 93
3. Microcirculation and vascular permeability 93
4. Effect of ginkgolide B on leukocyte adherence 95
5. Blood pressure regulation and endotoxic shock: Possible
role of PAF and effects of ginkgolides 95
a. PAF-antagonism and blood pressure 95
b. PAF-antagonism and shock states 96
C. Concluding Comments 96
Chapter IX
- Effects of EGb 761 on Transmembrane Ion Channels,
Ionic Shifts, and Electrical Activity of Single Cells 99
A. Introductory Comments 99
B. Effects of EGb 761 on the Action Potential and Associated
Transmembrane Ionic Currents in Cardiac Myocytes 99
C. Effect of EGb 761 on Ischaemia/Reperfusion-Induced Ionic
Shifts in Rat Retina 101
D. Effects of Repeated Treatments with EGb 761, Bilobalide
and Ginkgolide B on the Electrical Activity of Pancreatic (3
Cells of Normal or Alloxan-Diabetic Mice 102
E. Concluding Statements 104
XVIII Chapter X
- Effects of EGb 761 on Formed Elements of the Blood:
Basic Hemorheological Studies 105
A. Introduction 105
B. Erythrocytes 105
1. In vitro studies with human erythrocytes 105
a. Microrheological parameters 105
b. Hydrogen peroxide (H202)-induced damage 105
c. Experiments with an acidotic/hyperosmolar medium... 106
d. Comparison of EGb 761 and a Ginkgo biloba
extract devoid of terpenes 107 j
e. Studies with the blood of human patients with j
vascular disorders 107 i
2. In vivo effects of EGb 761 on capillary erythrocyte velocity . 107 f
C. Leukocytes 108 j
1. Comparison of in vitro and ex vivo responses of human !
neutrophils to EGb 761 108
2. Inhibition of H202 release from human neutrophils by
phenolic acid constituents of EGb 761 108
3. Actions of PAF-antagonistic ginkgolides in neutrophils
and eosinophils 108
4. Inhibition of neutrophil adherence in rat cremaster
venules by ginkgolide B 109
5. Inhibition of neutrophil adhesion to vascular endothelium
by EGb 761 109
D. Interactions of EGb 761 and Platelets no
E. Concluding Remarks 112
Chapter XI
- Effects of EGb 761 on Other Organs, Tissues and Cells:
Basic Studies in Vitro and in Vivo 113
A. Introduction 113
B. In Vitro Preparations 113
1. Guinea pig ileum 113
2. Guinea pig trachea 113
3. Collagen fibers 113
4. Kidney mitochondria 114
5. Human tibroblasts 114
C. In Vivo Studies 114
1. Damage to the peripheral nervous system 114
a. Peripheral nerve injury 114
b. Experimental autoimmune disease 115
2. Adriamycin-induced inflammation 115
3. Liver and muscle glycogen contents in the non-insulin-
dependent diabetic rat 116
4. Mucosal damage associated with small intestinal ischaemia.. 116 j
5. Hypoxia-dependent changes in rat skeletal muscle 117 j
6. Pancreatitis and nephrotoxicity: Effects of ginkgolide B .... 117 f
D. Concluding Comments 117 I
XIX
Chapter XII
- Free Radical-Scavenging, Antioxidant, and Related Mechanisms of
Action of EGb 761 and its Constituents 119
A. Introductory comments 119
B. Studies with Acellular Preparations 120
1. Free radical-scavenging activity of EGb 761: A study with
7-radiolysis 120
2. Protection of human low-density lipoproteins (LDL)
by EGb 761 121
3. EGb 761 and ferryl ion-induced peroxidations 121
4. Peroxyl radical-scavenging by EGb 761 122
5. Scavenging of nitric oxide (NO) by EGb 761 123
C. Studies with Cellular and Subcellular Preparations 123
1. Inhibitory effect of EGb 761 on 02 production by
human neutrophils 123
2. Antioxidant effects of EGb 761 in human lymphocytes
and in rat brain 124
3. Antioxidant effect of EGb 761 in human leukocytes 124
4. Inhibition of lymphocyte-induced angiogenesis by EGb 761.. 124
5. Anti-radical effect of EGb 761 in the retina 125
