Ginger, a Possible Candidate for the Treatment of Dementias?
Abstract
:1. Introduction
2. Methodology
3. Ginger: Chemical Structure, Properties, and Therapeutic Potential
4. Alzheimer’s Disease
5. Effects of Ginger in AD Studies
5.1. Computational Studies
5.2. In Vivo and In Vitro Studies
6. Vascular Dementia
7. Effects of Ginger in VD Studies
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
DSM-5 | Diagnostic and Statistical Manual of Mental Disorders |
AD | Alzheimer’s Disease |
VD | Vascular Dementia |
NFTs | Neurofibrillary tangles |
Aβ | Beta-amyloid |
BBB | Blood-brain barrier |
COX-1 | Cyclooxygenase 1 |
APOE | Apolipoprotein E |
PSEN 1 | Presenilin 1 |
PSEN 2 | Presenilin 2 |
APP | Amyloid precursor protein |
GSK-3 | Glycogen synthase kinase-3 |
ROS | Reactive oxygen species reactive |
MDA | Malondialdehyde |
NSAIDs | Non-steroidal anti-inflammatory drugs |
COX-2 | Cyclooxygenase-2 |
5-LOX | 5-lipoxygenase |
LTs | Leukotrienes |
SAD | Late-onset sporadic Alzheimer Disease |
FAD | Early-onset familial Alzheimer Disease |
APH1a | Gamma-secretase subunit APH-1A |
AChE | Acetylcholinesterase |
ACh | Acetylcholine |
Zo.Cr | Dried ginger |
BChE | Butyrylcholinesterase |
SOD | Superoxide dismutase |
CAT | Catalase |
ERK | eEtracellular signal-regulated kinase |
BDNF | Brain-derived neurotrophic factor |
GRE | Ginger root extract |
NF-κB | Nuclear factor kappa-B |
IL | Interleukin |
GFAP | Glial fibrillary acid protein |
Mac-1 | Macrophage-1 antigen |
CysLT1R | Cysteinyl leukotriene 1 receptor |
CysLTs | Cysteinyl leukotrienes |
AA | Arachidonic acid |
SORL1 | Sortilin-related receptor 1 |
siRNA | Small interfering RNA |
BACE1 | Beta-site amyloid precursor protein cleaving enzyme 1 |
GABA | Gamma-Aminobutyric acid |
MAPK | Mitogen-activated protein kinase |
PGE2 | Prostaglandin E2 |
iNOS | Inducible nitric oxide synthetase |
JNK | C-jun N-terminal kinase |
ER | Estrogen receptor |
Bcl-2 | B-cell lymphoma 2 |
BAX | BCL2-associated X: apoptosis regulator |
NRF2 | Nuclear factor erythroid 2-related factor 2 |
GCL | C-glutamylcysteine ligase |
HO-1 | Heme Oxygenase-1 |
NO | Nitric oxide |
GE | Ginger extracts |
LPS | Lipopolysaccharide |
TNF-α | Tumour necrosis factor-α |
MCP-1 | Monocyte chemoattractant protein-1 |
CCL2 | C-C motif chemokine ligand 2 |
MIP-1α | Macrophage inflammatory protein-1α |
CCL3 | C-C motif chemokine ligand 3 |
ATP | Adenosine 5’-triphosphate |
NLRP3 | Nucleotide-binding domain and leucine-rich repeat-containing family, pyrin do-main-containing 3 |
ELNs | Exosome-like nanoparticles |
G-ELNs | Ginger rhizomes |
ASC | Apoptotic speck protein containing a caspase recruitment domain |
TACE | TNF-α converting enzyme |
NMDA | N-methyl-D-aspartate |
Mol1 | [(E)-1,7-bis (4-hydroxy-3-methoxyphenyl) hept-4-en-3-on] |
Mol2 | [1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-ethoxyphenyl) heptane-3,5-diyl diacetate] |
G3 | 5-[(2S,4R,6R)-4-hydroxy-6-[2-(4-methoxyphenyl)ethyl]oxan-2-yl]-3-methoxybenzene-1,2-diol |
PPARγ | Peroxisome proliferation activator receptor γ |
MCI | Mild Cognitive Impairment |
VaMCI | Vascular Mild Cognitive Impairment |
VCI | Vascular Cognitive Impairment |
MetS | Metabolic syndrome |
PMG | Mulberry fruit and ginger |
Rt. MCAO | Right middle cerebral artery |
GPx | Glutathione peroxidase |
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Experimental Model | Compound | Route/Dose | Effects | Reference |
---|---|---|---|---|
