CIDeRplusGeneral Information:
| Id: | 5,172 |
| Diseases: |
Alzheimer disease
- [OMIM]
Neurological |
| Mammalia | |
| review | |
| Reference: | Sokolov AN et al.(2013) Chocolate and the brain: neurobiological impact of cocoa flavanols on cognition and behavior Neurosci Biobehav Rev 37: 2445-2453 [PMID: 23810791] |
Interaction Information:
| Comment | Cocoa products and chocolate have recently been recognized as a rich source of flavonoids, mainly flavanols, potent antioxidant and anti-inflammatory agents with established benefits for cardiovascular health but largely unproven effects on neurocognition and behavior. Absorbed cocoa flavonoids penetrate and accumulate in the brain regions involved in learning and memory, especially the hippocampus. The neurobiological actions of flavanols (part of the flavonoids) are believed to occur in two major ways: (i) via direct interactions with cellular cascades yielding expression of neuroprotective and neuromodulatory proteins that promote neurogenesis, neuronal function and brain connectivity, and (ii) via blood-flow improvement and angiogenesis in the brain and sensory systems. Protective effects of long-term flavanol consumption on neurocognition and behavior, including age- and disease-related cognitive decline, were shown in animal models of normal aging, dementia, and stroke. A few human observational and intervention studies appear to corroborate these findings. |
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Formal Description Interaction-ID: 50620 |
drug/chemical compound Cocoa flavonoid is localized in tissue/cell line |
| Comment | Animal studies show that flavanols and their metabolites can cross the blood‚Äďbrain barrier, inducing beneficial effects on the brain tissue and function (angio- and neurogenesis, changes in neuron morphology) and stimulating widespread blood circulation in the brain. |
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Formal Description Interaction-ID: 50636 |
drug/chemical compound Flavanol affects_activity of tissue/cell line |
| Comment | Animal studies show that flavanols and their metabolites can cross the blood‚Äďbrain barrier, inducing beneficial effects on the brain tissue and function (angio- and neurogenesis, changes in neuron morphology) and stimulating widespread blood circulation in the brain. |
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Formal Description Interaction-ID: 50637 |
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| Comment | Daily oral administration of Acticoa powder (a cocoa polyphenolic extract) or vitamin E counteract the overproduction of free radicals, and thereby protect rats from cognitive impairments caused by heat exposure. |
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Formal Description Interaction-ID: 50652 |
drug/chemical compound Cocoa polyphenolic extract decreases_quantity of drug/chemical compound Free radical |
| Comment | Daily oral administration of Acticoa powder (a cocoa polyphenolic extract) or vitamin E counteract the overproduction of free radicals, and thereby protect rats from cognitive impairments caused by heat exposure. |
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Formal Description Interaction-ID: 50653 |
process increases_quantity of drug/chemical compound Free radical |
| Comment | Daily oral administration of Acticoa powder (a cocoa polyphenolic extract) or vitamin E counteract the overproduction of free radicals, and thereby protect rats from cognitive impairments caused by heat exposure. |
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Formal Description Interaction-ID: 50654 |
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| Comment | Daily oral administration of Acticoa powder (a cocoa polyphenolic extract) or vitamin E counteract the overproduction of free radicals, and thereby protect rats from cognitive impairments caused by heat exposure. |
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Formal Description Interaction-ID: 50655 |
drug/chemical compound decreases_quantity of drug/chemical compound Free radical |
| Comment | LMN diet (a diet rich in polyunsaturated fatty acids and polyphenols from dry fruits and cocoa) administered at an age of 10 months (before the amyloid plaques (Abeta) occurred) led to a decreasing tendency of soluble (sAbeta) and fibrillar Abeta (fAbeta) levels in the hippocampus of Tg2576 mice along with a decrease in Abeta plasma content suggesting a putative role of the diet in delaying plaque formation compared to wild type mice. |
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Formal Description Interaction-ID: 50656 |
environment LMN diet decreases_quantity of complex/PPI Amyloid beta peptide (soluble) |
| Comment | LMN diet (a diet rich in polyunsaturated fatty acids and polyphenols from dry fruits and cocoa) administered at an age of 10 months (before the amyloid plaques (Abeta) occurred) led to a decreasing tendency of soluble (sAbeta) and fibrillar Abeta (fAbeta) levels in the hippocampus of Tg2576 mice along with a decrease in Abeta plasma content suggesting a putative role of the diet in delaying plaque formation compared to wild type mice. |