6. Effect of EGb 761 and its constituents on neuronal
oxidative metabolism 126
7. Studies on nitric oxide as a free radical 126
8. Lipid peroxidation and free radical generation in
microsomal preparations 127
9. Anti-lipoperoxidative and scavenging properties of
EGb 761 constituents 129
10. Effect of EGb 761 on oxidative stress-induced
modification of gene expression: Transcription factors .... 129
D. Studies with In Vivo/Ex Vivo Preparations 131
1. Effect of EGb 761 on lipid peroxidation 131
2. Cytosolic free radicals and scavenging enzymes in
relation to ageing 131
E. Concluding Remarks 131
Chapter XIII
- Clinical Studies of the Effects of EGb 761 on the
Central Nervous System 157
A. Introductory Comments 157
B. Clinical Pharmacology: Pharmacodynamics 138
1. Studies of hypoxia in normal volunteers 138
2. EEG studies in normal, healthy volunteers 138
a. Analyses of EGb 761 and its subfractions 138
b. Effects of increasing doses of EGb 761 139
c. EEG mapping profile of EGb 761 139
d. Studies with the Quantitative Pharmaco-EEG method .. 140
3. Studies of memory in normal volunteers 141
XX C. Treatment of Disturbances of CNS Functions with EGb 761 .. 142
1. Dementia and related problems 142
2. Chronic cerebral insufficiency 143 j
a. Studies on cerebral blood flow 143 |
b. Initial studies on cerebrovascular insufficiency ;
and related conditions 144
c. Further studies on cerebrovascular insufficiency and j
related conditions 146 }
d. Alzheimer s disease, vascular dementia or mixed-type i
dementia 150 i
e. EEG studies of vigilance and mental performance 154
f. Memory difficulties of everyday life 155
g. Memory training combined with EGb 761 therapy 156 ;
h. EGb 761 therapy for depressive mood in association j
with dementia 156 i
i. Combination therapy with EGb 761 and antidepressants .. 157
j. Dual-coding test in elderly subjects with memory
impairment 158
D. Concluding Remarks 159
Chapter XIV
- Treatment of Peripheral Arterial Occlusive Disease with EGb 761 .. 165
A. Introductory Comments 165
B. Initial Studies: EGb 761 as Therapy for pAOD 166
C. More Recent Studies with EGb 761 as Therapy for pAOD 166
1. Intermittent daudication (Fontaine s Stage II or lib) 166
a. Studies by individual research groups 166
b. Bicentric or multicentric studies 169
c. Combination therapy with EGb 761 and physical training. 170
d. Determination of transcutaneous oxygen partial
pressure in pAOD patients 171
2. pAOD (Fontaine s Stages III and IV) 171
3. Trophic disorders of the lower limbs (leg ulcers) 172
4. Correlation of hemorheological and clinical effects
of EGb 761 in patients with pAOD 172
D. Conclusions 173
Chapter XV
- Clinical Studies on EGb 761 and Neurosensory Disturbances .... 175
A. Introduction 175
B. EGb 761 and Vestibular/Auditory Disturbances 175
1. Introductory comments 175
2. Vertigo, tinnitus and associated hearing loss 176
3. Acute cochlear deafness (sudden deafness) 178
C. EGb 761 and Retinal Pathology 180
1. Introductory comments 180
2. Venous retinal occlusions 180
XXI
3. Retinal problems related to chronic cerebrovascular
insufficiency 181
4. Senile macular degeneration 182
5. Diabetic retinopathy 182
D. Concluding Comments 182
Chapter XVI
- Other Clinical Pharmacological Trials, Clinical Perspectives and
Possible Future Uses for EGb 761 185
A. Introduction 185
B. Rheological Studies 185
1. Whole blood rheology 185
2. Erythrocyte microrheology in healthy humans 186
3. Studies in human patients with vascular disorders 187
4. Leukocyte filterability and EGb 761 187
