Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation
Abstract
:1. Introduction
1.1. Endogenous and Exogenous Sources of Free Radicals
1.2. Free Radicals: A Double Edge Sword
2. Oxidative Stress and Neurodegenerative Diseases
2.1. Progressive Neurodegenerative Diseases
2.1.1. Alzheimer’s Disease (AD)
2.1.2. Parkinson’s Disease (PD)
2.1.3. Amyotrophic Lateral Sclerosis (ALS)
2.2. Injury-Induced Oxidative Stress
2.2.1. Stroke
2.2.2. Spinal Cord Injury (SCI)
2.2.3. Peripheral Nerve Injury (PNI)
3. Antioxidants
3.1. Endogenous Antioxidants
3.1.1. Antioxidant Enzymes
3.1.2. Antioxidant Non-Enzymes
3.2. Exogenous Antioxidants
3.3. Synthetic Antioxidants
4. Preclinical Studies with Antioxidant Agents
4.1. Antioxidant-Based Therapy in Neurodegenerative Diseases
4.2. Antioxidant-Based Therapy in Neurological Injury
4.3. Clinical Trials with Antioxidants
4.4. Drug Delivery Challenges
- Low permeability to the CNS: The presence of a physiological barrier such as the BBB or spinal–blood barrier (SBB) restricts the accessibility of antioxidant compounds to the CNS and hence could not achieve a prolonged therapeutic dose to impart an antioxidant effect in chronic neurodegenerative diseases [280]. In certain pathological conditions, the BBB/SBB may be compromised due to inflammation or injury (e.g., stroke and spinal cord injury) but still may not be able to achieve the desired dose for a prolonged period due to transient and limited permeability of the BBB/SBB, giving a narrow time window for delivery of therapeutics [281].
- Low bioavailability: Most antioxidants are given orally, and they are insoluble or unstable in a gastric environment that could result in low bioavailability to provide high systemic levels for transport to the CNS at effective doses [282,283]. Antioxidant compounds that are administered via systemic routes have short half-lives [284], which could also limit their transport to the CNS.
- Low catalytic activity: High doses of antioxidant compounds are needed to detoxify the effect of free radicals, which could not be given to humans because of the dose-limiting toxicity [285]. Noncatalytic antioxidant becomes ineffective, once these molecules interact with free radicals [286], and hence, maintaining high antioxidant levels in the target tissue to counteract free radicals that are formed over a period of time in chronic conditions could be challenging.
- Toxicity: Due to toxicity concerns, human doses could have been significantly lower than those used in animal model studies. This could also constrain the duration of treatment necessary to see the beneficial outcome in clinical trials [287].
- Oxidative stress target and other factors: Although oxidative stress is considered as the driving force behind neurodegenerative diseases, there could be other cofounding pathological factors in humans that may not have been targeted solely by antioxidants [288,289]. In addition, the question raised is also how close animal models are to human pathology [290].
5. Antioxidant-Based Nanotherapy
Antioxidant Enzymes
6. Concluding Remarks/Future Perspective
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ALA | α-Lipoic acid |
ALSFRSr | Amyotrophic Lateral Sclerosis Functional Rating Scale Revised |
APP | Amyloid Precursor Protein |
ARE | Antioxidant Response Element |
BBB | Blood-Brain Barrier |
CAT | Catalase |
CNS | Central Nervous System |
CoQ10 | Coenzyme Q10 |
EGCG | Epigallocatechin Gallates |
ETC | Electron Transport Chain |
GSH | Glutathione |
GST | Glutathione S-Transferase |
GPx | Glutathione Peroxidases |
GR | Glutathione Reductase |
HO-1 | Heme Oxygenase 1 |
4-HNE | 4-Hydroxynonenal |
KEAP1 | Kelch-like ECH-Associated Protein 1 |
LDL | Low-Density Lipoproteins |
LPO | Lipid Peroxidation |
MCAO | Middle Cerebral Artery Occlusion |
MDA | Malondialdehyde |
MMP | Matrix Metalloproteinases |
NF-κB | Nuclear Factor Kappa B |
NFTs | Neurofibrillary Tangles |
Nrf2 | Nuclear Factor Erythroid 2-Related Factor 2 |
NQO1 | NADPH Quinine Oxidoreductase 1 |
PLGA | Poly(Lactic-co-Glycolic Acid) |
PNS | Peripheral Nervous System |
RA | Retinoic Acid |
ROS | Reactive Oxygen Species |
RNS | Reactive Nitrogen Species |
SIRT-1 | Sirtuin 1 |
SOD | Superoxide Dismutase |
TAC | Total Antioxidant Capacity |
UPDRS | Unified Parkinson’s Disease Rating Scale |
References
- Singh, A.; Kukreti, R.; Saso, L.; Kukreti, S. Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules 2019, 24, 1583. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, Y.; Lu, Y.; Saredy, J.; Wang, X.; Drummer Iv, C.; Shao, Y.; Saaoud, F.; Xu, K.; Liu, M.; Yang, W.Y.; et al. ROS systems are a new integrated network for sensing homeostasis and alarming stresses in organelle metabolic processes. Redox Biol. 2020, 37, 101696. [Google Scholar] [CrossRef] [PubMed]
- Collin, F. Chemical Basis of Reactive Oxygen Species Reactivity and Involvement in Neurodegenerative Diseases. Int. J. Mol. Sci. 2019, 20, 2407. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sharifi-Rad, M.; Anil Kumar, N.V.; Zucca, P.; Varoni, E.M.; Dini, L.; Panzarini, E.; Rajkovic, J.; Tsouh Fokou, P.V.; Azzini, E.; Peluso, I.; et al. Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front. Physiol. 2020, 11, 694. [Google Scholar] [CrossRef] [PubMed]
- Man, A.W.C.; Li, H.; Xia, N. Impact of Lifestyles (Diet and Exercise) on Vascular Health: Oxidative Stress and Endothelial Function. Oxid. Med. Cell Longev. 2020, 2020, 1496462. [Google Scholar] [CrossRef] [PubMed]
- Kurutas, E.B. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: Current state. Nutr. J. 2016, 15, 71. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cunha-Oliveira, T.; Montezinho, L.; Mendes, C.; Firuzi, O.; Saso, L.; Oliveira, P.J.; Silva, F.S.G. Oxidative Stress in Amyotrophic Lateral Sclerosis: Pathophysiology and Opportunities for Pharmacological Intervention. Oxid. Med. Cell Longev. 2020, 2020, 5021694. [Google Scholar] [CrossRef] [PubMed]
- Birben, E.; Sahiner, U.M.; Sackesen, C.; Erzurum, S.; Kalayci, O. Oxidative stress and antioxidant defense. World Allergy Organ. J. 2012, 5, 9–19. [Google Scholar] [CrossRef] [Green Version]
- Journey through the Diagnosis of Dementia—World Alzheimer Report 2021. Available online: https://www.alzint.org/resource/world-alzheimer-report-2021/ (accessed on 14 January 2022).
- Anjum, A.; Yazid, M.D.; Fauzi Daud, M.; Idris, J.; Ng, A.M.H.; Selvi Naicker, A.; Ismail, O.H.R.; Athi Kumar, R.K.; Lokanathan, Y. Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms. Int. J. Mol. Sci. 2020, 21, 7533. [Google Scholar] [CrossRef]
- von Arnim, C.A.; Herbolsheimer, F.; Nikolaus, T.; Peter, R.; Biesalski, H.K.; Ludolph, A.C.; Riepe, M.; Nagel, G.; Acti, F.E.U.S.G. Dietary antioxidants and dementia in a population-based case-control study among older people in South Germany. J. Alzheimers Dis. 2012, 31, 717–724. [Google Scholar] [CrossRef] [Green Version]
- Urano, S.; Asai, Y.; Makabe, S.; Matsuo, M.; Izumiyama, N.; Ohtsubo, K.; Endo, T. Oxidative injury of synapse and alteration of antioxidative defense systems in rats, and its prevention by vitamin E. Eur. J. Biochem. 1997, 245, 64–70. [Google Scholar] [CrossRef] [Green Version]
- Magistretti, P.J.; Allaman, I. A cellular perspective on brain energy metabolism and functional imaging. Neuron 2015, 86, 883–901. [Google Scholar] [CrossRef] [Green Version]
- Siraki, A.G.; O’Brien, P.J. Prooxidant activity of free radicals derived from phenol-containing neurotransmitters. Toxicology 2002, 177, 81–90. [Google Scholar] [CrossRef]
- Salim, S. Oxidative Stress and the Central Nervous System. J. Pharmacol. Exp. Ther. 2017, 360, 201–205. [Google Scholar] [CrossRef]
- Cobley, J.N.; Fiorello, M.L.; Bailey, D.M. 13 reasons why the brain is susceptible to oxidative stress. Redox Biol. 2018, 15, 490–503. [Google Scholar] [CrossRef]
- Liguori, I.; Russo, G.; Curcio, F.; Bulli, G.; Aran, L.; Della-Morte, D.; Gargiulo, G.; Testa, G.; Cacciatore, F.; Bonaduce, D.; et al. Oxidative stress, aging, and diseases. Clin. Interv. Aging 2018, 13, 757–772. [Google Scholar] [CrossRef] [Green Version]
- Phaniendra, A.; Jestadi, D.B.; Periyasamy, L. Free radicals: Properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem. 2015, 30, 11–26. [Google Scholar] [CrossRef] [Green Version]
- Popa-Wagner, A.; Mitran, S.; Sivanesan, S.; Chang, E.; Buga, A.M. ROS and brain diseases: The good, the bad, and the ugly. Oxid. Med. Cell Longev. 2013, 2013, 963520. [Google Scholar] [CrossRef]
- Selivanov, V.A.; Votyakova, T.V.; Pivtoraiko, V.N.; Zeak, J.; Sukhomlin, T.; Trucco, M.; Roca, J.; Cascante, M. Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain. PLoS Comput. Biol. 2011, 7, e1001115. [Google Scholar] [CrossRef] [Green Version]
- Mailloux, R.J.; McBride, S.L.; Harper, M.E. Unearthing the secrets of mitochondrial ROS and glutathione in bioenergetics. Trends Biochem. Sci. 2013, 38, 592–602. [Google Scholar] [CrossRef]
- Walker, C.L.; Pomatto, L.C.D.; Tripathi, D.N.; Davies, K.J.A. Redox Regulation of Homeostasis and Proteostasis in Peroxisomes. Physiol. Rev. 2018, 98, 89–115. [Google Scholar] [CrossRef] [PubMed]
- Davies, M.J.; Hawkins, C.L. The Role of Myeloperoxidase in Biomolecule Modification, Chronic Inflammation, and Disease. Antioxid. Redox Signal. 2020, 32, 957–981. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ballance, W.C.; Qin, E.C.; Chung, H.J.; Gillette, M.U.; Kong, H. Reactive oxygen species-responsive drug delivery systems for the treatment of neurodegenerative diseases. Biomaterials 2019, 217, 119292. [Google Scholar] [CrossRef] [PubMed]
- Veith, A.; Moorthy, B. Role of Cytochrome P450s in the Generation and Metabolism of Reactive Oxygen Species. Curr. Opin. Toxicol. 2018, 7, 44–51. [Google Scholar] [CrossRef]
- Araujo, J.E.; Jorge, S.; Santos, H.M.; Chiechi, A.; Galstyan, A.; Lodeiro, C.; Diniz, M.; Kleinman, M.T.; Ljubimova, J.Y.; Capelo, J.L. Proteomic changes driven by urban pollution suggest particulate matter as a deregulator of energy metabolism, mitochondrial activity, and oxidative pathways in the rat brain. Sci. Total Environ. 2019, 687, 839–848. [Google Scholar] [CrossRef]
- Calderon-Garciduenas, L.; Leray, E.; Heydarpour, P.; Torres-Jardon, R.; Reis, J. Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond. Rev. Neurol. 2016, 172, 69–80. [Google Scholar] [CrossRef]
