The Neuroprotective Potentiality of Flavonoids on Alzheimer’s Disease
Abstract
:1. Introduction
2. Oxidative Stress and Alzheimer
3. Flavonoids
3.1. Chemical Structure and Flavonoids Classification
3.2. Biological Activities of Flavonoids
3.3. Flavonoids in Neurodegeneration
3.4. Potential Role of Flavonoids in AD Therapy
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
Alzheimer disease (AD); |
Presenilin1 (PS1); |
Presenilin 2 (PS2); |
Amyloid Precursor Protein (APP); |
Apolipoprotein E (ApoE); |
Amyloid beta peptide (Aβ); |
Intraneuronal Neurofibrillary Tangles (NFTs); |
Central Nervous System (CNS); |
malondialdehyde (MDA); |
4-hydroxynonenal (4-HNE); |
Mild Cognitive Impairment (MCI); |
Reactive Oxygen Species (ROS); |
Carbonyl formation 3-nitrotyrosine (3-NT); |
superoxide dismutase (SOD); |
red blood cells (RBC); |
Reactive Nitrogen Species (RNS); |
AMP Activated Protein Kinase (AMPK); |
Glycogen Synthase Kinase 3 beta (GSK3β); |
cyclin-dependent kinase 5 (cdk5); |
Protein Phosphatase 2A (PP2A); |
nitric oxide synthase (NOS); |
Peroxisome proliferator-activated receptor-γ coactivator (PGC-1α); |
glutathione (GSH); |
catalase (CAT); |
glutathione peroxidase (GPx); |
Acetylcholinesterase (AchE); |
Butyrylcholinesterase (BchE); |
Acetylcholine (ACh); |
nuclear factor-kB (NF-kB); |
tumor necrosis factor-α (TNF-α); |
interleukin (IL); |
sirtuin 1 (SIRT1); |
inducible nitric oxide synthase (iNOS); |
cyclooxygenase 2 (COX-2); |
glutathione reductase (GR); |
hydrogen peroxide (H2O2); |
Epigallocatechin-3-gallate (EGCG), |
blood–brain barrier (BBB). |
References
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Flavonoids | Molecular Targets | Model | Dose | References |
---|---|---|---|---|
Quercetin | Regulates MAPK signaling | HT22 cells | 5 μmol/L | [103] |
Decreases phosphorylation of Tau protein | HT22 cells | 5–10 μmol/L | [104] | |
Reduces apoptosis and caspase 3 activation | PC-12 cell line | 500 μM | [108] | |
Restores antioxidant cellular defenses | Gerbilli’s CA1 pyramidal neurons, HepG2 cells, C57BL/6J mice | 20 mg/kg, 50 μM 1% quercetin diet | [113,114,115,116] | |
Inhibits AChE and BChE | AChE (EC 3.1.1.7 Sigma) BChE (EC 3.1.1.8, Sigma) | 1 mg/mL | [118,119] | |
Naringerin | Decreases phosphorylation of Tau protein | PC12 cells | 400 μM | [128,129,130] |
Reduces apoptosis and caspase 3 activation | Rat pups | 50–100 mM | [128,129,130,131] | |
Decreases the inflammatory pathway | Male rats, glial cells | 20 mg/kg/day, 0.1–0.3 μmol/L | [132,133,134,135] | |
Regulates the MAPK signaling pathway | BV-2 microglial cell line | 100 mM | [136] | |
Improves the antioxidant system | C57BL/6J mice | 25–100 mg/kg | [137,138,139,140] | |
Epigallocatechin-3-gallate | Reduces the accumulation of b amyloid | mice P8 (SAMP8), SweAPP N2 a cells, mouse model, MC65 cells | 5–15 mg/kg/day, 20 mM, 1–3 mg/kg, 5–20 μM | [144,145,146,147,148] |
Restores antioxidant cellular defenses | EOC 13.31 microglial cell line, chicken lymphocytes | 5–20 μM, 22.5–90 μM | [149,150] | |
Myricetin | Improves learning and memory | Rat models | 5 or 10 mg/kg | [160] |
Decreases Ab aggregation | [156,157,158,159,160] | [162,163,164,165,166] | ||
Regulates a and b secretase activity | rat primary cortical neurons | 10 μM | [166] | |
Inhibits oxidative stress | Murine models | 40–80 µM | [158,169,170] | |
Gossypetin | Inhibits lipid peroxidation | Murine macrophage cell line J774A.1 | 1–1000 μM | [182] |
Fights against Atherosclerosis | vascular smooth muscle cells | 0.1–0.5 μM | [183] | |
Genistein | Reduces the production and deposition of Ab aggregates | Rat model | 10 mg/kg | [187,188,189] |
Prevents Tau hyperphosphorylation | Rat model | 10 mg/kg | [190] | |
Regulates a and b secretase activity | Rat hippocampal neurons | 0.375 µg/mL | [194] | |
Prevents neuro-inflammation | RAW 264.7 cell model | 20 μM | [199] | |
Apigenin | Reduces Tau hyperphosphorylation | Rat model | 50 mg/kg | [203] |
Inhibits the production of IL-6 and IL-1b | Human THP-1 monotypic cells | 25 µM | [204,205,206] | |
Cyanidin | Regulates NF-κB and p38 MAPK signaling pathways | LPS-stimulated BV2 microglia | 2.5–10 mM | [220] |
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Calderaro, A.; Patanè, G.T.; Tellone, E.; Barreca, D.; Ficarra, S.; Misiti, F.; Laganà, G. The Neuroprotective Potentiality of Flavonoids on Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 23, 14835. https://doi.org/10.3390/ijms232314835
Calderaro A, Patanè GT, Tellone E, Barreca D, Ficarra S, Misiti F, Laganà G. The Neuroprotective Potentiality of Flavonoids on Alzheimer’s Disease. International Journal of Molecular Sciences. 2022; 23(23):14835. https://doi.org/10.3390/ijms232314835
Chicago/Turabian StyleCalderaro, Antonella, Giuseppe Tancredi Patanè, Ester Tellone, Davide Barreca, Silvana Ficarra, Francesco Misiti, and Giuseppina Laganà. 2022. "The Neuroprotective Potentiality of Flavonoids on Alzheimer’s Disease" International Journal of Molecular Sciences 23, no. 23: 14835. https://doi.org/10.3390/ijms232314835