5. Inhibition of platelet aggregation by EGb 761 187
6. Effect of EGb 761 on the venous microembolic index .... 188
C. EGb 761 and Open Heart Surgery 188
D. Treatment of Diabetic Polyneuropathy with EGb 761 and
Folk Acid (Combination Therapy) 189
E. UV-Light-Induced Oxidative Stress 190
F. Idiopathic Cyclic Edema 190
G. Acute Mountain Sickness and Cold Exposure 190
H. Anti-Clastogenic Effect of EGb 761 191
I. Studies with Ginkgolide B, a PAF-Antagonist 192
1. Multiple sclerosis 192
2. Hematological changes and blood loss during
cardiopulmonary bypass 193
3. Sepsis 193
4. Post-transplant renal failure 194
J. Stroke (Apoplexy) 194
K. Migraine and Cerebral Vasospasm 195
L. Traumatic Brain Injury 195
M.Concluding Comments 196
Chapter XVII
- Toxicology of EGb 761 in Experimental Animals and Humans:
Safety of EGb 761-Containing Products 197
A. Toxicological Studies 197
1. Studies with experimental animals 197
2. Studies with humans 197
B. Endocrine Parameters, and Microsomal Enzyme Induction. . . 197
1. Endocrine parameters 197
2. Enzyme induction 198
C. Safety Issues (Side-Effects) 198
1. Clinical analyses of safety: Surveillance studies 198
2. Incidence of side-effects 199
D. Conclusion 201
XXII Chapter XVIII
- General Conclusions 203
A. Standardization of EGb 761 and Bioavailability of its
Constituents 203
B. Basic Studies on the CNS 203
C. Behavior, Learning and Memory, Traumatic Brain Injury
and Neuronal Plasticity 204
D. Stress-Alleviating Action of EGb 761 205
E. Neurosensory Systems: Basic Studies 207
F. Basic Studies with Cardiovascular Preparations 207
G. Transmembrane Ion Channels, Ionic Shifts and
Single-Cell Electrical Activity 208
H. Formed Elements of the Blood: Basic Hemorheology 208
I. Basic Studies on Other Organs and Tissues 209
J. Free Radical-Scavenging and Antioxidant Actions of EGb 761 209 ;
K. Effects of EGb 761 on Energy Metabolism 210
L. Clinical Studies on the CNS 212
M.Clinical Studies on pAOD 215
N. Clinical Studies on Neurosensory Systems 216
O. Possible New Clinical Uses for EGb 761 216
P. Concepts of Action of EGb 761 216
References 219
Figures 279
Tables 363
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| adam_txt |
Contents
Prologue V
list of Abbreviations VII
Table of Contents XIII
Chapter I
- Introduction i
A. The Ginkgo Tree I
B. History of the Medicinal Properties of Ginkgo biloba 2
C. Polyvalent Mechanism of Action of EGb 761 3
D. Some Problems Inherent to Pharmacological Studies of EGb 761. 4
E. Primary Clinical Indications for EGb 761 4
F. Scope and Target Audience of This Volume 6
Chapter II
- Chemical Composition of Ginkgo biloba Extract (EGb 761):
Methods of Standardization of the Extract 7
A. Introductory Comments 7
B. Cultivation of the Trees, Harvesting of the Leaves, and
Extraction/Standardization of EGb 761 7
1. Cultivation, harvesting and production of EGb 761 7
2. Patenting, extraction and standardization of EGb 761 9
C. Details Concerning the Chemical Constituents of EGb 761 11
1. Flavonoids 11
2. Terpenoids 12
a. Ginkgolides 13
b. Bilobalide 13
3. Proanthocyanidins (prodelphinidins) 14
4. Organic acids 14
5. Constituents of Ginkgo biloba leaves that are not present
in EGb 761 14
6. A note on the quality of plant extracts 15
D. Concluding Comments 15
Chapter III
- Biosynthetic Mechanisms and Pharmacokinetic Studies of EGb 761
and its Constituents 17
A. Biosynthesis of Components of EGb 761 17
1. Flavonoids 17
2. Ginkgolides and bilobalide 17
XIV J
B. Pharmacokinetic Studies 18
1. Introductory comments 18
2. Studies with experimental animals 18