- Rai, Y.; Anita; Kumari, N.; Singh, S.; Kalra, N.; Soni, R.; Bhatt, A.N. Mild mitochondrial uncoupling protects from ionizing radiation induced cell death by attenuating oxidative stress and mitochondrial damage. Biochim. Biophys. Acta Bioenerg. 2021, 1862, 148325. [Google Scholar] [CrossRef]
- Mullenders, L.H.F. Solar UV damage to cellular DNA: From mechanisms to biological effects. Photochem. Photobiol. Sci. 2018, 17, 1842–1852. [Google Scholar] [CrossRef]
- Akakin, D.; Tok, O.E.; Anil, D.; Akakin, A.; Sirvanci, S.; Sener, G.; Ercan, F. Electromagnetic Waves from Mobile Phones may Affect Rat Brain During Development. Turk. Neurosurg. 2021, 31, 412–421. [Google Scholar] [CrossRef]
- Choi, S.; Krishnan, J.; Ruckmani, K. Cigarette smoke and related risk factors in neurological disorders: An update. Biomed. Pharmacother. 2017, 85, 79–86. [Google Scholar] [CrossRef]
- Naha, N.; Gandhi, D.N.; Gautam, A.K.; Prakash, J.R. Nicotine and cigarette smoke modulate Nrf2-BDNF-dopaminergic signal and neurobehavioral disorders in adult rat cerebral cortex. Hum. Exp. Toxicol. 2018, 37, 540–556. [Google Scholar] [CrossRef]
- Rodriguez-Martinez, E.; Nava-Ruiz, C.; Escamilla-Chimal, E.; Borgonio-Perez, G.; Rivas-Arancibia, S. The Effect of Chronic Ozone Exposure on the Activation of Endoplasmic Reticulum Stress and Apoptosis in Rat Hippocampus. Front. Aging Neurosci. 2016, 8, 245. [Google Scholar] [CrossRef]
- Gargouri, B.; Bhatia, H.S.; Bouchard, M.; Fiebich, B.L.; Fetoui, H. Inflammatory and oxidative mechanisms potentiate bifenthrin-induced neurological alterations and anxiety-like behavior in adult rats. Toxicol. Lett. 2018, 294, 73–86. [Google Scholar] [CrossRef]
- Lahouel, A.; Kebieche, M.; Lakroun, Z.; Rouabhi, R.; Fetoui, H.; Chtourou, Y.; Djamila, Z.; Soulimani, R. Neurobehavioral deficits and brain oxidative stress induced by chronic low dose exposure of persistent organic pollutants mixture in adult female rat. Environ. Sci. Pollut. Res. Int. 2016, 23, 19030–19040. [Google Scholar] [CrossRef]
- Cruces-Sande, A.; Rodriguez-Perez, A.I.; Herbello-Hermelo, P.; Bermejo-Barrera, P.; Mendez-Alvarez, E.; Labandeira-Garcia, J.L.; Soto-Otero, R. Copper Increases Brain Oxidative Stress and Enhances the Ability of 6-Hydroxydopamine to Cause Dopaminergic Degeneration in a Rat Model of Parkinson’s Disease. Mol. Neurobiol. 2019, 56, 2845–2854. [Google Scholar] [CrossRef]
- Yauger, Y.J.; Bermudez, S.; Moritz, K.E.; Glaser, E.; Stoica, B.; Byrnes, K.R. Iron accentuated reactive oxygen species release by NADPH oxidase in activated microglia contributes to oxidative stress in vitro. J. Neuroinflamm. 2019, 16, 41. [Google Scholar] [CrossRef]
- Langley, M.R.; Ghaisas, S.; Ay, M.; Luo, J.; Palanisamy, B.N.; Jin, H.; Anantharam, V.; Kanthasamy, A.; Kanthasamy, A.G. Manganese exposure exacerbates progressive motor deficits and neurodegeneration in the MitoPark mouse model of Parkinson’s disease: Relevance to gene and environment interactions in metal neurotoxicity. Neurotoxicology 2018, 64, 240–255. [Google Scholar] [CrossRef]
- Ashok, A.; Rai, N.K.; Tripathi, S.; Bandyopadhyay, S. Exposure to As-, Cd-, and Pb-mixture induces Abeta, amyloidogenic APP processing and cognitive impairments via oxidative stress-dependent neuroinflammation in young rats. Toxicol. Sci 2015, 143, 64–80. [Google Scholar] [CrossRef] [Green Version]
- Di Meo, S.; Reed, T.T.; Venditti, P.; Victor, V.M. Role of ROS and RNS Sources in Physiological and Pathological Conditions. Oxid. Med. Cell Longev. 2016, 2016, 1245049. [Google Scholar] [CrossRef]
- Forstermann, U.; Sessa, W.C. Nitric oxide synthases: Regulation and function. Eur. Heart J. 2012, 33, 829–837. [Google Scholar] [CrossRef] [Green Version]
- Rahal, A.; Kumar, A.; Singh, V.; Yadav, B.; Tiwari, R.; Chakraborty, S.; Dhama, K. Oxidative stress, prooxidants, and antioxidants: The interplay. Biomed. Res. Int. 2014, 2014, 761264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sies, H. Oxidative stress: Oxidants and antioxidants. Exp. Physiol. 1997, 82, 291–295. [Google Scholar] [CrossRef] [PubMed]
- Juan, C.A.; Perez de la Lastra, J.M.; Plou, F.J.; Perez-Lebena, E. The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies. Int. J. Mol. Sci. 2021, 22, 4642. [Google Scholar] [CrossRef] [PubMed]
- Damiano, M.; Starkov, A.A.; Petri, S.; Kipiani, K.; Kiaei, M.; Mattiazzi, M.; Flint Beal, M.; Manfredi, G. Neural mitochondrial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J. Neurochem. 2006, 96, 1349–1361. [Google Scholar] [CrossRef]
- Singh, B.K.; Tripathi, M.; Pandey, P.K.; Kakkar, P. Alteration in mitochondrial thiol enhances calcium ion dependent membrane permeability transition and dysfunction in vitro: A cross-talk between mtThiol, Ca(2+), and ROS. Mol. Cell Biochem. 2011, 357, 373–385. [Google Scholar] [CrossRef]
- Chiang, S.C.; Meagher, M.; Kassouf, N.; Hafezparast, M.; McKinnon, P.J.; Haywood, R.; El-Khamisy, S.F. Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage. Sci. Adv. 2017, 3, e1602506. [Google Scholar] [CrossRef] [Green Version]
- Eratne, D.; Loi, S.M.; Farrand, S.; Kelso, W.; Velakoulis, D.; Looi, J.C. Alzheimer’s disease: Clinical update on epidemiology, pathophysiology and diagnosis. Australas. Psychiatry 2018, 26, 347–357. [Google Scholar] [CrossRef]
- DeTure, M.A.; Dickson, D.W. The neuropathological diagnosis of Alzheimer’s disease. Mol. Neurodegener. 2019, 14, 32. [Google Scholar] [CrossRef] [Green Version]
- Markesbery, W.R. Oxidative stress hypothesis in Alzheimer’s disease. Free Radic. Biol. Med. 1997, 23, 134–147. [Google Scholar] [CrossRef]
- Sharma, C.; Kim, S.R. Linking Oxidative Stress and Proteinopathy in Alzheimer’s Disease. Antioxidants 2021, 10, 1231. [Google Scholar] [CrossRef]
- Harman, D. Free radical theory of aging. Mutat. Res. 1992, 275, 257–266. [Google Scholar] [CrossRef]
- Adav, S.S.; Park, J.E.; Sze, S.K. Quantitative profiling brain proteomes revealed mitochondrial dysfunction in Alzheimer’s disease. Mol. Brain 2019, 12, 8. [Google Scholar] [CrossRef]
- Kim, S.H.; Vlkolinsky, R.; Cairns, N.; Lubec, G. Decreased levels of complex III core protein 1 and complex V beta chain in brains from patients with Alzheimer’s disease and Down syndrome. Cell Mol. Life Sci. 2000, 57, 1810–1816. [Google Scholar] [CrossRef]
- Kim, S.H.; Vlkolinsky, R.; Cairns, N.; Fountoulakis, M.; Lubec, G. The reduction of NADH ubiquinone oxidoreductase 24- and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer’s disease. Life Sci. 2001, 68, 2741–2750. [Google Scholar] [CrossRef]
- Liang, W.S.; Reiman, E.M.; Valla, J.; Dunckley, T.; Beach, T.G.; Grover, A.; Niedzielko, T.L.; Schneider, L.E.; Mastroeni, D.; Caselli, R.; et al. Alzheimer’s disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc. Natl. Acad. Sci. USA 2008, 105, 4441–4446. [Google Scholar] [CrossRef] [Green Version]
- Gauba, E.; Chen, H.; Guo, L.; Du, H. Cyclophilin D deficiency attenuates mitochondrial F1Fo ATP synthase dysfunction via OSCP in Alzheimer’s disease. Neurobiol. Dis. 2019, 121, 138–147. [Google Scholar] [CrossRef]
- Beck, S.J.; Guo, L.; Phensy, A.; Tian, J.; Wang, L.; Tandon, N.; Gauba, E.; Lu, L.; Pascual, J.M.; Kroener, S.; et al. Deregulation of mitochondrial F1FO-ATP synthase via OSCP in Alzheimer’s disease. Nat. Commun. 2016, 7, 11483. [Google Scholar] [CrossRef] [Green Version]
- Lu, T.; Pan, Y.; Kao, S.Y.; Li, C.; Kohane, I.; Chan, J.; Yankner, B.A. Gene regulation and DNA damage in the ageing human brain. Nature 2004, 429, 883–891. [Google Scholar] [CrossRef]
- Reed, T.; Perluigi, M.; Sultana, R.; Pierce, W.M.; Klein, J.B.; Turner, D.M.; Coccia, R.; Markesbery, W.R.; Butterfield, D.A. Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: Insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer’s disease. Neurobiol. Dis. 2008, 30, 107–120. [Google Scholar] [CrossRef]
- Esposito, L.; Raber, J.; Kekonius, L.; Yan, F.; Yu, G.Q.; Bien-Ly, N.; Puolivali, J.; Scearce-Levie, K.; Masliah, E.; Mucke, L. Reduction in mitochondrial superoxide dismutase modulates Alzheimer’s disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice. J. Neurosci. 2006, 26, 5167–5179. [Google Scholar] [CrossRef] [Green Version]
- Mattson, M.P.; Fu, W.; Waeg, G.; Uchida, K. 4-Hydroxynonenal, a product of lipid peroxidation, inhibits dephosphorylation of the microtubule-associated protein tau. Neuroreport 1997, 8, 2275–2281. [Google Scholar] [CrossRef] [PubMed]
- Misrani, A.; Tabassum, S.; Yang, L. Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease. Front. Aging Neurosci. 2021, 13, 617588. [Google Scholar] [CrossRef] [PubMed]
- Patten, D.A.; Germain, M.; Kelly, M.A.; Slack, R.S. Reactive oxygen species: Stuck in the middle of neurodegeneration. J. Alzheimers Dis. 2010, 20 (Suppl. 2), S357–S367. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marcus, D.L.; Thomas, C.; Rodriguez, C.; Simberkoff, K.; Tsai, J.S.; Strafaci, J.A.; Freedman, M.L. Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer’s disease. Exp. Neurol. 1998, 150, 40–44. [Google Scholar] [CrossRef]
- Chen, L.; Na, R.; Gu, M.; Richardson, A.; Ran, Q. Lipid peroxidation up-regulates BACE1 expression in vivo: A possible early event of amyloidogenesis in Alzheimer’s disease. J. Neurochem. 2008, 107, 197–207. [Google Scholar] [CrossRef] [Green Version]
- Poewe, W.; Seppi, K.; Tanner, C.M.; Halliday, G.M.; Brundin, P.; Volkmann, J.; Schrag, A.E.; Lang, A.E. Parkinson disease. Nat. Rev. Dis. Primers 2017, 3, 17013. [Google Scholar] [CrossRef]
- Simon, D.K.; Tanner, C.M.; Brundin, P. Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology. Clin. Geriatr. Med. 2020, 36, 1–12. [Google Scholar] [CrossRef]
- Gomez-Benito, M.; Granado, N.; Garcia-Sanz, P.; Michel, A.; Dumoulin, M.; Moratalla, R. Modeling Parkinson’s Disease With the Alpha-Synuclein Protein. Front. Pharmacol. 2020, 11, 356. [Google Scholar] [CrossRef]
- Dias, V.; Junn, E.; Mouradian, M.M. The role of oxidative stress in Parkinson’s disease. J. Parkinsons Dis. 2013, 3, 461–491. [Google Scholar] [CrossRef] [Green Version]
- Puspita, L.; Chung, S.Y.; Shim, J.W. Oxidative stress and cellular pathologies in Parkinson’s disease. Mol. Brain 2017, 10, 53. [Google Scholar] [CrossRef] [Green Version]
- Trist, B.G.; Hare, D.J.; Double, K.L. Oxidative stress in the aging substantia nigra and the etiology of Parkinson’s disease. Aging Cell 2019, 18, e13031. [Google Scholar] [CrossRef] [Green Version]
- Tong, H.; Zhang, X.; Meng, X.; Lu, L.; Mai, D.; Qu, S. Simvastatin Inhibits Activation of NADPH Oxidase/p38 MAPK Pathway and Enhances Expression of Antioxidant Protein in Parkinson Disease Models. Front. Mol. Neurosci. 2018, 11, 165. [Google Scholar] [CrossRef] [Green Version]