Molecular docking | Ginger compounds | . | Evaluation of molecular targets based on the measure of the binding energy is AChE. | [41] |
Molecular docking | Active compounds of ginger extracts | . | Inhibition of AChE activity by the Trp86 choline binding site. | [42] |
Molecular docking | Ginger compounds | . | Inhibition of BChE activity. | [43] |
In vitro target enzyme assays, silico docking and simulation of absorption, distribution, metabolism, excretion, and toxicity | Zerumbone | . | Reduction of AChE and BChE activity. | [44] |
Computational model: koniocortex | Terpenoid-based nutrients | . | Expression of GABA-A receptor and improve cognitive function. | [45] |
Male Swiss albino mice | Gingerol | Intraperitoneal 10 and 20 mg/kg | Reduction of the levels of Aβ42, β-secretase, APH1a and COX-2. Increased of α-secretase activity. No behavioural and memory deficits. Probable improvement of neuroinflammation and amyloidogenesis. | [46] |
Sprague Dawley rats stomach | Zo.Cr | 0.03–5.00 mg/mL | Possible calcium antagonism and cholinesterase inhibition. | [47] |
Male Wistar rats | Extract of Cyperus rotundus and Zingiber officinale (CP1) | Gavage 100, 200 and 300 mg/kg | Oxidative stress reduction in hippocampus. Improved cholinergic function. Improved memory deficit. | [48] |
Male C57BL/6 mice | fresh ginger, dried ginger, 6-gingerol | Gavage fresh ginger 100 or 200 mg/kg dried ginger 100 or 200 mg/kg 6-gingerol 10 or 25 mg/kg | Upregulation of BDNF. Prevention of memory deficits. | [49] |
Sprague-Dawley rats | Ginger root extract (GRE) | Intragastric GRE high-dose group 4 gr/kg, GRE medium-dose group 2 gr/kg, GRE low-dose group 1 gr/kg huperzine A group 100 mg/kg | Reduction of inflammatory markers (high-dose group). Improved behavioural tests (high-dose group). | [50] |
Male APP/PSEN1 mice | Ginger and peony root (OCGP) | Gavage 50 or 100 mg/kg/day 14 weeks | Aβ aggregation inhibition in hippocampus. Behavioural and memory deficits prevention. Reduction of inflammatory marker expression. Reduction of astrocytes activation. | [51] |
Male ICR mice | 6-shogaol | Gavage 10 mg/kg/day | Reduced astrocytes and microglia activation. Inflammation and neuronal death reduction. Improvement in learning and memory. | [52] |
APP/PSEN1 mice and HT22 cells | 6-shogaol | Gavage 5 and 20 mg/kg and pre-treatment 10 μM | Improving of behavioural and memory deficits (in vivo). Increased cell availability (in vitro). Inhibition of cytotoxicity Aβ1–42-induced (in vitro). | [53] |
HT22 cells and APP/PSEN1 mice | 6-shogaol | 1, 5, 10 and 20 mM Gavage 5 or 20 mg/kg every 2 days for 2 months | Aβ aggregation suppression. | [54] |
Male ICR mice | Ginger + 6-paradol unfermented ginger fermented ginger | Gavage ginger + 6-paradol 100 mg/kg unfermented ginger 100 mg/kg fermented ginger 50,100,200 mg/kg per day | Neuroprotective effect (ginger + 6-paradol). Protection to neurodegeneration in hippocampus (fermented ginger). Improved memory deficits (fermented ginger). | [55] |
Sprague-Dawley rats | Zerumbone | Intraperitoneal 1 and 10 mg/kg | Improved the memory deficits. Ameliorate anxiety-like behaviours. | [56] |
Transgenic APP/PSEN1 mice and N9 microglial cells and primary microglial cells from C57BL/6J mice | Zerumbone | Gavage 25 mg/kg and 1, 3 o 10 μg/ml | Improved memory, learning, social interaction, and nesting (in vivo). Reduced Aβ aggregate formation and neuroinflammation in hippocampus and cortex (in vivo). Neuroinflammation suppression (in vitro). | [57] |