a. Radiolabelled EGb 761 18
b. Flavonoids 19
c. Ginkgolides and bilobalide 20
3. Studies with humans 20
a. Flavonol glycosides 20
b. Ginkgolides and bilobalide 21
C. Concluding Comments 22
Chapter IV
- Effects of EGb 761 on the Central Nervous System: Basic Studies . 25
A. Introductory Remarks 25
B. In Vitro CNS Preparations 25
1. Experiments with CNS subcellular particles 25
a. Lipid peroxidation in brain homogenates 25 \
b. Uptake of biogenic amines by synaptosome-enriched
preparations 25
c. Excitatory amino acid receptors in
synaptosome-enriched preparations 26
d. Synaptosomal uptake of DA and 5-HT following
prolonged incubation 27
e. Synaptosomal membrane fluidity 27
f. Protein kinase C 28
2. Experiments with cell cultures 29
a. Enzymes of energy metabolism 29
b. Hydroxyl radical-induced neuronal damage 29
c. Excitotoxic neuronal damage 30
C. In Vivo and Ex Vivo Studies of the CNS 30
1. Cerebral blood flow and glucose utilization under
normal conditions 30
2. Cerebral ischaemia and hypoxia 32
a. Hypobaric hypoxia and hypoxic hypoxia 32
b. Focal and global cerebral ischaemia 33
3. Lipid-derived second messengers, phospholipases
and cerebral ischaemia 34
4. Cerebral edema 35
a. Triethyltin- and hexachlorophene-induced cerebral edema . 35
b. Bromethalin-induced cerebral edema 38
c. Vasogenic cerebral edema 38
5. EGb 761 and blood-brain-barrier permeability 38
6. Vasoconstriction of pial arteries 39
7. Neurotransmitter systems 39
a. Ageing and central neurotransmitter receptors 39 i
b. Effect of EGb 761 on brain muscarinic receptors 40 j
c. Effect of EGb 761 on high-affinity choline uptake 40 f
1
xv_
d. EGb 761 and brain noradrenergic receptors 40
e. EGb 761 and brain dopaminergic systems 41
f. EGb 761 and brain serotoninergic (5-HT) receptors 41
8. Age-associated impairment of rat brain mitochondria 41
D. Concluding Comments 42
Chapter V
- Effects of EGb 761 on Behavior, Learning and Memory,
and Recovery from Traumatic Brain Injury: Evidence for an
Involvement of Neuronal Plasticity 45
A. Introductory Comments 45
B. Acquisition and Retention -- Learning and Memory 45
1. Acquisition and retention 45
2. Scopolamine-induced amnesia 46
3. Cognitive dysfunction induced by brain irradiation 47
C. Behavior in Relation to Recovery from Brain Injury 47
1. Introductory comments 47
2. Recovery of function after bilateral frontal lobotomy 48
3. Recovery of function in animal models of cortical hemiplegia. 48
4. Recovery of function after septohippocampal damage 50
D. Learning and Behavior in Relation to Ageing 50
1. "Cage-climbing" behavior in mice 50
2. Performance of rats in an eight-arm radial maze 51
3. Studies with genetically different mouse strains 51
4. Related studies 52
F. Effects of EGb 761 on Neuronal Plasticity 52
1. Behavioral recovery and expression of "neurotrophins"
after lesions to the entorhinal cortex 52
2. Release of apolipoproteins E and J by astrocytes after lipid
peroxidation and apolipoprotein E after entorhinal cortex
lesions 53
3. Plasticity of visual pathways during postnatal development. . 54
4. Apoptosis and regeneration of primary olfactory neurones
following target lesions 54
5. Age-dependent structural changes in mouse hippocampus. . 55
6. Post-lesion neuronal plasticity of rat sympathetic ganglia . 56
G. Concluding Remarks 57
Chapter VI
- "Stress-Alleviating" Action of EGb 761: A Basis for
Neuropsychological Adaptation 59
A. Introductory Comments 59
B. "Anti-Stress" or "Stress-Alleviating" Activity of EGb 761 59
C. Effects of EGb 761 in Rodent Models of Stress 60