- Park, H.R.; Yang, E.J. Oxidative Stress as a Therapeutic Target in Amyotrophic Lateral Sclerosis: Opportunities and Limitations. Diagnostics 2021, 11, 1546. [Google Scholar] [CrossRef]
- Petrov, D.; Daura, X.; Zagrovic, B. Effect of Oxidative Damage on the Stability and Dimerization of Superoxide Dismutase 1. Biophys. J. 2016, 110, 1499–1509. [Google Scholar] [CrossRef] [Green Version]
- Richardson, K.; Allen, S.P.; Mortiboys, H.; Grierson, A.J.; Wharton, S.B.; Ince, P.G.; Shaw, P.J.; Heath, P.R. The effect of SOD1 mutation on cellular bioenergetic profile and viability in response to oxidative stress and influence of mutation-type. PLoS ONE 2013, 8, e68256. [Google Scholar] [CrossRef]
- Pansarasa, O.; Bordoni, M.; Diamanti, L.; Sproviero, D.; Gagliardi, S.; Cereda, C. SOD1 in Amyotrophic Lateral Sclerosis: “Ambivalent” Behavior Connected to the Disease. Int. J. Mol. Sci. 2018, 19, 1345. [Google Scholar] [CrossRef] [Green Version]
- Huai, J.; Zhang, Z. Structural Properties and Interaction Partners of Familial ALS-Associated SOD1 Mutants. Front. Neurol. 2019, 10, 527. [Google Scholar] [CrossRef] [Green Version]
- Obrador, E.; Salvador, R.; Lopez-Blanch, R.; Jihad-Jebbar, A.; Valles, S.L.; Estrela, J.M. Oxidative Stress, Neuroinflammation and Mitochondria in the Pathophysiology of Amyotrophic Lateral Sclerosis. Antioxidants 2020, 9, 901. [Google Scholar] [CrossRef]
- Blasco, H.; Garcon, G.; Patin, F.; Veyrat-Durebex, C.; Boyer, J.; Devos, D.; Vourc’h, P.; Andres, C.R.; Corcia, P. Panel of Oxidative Stress and Inflammatory Biomarkers in ALS: A Pilot Study. Can. J. Neurol. Sci. 2017, 44, 90–95. [Google Scholar] [CrossRef] [Green Version]
- Bellezza, I.; Grottelli, S.; Costanzi, E.; Scarpelli, P.; Pigna, E.; Morozzi, G.; Mezzasoma, L.; Peirce, M.J.; Moresi, V.; Adamo, S.; et al. Peroxynitrite Activates the NLRP3 Inflammasome Cascade in SOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis. Mol. Neurobiol. 2018, 55, 2350–2361. [Google Scholar] [CrossRef] [Green Version]
- Wang, Z.; Bai, Z.; Qin, X.; Cheng, Y. Aberrations in Oxidative Stress Markers in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis. Oxid. Med. Cell Longev. 2019, 2019, 1712323. [Google Scholar] [CrossRef] [PubMed]
- Kazama, M.; Kato, Y.; Kakita, A.; Noguchi, N.; Urano, Y.; Masui, K.; Niida-Kawaguchi, M.; Yamamoto, T.; Watabe, K.; Kitagawa, K.; et al. Astrocytes release glutamate via cystine/glutamate antiporter upregulated in response to increased oxidative stress related to sporadic amyotrophic lateral sclerosis. Neuropathology 2020, 40, 587–598. [Google Scholar] [CrossRef] [PubMed]
- Kolarcik, C.L.; Bowser, R. Retinoid signaling alterations in amyotrophic lateral sclerosis. Am. J. Neurodegener. Dis. 2012, 1, 130–145. [Google Scholar] [CrossRef]
- Sun, M.S.; Jin, H.; Sun, X.; Huang, S.; Zhang, F.L.; Guo, Z.N.; Yang, Y. Free Radical Damage in Ischemia-Reperfusion Injury: An Obstacle in Acute Ischemic Stroke after Revascularization Therapy. Oxid. Med. Cell Longev. 2018, 2018, 3804979. [Google Scholar] [CrossRef]
- Kalogeris, T.; Baines, C.P.; Krenz, M.; Korthuis, R.J. Cell biology of ischemia/reperfusion injury. Int. Rev. Cell Mol. Biol. 2012, 298, 229–317. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, L.; Xiong, X.; Wu, X.; Ye, Y.; Jian, Z.; Zhi, Z.; Gu, L. Targeting Oxidative Stress and Inflammation to Prevent Ischemia-Reperfusion Injury. Front. Mol. Neurosci. 2020, 13, 28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Al-Qazzaz, N.K.; Ali, S.H.; Ahmad, S.A.; Islam, S.; Mohamad, K. Cognitive impairment and memory dysfunction after a stroke diagnosis: A post-stroke memory assessment. Neuropsychiatr. Dis. Treat. 2014, 10, 1677–1691. [Google Scholar] [CrossRef] [Green Version]
- Ahad, M.A.; Kumaran, K.R.; Ning, T.; Mansor, N.I.; Effendy, M.A.; Damodaran, T.; Lingam, K.; Wahab, H.A.; Nordin, N.; Liao, P.; et al. Insights into the neuropathology of cerebral ischemia and its mechanisms. Rev. Neurosci. 2020, 31, 521–538. [Google Scholar] [CrossRef]
- Lorenzano, S.; Rost, N.S.; Khan, M.; Li, H.; Lima, F.O.; Maas, M.B.; Green, R.E.; Thankachan, T.K.; Dipietro, A.J.; Arai, K.; et al. Oxidative Stress Biomarkers of Brain Damage: Hyperacute Plasma F2-Isoprostane Predicts Infarct Growth in Stroke. Stroke 2018, 49, 630–637. [Google Scholar] [CrossRef]
- Nakano, Y.; Yamashita, T.; Li, Q.; Sato, K.; Ohta, Y.; Morihara, R.; Hishikawa, N.; Abe, K. Time-dependent change of in vivo optical imaging of oxidative stress in a mouse stroke model. J. Neurosci. Res. 2017, 95, 2030–2039. [Google Scholar] [CrossRef] [Green Version]
- Kishimoto, M.; Suenaga, J.; Takase, H.; Araki, K.; Yao, T.; Fujimura, T.; Murayama, K.; Okumura, K.; Ueno, R.; Shimizu, N.; et al. Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in cerebral ischemia/reperfusion injury. Sci. Rep. 2019, 9, 13512. [Google Scholar] [CrossRef]
- Sacco, R.L.; Kasner, S.E.; Broderick, J.P.; Caplan, L.R.; Connors, J.J.; Culebras, A.; Elkind, M.S.; George, M.G.; Hamdan, A.D.; Higashida, R.T.; et al. An updated definition of stroke for the 21st century: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013, 44, 2064–2089. [Google Scholar] [CrossRef] [Green Version]
- Lou, Z.; Wang, A.P.; Duan, X.M.; Hu, G.H.; Song, G.L.; Zuo, M.L.; Yang, Z.B. Upregulation of NOX2 and NOX4 Mediated by TGF-beta Signaling Pathway Exacerbates Cerebral Ischemia/Reperfusion Oxidative Stress Injury. Cell Physiol. Biochem. 2018, 46, 2103–2113. [Google Scholar] [CrossRef]
- Xu, N.; Meng, H.; Liu, T.; Feng, Y.; Qi, Y.; Wang, H. TRPC1 Deficiency Exacerbates Cerebral Ischemia/Reperfusion-Induced Neurological Injury by Potentiating Nox4-Derived Reactive Oxygen Species Generation. Cell Physiol. Biochem. 2018, 51, 1723–1738. [Google Scholar] [CrossRef]
- Staiculescu, M.C.; Foote, C.; Meininger, G.A.; Martinez-Lemus, L.A. The role of reactive oxygen species in microvascular remodeling. Int. J. Mol. Sci. 2014, 15, 23792–23835. [Google Scholar] [CrossRef] [Green Version]
- Rempe, R.G.; Hartz, A.M.S.; Bauer, B. Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers. J. Cereb. Blood Flow Metab. 2016, 36, 1481–1507. [Google Scholar] [CrossRef] [Green Version]
- Chen, S.; Shao, L.; Ma, L. Cerebral Edema Formation After Stroke: Emphasis on Blood-Brain Barrier and the Lymphatic Drainage System of the Brain. Front. Cell Neurosci. 2021, 15, 716825. [Google Scholar] [CrossRef]
- van Den Hauwe, L.; Sundgren, P.C.; Flanders, A.E. Spinal Trauma and Spinal Cord Injury (SCI). In Diseases of the Brain, Head and Neck, Spine 2020–2023: Diagnostic Imaging; Hodler, J., Kubik-Huch, R.A., von Schulthess, G.K., Eds.; IDKD Springer Series: Cham, Switzerland, 2020. [Google Scholar] [CrossRef] [Green Version]
- Eckert, M.J.; Martin, M.J. Trauma: Spinal Cord Injury. Surg. Clin. N. Am. 2017, 97, 1031–1045. [Google Scholar] [CrossRef]
- Ahuja, C.S.; Nori, S.; Tetreault, L.; Wilson, J.; Kwon, B.; Harrop, J.; Choi, D.; Fehlings, M.G. Traumatic Spinal Cord Injury-Repair and Regeneration. Neurosurgery 2017, 80, S9–S22. [Google Scholar] [CrossRef]
- Lin, J.; Xiong, Z.; Gu, J.; Sun, Z.; Jiang, S.; Fan, D.; Li, W. Sirtuins: Potential Therapeutic Targets for Defense against Oxidative Stress in Spinal Cord Injury. Oxid. Med. Cell Longev. 2021, 2021, 7207692. [Google Scholar] [CrossRef]
- Bock, F.J.; Tait, S.W.G. Mitochondria as multifaceted regulators of cell death. Nat. Rev. Mol. Cell Biol. 2020, 21, 85–100. [Google Scholar] [CrossRef]
- Rabchevsky, A.G.; Michael, F.M.; Patel, S.P. Mitochondria focused neurotherapeutics for spinal cord injury. Exp. Neurol. 2020, 330, 113332. [Google Scholar] [CrossRef]
- Popa, C.; Popa, F.; Grigorean, V.T.; Onose, G.; Sandu, A.M.; Popescu, M.; Burnei, G.; Strambu, V.; Sinescu, C. Vascular dysfunctions following spinal cord injury. J. Med. Life 2010, 3, 275–285. [Google Scholar]
- Hussain, G.; Wang, J.; Rasul, A.; Anwar, H.; Qasim, M.; Zafar, S.; Aziz, N.; Razzaq, A.; Hussain, R.; de Aguilar, J.G.; et al. Current Status of Therapeutic Approaches against Peripheral Nerve Injuries: A Detailed Story from Injury to Recovery. Int. J. Biol. Sci. 2020, 16, 116–134. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Walco, G.A.; Dworkin, R.H.; Krane, E.J.; LeBel, A.A.; Treede, R.D. Neuropathic pain in children: Special considerations. Mayo Clin. Proc. 2010, 85, S33–S41. [Google Scholar] [CrossRef] [Green Version]
- Agbaje, J.O.; Van de Casteele, E.; Hiel, M.; Verbaanderd, C.; Lambrichts, I.; Politis, C. Neuropathy of Trigeminal Nerve Branches After Oral and Maxillofacial Treatment. J. Maxillofac. Oral Surg. 2016, 15, 321–327. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Menorca, R.M.; Fussell, T.S.; Elfar, J.C. Nerve physiology: Mechanisms of injury and recovery. Hand Clin. 2013, 29, 317–330. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khezri, M.K.; Turkkan, A.; Koc, C.; Salman, B.; Levent, P.; Cakir, A.; Kafa, I.M.; Cansev, M.; Bekar, A. Anti-Apoptotic and Anti-Oxidant Effects of Systemic Uridine Treatment in an Experimental Model of Sciatic Nerve Injury. Turk. Neurosurg. 2021, 31, 373–378. [Google Scholar] [CrossRef]
- Lattimore, M.R., Jr.; Varr, W.F., 3rd. Disposable soft lens ulcerative keratitis in an Army aviator: A case report. Aviat. Space Environ. Med. 1991, 62, 888–889. [Google Scholar]
- Costa, L.S.; Aidar, F.J.; Matos, D.G.; Oliveira, J.U.; Santos, J.L.D.; Almeida-Neto, P.F.; Souza, R.F.; Pereira, D.D.; Garrido, N.D.; Nunes-Silva, A.; et al. Effects of Resistance Training and Bowdichia virgilioides Hydroethanolic Extract on Oxidative Stress Markers in Rats Submitted to Peripheral Nerve Injury. Antioxidants 2020, 9, 941. [Google Scholar] [CrossRef]
- Zafar, S.; Anwar, H.; Qasim, M.; Irfan, S.; Maqbool, J.; Sajid, F.; Naqvi, S.A.R.; Hussain, G. Calotropis procera (root) escalates functions rehabilitation and attenuates oxidative stress in a mouse model of peripheral nerve injury. Pak. J. Pharm. Sci. 2020, 33, 2801–2807. [Google Scholar]
- Tang, C.; Han, R.; Wu, J.; Fang, F. Effects of baicalin capsules combined with alpha-lipoic acid on nerve conduction velocity, oxidative stress and inflammatory injury in patients wi.ith diabetic peripheral neuropathy. Am. J. Transl. Res. 2021, 13, 2774–2783. [Google Scholar]
- Luca, M.; Luca, A.; Calandra, C. The Role of Oxidative Damage in the Pathogenesis and Progression of Alzheimer’s Disease and Vascular Dementia. Oxid. Med. Cell Longev. 2015, 2015, 504678. [Google Scholar] [CrossRef] [Green Version]
