Natural Compounds for Alzheimer’s Disease Therapy: A Systematic Review of Preclinical and Clinical Studies
Abstract
:1. Introduction
2. Natural Compounds in Clinical Trials and Their Effects on AD
2.1. Bioactive Compounds
2.2. Natural Extracts and Other Natural Products
3. Preclinical In Vivo Studies of Natural Compounds and Their Effects on AD
3.1. Bioactive Compounds
3.2. Natural Extracts and Other Natural Products
4. Preclinical In Vitro Studies of Natural Compounds and Their Effects on AD
5. Discussion
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
Aβ | β-amyloid |
ACH | Amyloid cascade hypothesis |
AD | Alzheimer’s disease |
APP | Amyloid precursor protein |
BBB | Blood-brain barrier |
DDS | Drug delivery systems |
DHA | Docosahexanoic acid |
EGCG | Epigallocatechin gallate |
NDGA | Nordihydroguaiaretic acid |
NFTs | Neurofibrillary tangles |
PGG | 1,2,3,4,6-Penta-O-galloyl-β-d-glucopyranose |
ROS | Reactive oxygen species |
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Bioactive Compound | Condition of Participants | Number of Subjects | Duration | Outcomes | Ref. |
---|---|---|---|---|---|
Vitamin D | Mild cognitive impairment | 8 | 8 weeks | Reduction of Aβ level | [35] |
Mild cognitive impairment and early AD | 48 | 20 months | Reduction of Aβ level; Improvement of cognitive functions | [36] | |
Vitamin D and memantine | Moderate AD | 43 | 24 weeks | Improvement of cognitive functions | [37] |
Vitamin D and antioxidants | Mild to moderate AD | 78 | 16 weeks | Reduction of oxidative stress | [38] |
Vitamin E and vitamin C | AD | 20 | 1 month | Reduction of oxidative stress | [39] |
Vitamin E and selegiline | Moderate AD | 341 | 2 years | Delay of AD progression | [40] |
Vitamin E and donepezil | Mild cognitive impairment | 769 | 5 years | No effectiveness in delaying AD progression | [41] |
Vitamin E and memantine | Mild to moderate AD | 613 | 5 years | Delay of AD progression | [42] |
Vitamin E and selenium | Healthy patients | 3786 | 13 years | No prevention of dementia | [43] |
Docosahexaenoic acid (DHA) and eicosapentaenoic acid | AD | 204 | 12 months | Safe and well tolerated; No effectiveness in delaying cognitive decline | [44] |
DHA | AD | 295 | 18 months | No effectiveness in delaying cognitive decline | [45] |
Cognitive impairments | 485 | 24 weeks | Improvement of cognitive functions | [46] | |
Mild cognitive impairment | 36 | 1 year | Safe and well tolerated; Improvement of memory | [47] | |
Homotaurine | Mild to moderate AD | 1052 | 78 weeks | Improvement of cognitive functions | [48,49] |
58 | 3 months | No harmful effects on vital signs; Side effects | [50] | ||
10 | 4 weeks | Improvement of the central cholinergic transmission | [51] | ||
Huperzine A | AD | 103 | 8 weeks | Safe and well tolerated; Improvement of memory and behaviour | [52] |
60 | 60 days | Safe and well tolerated; Reduction of oxidative stress | [53] | ||
Mild to moderate AD | 177 | 16 weeks | Safe and well tolerated; Improvement of cognitive functions | [54] | |
Bryostatin | AD | 9 | 46 weeks | Safe and well tolerated: Improvement of cognitive functions | [55] |
150 | 12 weeks | Improvement of cognitive functions | [56] | ||
Melatonin | AD | 150 | 12 weeks | Improvement of memory | [57] |
14 | 22 to 35 months | Improvement of cognitive functions | [58] | ||
Mild cognitive impairment | 50 | 9 to 18 months | Improvement of cognitive functions | [59] | |
Mild to moderate AD | 80 | 24 weeks | Safe; Improvement of cognitive functions | [60] | |
Resveratrol | Mild to moderate AD | 119 | 52 weeks | Side effects; No effectiveness in reducing biomarkers levels | [61] |
39 | 1 year | Safe and well tolerated; No effectiveness in treat AD | [62] | ||
Nicotine | AD | 70 | 2 weeks | Improvement of perceptual and visual attentional deficits | [63] |
6 | 9 weeks | Safe; Improvement of learning | [64] | ||
8 | 10 weeks | Improvement of attentional performance | [65] | ||
Curcumin | AD | 34 | 6 months | Safe and well tolerated | [66] |
Natural Extracts and Other Products | Condition of Participants | Number of Subjects | Duration | Outcomes | Ref. |
---|---|---|---|---|---|
Ginkgo biloba | Mild to moderate dementia | 410 | 24 weeks | Safe; Improvement of neuropsychiatric symptoms | [67,68] |
410 | 24 weeks | Improvement of cognitive and functional functions | [69] | ||
AD or vascular dementia | 404 | 24 weeks | Improvement of cognitive functions and functional abilities; Improvement of neuropsychiatric symptoms | [70] | |
Mild cognitive impairment | 160 | 24 weeks | Safe and well tolerated; Improvement of cognitive functions | [71] | |
Saffron | Mild to moderate AD | 46 | 16 weeks | Safe; Improvement of cognitive functions and memory | [72] |
Lemon balm | Mild to moderate AD | 40 | 4 months | Improvement of cognition function and agitation | [73] |
Green tea | Severe AD | 30 | 2 months | Improvement of cognitive functions | [74] |
Papaya | AD | 20 | 6 months | Reduction of oxidative stress | [75] |
Sage | Mild to moderate AD | 20 | 4 months | Improvement of cognitive functions; No side effects except agitation | [76] |
Coconut | AD | 44 | 21 days | Improvement of cognitive functions | [77] |
Apple | Moderate to severe AD | 21 | 1 month | No improvement of cognitive functions; Improvement behavioural and psychotic symptoms; Reduction of anxiety, agitation and delusion | [78] |
Blueberry | Early memory failures | 9 | 12 weeks | Improvement of learning; Reduction of depressive symptoms | [79] |
Colostrinin | AD | n. d. | 15 weeks | Improvement of cognitive and daily functions | [80] |
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Andrade, S.; Ramalho, M.J.; Loureiro, J.A.; Pereira, M.d.C. Natural Compounds for Alzheimer’s Disease Therapy: A Systematic Review of Preclinical and Clinical Studies. Int. J. Mol. Sci. 2019, 20, 2313. https://doi.org/10.3390/ijms20092313
Andrade S, Ramalho MJ, Loureiro JA, Pereira MdC. Natural Compounds for Alzheimer’s Disease Therapy: A Systematic Review of Preclinical and Clinical Studies. International Journal of Molecular Sciences. 2019; 20(9):2313. https://doi.org/10.3390/ijms20092313
Chicago/Turabian StyleAndrade, Stephanie, Maria João Ramalho, Joana Angélica Loureiro, and Maria do Carmo Pereira. 2019. "Natural Compounds for Alzheimer’s Disease Therapy: A Systematic Review of Preclinical and Clinical Studies" International Journal of Molecular Sciences 20, no. 9: 2313. https://doi.org/10.3390/ijms20092313