1. "Learned helplessness" 60
2. Vogel conflict, four-plates, staircase and eating tests,
and ethologically-based models 61
XVI I
3. Stress-induced polydipsia 61
4. Stress, learning ability and circulating stress hormones . 62
5. Surgical stress and the hypothalamo-pituitary-adrenal axis . 63
6. Stress and the down-regulation of hippocampal
glucocorticoid Type II receptors 63
7. "Social interaction" test 64
8. "Cold-hypoxia-restraint" model:Multiple stress 65
D. Neuroprotective Effects of EGb 761 Under Stressful
Conditions 66
1. Heat stress 66
2. Stress-induced 5-HTj^ receptor desensitization 66
E. Regulation of the Peripheral Benzodiazepine Receptor by
EGb 761 and Ginkgolides: Relation to Stress 68
F. Possible Molecular Mechanisms Mediating the
Stress-Alleviating Effect of EGb 761 69
G. Concluding Comments 7°
Chapter VII I
- Effects of EGb on Neurosensory Systems: Basic Studies 73 ' ¦
A. Effects of EGb 761 on the Visual System 73 :
1. Introductory comments 73
2. Models of diabetic retinopathy 73
a. Alloxan- or streptozotocin-induced diabetic retinopathy. 73
b. Chloroquine-induced retinopathy 74
c. Retinal tolerance to glucose 74
3. Reperfusion-induced histologic changes in rat retina 74
4. Tractional retinal detachment 75
5. Susceptibility of retinal cells to proteolytic enzymes 75
6. Retinal lipid peroxidation 75
7. Expression of protooncogene protein Bcl-2 76
8. Related studies 76
B. Effects of EGb 761 on the Vestibular and Auditory Systems 77
1. Vestibular compensation in the rat 77
2. Vestibular compensation in the guinea pig 7%
3. Vestibular compensation in the cat 7
4. Animal model of tinnitus 79
C. Effects of EGb 761 on the Olfactory System 80
D. Concluding Remarks 80
Chapter VIII
- Actions of EGb 761 on the Cardiovascular System 81
A. In Vitro Studies with EGb 761 81
1. Rabbit isolated aorta 81
a. Early studies: Implication of catecholaminergic systems . 81
b. "Papaverine-like" effect of EGb 761: Possible involvement
of cyclic-GMP phosphodiesterase 82 ,
c. EGb 761 and the EDRF/nitric oxide (NO) mechanism . 82 j
d. Rutin does not elicit EDRF/NO-mediated vasorelaxation. 83 I
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1
XVII
2. Rabbit isolated saphenous artery and vein 83
3. Rat isolated aorta 84
4. Rabbit isolated vena cava and portal vein 84
5. Isolated heart preparations 85
a. Guinea pig isolated heart 85
b. Rat isolated heart 85
c. Ischaemic preconditioning in the rat isolated heart 87
6. Cellular preparations 88
a. Exposure of endothelial cells to hypoxia-reoxygenation
or hypoxia 88
b. Exposure of endothelial cells to 02" 89
c. Glucose uptake and glycogen storage in vascular
smooth muscle cells 90
d. Glucose uptake and glycogen storage in erythrocytes. 90
B. In Vivo Studies with EGb 761 90
1. Platelets and thrombosis 90
a. Platelet hyperaggregation in the microcirculation 90
b. White-platelet thrombogenesis in rat mesenteric artery . 91
2. Myocardial ischaemia and cardiac arrhythmias 91
a. Myocardial ischaemia in the anaesthetized rat 91
b. Myocardial ischaemia and reperfusion injury in the
anaesthetized rabbit 91
c. "Myocardial stunning" in the anaesthetized pig 92
d. Early arrhythmia in the dog 92
e. Hypoxia-induced changes in myocardial enzyme activities. 92
f. Protection of the myocardium of old rats against hypoxia . 93
3. Microcirculation and vascular permeability 93
4. Effect of ginkgolide B on leukocyte adherence 95
5. Blood pressure regulation and endotoxic shock: Possible
role of PAF and effects of ginkgolides 95
a. PAF-antagonism and blood pressure 95