- Perluigi, M.; Butterfield, D.A. Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia. Curr. Gerontol. Geriatr. Res. 2012, 2012, 724904. [Google Scholar] [CrossRef] [Green Version]
- Pangrazzi, L.; Balasco, L.; Bozzi, Y. Oxidative Stress and Immune System Dysfunction in Autism Spectrum Disorders. Int. J. Mol. Sci. 2020, 21, 3293. [Google Scholar] [CrossRef]
- Oztop, D.; Altun, H.; Baskol, G.; Ozsoy, S. Oxidative stress in children with attention deficit hyperactivity disorder. Clin. Biochem 2012, 45, 745–748. [Google Scholar] [CrossRef]
- Paul, B.D.; Snyder, S.H. Impaired Redox Signaling in Huntington’s Disease: Therapeutic Implications. Front. Mol. Neurosci. 2019, 12, 68. [Google Scholar] [CrossRef] [Green Version]
- Ohl, K.; Tenbrock, K.; Kipp, M. Oxidative stress in multiple sclerosis: Central and peripheral mode of action. Exp. Neurol. 2016, 277, 58–67. [Google Scholar] [CrossRef]
- Bhatt, S.; Nagappa, A.N.; Patil, C.R. Role of oxidative stress in depression. Drug Discov. Today 2020, 25, 1270–1276. [Google Scholar] [CrossRef]
- Geronzi, U.; Lotti, F.; Grosso, S. Oxidative stress in epilepsy. Expert Rev. Neurother. 2018, 18, 427–434. [Google Scholar] [CrossRef]
- Khatri, N.; Thakur, M.; Pareek, V.; Kumar, S.; Sharma, S.; Datusalia, A.K. Oxidative Stress: Major Threat in Traumatic Brain Injury. CNS Neurol. Disord. Drug Targets 2018, 17, 689–695. [Google Scholar] [CrossRef]
- Elfawy, H.A.; Das, B. Crosstalk between mitochondrial dysfunction, oxidative stress, and age related neurodegenerative disease: Etiologies and therapeutic strategies. Life Sci. 2019, 218, 165–184. [Google Scholar] [CrossRef]
- Guo, C.; Sun, L.; Chen, X.; Zhang, D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen. Res. 2013, 8, 2003–2014. [Google Scholar] [CrossRef]
- Kumar, A.; Singh, A. A review on mitochondrial restorative mechanism of antioxidants in Alzheimer’s disease and other neurological conditions. Front. Pharmacol. 2015, 6, 206. [Google Scholar] [CrossRef] [Green Version]
- Gerhke, S.A.; Shibli, J.A.; Salles, M.B. Potential of the use of an antioxidant compound to promote peripheral nerve regeneration after injury. Neural Regen. Res. 2015, 10, 1063–1064. [Google Scholar] [CrossRef] [PubMed]
- Tan, H.Y.; Wang, N.; Li, S.; Hong, M.; Wang, X.; Feng, Y. The Reactive Oxygen Species in Macrophage Polarization: Reflecting Its Dual Role in Progression and Treatment of Human Diseases. Oxid. Med. Cell Longev. 2016, 2016, 2795090. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Amato, A.; Terzo, S.; Mule, F. Natural Compounds as Beneficial Antioxidant Agents in Neurodegenerative Disorders: A Focus on Alzheimer’s Disease. Antioxidants 2019, 8, 608. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- He, L.; He, T.; Farrar, S.; Ji, L.; Liu, T.; Ma, X. Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species. Cell Physiol. Biochem. 2017, 44, 532–553. [Google Scholar] [CrossRef] [PubMed]
- Vasconcelos, A.R.; Dos Santos, N.B.; Scavone, C.; Munhoz, C.D. Nrf2/ARE Pathway Modulation by Dietary Energy Regulation in Neurological Disorders. Front. Pharmacol. 2019, 10, 33. [Google Scholar] [CrossRef] [Green Version]
- Villavicencio Tejo, F.; Quintanilla, R.A. Contribution o.of the Nrf2 Pathway on Oxidative Damage and Mitochondrial Failure in Parkinson and Alzheimer’s Disease. Antioxidants 2021, 10, 1069. [Google Scholar] [CrossRef]
- Lee, K.H.; Cha, M.; Lee, B.H. Neuroprotective Effect of Antioxidants in the Brain. Int. J. Mol. Sci. 2020, 21, 7152. [Google Scholar] [CrossRef]
- Poljsak, B. Strategies for reducing or preventing the generation of oxidative stress. Oxid. Med. Cell Longev. 2011, 2011, 194586. [Google Scholar] [CrossRef] [Green Version]
- Pisoschi, A.M.; Pop, A.; Iordache, F.; Stanca, L.; Predoi, G.; Serban, A.I. Oxidative stress mitigation by antioxidants—An overview on their chemistry and influences on health status. Eur. J. Med. Chem. 2021, 209, 112891. [Google Scholar] [CrossRef]
- Wang, Y.; Branicky, R.; Noe, A.; Hekimi, S. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. J. Cell Biol. 2018, 217, 1915–1928. [Google Scholar] [CrossRef]
- Nandi, A.; Yan, L.J.; Jana, C.K.; Das, N. Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases. Oxid. Med. Cell Longev. 2019, 2019, 9613090. [Google Scholar] [CrossRef] [Green Version]
- Lubos, E.; Loscalzo, J.; Handy, D.E. Glutathione peroxidase-1 in health and disease: From molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signal. 2011, 15, 1957–1997. [Google Scholar] [CrossRef] [Green Version]
- Aquilano, K.; Baldelli, S.; Ciriolo, M.R. Glutathione: New roles in redox signaling for an old antioxidant. Front. Pharmacol. 2014, 5, 196. [Google Scholar] [CrossRef] [Green Version]
- Lushchak, V.I. Glutathione homeostasis and functions: Potential targets for medical interventions. J. Amino Acids 2012, 2012, 736837. [Google Scholar] [CrossRef] [Green Version]
- Bjorklund, G.; Aaseth, J.; Crisponi, G.; Rahman, M.M.; Chirumbolo, S. Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology. J. Inorg. Biochem. 2019, 195, 111–119. [Google Scholar] [CrossRef]
- Fabbrini, E.; Serafini, M.; Colic Baric, I.; Hazen, S.L.; Klein, S. Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects. Diabetes 2014, 63, 976–981. [Google Scholar] [CrossRef] [Green Version]
- Yang, X.; Zhang, Y.; Xu, H.; Luo, X.; Yu, J.; Liu, J.; Chang, R.C. Neuroprotection of Coenzyme Q10 in Neurodegenerative Diseases. Curr. Top. Med. Chem 2016, 16, 858–866. [Google Scholar] [CrossRef]
- Conti, V.; Izzo, V.; Corbi, G.; Russomanno, G.; Manzo, V.; De Lise, F.; Di Donato, A.; Filippelli, A. Antioxidant Supplementation in the Treatment of Aging-Associated Diseases. Front. Pharmacol. 2016, 7, 24. [Google Scholar] [CrossRef] [Green Version]
- Bouayed, J.; Bohn, T. Exogenous antioxidants—Double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxid. Med. Cell Longev. 2010, 3, 228–237. [Google Scholar] [CrossRef] [PubMed]
- Jakubczyk, K.; Kaldunska, J.; Dec, K.; Kawczuga, D.; Janda, K. Antioxidant properties of small-molecule non-enzymatic compounds. Pol. Merkur. Lekarski 2020, 48, 128–132. [Google Scholar]
- Kiokias, S.; Proestos, C.; Oreopoulou, V. Effect of Natural Food Antioxidants against LDL and DNA Oxidative Changes. Antioxidants 2018, 7, 133. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Janciauskiene, S. The Beneficial Effects of Antioxidants in Health and Diseases. Chronic Obstr. Pulm. Dis. 2020, 7, 182–202. [Google Scholar] [CrossRef] [PubMed]
- Rizvi, S.; Raza, S.T.; Ahmed, F.; Ahmad, A.; Abbas, S.; Mahdi, F. The role of vitamin e in human health and some diseases. Sultan Qaboos Univ. Med. J. 2014, 14, e157–e165. [Google Scholar]
- Lee, K.H.; Kim, U.J.; Cha, M.; Lee, B.H. Chronic Treatment of Ascorbic Acid Leads to Age-Dependent Neuroprotection against Oxidative Injury in Hippocampal Slice Cultures. Int. J. Mol. Sci. 2021, 22, 1608. [Google Scholar] [CrossRef]
- Ramani, M.; van Groen, T.; Kadish, I.; Ambalavanan, N.; McMahon, L.L. Vitamin A and retinoic acid combination attenuates neonatal hyperoxia-induced neurobehavioral impairment in adult mice. Neurobiol. Learn. Mem. 2017, 141, 209–216. [Google Scholar] [CrossRef]
- Chen, P.; Li, L.; Gao, Y.; Xie, Z.; Zhang, Y.; Pan, Z.; Tu, Y.; Wang, H.; Han, Q.; Hu, X.; et al. beta-carotene provides neuro protection after experimental traumatic brain injury via the Nrf2-ARE pathway. J. Integr. Neurosci. 2019, 18, 153–161. [Google Scholar] [CrossRef] [Green Version]
- Lim, S.; Hwang, S.; Yu, J.H.; Lim, J.W.; Kim, H. Lycopene inhibits regulator of calcineurin 1-mediated apoptosis by reducing oxidative stress and down-regulating Nucling in neuronal cells. Mol. Nutr. Food Res. 2017, 61. [Google Scholar] [CrossRef]
- Huang, C.; Wen, C.; Yang, M.; Gan, D.; Fan, C.; Li, A.; Li, Q.; Zhao, J.; Zhu, L.; Lu, D. Lycopene protects against t-BHP-induced neuronal oxidative damage and apoptosis via activation of the PI3K/Akt pathway. Mol. Biol. Rep. 2019, 46, 3387–3397. [Google Scholar] [CrossRef]
- Manochkumar, J.; Doss, C.G.P.; El-Seedi, H.R.; Efferth, T.; Ramamoorthy, S. The neuroprotective potential of carotenoids in vitro and in vivo. Phytomedicine 2021, 91, 153676. [Google Scholar] [CrossRef]
- Pandey, K.B.; Rizvi, S.I. Plant polyphenols as dietary antioxidants in human health and disease. Oxid. Med. Cell Longev. 2009, 2, 270–278. [Google Scholar] [CrossRef] [Green Version]
- Bodoira, R.; Maestri, D. Phenolic Compounds from Nuts: Extraction, Chemical Profiles, and Bioactivity. J. Agric. Food Chem. 2020, 68, 927–942. [Google Scholar] [CrossRef]
- Salehi, B.; Mishra, A.P.; Nigam, M.; Sener, B.; Kilic, M.; Sharifi-Rad, M.; Fokou, P.V.T.; Martins, N.; Sharifi-Rad, J. Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines 2018, 6, 91. [Google Scholar] [CrossRef] [Green Version]
- Syarifah-Noratiqah, S.B.; Naina-Mohamed, I.; Zulfarina, M.S.; Qodriyah, H.M.S. Natural Polyphenols in the Treatment of Alzheimer’s Disease. Curr. Drug Targets 2018, 19, 927–937. [Google Scholar] [CrossRef]
- Ma, H.; Johnson, S.L.; Liu, W.; DaSilva, N.A.; Meschwitz, S.; Dain, J.A.; Seeram, N.P. Evaluation of Polyphenol Anthocyanin-Enriched Extracts of Blackberry, Black Raspberry, Blueberry, Cranberry, Red Raspberry, and Strawberry for Free Radical Scavenging, Reactive Carbonyl Species Trapping, Anti-Glycation, Anti-beta-Amyloid Aggregation, and Microglial Neuroprotective Effects. Int. J. Mol. Sci. 2018, 19, 461. [Google Scholar] [CrossRef] [Green Version]
- Lourenco, S.C.; Moldao-Martins, M.; Alves, V.D. Antioxidants of Natural Plant Origins: From Sources to Food Industry Applications. Molecules 2019, 24, 4132. [Google Scholar] [CrossRef] [Green Version]
- Taghvaei, M.; Jafari, S.M. Application and stability of natural antioxidants in edible oils in order to substitute synthetic additives. J. Food Sci. Technol. 2015, 52, 1272–1282. [Google Scholar] [CrossRef] [Green Version]
- Jin, Y.; Tang, X.; Cao, X.; Yu, L.; Chen, J.; Zhao, H.; Chen, Y.; Han, L.; Bao, X.; Li, F.; et al. 4-((5-(Tert-butyl)-3-chloro-2-hydroxybenzyl) amino)-2-hydroxybenzoic acid protects against oxygen-glucose deprivation/reperfusion injury. Life Sci. 2018, 204, 46–54. [Google Scholar] [CrossRef]
- Mohsin Alvi, A.; Tariq Al Kury, L.; Umar Ijaz, M.; Ali Shah, F.; Tariq Khan, M.; Sadiq Sheikh, A.; Nadeem, H.; Khan, A.U.; Zeb, A.; Li, S. Post-Treatment of Synthetic Polyphenolic 1,3,4 Oxadiazole Compound A3, Attenuated Ischemic Stroke-Induced Neuroinflammation and Neurodegeneration. Biomolecules 2020, 10, 816. [Google Scholar] [CrossRef] [PubMed]