YPEN-1 rat prostate endothelial cells and rat kidney cells from male Fischer 344 rats | Zingerone | YPEN-1 cells pre-treated 1, 5, 10, or 20 μM and rat kidney cells obtained from male rats fed with zingerone 2 or 8 mg/kg/day for 10 days | Reduction in inflammation and oxidative stress. | [58] |
GT1–7 cells | Ginger essential oil | 25 ppm | Reduction of peroxide-induced neurotoxicity. Enhanced tamoxifen neurotoxicity. | [59] |
SH-SY5Y cells | [6]-gingerol | Pre-treatment 3, 10 μM | Improved cell viability. Reduction Aβ25–35 citotoxicity. Oxidative stress reduction. | [60] |
PC12 cells | 6-gingerol | Pre-treatment 40, 80, 120, 200, and 300 μM | Oxidative stress reduction. Decreased Tau hyperphosphorylation. Decreased Aβ formation. | [61] |
PC12 cells and primary neuronal cells | Ginger extract | 20 g/mL | Improved cell viability. | [62] |
Rat primary hippocampal cells | Dry ginger | 0.02, 0.1, and 0.2 mg in 2 μL of DMSO | Prevention of Aβ-aggregation. Neurotoxicity reduction. Improved cell survival. | [63] |
Brain tissue from AD transgenic mice | Ginger extract | Dilutions (1:20, 1:40 and 1:100) | Aggregation of Aβ prevention. | [64] |
Human monocytic THP-1 cells | Ginger extract composed by Zingiber officinale and Alpinia galangal | Pre-treatment 255 mg | Reduction of inflammation. | [65] |
THP-1 cells | Shogaols/gingerols | Pre-treatment 20 μM | Reduction of inflammation. | [66] |
Bone marrow-derived macrophages | Exosome-like nanoparticles of ginger rhizomes | / | Inhibition of inflammasome formation. | [67] |
Model | Compound | Route, Dose, Timing | Results | Reference |
---|---|---|---|---|
Male Wistar rats Rt. MCAO | PMG | Gavage. 50, 100, 200 mg/kg 21 days | Improved cognitive deficits. Reduced AChE activity. Decreased inflammation markers. Increased antioxidant levels. | [80] |
Male Wistar Rats Rt. MCAO | PMG | Gavage. 50, 100, 200 mg/kg 21 days | Improved cerebral ischemic damage. Improved cerebral edema. Decreased neurological deficits. Inflammation and oxidative stress reduction. | [81] |
Male Wistar Rats Rt. MCAO | Ginger rhizome | Gavage. 200 mg/kg Before and after surgery | Improved cognitive function. Reduced oxidative stress. Increased hippocampal neuron density. Reduced cerebral infarction volume. | [82] |
Rat Focal ischemia | Houshiheisan | Gavage. 2.59, 7.7 and 10.5 g/kg Before and after surgery. | Reduced damage to the ischemic penumbra. Vascular protection from Aβ deposition. Stabilization of neurovascular unit. | [83] |
Mice MCAO/reperfusion and BV2 cells LPS stimulation 100 ng/mL | 6-paradol | Gavage. 1, 5, 10 mg/kg after reperfusion and Pre-treatment 10 ug/mL | Reduced microglia activation. Reduced brain damage. Improved motor and sensory function. Neuroinflammation reduction. Reduction of iNOS. Reduction pro-inflammatory cytokines | [84] |
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Schepici, G.; Contestabile, V.; Valeri, A.; Mazzon, E. Ginger, a Possible Candidate for the Treatment of Dementias? Molecules 2021, 26, 5700. https://doi.org/10.3390/molecules26185700
Schepici G, Contestabile V, Valeri A, Mazzon E. Ginger, a Possible Candidate for the Treatment of Dementias? Molecules. 2021; 26(18):5700. https://doi.org/10.3390/molecules26185700
Chicago/Turabian StyleSchepici, Giovanni, Valentina Contestabile, Andrea Valeri, and Emanuela Mazzon. 2021. "Ginger, a Possible Candidate for the Treatment of Dementias?" Molecules 26, no. 18: 5700. https://doi.org/10.3390/molecules26185700