b. PAF-antagonism and shock states 96
C. Concluding Comments 96
Chapter IX
- Effects of EGb 761 on Transmembrane Ion Channels,
Ionic Shifts, and Electrical Activity of Single Cells 99
A. Introductory Comments 99
B. Effects of EGb 761 on the Action Potential and Associated
Transmembrane Ionic Currents in Cardiac Myocytes 99
C. Effect of EGb 761 on Ischaemia/Reperfusion-Induced Ionic
Shifts in Rat Retina 101
D. Effects of Repeated Treatments with EGb 761, Bilobalide
and Ginkgolide B on the Electrical Activity of Pancreatic (3
Cells of Normal or Alloxan-Diabetic Mice 102
E. Concluding Statements 104
XVIII Chapter X
- Effects of EGb 761 on Formed Elements of the Blood:
Basic Hemorheological Studies 105
A. Introduction 105
B. Erythrocytes 105
1. In vitro studies with human erythrocytes 105
a. Microrheological parameters 105
b. Hydrogen peroxide (H202)-induced damage 105
c. Experiments with an acidotic/hyperosmolar medium. 106
d. Comparison of EGb 761 and a Ginkgo biloba
extract devoid of terpenes 107 j
e. Studies with the blood of human patients with j
vascular disorders 107 i
2. In vivo effects of EGb 761 on capillary erythrocyte velocity . 107 f
C. Leukocytes 108 j
1. Comparison of in vitro and ex vivo responses of human !
neutrophils to EGb 761 108
2. Inhibition of H202 release from human neutrophils by
phenolic acid constituents of EGb 761 108
3. Actions of PAF-antagonistic ginkgolides in neutrophils
and eosinophils 108
4. Inhibition of neutrophil adherence in rat cremaster
venules by ginkgolide B 109
5. Inhibition of neutrophil adhesion to vascular endothelium
by EGb 761 109
D. Interactions of EGb 761 and Platelets no
E. Concluding Remarks 112
Chapter XI
- Effects of EGb 761 on Other Organs, Tissues and Cells:
Basic Studies in Vitro and in Vivo 113
A. Introduction 113
B. In Vitro Preparations 113
1. Guinea pig ileum 113
2. Guinea pig trachea 113
3. Collagen fibers 113
4. Kidney mitochondria 114
5. Human tibroblasts 114
C. In Vivo Studies 114
1. Damage to the peripheral nervous system 114
a. Peripheral nerve injury 114
b. Experimental autoimmune disease 115
2. Adriamycin-induced inflammation 115
3. Liver and muscle glycogen contents in the non-insulin-
dependent diabetic rat 116
4. Mucosal damage associated with small intestinal ischaemia. 116 j
5. Hypoxia-dependent changes in rat skeletal muscle 117 j
6. Pancreatitis and nephrotoxicity: Effects of ginkgolide B . 117 f
D. Concluding Comments 117 I
XIX
Chapter XII
- Free Radical-Scavenging, Antioxidant, and Related Mechanisms of
Action of EGb 761 and its Constituents 119
A. Introductory comments 119
B. Studies with Acellular Preparations 120
1. Free radical-scavenging activity of EGb 761: A study with
7-radiolysis 120
2. Protection of human low-density lipoproteins (LDL)
by EGb 761 121
3. EGb 761 and ferryl ion-induced peroxidations 121
4. Peroxyl radical-scavenging by EGb 761 122
5. Scavenging of nitric oxide (NO) by EGb 761 123
C. Studies with Cellular and Subcellular Preparations 123
1. Inhibitory effect of EGb 761 on 02" production by
human neutrophils 123
2. Antioxidant effects of EGb 761 in human lymphocytes
and in rat brain 124
3. Antioxidant effect of EGb 761 in human leukocytes 124
4. Inhibition of lymphocyte-induced angiogenesis by EGb 761. 124
5. Anti-radical effect of EGb 761 in the retina 125
6. Effect of EGb 761 and its constituents on neuronal
oxidative metabolism 126
7. Studies on nitric oxide as a free radical 126
8. Lipid peroxidation and free radical generation in
microsomal preparations 127