- Che, H.; Li, Q.; Zhang, T.; Wang, D.; Yang, L.; Xu, J.; Yanagita, T.; Xue, C.; Chang, Y.; Wang, Y. Effects of Astaxanthin and Docosahexaenoic-Acid-Acylated Astaxanthin on Alzheimer’s Disease in APP/PS1 Double-Transgenic Mice. J. Agric. Food Chem. 2018, 66, 4948–4957. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.C.; Shi, H.H.; Xu, J.; Yanagita, T.; Xue, C.H.; Zhang, T.T.; Wang, Y.M. Docosahexaenoic acid-acylated astaxanthin ester exhibits superior performance over non-esterified astaxanthin in preventing behavioral deficits coupled with apoptosis in MPTP-induced mice with Parkinson’s disease. Food Funct. 2020, 11, 8038–8050. [Google Scholar] [CrossRef] [PubMed]
- Akaishi, T.; Abe, K. CNB-001, a synthetic pyrazole derivative of curcumin, suppresses lipopolysaccharide-induced nitric oxide production through the inhibition of NF-kappaB and p38 MAPK pathways in microglia. Eur. J. Pharmacol. 2018, 819, 190–197. [Google Scholar] [CrossRef] [PubMed]
- Guo, Y.; Ma, Z.; Ning, X.; Chen, Y.; Tian, C.; Wang, X.; Zhang, Z.; Liu, J. A Novel Synthetic Precursor of Styryl Sulfone Neuroprotective Agents Inhibits Neuroinflammatory Responses and Oxidative Stress Damage through the P38 Signaling Pathway in the Cell and Animal Model of Parkinson’s Disease. Molecules 2021, 26, 5371. [Google Scholar] [CrossRef] [PubMed]
- Song, X.Y.; Hu, J.F.; Wu, D.H.; Ji, H.J.; Chen, N.H. IMM-H004, a Novel Coumarin Derivative Compound, Inhibits H2O2-Induced Neurotoxicity via Antioxidant and Antiapoptosis in PC12 Cells. J. Stroke Cerebrovasc. Dis. 2018, 27, 3396–3403. [Google Scholar] [CrossRef]
- Saleh, T.M.; Saleh, M.C.; Connell, B.J.; Kucukkaya, I.; Abd-El-Aziz, A.S. A novel synthetic chemical entity (UPEI-800) is neuroprotective in vitro and in an in vivo rat model of oxidative stress. Clin. Exp. Pharmacol. Physiol. 2017, 44, 993–1000. [Google Scholar] [CrossRef]
- Lee, S.Y.; Chiu, Y.J.; Yang, S.M.; Chen, C.M.; Huang, C.C.; Lee-Chen, G.J.; Lin, W.; Chang, K.H. Novel synthetic chalcone-coumarin hybrid for Abeta aggregation reduction, antioxidation, and neuroprotection. CNS Neurosci. Ther. 2018, 24, 1286–1298. [Google Scholar] [CrossRef]
- Uppakara, K.; Jamornwan, S.; Duan, L.X.; Yue, K.R.; Sunrat, C.; Dent, E.W.; Wan, S.B.; Saengsawang, W. Novel alpha-Lipoic Acid/3-n-Butylphthalide Conjugate Enhances Protective Effects against Oxidative Stress and 6-OHDA Induced Neuronal Damage. ACS Chem. Neurosci. 2020, 11, 1634–1642. [Google Scholar] [CrossRef]
- Villamena, F.A.; Das, A.; Nash, K.M. Potential implication of the chemical properties and bioactivity of nitrone spin traps for therapeutics. Future Med. Chem. 2012, 4, 1171–1207. [Google Scholar] [CrossRef] [Green Version]
- Davies, M.J. Detection and characterisation of radicals using electron paramagnetic resonance (EPR) spin trapping and related methods. Methods 2016, 109, 21–30. [Google Scholar] [CrossRef]
- Floyd, R.A.; Castro Faria Neto, H.C.; Zimmermaan, G.A.; Hensley, K.; Towner, R.A. Nitrone-based therapeutics for neurodegenerative diseases: Their use alone or in combination with lanthionines. Free Radic. Biol. Med. 2013, 62, 145–156. [Google Scholar] [CrossRef] [Green Version]
- Piotrowska, D.G.; Mediavilla, L.; Cuarental, L.; Glowacka, I.E.; Marco-Contelles, J.; Hadjipavlou-Litina, D.; Lopez-Munoz, F.; Oset-Gasque, M.J. Synthesis and Neuroprotective Properties of N-Substituted C-Dialkoxyphosphorylated Nitrones. ACS Omega 2019, 4, 8581–8587. [Google Scholar] [CrossRef] [Green Version]
- Yoshino, H. Edaravone for the treatment of amyotrophic lateral sclerosis. Expert. Rev. Neurother. 2019, 19, 185–193. [Google Scholar] [CrossRef]
- Watanabe, T.; Tahara, M.; Todo, S. The novel antioxidant edaravone: From bench to bedside. Cardiovasc. Ther. 2008, 26, 101–114. [Google Scholar] [CrossRef]
- Kang, L.; Liu, S.; Li, J.; Tian, Y.; Xue, Y.; Liu, X. The mitochondria-targeted anti-oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance. Cell Prolif. 2020, 53, 1–19. [Google Scholar] [CrossRef]
- Young, M.L.; Franklin, J.L. The mitochondria-targeted antioxidant MitoQ inhibits memory loss, neuropathology, and extends lifespan in aged 3xTg-AD mice. Mol. Cell Neurosci. 2019, 101, 103409. [Google Scholar] [CrossRef]
- Suarez-Rivero, J.M.; Pastor-Maldonado, C.J.; Povea-Cabello, S.; Alvarez-Cordoba, M.; Villalon-Garcia, I.; Munuera-Cabeza, M.; Suarez-Carrillo, A.; Talaveron-Rey, M.; Sanchez-Alcazar, J.A. Coenzyme Q10 Analogues: Benefits and Challenges for Therapeutics. Antioxidants 2021, 10, 236. [Google Scholar] [CrossRef]
- Shinn, L.J.; Lagalwar, S. Treating Neurodegenerative Disease with Antioxidants: Efficacy of the Bioactive Phenol Resveratrol and Mitochondrial-Targeted MitoQ and SkQ. Antioxidants 2021, 10, 573. [Google Scholar] [CrossRef]
- Fonseca-Fonseca, L.A.; Nunez-Figueredo, Y.; Sanchez, J.R.; Guerra, M.W.; Ochoa-Rodriguez, E.; Verdecia-Reyes, Y.; Hernadez, R.D.; Menezes-Filho, N.J.; Costa, T.C.S.; de Santana, W.A.; et al. KM-34, a Novel Antioxidant Compound, Protects against 6-Hydroxydopamine-Induced Mitochondrial Damage and Neurotoxicity. Neurotox Res. 2019, 36, 279–291. [Google Scholar] [CrossRef]
- Federico, A.; Cardaioli, E.; Da Pozzo, P.; Formichi, P.; Gallus, G.N.; Radi, E. Mitochondria, oxidative stress and neurodegeneration. J. Neurol. Sci. 2012, 322, 254–262. [Google Scholar] [CrossRef]
- Yang, M.; Lian, N.; Yu, Y.; Wang, Y.; Xie, K.; Yu, Y. Coenzyme Q10 alleviates sevofluraneinduced neuroinflammation by regulating the levels of apolipoprotein E and phosphorylated tau protein in mouse hippocampal neurons. Mol. Med. Rep. 2020, 22, 445–453. [Google Scholar] [CrossRef] [PubMed]
- Komaki, H.; Faraji, N.; Komaki, A.; Shahidi, S.; Etaee, F.; Raoufi, S.; Mirzaei, F. Investigation of protective effects of coenzyme Q10 on impaired synaptic plasticity in a male rat model of Alzheimer’s disease. Brain Res. Bull. 2019, 147, 14–21. [Google Scholar] [CrossRef]
- Wang, J.; Li, L.; Wang, Z.; Cui, Y.; Tan, X.; Yuan, T.; Liu, Q.; Liu, Z.; Liu, X. Supplementation of lycopene attenuates lipopolysaccharide-induced amyloidogenesis and cognitive impairments via mediating neuroinflammation and oxidative stress. J. Nutr. Biochem. 2018, 56, 16–25. [Google Scholar] [CrossRef]
- Han, J.H.; Lee, Y.S.; Im, J.H.; Ham, Y.W.; Lee, H.P.; Han, S.B.; Hong, J.T. Astaxanthin Ameliorates Lipopolysaccharide-Induced Neuroinflammation, Oxidative Stress and Memory Dysfunction through Inactivation of the Signal Transducer and Activator of Transcription 3 Pathway. Mar. Drugs 2019, 17, 123. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hira, S.; Saleem, U.; Anwar, F.; Sohail, M.F.; Raza, Z.; Ahmad, B. beta-Carotene: A Natural Compound Improves Cognitive Impairment and Oxidative Stress in a Mouse Model of Streptozotocin-Induced Alzheimer’s Disease. Biomolecules 2019, 9, 441. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dhami, M.; Raj, K.; Singh, S. Neuroprotective Effect of Fucoxanthin against Intracerebroventricular Streptozotocin (ICV-STZ) Induced Cognitive Impairment in Experimental Rats. Curr. Alzheimer Res. 2021, 18, 623–637. [Google Scholar] [CrossRef]
- Wang, H.; Jiang, T.; Li, W.; Gao, N.; Zhang, T. Resveratrol attenuates oxidative damage through activating mitophagy in an in vitro model of Alzheimer’s disease. Toxicol. Lett. 2018, 282, 100–108. [Google Scholar] [CrossRef]
- Khan, M.S.; Muhammad, T.; Ikram, M.; Kim, M.O. Dietary Supplementation of the Antioxidant Curcumin Halts Systemic LPS-Induced Neuroinflammation-Associated Neurodegeneration and Memory/Synaptic Impairment via the JNK/NF-kappaB/Akt Signaling Pathway in Adult Rats. Oxid. Med. Cell Longev. 2019, 2019, 7860650. [Google Scholar] [CrossRef] [Green Version]
- Doghri, R.; Ellefi, A.; Degrach, I.; Srairi-Abid, N.; Gati, A. Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer’s Disease. Molecules 2021, 26, 3011. [Google Scholar] [CrossRef]
- Kong, D.; Yan, Y.; He, X.Y.; Yang, H.; Liang, B.; Wang, J.; He, Y.; Ding, Y.; Yu, H. Effects of Resveratrol on the Mechanisms of Antioxidants and Estrogen in Alzheimer’s Disease. Biomed. Res. Int 2019, 2019, 8983752. [Google Scholar] [CrossRef] [Green Version]
- Khan, M.S.; Ali, T.; Kim, M.W.; Jo, M.H.; Jo, M.G.; Badshah, H.; Kim, M.O. Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Neurochem. Int. 2016, 100, 1–10. [Google Scholar] [CrossRef]
- Ali, T.; Kim, T.; Rehman, S.U.; Khan, M.S.; Amin, F.U.; Khan, M.; Ikram, M.; Kim, M.O. Natural Dietary Supplementation of Anthocyanins via PI3K/Akt/Nrf2/HO-1 Pathways Mitigate Oxidative Stress, Neurodegeneration, and Memory Impairment in a Mouse Model of Alzheimer’s Disease. Mol. Neurobiol. 2018, 55, 6076–6093. [Google Scholar] [CrossRef]
- Khan, M.S.; Ali, T.; Kim, M.W.; Jo, M.H.; Chung, J.I.; Kim, M.O. Anthocyanins Improve Hippocampus-Dependent Memory Function and Prevent Neurodegeneration via JNK/Akt/GSK3beta Signaling in LPS-Treated Adult Mice. Mol. Neurobiol. 2019, 56, 671–687. [Google Scholar] [CrossRef]
- Kushairi, N.; Phan, C.W.; Sabaratnam, V.; David, P.; Naidu, M. Lion’s Mane Mushroom, Hericium erinaceus (Bull.: Fr.) Pers. Suppresses H2O2-Induced Oxidative Damage and LPS-Induced Inflammation in HT22 Hippocampal Neurons and BV2 Microglia. Antioxidants 2019, 8, 261. [Google Scholar] [CrossRef] [Green Version]
- Cordaro, M.; Salinaro, A.T.; Siracusa, R.; D’Amico, R.; Impellizzeri, D.; Scuto, M.; Ontario, M.L.; Cuzzocrea, S.; Di Paola, R.; Fusco, R.; et al. Key Mechanisms and Potential Implications of Hericium erinaceus in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer’s Disease. Antioxidants 2021, 10, 1664. [Google Scholar] [CrossRef]
- Frontinan-Rubio, J.; Sancho-Bielsa, F.J.; Peinado, J.R.; LaFerla, F.M.; Gimenez-Llort, L.; Duran-Prado, M.; Alcain, F.J. Sex-dependent co-occurrence of hypoxia and beta-amyloid plaques in hippocampus and entorhinal cortex is reversed by long-term treatment with ubiquinol and ascorbic acid in the 3xTg-AD mouse model of Alzheimer’s disease. Mol. Cell Neurosci. 2018, 92, 67–81. [Google Scholar] [CrossRef]
- Yu, L.; Wang, W.; Pang, W.; Xiao, Z.; Jiang, Y.; Hong, Y. Dietary Lycopene Supplementation Improves Cognitive Performances in Tau Transgenic Mice Expressing P301L Mutation via Inhibiting Oxidative Stress and Tau Hyperphosphorylation. J. Alzheimers Dis. 2017, 57, 475–482. [Google Scholar] [CrossRef]
- Ibrahim Fouad, G. Combination of Omega 3 and Coenzyme Q10 Exerts Neuroprotective Potential against Hypercholesterolemia-Induced Alzheimer’s-Like Disease in Rats. Neurochem. Res. 2020, 45, 1142–1155. [Google Scholar] [CrossRef]