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Formal Description Interaction-ID: 50658 |
environment LMN diet decreases_quantity of complex/PPI Amyloid beta peptide (fibrillar) |
| Comment | A treatment with dark chocolate prevents the inflammation of the vagus nerve resulting from a 16-month exposure of mice to the polluted air of Mexico City. Mice exposed to polluted air had a significant imbalance in genes coding for antioxidant defenses, apoptosis and neurodegeneration at the level of the dorsal vagal complex and this imbalance was mitigated by chocolate administration. |
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Formal Description Interaction-ID: 50682 |
environment flavonoid supplementation decreases_activity of process |
| Comment | In a cross-sectional study of the elderly Norwegian population, the association between cognitive performance and flavonoid intake from chocolate, wine, and tea was investigated. The participants aged 70‚Äď74 years completed a comprehensive cognitive test battery. Habitual food intake was assessed by a self-reported food frequency questionnaire. Chocolate, wine, or tea consumers yielded significantly better mean test scores and lower prevalence of poor cognitive performance. Those consuming all three items had the best test scores and the lowest risk for poor test performance. The association between intake of the foods and cognition were dose-dependent. |
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Formal Description Interaction-ID: 50688 |
environment flavonoid supplementation increases_activity of process |
| Comment | In a cross-sectional study of the elderly Norwegian population, the association between cognitive performance and flavonoid intake from chocolate, wine, and tea was investigated. The participants aged 70‚Äď74 years completed a comprehensive cognitive test battery. Habitual food intake was assessed by a self-reported food frequency questionnaire. Chocolate, wine, or tea consumers yielded significantly better mean test scores and lower prevalence of poor cognitive performance. Those consuming all three items had the best test scores and the lowest risk for poor test performance. The association between intake of the foods and cognition were dose-dependent. |
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Formal Description Interaction-ID: 50689 |
environment flavonoid supplementation increases_activity of process |
| Comment | In a cross-sectional study of the elderly Norwegian population, the association between cognitive performance and flavonoid intake from chocolate, wine, and tea was investigated. The participants aged 70‚Äď74 years completed a comprehensive cognitive test battery. Habitual food intake was assessed by a self-reported food frequency questionnaire. Chocolate, wine, or tea consumers yielded significantly better mean test scores and lower prevalence of poor cognitive performance. Those consuming all three items had the best test scores and the lowest risk for poor test performance. The association between intake of the foods and cognition were dose-dependent. |
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Formal Description Interaction-ID: 50690 |
environment flavonoid supplementation increases_activity of process |
| Comment | Dietary high-flavanol cocoa intake is associated with an increased cerebral blood flow velocity in the middle cerebral artery, suggesting a promising role for high-flavanol cocoa consumption in the treatment of cerebrovascular ischemic syndromes such as dementia and stroke. |
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Formal Description Interaction-ID: 50694 |
environment high-flavanol cocoa supplementation increases_activity of phenotype |
| Comment | A work in cultured human neuroblastoma cells shows that low concentrations of nitric oxide up-regulate the expression of alpha-secretase and down-regulate that of gamma-secretase. This suggests the cerebrovascular nitric oxide might inhibit Abeta production. |
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Formal Description Interaction-ID: 50704 |
drug/chemical compound increases_expression of gene/protein Alpha-secretase |
| Comment | A work in cultured human neuroblastoma cells shows that low concentrations of nitric oxide up-regulate the expression of alpha-secretase and down-regulate that of gamma-secretase. This suggests the cerebrovascular nitric oxide might inhibit Abeta production. |
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Formal Description Interaction-ID: 50705 |
drug/chemical compound decreases_expression of complex/PPI Gamma-secretase complex |
| Comment | Cocoa flavanols, especially epicatechin, act directly on the endothelium of brain vessels, stimulating activity of the endothelial nitric oxide synthase that in turn induces vasodilation and improves cerebrovascular perfusion. |
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Formal Description Interaction-ID: 50706 |
drug/chemical compound Cocoa flavanol affects_activity of tissue/cell line |