9. Anti-lipoperoxidative and scavenging properties of
EGb 761 constituents 129
10. Effect of EGb 761 on oxidative stress-induced
modification of gene expression: Transcription factors . 129
D. Studies with In Vivo/Ex Vivo Preparations 131
1. Effect of EGb 761 on lipid peroxidation 131
2. Cytosolic free radicals and scavenging enzymes in
relation to ageing 131
E. Concluding Remarks 131
Chapter XIII
- Clinical Studies of the Effects of EGb 761 on the
Central Nervous System 157
A. Introductory Comments 157
B. Clinical Pharmacology: Pharmacodynamics 138
1. Studies of hypoxia in normal volunteers 138
2. EEG studies in normal, healthy volunteers 138
a. Analyses of EGb 761 and its subfractions 138
b. Effects of increasing doses of EGb 761 139
c. EEG mapping profile of EGb 761 139
d. Studies with the "Quantitative Pharmaco-EEG" method . 140
3. Studies of memory in normal volunteers 141
XX C. Treatment of Disturbances of CNS Functions with EGb 761 . 142
1. Dementia and related problems 142
2. Chronic cerebral insufficiency 143 j
a. Studies on cerebral blood flow 143 |
b. Initial studies on cerebrovascular insufficiency ;
and related conditions 144 \
c. Further studies on cerebrovascular insufficiency and j
related conditions 146 }
d. Alzheimer's disease, vascular dementia or mixed-type i
dementia 150 i
e. EEG studies of vigilance and mental performance 154 \
f. Memory difficulties of everyday life 155
g. Memory training combined with EGb 761 therapy 156 ;
h. EGb 761 therapy for depressive mood in association j
with dementia 156 i
i. Combination therapy with EGb 761 and antidepressants . 157
j. Dual-coding test in elderly subjects with memory
impairment 158
D. Concluding Remarks 159
Chapter XIV
- Treatment of Peripheral Arterial Occlusive Disease with EGb 761 . 165
A. Introductory Comments 165
B. Initial Studies: EGb 761 as Therapy for pAOD 166
C. More Recent Studies with EGb 761 as Therapy for pAOD 166
1. Intermittent daudication (Fontaine's Stage II or lib) 166
a. Studies by individual research groups 166
b. Bicentric or multicentric studies 169
c. Combination therapy with EGb 761 and physical training. 170
d. Determination of transcutaneous oxygen partial
pressure in pAOD patients 171
2. pAOD (Fontaine's Stages III and IV) 171
3. Trophic disorders of the lower limbs (leg ulcers) 172
4. Correlation of hemorheological and clinical effects
of EGb 761 in patients with pAOD 172
D. Conclusions 173
Chapter XV
- Clinical Studies on EGb 761 and Neurosensory Disturbances . 175
A. Introduction 175
B. EGb 761 and Vestibular/Auditory Disturbances 175
1. Introductory comments 175
2. Vertigo, tinnitus and associated hearing loss 176
3. Acute cochlear deafness (sudden deafness) 178
C. EGb 761 and Retinal Pathology 180
1. Introductory comments 180
2. Venous retinal occlusions 180
XXI
3. Retinal problems related to chronic cerebrovascular
insufficiency 181
4. Senile macular degeneration 182
5. Diabetic retinopathy 182
D. Concluding Comments 182
Chapter XVI
- Other Clinical Pharmacological Trials, Clinical Perspectives and
Possible Future Uses for EGb 761 185
A. Introduction 185
B. Rheological Studies 185
1. Whole blood rheology 185
2. Erythrocyte microrheology in healthy humans 186
3. Studies in human patients with vascular disorders 187
4. Leukocyte filterability and EGb 761 187
5. Inhibition of platelet aggregation by EGb 761 187
6. Effect of EGb 761 on the "venous microembolic index". 188
C. EGb 761 and Open Heart Surgery 188
D. Treatment of Diabetic Polyneuropathy with EGb 761 and
Folk Acid (Combination Therapy) 189