- Zaky, A.; Bassiouny, A.; Farghaly, M.; El-Sabaa, B.M. A Combination of Resveratrol and Curcumin is Effective Against Aluminum Chloride-Induced Neuroinflammation in Rats. J. Alzheimers Dis. 2017, 60, S221–S235. [Google Scholar] [CrossRef] [PubMed]
- Wan, T.; Wang, Z.; Luo, Y.; Zhang, Y.; He, W.; Mei, Y.; Xue, J.; Li, M.; Pan, H.; Li, W.; et al. FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Protects against Oxidative Stress-Mediated Neuronal Cell Apoptosis and Scopolamine-Induced Cognitive Impairment by Activating Nrf2/HO-1 Signaling. Oxid. Med. Cell Longev. 2019, 2019, 8239642. [Google Scholar] [CrossRef] [PubMed]
- Schirinzi, T.; Martella, G.; Imbriani, P.; Di Lazzaro, G.; Franco, D.; Colona, V.L.; Alwardat, M.; Sinibaldi Salimei, P.; Mercuri, N.B.; Pierantozzi, M.; et al. Dietary Vitamin E as a Protective Factor for Parkinson’s Disease: Clinical and Experimental Evidence. Front. Neurol. 2019, 10, 148. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Nuccio, F.; Cianciulli, A.; Porro, C.; Kashyrina, M.; Ruggiero, M.; Calvello, R.; Miraglia, A.; Nicolardi, G.; Lofrumento, D.D.; Panaro, M.A. Inflammatory Response Modulation by Vitamin C in an MPTP Mouse Model of Parkinson’s Disease. Biology 2021, 10, 1155. [Google Scholar] [CrossRef]
- Zeng, X.; Xu, K.; Wang, J.; Xu, Y.; Qu, S. Pretreatment of Ascorbic Acid Inhibits MPTP-Induced Astrocytic Oxidative Stress through Suppressing NF-kappaB Signaling. Neural Plast. 2020, 2020, 8872296. [Google Scholar] [CrossRef]
- Attia, H.N.; Maklad, Y.A. Neuroprotective effects of coenzyme Q10 on paraquat-induced Parkinson’s disease in experimental animals. Behav. Pharmacol. 2018, 29, 79–86. [Google Scholar] [CrossRef]
- Park, E.; Gim, J.; Kim, D.K.; Kim, C.S.; Chun, H.S. Protective Effects of Alpha-Lipoic Acid on Glutamate-Induced Cytotoxicity in C6 Glioma Cells. Biol. Pharm. Bull. 2019, 42, 94–102. [Google Scholar] [CrossRef] [Green Version]
- Zhou, L.; Cheng, Y. Alpha-lipoic acid alleviated 6-OHDA-induced cell damage by inhibiting AMPK/mTOR mediated autophagy. Neuropharmacology 2019, 155, 98–103. [Google Scholar] [CrossRef]
- Rao, S.V.; Hemalatha, P.; Yetish, S.; Muralidhara, M.; Rajini, P.S. Prophylactic neuroprotective propensity of Crocin, a carotenoid against rotenone induced neurotoxicity in mice: Behavioural and biochemical evidence. Metab. Brain Dis. 2019, 34, 1341–1353. [Google Scholar] [CrossRef]
- Wu, W.; Han, H.; Liu, J.; Tang, M.; Wu, X.; Cao, X.; Zhao, T.; Lu, Y.; Niu, T.; Chen, J.; et al. Fucoxanthin Prevents 6-OHDA-Induced Neurotoxicity by Targeting Keap1. Oxid. Med. Cell Longev. 2021, 2021, 6688708. [Google Scholar] [CrossRef]
- Abolaji, A.O.; Adedara, A.O.; Adie, M.A.; Vicente-Crespo, M.; Farombi, E.O. Resveratrol prolongs lifespan and improves 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced oxidative damage and behavioural deficits in Drosophila melanogaster. Biochem. Biophys. Res. Commun. 2018, 503, 1042–1048. [Google Scholar] [CrossRef]
- Zhang, L.F.; Yu, X.L.; Ji, M.; Liu, S.Y.; Wu, X.L.; Wang, Y.J.; Liu, R.T. Resveratrol alleviates motor and cognitive deficits and neuropathology in the A53T alpha-synuclein mouse model of Parkinson’s disease. Food Funct. 2018, 9, 6414–6426. [Google Scholar] [CrossRef]
- Singh, S.; Jamwal, S.; Kumar, P. Neuroprotective potential of Quercetin in combination with piperine against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. Neural Regen. Res. 2017, 12, 1137–1144. [Google Scholar] [CrossRef] [PubMed]
- Rasheed, M.S.U.; Tripathi, M.K.; Patel, D.K.; Singh, M.P. Resveratrol Regulates Nrf2-Mediated Expression of Antioxidant and Xenobiotic Metabolizing Enzymes in Pesticides-Induced Parkinsonism. Protein Pept. Lett. 2020, 27, 1038–1045. [Google Scholar] [CrossRef]
- Chen, Y.F.; Wu, S.N.; Gao, J.M.; Liao, Z.Y.; Tseng, Y.T.; Fulop, F.; Chang, F.R.; Lo, Y.C. The Antioxidant, Anti-Inflammatory, and Neuroprotective Properties of the Synthetic Chalcone Derivative AN07. Molecules 2020, 25, 2907. [Google Scholar] [CrossRef]
- Lee, J.A.; Son, H.J.; Choi, J.W.; Kim, J.; Han, S.H.; Shin, N.; Kim, J.H.; Kim, S.J.; Heo, J.Y.; Kim, D.J.; et al. Activation of the Nrf2 signaling pathway and neuroprotection of nigral dopaminergic neurons by a novel synthetic compound KMS99220. Neurochem. Int. 2018, 112, 96–107. [Google Scholar] [CrossRef]
- Drummond, N.J.; Davies, N.O.; Lovett, J.E.; Miller, M.R.; Cook, G.; Becker, T.; Becker, C.G.; McPhail, D.B.; Kunath, T. A synthetic cell permeable antioxidant protects neurons against acute oxidative stress. Sci. Rep. 2017, 7, 11857. [Google Scholar] [CrossRef] [Green Version]
- Wang, T.; Cheng, J.; Wang, S.; Wang, X.; Jiang, H.; Yang, Y.; Wang, Y.; Zhang, C.; Liang, W.; Feng, H. alpha-Lipoic acid attenuates oxidative stress and neurotoxicity via the ERK/Akt-dependent pathway in the mutant hSOD1 related Drosophila model and the NSC34 cell line of amyotrophic lateral sclerosis. Brain Res. Bull. 2018, 140, 299–310. [Google Scholar] [CrossRef]
- Bhatia, N.K.; Srivastava, A.; Katyal, N.; Jain, N.; Khan, M.A.; Kundu, B.; Deep, S. Curcumin binds to the pre-fibrillar aggregates of Cu/Zn superoxide dismutase (SOD1) and alters its amyloidogenic pathway resulting in reduced cytotoxicity. Biochim. Biophys. Acta 2015, 1854, 426–436. [Google Scholar] [CrossRef]
- Winter, A.N.; Ross, E.K.; Wilkins, H.M.; Stankiewicz, T.R.; Wallace, T.; Miller, K.; Linseman, D.A. An anthocyanin-enriched extract from strawberries delays disease onset and extends survival in the hSOD1(G93A) mouse model of amyotrophic lateral sclerosis. Nutr. Neurosci. 2018, 21, 414–426. [Google Scholar] [CrossRef]
- Zhao, B.; Zhuang, X.; Pi, Z.; Liu, S.; Liu, Z.; Song, F. Determining the Effect of Catechins on SOD1 Conformation and Aggregation by Ion Mobility Mass Spectrometry Combined with Optical Spectroscopy. J. Am. Soc. Mass. Spectrom. 2018, 29, 734–741. [Google Scholar] [CrossRef] [PubMed]
- Srinivasan, E.; Rajasekaran, R. Probing the inhibitory activity of epigallocatechin-gallate on toxic aggregates of mutant (L84F) SOD1 protein through geometry based sampling and steered molecular dynamics. J. Mol. Graph. Model. 2017, 74, 288–295. [Google Scholar] [CrossRef] [PubMed]
- Ip, P.; Sharda, P.R.; Cunningham, A.; Chakrabartty, S.; Pande, V.; Chakrabartty, A. Quercitrin and quercetin 3-beta-d-glucoside as chemical chaperones for the A4V SOD1 ALS-causing mutant. Protein Eng. Des. Sel. 2017, 30, 431–440. [Google Scholar] [CrossRef] [PubMed]
- Ueda, T.; Inden, M.; Shirai, K.; Sekine, S.I.; Masaki, Y.; Kurita, H.; Ichihara, K.; Inuzuka, T.; Hozumi, I. The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutase-mediated toxicity. Sci. Rep. 2017, 7, 2882. [Google Scholar] [CrossRef] [Green Version]
- Wang, T.H.; Wang, S.Y.; Wang, X.D.; Jiang, H.Q.; Yang, Y.Q.; Wang, Y.; Cheng, J.L.; Zhang, C.T.; Liang, W.W.; Feng, H.L. Fisetin Exerts Antioxidant and Neuroprotective Effects in Multiple Mutant hSOD1 Models of Amyotrophic Lateral Sclerosis by Activating ERK. Neuroscience 2018, 379, 152–166. [Google Scholar] [CrossRef]
- Koza, L.A.; Winter, A.N.; Holsopple, J.; Baybayon-Grandgeorge, A.N.; Pena, C.; Olson, J.R.; Mazzarino, R.C.; Patterson, D.; Linseman, D.A. Protocatechuic Acid Extends Survival, Improves Motor Function, Diminishes Gliosis, and Sustains Neuromuscular Junctions in the hSOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis. Nutrients 2020, 12, 1824. [Google Scholar] [CrossRef]
- Lv, C.; Maharjan, S.; Wang, Q.; Sun, Y.; Han, X.; Wang, S.; Mao, Z.; Xin, Y.; Zhang, B. alpha-Lipoic Acid Promotes Neurological Recovery after Ischemic Stroke by Activating the Nrf2/HO-1 Pathway to Attenuate Oxidative Damage. Cell Physiol. Biochem. 2017, 43, 1273–1287. [Google Scholar] [CrossRef]
- Haghnejad Azar, A.; Oryan, S.; Bohlooli, S.; Panahpour, H. Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats. Med. Princ. Pract. 2017, 26, 17–22. [Google Scholar] [CrossRef] [Green Version]
- Chang, C.Y.; Chen, J.Y.; Wu, M.H.; Hu, M.L. Therapeutic treatment with vitamin C reduces focal cerebral ischemia-induced brain infarction in rats by attenuating disruptions of blood brain barrier and cerebral neuronal apoptosis. Free Radic. Biol. Med. 2020, 155, 29–36. [Google Scholar] [CrossRef]
- Zhang, X.; Fan, Z.; Jin, T. Crocin protects against cerebral- ischemia-induced damage in aged rats through maintaining the integrity of blood-brain barrier. Restor. Neurol. Neurosci. 2017, 35, 65–75. [Google Scholar] [CrossRef]
- Yang, J.; Huang, J.; Shen, C.; Cheng, W.; Yu, P.; Wang, L.; Tang, F.; Guo, S.; Yang, Q.; Zhang, J. Resveratrol Treatment in Different Time-Attenuated Neuronal Apoptosis After Oxygen and Glucose Deprivation/Reoxygenation via Enhancing the Activation of Nrf-2 Signaling Pathway In Vitro. Cell Transplant. 2018, 27, 1789–1797. [Google Scholar] [CrossRef]
- Zhou, X.; Qi, Y.; Chen, T. Long-term pre-treatment of antioxidant Ginkgo biloba extract EGb-761 attenuates cerebral-ischemia-induced neuronal damage in aged mice. Biomed. Pharmacother. 2017, 85, 256–263. [Google Scholar] [CrossRef]
- Nai, Y.; Liu, H.; Bi, X.; Gao, H.; Ren, C. Protective effect of astaxanthin on acute cerebral infarction in rats. Hum. Exp. Toxicol. 2018, 37, 929–936. [Google Scholar] [CrossRef]
- Li, X.; Zhan, J.; Hou, Y.; Chen, S.; Hou, Y.; Xiao, Z.; Luo, D.; Lin, D. Coenzyme Q10 suppresses oxidative stress and apoptosis via activating the Nrf-2/NQO-1 and NF-kappaB signaling pathway after spinal cord injury in rats. Am. J. Transl. Res. 2019, 11, 6544–6552. [Google Scholar]
- Cordero, K.; Coronel, G.G.; Serrano-Illan, M.; Cruz-Bracero, J.; Figueroa, J.D.; De Leon, M. Effects of Dietary Vitamin E Supplementation in Bladder Function and Spasticity during Spinal Cord Injury. Brain Sci 2018, 8, 38. [Google Scholar] [CrossRef] [Green Version]
- Hu, W.; Wang, H.; Liu, Z.; Liu, Y.; Wang, R.; Luo, X.; Huang, Y. Neuroprotective effects of lycopene in spinal cord injury in rats via antioxidative and anti-apoptotic pathway. Neurosci. Lett. 2017, 642, 107–112. [Google Scholar] [CrossRef]
- Zhou, L.; Ouyang, L.; Lin, S.; Chen, S.; Liu, Y.; Zhou, W.; Wang, X. Protective role of beta-carotene against oxidative stress and neuroinflammation in a rat model of spinal cord injury. Int. Immunopharmacol. 2018, 61, 92–99. [Google Scholar] [CrossRef]