| Comment | Cocoa flavanols, especially epicatechin, act directly on the endothelium of brain vessels, stimulating activity of the endothelial nitric oxide synthase that in turn induces vasodilation and improves cerebrovascular perfusion. It is conceivable that beneficial properties of cocoa flavanols may slow down the transition from mild cognitive impairment to Alzheimer’s disease. |
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Formal Description Interaction-ID: 50710 |
drug/chemical compound Cocoa flavanol increases_activity of gene/protein |
| Drugbank entries | Show/Hide entries for NOS3 |
| Comment | Cocoa flavanols, especially epicatechin, act directly on the endothelium of brain vessels, stimulating activity of the endothelial nitric oxide synthase that in turn induces vasodilation and improves cerebrovascular perfusion. It is conceivable that beneficial properties of cocoa flavanols may slow down the transition from mild cognitive impairment to Alzheimer’s disease. |
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Formal Description Interaction-ID: 50711 |
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| Drugbank entries | Show/Hide entries for NOS3 |
| Comment | Cocoa flavanols, especially epicatechin, act directly on the endothelium of brain vessels, stimulating activity of the endothelial nitric oxide synthase that in turn induces vasodilation and improves cerebrovascular perfusion. It is conceivable that beneficial properties of cocoa flavanols may slow down the transition from mild cognitive impairment to Alzheimer’s disease. |
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Formal Description Interaction-ID: 50729 |
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| Drugbank entries | Show/Hide entries for NOS3 |
| Comment | 90 elderly individuals with mild cognitive impairment (mean age, 71 years; 43 males) consumed once daily for eight weeks a drink containing either 990 mg (high), 520 mg (moderate), or 45 mg (low-flavanol) of cocoa flavanols. In the high- and moderate-flavanol compared to the low-flavanol groups time required to complete different Trail Making Tests was significantly lower and also the verbal fluency score was significantly better. The high- and moderate-flavanol groups also exhibited decreased insulin resistance, blood pressure, and lipid peroxidation. |
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Formal Description Interaction-ID: 50733 |
drug/chemical compound Cocoa flavanol increases_activity of phenotype verbal fluency |
| Comment | 90 elderly individuals with mild cognitive impairment (mean age, 71 years; 43 males) consumed once daily for eight weeks a drink containing either 990 mg (high), 520 mg (moderate), or 45 mg (low-flavanol) of cocoa flavanols. In the high- and moderate-flavanol compared to the low-flavanol groups time required to complete different Trail Making Tests was significantly lower and also the verbal fluency score was significantly better. The high- and moderate-flavanol groups also exhibited decreased insulin resistance, blood pressure, and lipid peroxidation. |
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Formal Description Interaction-ID: 50754 |
drug/chemical compound Cocoa flavanol decreases_activity of phenotype |
| Comment | 90 elderly individuals with mild cognitive impairment (mean age, 71 years; 43 males) consumed once daily for eight weeks a drink containing either 990 mg (high), 520 mg (moderate), or 45 mg (low-flavanol) of cocoa flavanols. In the high- and moderate-flavanol compared to the low-flavanol groups time required to complete different Trail Making Tests was significantly lower and also the verbal fluency score was significantly better. The high- and moderate-flavanol groups also exhibited decreased insulin resistance, blood pressure, and lipid peroxidation. |
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Formal Description Interaction-ID: 50755 |
drug/chemical compound Cocoa flavanol decreases_activity of phenotype blood pressure |
| Comment | 90 elderly individuals with mild cognitive impairment (mean age, 71 years; 43 males) consumed once daily for eight weeks a drink containing either 990 mg (high), 520 mg (moderate), or 45 mg (low-flavanol) of cocoa flavanols. In the high- and moderate-flavanol compared to the low-flavanol groups time required to complete different Trail Making Tests was significantly lower and also the verbal fluency score was significantly better. The high- and moderate-flavanol groups also exhibited decreased insulin resistance, blood pressure, and lipid peroxidation. |
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Formal Description Interaction-ID: 50756 |
drug/chemical compound Cocoa flavanol decreases_activity of process lipid peroxidation |
| Comment | Mice treated with one of the major chocolate flavanols, epicatechin, showed pronounced angiogenesis in the hippocampus. Epicatechin treatment combined with exercise (running a wheel) improved retention of spatial memory and increased dendritic spine density in the dentate gyrus of the hippocampus. Moreover, epicatechin treatment facilitated gene expression associated with learning in the hippocampus but did not affect hippocampal adult neurogenesis. |
