Phenolic Compounds of Therapeutic Interest in Neuroprotection
Abstract
:1. Introduction
2. Physiopathology of Neurodegenerative Diseases
3. General Aspects of Phenolic Compounds
4. Molecular Mechanisms of Phenols to Prevent Neurodegeneration
5. Metabolism of Phenol Compounds
6. Effect of Phenolic Compounds In Vitro in Models of Neurodegeneration
7. Effect of Phenolic Compounds in Models of Neurodegeneration In Vivo
8. Effect of Phenolic Compounds on Neurodegeneration in Clinical Trials
9. Mechanisms of Damage Modulation by Phenolic Compounds
10. Conclusions and Perspectives
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Assay | Disease | Model | Treatment | Phenolic Compound | Finds | Ref. |
---|---|---|---|---|---|---|
In vitro | ALS | Mouse motor neuron (NSC-34) mutant hSOD1G93A gene | 10 µM 4 h before the damage with H2O2 | Fisetin | Fisetin reduced ROS damage, increased cell survival and the expression of phosphorylated ERK, and upregulated antioxidant factors, which were reversed by MAPK/ERK inhibition. | [99] |
AD | HT-22 Mouse Hippocampal Neuronal Cell Line | 20 μM (No time specified at the same time with Aβ) | Luteolin | Decrease of inflammatory markers p-NF-kB, TNF-α, and IL-1β. Decreased proapoptotic proteins Bax, Bcl-2, Caspase-3, and Cox-2. Decrease in BACE-1 enzyme and subsequent decrease in Aβ. | [100] | |
Caloric restriction associated with neurodegenerative diseases in general | Neuro2a neuroblastoma cells | 10 μM (2–72 h) cells grown under serum starvation conditions | Resveratrol | Resveratrol increases AMP activation (AMPK) during caloric restriction, promoting energy conservation, cell survival, and neurite outgrowth. | [101] | |
PD | PC-12 cells (6-hydroxy-dopamine) (6-OHDA) | 3.1, 12.5, 50 µM or without luteolin for 2 h | Luteolin | Increased cell viability and decreased expression of proapoptotic proteins Bax and Bcl-2. | [102] | |
In vivo | PD | Male Wistar rats—using rotenone (ROT)-induced rat model of PD | 4 weeks at the dose of 50 mg/kg, 30 min before damage is induced. | Ferulic acid | Protection of dopaminergic neurons, lipid peroxidation, and reduced levels of inflammatory markers IL-1β, IL-6, and TNF-α | [103] |
PD | (6-OHDA lesioned rats). | 10 and 30 mg/kg injection 2 h before surgery and for 14 days afterward | Catechin | After treatments, they significantly reversed this abnormal motor behavior and memory deficits and protected animals from the observed decrease in dopamine and noradrenaline. | [104] | |
AD | Male wildtype C57BL/6N mice | 20 mg/kg/day for 2 weeks, starting 24 h after Aβ injection | Fisetin | Decreased the expression of BACE-1 and the formation of Aβ aggregates. Decreased synaptic dysfunction (promoted the expression of postsynaptic proteins PSD-95, SNAP-23, p-GluR1). Promoted activation of p-PI3K, p-AKT, and p-GSK3β and subsequent cell survival. Decreased proinflammatory proteins p-IKKβ, p-NFKB, TNFα, and IL-1β. | [105] | |
PD | Male C57BL/6 mice (Parkinson’s disease model) | 50 mg/kg/day for 7 days after damage with MPTP | Astilbin | Increased cell survival by promoting phosphorylation of p-PI3K/p-AKT. Decreased oxidative stress by increasing GSH and SOD activity. Reduced the loss of dopaminergic neurons and the activation of microglia (Iba-1) and astrocytes in the substantia nigra. | [106] | |
Hypoxia/ischemia | Male Sprague–Dawley rats and pheochromocytoma (PC-12) cells | 28, 56, and 112 mg/kg/day after ischemia for 5 consecutive days | Ferulic acid | Attenuated memory impairment reduced hippocampal neuronal apoptosis and oxidative stress in a dose-dependent manner and inactivated the Toll-like receptor TLR4 and MyD88. Increased levels of Bcl-2 and decreased levels of caspase-3 and Bax. | [107] | |
TBI | Adult male ICR mice, traumatic brain injury model | 50 and 100 mg/kg 30 min after TBI | Curcumin | Reduced proapoptotic proteins Bcl-2 and cleaved caspase 3. Promoted activation of the Nrf2–ARE pathway and subsequent enhancement of SOD, GPx, and MDA expression. | [108] | |
Ischemic | Nine-week-old Sprague–Dawley male rats/culture primary cortical neurons | 300 mg/kg 1 h after Ischemic brain injury | Curcumin | Attenuated infarction volumes, upregulated NAD(P)H, NQO1 levels. Promoted p-AKT/Nrf2 activation. | [109] | |
Ischemic | Adult male C57/BL6J mice | 10 mg/kg for 2 weeks before cerebral ischemia | Genistein | It decreased infarct volume, improved neurological scores, attenuated cleaved caspase-1 apoptosis, decreased the release of inflammatory factors TNF-α, IL-1β, IL-18, and IL-6, and negatively regulated inflammasome activation assessed with the NLRP3 marker. | [110] | |
Clinical trial/Randomized Controlled Trial | AD | Alzheimer’s disease patients | 120 mg for 12 months | Genistein | The cognitive ability of the treated patients improved, and there was no increase in Aβ deposition compared to the placebo control. | [111] |
PD | Idiopathic PD patients aged ≥30 | 30, 80 mg/day for nine months | Curcumin | This trial was unsuccessful in showing its efficacy in quality of life and clinical symptoms of PD patients | [112] | |
AD | Patients at high risk of developing Alzheimer’s disease | 180 mg/day for 12 weeks | Curcumin | Reduction of circulating levels of Amyloid Polypeptide compared to the placebo control. | [113] |
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Nájera-Maldonado, J.M.; Salazar, R.; Alvarez-Fitz, P.; Acevedo-Quiroz, M.; Flores-Alfaro, E.; Hernández-Sotelo, D.; Espinoza-Rojo, M.; Ramírez, M. Phenolic Compounds of Therapeutic Interest in Neuroprotection. J. Xenobiot. 2024, 14, 227-246. https://doi.org/10.3390/jox14010014
Nájera-Maldonado JM, Salazar R, Alvarez-Fitz P, Acevedo-Quiroz M, Flores-Alfaro E, Hernández-Sotelo D, Espinoza-Rojo M, Ramírez M. Phenolic Compounds of Therapeutic Interest in Neuroprotection. Journal of Xenobiotics. 2024; 14(1):227-246. https://doi.org/10.3390/jox14010014
Chicago/Turabian StyleNájera-Maldonado, José Manuel, Ricardo Salazar, Patricia Alvarez-Fitz, Macdiel Acevedo-Quiroz, Eugenia Flores-Alfaro, Daniel Hernández-Sotelo, Mónica Espinoza-Rojo, and Mónica Ramírez. 2024. "Phenolic Compounds of Therapeutic Interest in Neuroprotection" Journal of Xenobiotics 14, no. 1: 227-246. https://doi.org/10.3390/jox14010014