- Xi, J.; Luo, X.; Wang, Y.; Li, J.; Guo, L.; Wu, G.; Li, Q. Tetrahydrocurcumin protects against spinal cord injury and inhibits the oxidative stress response by regulating FOXO4 in model rats. Exp. Ther. Med. 2019, 18, 3681–3687. [Google Scholar] [CrossRef] [Green Version]
- Machova Urdzikova, L.; Ruzicka, J.; Karova, K.; Kloudova, A.; Svobodova, B.; Amin, A.; Dubisova, J.; Schmidt, M.; Kubinova, S.; Jhanwar-Uniyal, M.; et al. A green tea polyphenol epigallocatechin-3-gallate enhances neuroregeneration after spinal cord injury by altering levels of inflammatory cytokines. Neuropharmacology 2017, 126, 213–223. [Google Scholar] [CrossRef]
- Masoudi, A.; Jorjani, M.; Alizadeh, M.; Mirzamohammadi, S.; Mohammadi, M. Anti-inflammatory and antioxidant effects of astaxanthin following spinal cord injury in a rat animal model. Brain Res. Bull. 2021, 177, 324–331. [Google Scholar] [CrossRef]
- Senturk, S.; Yaman, M.E.; Aydin, H.E.; Guney, G.; Bozkurt, I.; Paksoy, K.; Abdioglu, A.A. Effects of Resveratrol on Inflammation and Apoptosis After Experimental Spinal Cord Injury. Turk. Neurosurg. 2018, 28, 889–896. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Botchway, B.O.A.; Tan, X.; Zhang, Y.; Fang, M. Resveratrol treatment of spinal cord injury in rat model. Microsc. Res. Tech. 2019, 82, 296–303. [Google Scholar] [CrossRef] [PubMed]
- Zhao, H.; Mei, X.; Yang, D.; Tu, G. Resveratrol inhibits inflammation after spinal cord injury via SIRT-1/NF-kappaB signaling pathway. Neurosci. Lett. 2021, 762, 136151. [Google Scholar] [CrossRef] [PubMed]
- Meng, H.Y.; Shao, D.C.; Li, H.; Huang, X.D.; Yang, G.; Xu, B.; Niu, H.Y. Resveratrol improves neurological outcome and neuroinflammation following spinal cord injury through enhancing autophagy involving the AMPK/mTOR pathway. Mol. Med. Rep. 2018, 18, 2237–2244. [Google Scholar] [CrossRef] [Green Version]
- Zhao, H.; Chen, S.; Gao, K.; Zhou, Z.; Wang, C.; Shen, Z.; Guo, Y.; Li, Z.; Wan, Z.; Liu, C.; et al. Resveratrol protects against spinal cord injury by activating autophagy and inhibiting apoptosis mediated by the SIRT1/AMPK signaling pathway. Neuroscience 2017, 348, 241–251. [Google Scholar] [CrossRef]
- Wang, Y.; Li, W.; Wang, M.; Lin, C.; Li, G.; Zhou, X.; Luo, J.; Jin, D. Quercetin reduces neural tissue damage and promotes astrocyte activation after spinal cord injury in rats. J. Cell Biochem. 2018, 119, 2298–2306. [Google Scholar] [CrossRef]
- Fan, H.; Tang, H.B.; Shan, L.Q.; Liu, S.C.; Huang, D.G.; Chen, X.; Chen, Z.; Yang, M.; Yin, X.H.; Yang, H.; et al. Quercetin prevents necroptosis of oligodendrocytes by inhibiting macrophages/microglia polarization to M1 phenotype after spinal cord injury in rats. J. Neuroinflamm. 2019, 16, 206. [Google Scholar] [CrossRef] [Green Version]
- Chen, C.; Yang, Q.; Ma, X. Synergistic effect of ascorbic acid and taurine in the treatment of a spinal cord injury-induced model in rats. 3Biotech 2020, 10, 50. [Google Scholar] [CrossRef]
- Baum, L.; Lam, C.W.; Cheung, S.K.; Kwok, T.; Lui, V.; Tsoh, J.; Lam, L.; Leung, V.; Hui, E.; Ng, C.; et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J. Clin. Psychopharmacol. 2008, 28, 110–113. [Google Scholar] [CrossRef] [Green Version]
- Chico, L.; Ienco, E.C.; Bisordi, C.; Lo Gerfo, A.; Petrozzi, L.; Petrucci, A.; Mancuso, M.; Siciliano, G. Amyotrophic Lateral Sclerosis and Oxidative Stress: A Double-Blind Therapeutic Trial after Curcumin Supplementation. CNS Neurol. Disord. Drug Targets 2018, 17, 767–779. [Google Scholar] [CrossRef]
- Moussa, C.; Hebron, M.; Huang, X.; Ahn, J.; Rissman, R.A.; Aisen, P.S.; Turner, R.S. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J. Neuroinflamm. 2017, 14, 1. [Google Scholar] [CrossRef] [Green Version]
- Chen, J.; Bai, Q.; Zhao, Z.; Sui, H.; Xie, X. Resveratrol improves delayed r-tPA treatment outcome by reducing MMPs. Acta Neurol. Scand. 2016, 134, 54–60. [Google Scholar] [CrossRef]
- Wang, X.H.; You, Y.P. Epigallocatechin Gallate Extends Therapeutic Window of Recombinant Tissue Plasminogen Activator Treatment for Brain Ischemic Stroke: A Randomized Double-Blind and Placebo-Controlled Trial. Clin. Neuropharmacol. 2017, 40, 24–28. [Google Scholar] [CrossRef]
- Mischley, L.K.; Leverenz, J.B.; Lau, R.C.; Polissar, N.L.; Neradilek, M.B.; Samii, A.; Standish, L.J. A randomized, double-blind phase I/IIa study of intranasal glutathione in Parkinson’s disease. Mov. Disord. 2015, 30, 1696–1701. [Google Scholar] [CrossRef]
- Mischley, L.K.; Lau, R.C.; Shankland, E.G.; Wilbur, T.K.; Padowski, J.M. Phase IIb Study of Intranasal Glutathione in Parkinson’s Disease. J. Parkinsons Dis. 2017, 7, 289–299. [Google Scholar] [CrossRef] [Green Version]
- Seet, R.C.; Lim, E.C.; Tan, J.J.; Quek, A.M.; Chow, A.W.; Chong, W.L.; Ng, M.P.; Ong, C.N.; Halliwell, B. Does high-dose coenzyme Q10 improve oxidative damage and clinical outcomes in Parkinson’s disease? Antioxid. Redox. Signal. 2014, 21, 211–217. [Google Scholar] [CrossRef]
- Parkinson Study Group, Q.E.I.; Beal, M.F.; Oakes, D.; Shoulson, I.; Henchcliffe, C.; Galpern, W.R.; Haas, R.; Juncos, J.L.; Nutt, J.G.; Voss, T.S.; et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: No evidence of benefit. JAMA Neurol. 2014, 71, 543–552. [Google Scholar] [CrossRef]
- Kaufmann, P.; Thompson, J.L.; Levy, G.; Buchsbaum, R.; Shefner, J.; Krivickas, L.S.; Katz, J.; Rollins, Y.; Barohn, R.J.; Jackson, C.E.; et al. Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III. Ann. Neurol. 2009, 66, 235–244. [Google Scholar] [CrossRef] [Green Version]
- Snitz, B.E.; O’Meara, E.S.; Carlson, M.C.; Arnold, A.M.; Ives, D.G.; Rapp, S.R.; Saxton, J.; Lopez, O.L.; Dunn, L.O.; Sink, K.M.; et al. Ginkgo biloba for preventing cognitive decline in older adults: A randomized trial. JAMA 2009, 302, 2663–2670. [Google Scholar] [CrossRef] [Green Version]
- Writing, G.; Edaravone, A.L.S.S.G. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: A randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017, 16, 505–512. [Google Scholar] [CrossRef]
- Takei, K.; Takahashi, F.; Liu, S.; Tsuda, K.; Palumbo, J. Post-hoc analysis of randomised, placebo-controlled, double-blind study (MCI186-19) of edaravone (MCI-186) in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Frontotemporal Degener. 2017, 18, 49–54. [Google Scholar] [CrossRef]
- Shinohara, Y.; Saito, I.; Kobayashi, S.; Uchiyama, S. Edaravone (radical scavenger) versus sodium ozagrel (antiplatelet agent) in acute noncardioembolic ischemic stroke (EDO trial). Cerebrovasc. Dis. 2009, 27, 485–492. [Google Scholar] [CrossRef] [PubMed]
- Isahaya, K.; Yamada, K.; Yamatoku, M.; Sakurai, K.; Takaishi, S.; Kato, B.; Hirayama, T.; Hasegawa, Y. Effects of edaravone, a free radical scavenger, on serum levels of inflammatory biomarkers in acute brain infarction. J. Stroke Cerebrovasc. Dis. 2012, 21, 102–107. [Google Scholar] [CrossRef] [PubMed]
- Xu, J.; Wang, Y.; Wang, A.; Gao, Z.; Gao, X.; Chen, H.; Zhou, J.; Zhao, X.; Wang, Y. Safety and efficacy of Edaravone Dexborneol versus edaravone for patients with acute ischaemic stroke: A phase II, multicentre, randomised, double-blind, multiple-dose, active-controlled clinical trial. Stroke Vasc. Neurol. 2019, 4, 109–114. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- NCT04714177; Edaravone Dexborneol for Treatment of Hypertensive Intracerebral Hemorrhage (ED-ICH). US National Library of Medicine: Bethesda, MD, USA, 2021.
- Shinto, L.; Quinn, J.; Montine, T.; Dodge, H.H.; Woodward, W.; Baldauf-Wagner, S.; Waichunas, D.; Bumgarner, L.; Bourdette, D.; Silbert, L.; et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease. J. Alzheimers Dis. 2014, 38, 111–120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dysken, M.W.; Sano, M.; Asthana, S.; Vertrees, J.E.; Pallaki, M.; Llorente, M.; Love, S.; Schellenberg, G.D.; McCarten, J.R.; Malphurs, J.; et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: The TEAM-AD VA cooperative randomized trial. JAMA 2014, 311, 33–44. [Google Scholar] [CrossRef] [PubMed]
- Galasko, D.R.; Peskind, E.; Clark, C.M.; Quinn, J.F.; Ringman, J.M.; Jicha, G.A.; Cotman, C.; Cottrell, B.; Montine, T.J.; Thomas, R.G.; et al. Antioxidants for Alzheimer disease: A randomized clinical trial with cerebrospinal fluid biomarker measures. Arch. Neurol. 2012, 69, 836–841. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taghizadeh, M.; Tamtaji, O.R.; Dadgostar, E.; Daneshvar Kakhaki, R.; Bahmani, F.; Abolhassani, J.; Aarabi, M.H.; Kouchaki, E.; Memarzadeh, M.R.; Asemi, Z. The effects of omega-3 fatty acids and vitamin E co-supplementation on clinical and metabolic status in patients with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Neurochem. Int. 2017, 108, 183–189. [Google Scholar] [CrossRef]
- Ahmadi, M.; Agah, E.; Nafissi, S.; Jaafari, M.R.; Harirchian, M.H.; Sarraf, P.; Faghihi-Kashani, S.; Hosseini, S.J.; Ghoreishi, A.; Aghamollaii, V.; et al. Safety and Efficacy of Nanocurcumin as Add-On Therapy to Riluzole in Patients With Amyotrophic Lateral Sclerosis: A Pilot Randomized Clinical Trial. Neurotherapeutics 2018, 15, 430–438. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cox, K.H.; Pipingas, A.; Scholey, A.B. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J. Psychopharmacol. 2015, 29, 642–651. [Google Scholar] [CrossRef]
- NCT01001637; Efficacy and Safety of Curcumin Formulation in Alzheimer’s Disease. US National Library of Medicine: Bethesda, MD, USA, 2009.
- Dang, L.; Dong, X.; Yang, J. Influence of Nanoparticle-Loaded Edaravone on Postoperative Effects in Patients with Cerebral Hemorrhage. J. Nanosci. Nanotechnol. 2021, 21, 1202–1211. [Google Scholar] [CrossRef] [PubMed]
- Li, S.; Zhang, X.; Fang, Q.; Zhou, J.; Zhang, M.; Wang, H.; Chen, Y.; Xu, B.; Wu, Y.; Qian, L.; et al. Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: A randomised controlled trial. Stroke Vasc. Neurol. 2017, 2, 189–197. [Google Scholar] [CrossRef]
- Allison, D.J.; Ditor, D.S. Targeting inflammation to influence mood following spinal cord injury: A randomized clinical trial. J. Neuroinflamm. 2015, 12, 204. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Breiner, A.; Zinman, L.; Bourque, P.R. Edaravone for amyotrophic lateral sclerosis: Barriers to access and lifeboat ethics. CMAJ 2020, 192, E319–E320. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- European Medicine Agency. Radicava: Withdrawal of the Marketing Authorisation Application; European Medicine Agency: Amsterdam, The Netherlands, 2019; Available online: https://www.ema.europa.eu/en/medicines/human/withdrawn-applications/radicava (accessed on 14 January 2022).