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Formal Description Interaction-ID: 50757 |
cellular component Epicatechin increases_activity of process |
| Comment | Mice treated with one of the major chocolate flavanols, epicatechin, showed pronounced angiogenesis in the hippocampus. Epicatechin treatment combined with exercise (running a wheel) improved retention of spatial memory and increased dendritic spine density in the dentate gyrus of the hippocampus. Moreover, epicatechin treatment facilitated gene expression associated with learning in the hippocampus but did not affect hippocampal adult neurogenesis. |
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Formal Description Interaction-ID: 50758 |
cellular component Epicatechin increases_activity of process spatial memory |
| Comment | Mice treated with one of the major chocolate flavanols, epicatechin, showed pronounced angiogenesis in the hippocampus. Epicatechin treatment combined with exercise (running a wheel) improved retention of spatial memory and increased dendritic spine density in the dentate gyrus of the hippocampus. Moreover, epicatechin treatment facilitated gene expression associated with learning in the hippocampus but did not affect hippocampal adult neurogenesis. |
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Formal Description Interaction-ID: 50759 |
cellular component Epicatechin increases_activity of phenotype increased hippocampal dendritic spine density |
| Comment | Mice treated with one of the major chocolate flavanols, epicatechin, showed pronounced angiogenesis in the hippocampus. Epicatechin treatment combined with exercise (running a wheel) improved retention of spatial memory and increased dendritic spine density in the dentate gyrus of the hippocampus. Moreover, epicatechin treatment facilitated gene expression associated with learning in the hippocampus but did not affect hippocampal adult neurogenesis. |
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Formal Description Interaction-ID: 50760 |
cellular component Epicatechin increases_activity of process |
| Comment | Mice treated with one of the major chocolate flavanols, epicatechin, showed pronounced angiogenesis in the hippocampus. Epicatechin treatment combined with exercise (running a wheel) improved retention of spatial memory and increased dendritic spine density in the dentate gyrus of the hippocampus. Moreover, epicatechin treatment facilitated gene expression associated with learning in the hippocampus but did not affect hippocampal adult neurogenesis. |
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Formal Description Interaction-ID: 50761 |
cellular component Epicatechin NOT affects_activity of process |
| Comment | The effects of short-term versus long-term (two-week) oral administration of cocoa mass in large amounts (100 mg/100 g body weight) were compared in the rat elevated T-maze test, an animal model of anxiety. Short-term administration significantly abolished avoidance behavior during immediate test performance, suggesting a reduced fear conditioning. Long-term administration enhanced brain concentration of emotion-related neurotransmitter serotonin and its turnover. |
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Formal Description Interaction-ID: 50762 |
drug/chemical compound Cocoa increases_activity of phenotype |
| Comment | The effects of short-term versus long-term (two-week) oral administration of cocoa mass in large amounts (100 mg/100 g body weight) were compared in the rat elevated T-maze test, an animal model of anxiety. Short-term administration significantly abolished avoidance behavior during immediate test performance, suggesting a reduced fear conditioning. Long-term administration enhanced brain concentration of emotion-related neurotransmitter serotonin and its turnover. long-term intake of cocoa mass affects brain monoamine metabolism. |
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Formal Description Interaction-ID: 50763 |
drug/chemical compound Cocoa increases_quantity of drug/chemical compound |
| Comment | In human studies one of them reported an immediate improvement of cognitive function and another an immediate improvement of visual function following high-flavanol cocoa consumption in healthy young adults. |
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Formal Description Interaction-ID: 50764 |
environment high-flavanol cocoa supplementation increases_activity of phenotype increased cognitive function |
| Comment | In human studies one of them reported an immediate improvement of cognitive function and another an immediate improvement of visual function following high-flavanol cocoa consumption in healthy young adults. |
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Formal Description Interaction-ID: 50765 |
environment high-flavanol cocoa supplementation increases_activity of phenotype increased visual function |