E. UV-Light-Induced Oxidative Stress 190
F. Idiopathic Cyclic Edema 190
G. Acute Mountain Sickness and Cold Exposure 190
H. Anti-Clastogenic Effect of EGb 761 191
I. Studies with Ginkgolide B, a PAF-Antagonist 192
1. Multiple sclerosis 192
2. Hematological changes and blood loss during
cardiopulmonary bypass 193
3. Sepsis 193
4. Post-transplant renal failure 194
J. Stroke (Apoplexy) 194
K. Migraine and Cerebral Vasospasm 195
L. Traumatic Brain Injury 195
M.Concluding Comments 196
Chapter XVII
- Toxicology of EGb 761 in Experimental Animals and Humans:
Safety of EGb 761-Containing Products 197
A. Toxicological Studies 197
1. Studies with experimental animals 197
2. Studies with humans 197
B. Endocrine Parameters, and Microsomal Enzyme Induction. . . 197
1. Endocrine parameters 197
2. Enzyme induction 198
C. Safety Issues (Side-Effects) 198
1. Clinical analyses of safety: Surveillance studies 198
2. Incidence of side-effects 199
D. Conclusion 201
XXII Chapter XVIII
- General Conclusions 203
A. Standardization of EGb 761 and Bioavailability of its
Constituents 203
B. Basic Studies on the CNS 203
C. Behavior, Learning and Memory, Traumatic Brain Injury
and Neuronal Plasticity 204
D. "Stress-Alleviating" Action of EGb 761 205
E. Neurosensory Systems: Basic Studies 207
F. Basic Studies with Cardiovascular Preparations 207
G. Transmembrane Ion Channels, Ionic Shifts and
Single-Cell Electrical Activity 208
H. Formed Elements of the Blood: Basic Hemorheology 208
I. Basic Studies on Other Organs and Tissues 209
J. Free Radical-Scavenging and Antioxidant Actions of EGb 761 209 ;
K. Effects of EGb 761 on Energy Metabolism 210
L. Clinical Studies on the CNS 212
M.Clinical Studies on pAOD 215
N. Clinical Studies on Neurosensory Systems 216
O. Possible New Clinical Uses for EGb 761 216
P. "Concepts of Action" of EGb 761 216
References 219
Figures 279
Tables 363 |
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| spelling | DeFeudis, Francis Vincent Verfasser aut Ginkgo biloba extract (EGb 761) from chemistry to the clinic Francis V. DeFeudis Wiesbaden Ullstein Med. 1998 XXII, 401 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Ginkgoblatt-Extrakt Ginkgoblatt-Extrakt (DE-588)4216360-2 gnd rswk-swf Ginkgoblatt-Extrakt (DE-588)4216360-2 s DE-604 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016559305&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | DeFeudis, Francis Vincent Ginkgo biloba extract (EGb 761) from chemistry to the clinic Ginkgoblatt-Extrakt Ginkgoblatt-Extrakt (DE-588)4216360-2 gnd |
| subject_GND | (DE-588)4216360-2 |
| title | Ginkgo biloba extract (EGb 761) from chemistry to the clinic |
| title_auth | Ginkgo biloba extract (EGb 761) from chemistry to the clinic |
| title_exact_search | Ginkgo biloba extract (EGb 761) from chemistry to the clinic |
| title_exact_search_txtP | Ginkgo biloba extract (EGb 761) from chemistry to the clinic |
| title_full | Ginkgo biloba extract (EGb 761) from chemistry to the clinic Francis V. DeFeudis |
| title_fullStr | Ginkgo biloba extract (EGb 761) from chemistry to the clinic Francis V. DeFeudis |
| title_full_unstemmed | Ginkgo biloba extract (EGb 761) from chemistry to the clinic Francis V. DeFeudis |
| title_short | Ginkgo biloba extract (EGb 761) |
| title_sort | ginkgo biloba extract egb 761 from chemistry to the clinic |
| title_sub | from chemistry to the clinic |
| topic | Ginkgoblatt-Extrakt Ginkgoblatt-Extrakt (DE-588)4216360-2 gnd |
| topic_facet | Ginkgoblatt-Extrakt |
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