- Panzarini, E.; Mariano, S.; Tacconi, S.; Carata, E.; Tata, A.M.; Dini, L. Novel Therapeutic Delivery of Nanocurcumin in Central Nervous System Related Disorders. Nanomaterials 2020, 11, 2. [Google Scholar] [CrossRef] [PubMed]
- Dong, X. Current Strategies for Brain Drug Delivery. Theranostics 2018, 8, 1481–1493. [Google Scholar] [CrossRef] [PubMed]
- Ringman, J.M.; Frautschy, S.A.; Teng, E.; Begum, A.N.; Bardens, J.; Beigi, M.; Gylys, K.H.; Badmaev, V.; Heath, D.D.; Apostolova, L.G.; et al. Oral curcumin for Alzheimer’s disease: Tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res. Ther. 2012, 4, 43. [Google Scholar] [CrossRef] [Green Version]
- Kokjohn, T.A.; Roher, A.E. Amyloid precursor protein transgenic mouse models and Alzheimer’s disease: Understanding the paradigms, limitations, and contributions. Alzheimers Dement. 2009, 5, 340–347. [Google Scholar] [CrossRef] [Green Version]
- Schwedhelm, E.; Maas, R.; Troost, R.; Boger, R.H. Clinical pharmacokinetics of antioxidants and their impact on systemic oxidative stress. Clin. Pharmacokinet. 2003, 42, 437–459. [Google Scholar] [CrossRef]
- Bast, A.; Haenen, G.R. The toxicity of antioxidants and their metabolites. Environ. Toxicol. Pharmacol. 2002, 11, 251–258. [Google Scholar] [CrossRef]
- Nimse, D.P. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv. 2015, 5, 27986–28006. [Google Scholar] [CrossRef] [Green Version]
- Van Norman, G.A. Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach? JACC Basic Transl. Sci. 2019, 4, 845–854. [Google Scholar] [CrossRef] [PubMed]
- Forman, H.J.; Zhang, H. Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy. Nat. Rev. Drug Discov. 2021, 20, 689–709. [Google Scholar] [CrossRef] [PubMed]
- Jurcau, A. The Role of Natural Antioxidants in the Prevention of Dementia-Where Do We Stand and Future Perspectives. Nutrients 2021, 13, 282. [Google Scholar] [CrossRef] [PubMed]
- van der Worp, H.B.; Howells, D.W.; Sena, E.S.; Porritt, M.J.; Rewell, S.; O’Collins, V.; Macleod, M.R. Can animal models of disease reliably inform human studies? PLoS Med. 2010, 7, e1000245. [Google Scholar] [CrossRef] [Green Version]
- Li, M.; Al-Jamal, K.T.; Kostarelos, K.; Reineke, J. Physiologically based pharmacokinetic modeling of nanoparticles. ACS Nano 2010, 4, 6303–6317. [Google Scholar] [CrossRef]
- De Matteis, V.; Rinaldi, R. Toxicity Assessment in the Nanoparticle Era. Adv. Exp. Med. Biol. 2018, 1048, 1–19. [Google Scholar] [CrossRef]
- Karthikeyan, A.; Senthil, N.; Min, T. Nanocurcumin: A Promising Candidate for Therapeutic Applications. Front. Pharmacol. 2020, 11, 487. [Google Scholar] [CrossRef]
- Fan, S.; Zheng, Y.; Liu, X.; Fang, W.; Chen, X.; Liao, W.; Jing, X.; Lei, M.; Tao, E.; Ma, Q.; et al. Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease. Drug Deliv. 2018, 25, 1091–1102. [Google Scholar] [CrossRef] [Green Version]
- Fidelis, E.M.; Savall, A.S.P.; da Luz Abreu, E.; Carvalho, F.; Teixeira, F.E.G.; Haas, S.E.; Bazanella Sampaio, T.; Pinton, S. Curcumin-Loaded Nanocapsules Reverses the Depressant-Like Behavior and Oxidative Stress Induced by beta-Amyloid in Mice. Neuroscience 2019, 423, 122–130. [Google Scholar] [CrossRef]
- Huo, X.; Zhang, Y.; Jin, X.; Li, Y.; Zhang, L. A novel synthesis of selenium nanoparticles encapsulated PLGA nanospheres with curcumin molecules for the inhibition of amyloid beta aggregation in Alzheimer’s disease. J. Photochem. Photobiol. B 2019, 190, 98–102. [Google Scholar] [CrossRef]
- Ashafaq, M.; Intakhab Alam, M.; Khan, A.; Islam, F.; Khuwaja, G.; Hussain, S.; Ali, R.; Alshahrani, S.; Antar Makeen, H.; Alhazmi, H.A.; et al. Nanoparticles of resveratrol attenuates oxidative stress and inflammation after ischemic stroke in rats. Int. Immunopharmacol. 2021, 94, 107494. [Google Scholar] [CrossRef]
- Lu, X.; Dong, J.; Zheng, D.; Li, X.; Ding, D.; Xu, H. Reperfusion combined with intraarterial administration of resveratrol-loaded nanoparticles improved cerebral ischemia-reperfusion injury in rats. Nanomedicine 2020, 28, 102208. [Google Scholar] [CrossRef]
- Kannan, S.; Dai, H.; Navath, R.S.; Balakrishnan, B.; Jyoti, A.; Janisse, J.; Romero, R.; Kannan, R.M. Dendrimer-based postnatal therapy for neuroinflammation and cerebral palsy in a rabbit model. Sci. Transl. Med. 2012, 4, 130ra46. [Google Scholar] [CrossRef] [Green Version]
- Tardiolo, G.; Bramanti, P.; Mazzon, E. Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases. Molecules 2018, 23, 3305. [Google Scholar] [CrossRef] [Green Version]
- Yang, M.; Jin, L.; Wu, Z.; Xie, Y.; Zhang, P.; Wang, Q.; Yan, S.; Chen, B.; Liang, H.; Naman, C.B.; et al. PLGA-PEG Nanoparticles Facilitate In Vivo Anti-Alzheimer’s Effects of Fucoxanthin, a Marine Carotenoid Derived from Edible Brown Algae. J. Agric. Food Chem. 2021, 69, 9764–9777. [Google Scholar] [CrossRef]
- Dhas, N.; Mehta, T. Cationic biopolymer functionalized nanoparticles encapsulating lutein to attenuate oxidative stress in effective treatment of Alzheimer’s disease: A non-invasive approach. Int. J. Pharm. 2020, 586, 119553. [Google Scholar] [CrossRef]
- Singh, N.A.; Mandal, A.K.A.; Khan, Z.A. Inhibition of Al(III)-Induced Abeta42 Fibrillation and Reduction of Neurotoxicity by Epigallocatechin-3-Gallate Nanoparticles. J. Biomed. Nanotechnol. 2018, 14, 1147–1158. [Google Scholar] [CrossRef]
- Liu, Z.; Li, X.; Wu, X.; Zhu, C. A dual-inhibitor system for the effective antifibrillation of Abeta40 peptides by biodegradable EGCG-Fe(iii)/PVP nanoparticles. J. Mater. Chem. B 2019, 7, 1292–1299. [Google Scholar] [CrossRef]
- Liu, H.; Yu, L.; Dong, X.; Sun, Y. Synergistic effects of negatively charged hydrophobic nanoparticles and (-)-epigallocatechin-3-gallate on inhibiting amyloid beta-protein aggregation. J. Colloid Interface Sci. 2017, 491, 305–312. [Google Scholar] [CrossRef]
- Cano, A.; Ettcheto, M.; Chang, J.H.; Barroso, E.; Espina, M.; Kuhne, B.A.; Barenys, M.; Auladell, C.; Folch, J.; Souto, E.B.; et al. Dual-drug loaded nanoparticles of Epigallocatechin-3-gallate (EGCG)/Ascorbic acid enhance therapeutic efficacy of EGCG in a APPswe/PS1dE9 Alzheimer’s disease mice model. J. Control. Release 2019, 301, 62–75. [Google Scholar] [CrossRef] [PubMed]
- Amin, F.U.; Shah, S.A.; Badshah, H.; Khan, M.; Kim, M.O. Anthocyanins encapsulated by PLGA@PEG nanoparticles potentially improved its free radical scavenging capabilities via p38/JNK pathway against Abeta1-42-induced oxidative stress. J. Nanobiotechnology 2017, 15, 12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Loureiro, J.A.; Andrade, S.; Duarte, A.; Neves, A.R.; Queiroz, J.F.; Nunes, C.; Sevin, E.; Fenart, L.; Gosselet, F.; Coelho, M.A.; et al. Resveratrol and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer’s Disease. Molecules 2017, 22, 277. [Google Scholar] [CrossRef] [PubMed]
- Amanzadeh Jajin, E.; Esmaeili, A.; Rahgozar, S.; Noorbakhshnia, M. Quercetin-Conjugated Superparamagnetic Iron Oxide Nanoparticles Protect AlCl3-Induced Neurotoxicity in a Rat Model of Alzheimer’s Disease via Antioxidant Genes, APP Gene, and miRNA-101. Front. Neurosci. 2020, 14, 598617. [Google Scholar] [CrossRef]
- Halevas, E.; Mavroidi, B.; Nday, C.M.; Tang, J.; Smith, G.C.; Boukos, N.; Litsardakis, G.; Pelecanou, M.; Salifoglou, A. Modified magnetic core-shell mesoporous silica nano-formulations with encapsulated quercetin exhibit anti-amyloid and antioxidant activity. J. Inorg. Biochem. 2020, 213, 111271. [Google Scholar] [CrossRef]
- Pinheiro, R.G.R.; Granja, A.; Loureiro, J.A.; Pereira, M.C.; Pinheiro, M.; Neves, A.R.; Reis, S. Quercetin lipid nanoparticles functionalized with transferrin for Alzheimer’s disease. Eur. J. Pharm. Sci. 2020, 148, 105314. [Google Scholar] [CrossRef]
- Sun, D.; Li, N.; Zhang, W.; Zhao, Z.; Mou, Z.; Huang, D.; Liu, J.; Wang, W. Design of PLGA-functionalized quercetin nanoparticles for potential use in Alzheimer’s disease. Colloids Surf. B Biointerfaces 2016, 148, 116–129. [Google Scholar] [CrossRef]
- Rifaai, R.A.; Mokhemer, S.A.; Saber, E.A.; El-Aleem, S.A.A.; El-Tahawy, N.F.G. Neuroprotective effect of quercetin nanoparticles: A possible prophylactic and therapeutic role in alzheimer’s disease. J. Chem. Neuroanat. 2020, 107, 101795. [Google Scholar] [CrossRef]
- Moreno, L.; Puerta, E.; Suarez-Santiago, J.E.; Santos-Magalhaes, N.S.; Ramirez, M.J.; Irache, J.M. Effect of the oral administration of nanoencapsulated quercetin on a mouse model of Alzheimer’s disease. Int. J. Pharm. 2017, 517, 50–57. [Google Scholar] [CrossRef]
- Ramires Junior, O.V.; Alves, B.D.S.; Barros, P.A.B.; Rodrigues, J.L.; Ferreira, S.P.; Monteiro, L.K.S.; Araujo, G.M.S.; Fernandes, S.S.; Vaz, G.R.; Dora, C.L.; et al. Nanoemulsion Improves the Neuroprotective Effects of Curcumin in an Experimental Model of Parkinson’s Disease. Neurotox. Res. 2021, 39, 787–799. [Google Scholar] [CrossRef]
- Kundu, P.; Das, M.; Tripathy, K.; Sahoo, S.K. Delivery of Dual Drug Loaded Lipid Based Nanoparticles across the Blood-Brain Barrier Impart Enhanced Neuroprotection in a Rotenone Induced Mouse Model of Parkinson’s Disease. ACS Chem. Neurosci. 2016, 7, 1658–1670. [Google Scholar] [CrossRef]
- Fernandes, E.J.; Poetini, M.R.; Barrientos, M.S.; Bortolotto, V.C.; Araujo, S.M.; Santos Musachio, E.A.; De Carvalho, A.S.; Leimann, F.V.; Goncalves, O.H.; Ramborger, B.P.; et al. Exposure to lutein-loaded nanoparticles attenuates Parkinson’s model-induced damage in Drosophila melanogaster: Restoration of dopaminergic and cholinergic system and oxidative stress indicators. Chem. Biol. Interact. 2021, 340, 109431. [Google Scholar] [CrossRef]
- Palle, S.; Neerati, P. Improved neuroprotective effect of resveratrol nanoparticles as evinced by abrogation of rotenone-induced behavioral deficits and oxidative and mitochondrial dysfunctions in rat model of Parkinson’s disease. Naunyn. Schmiedebergs Arch. Pharmacol. 2018, 391, 445–453. [Google Scholar] [CrossRef]
- Gaba, B.; Khan, T.; Haider, M.F.; Alam, T.; Baboota, S.; Parvez, S.; Ali, J. Vitamin E Loaded Naringenin Nanoemulsion via Intranasal Delivery for the Management of Oxidative Stress in a 6-OHDA Parkinson’s Disease Model. Biomed. Res. Int. 2019, 2019, 2382563. [Google Scholar] [CrossRef]
- Trapani, A.; Guerra, L.; Corbo, F.; Castellani, S.; Sanna, E.; Capobianco, L.; Monteduro, A.G.; Manno, D.E.; Mandracchia, D.; Di Gioia, S.; et al. Cyto/Biocompatibility of Dopamine Combined with the Antioxidant Grape Seed-Derived Polyphenol Compounds in Solid Lipid Nanoparticles. Molecules 2021, 26, 916. [Google Scholar] [CrossRef]
- Chen, L.; Watson, C.; Morsch, M.; Cole, N.J.; Chung, R.S.; Saunders, D.N.; Yerbury, J.J.; Vine, K.L. Improving the Delivery of SOD1 Antisense Oligonucleotides to Motor Neurons Using Calcium Phosphate-Lipid Nanoparticles. Front. Neurosci. 2017, 11, 476. [Google Scholar] [CrossRef]
- Medina, D.X.; Chung, E.P.; Teague, C.D.; Bowser, R.; Sirianni, R.W. Intravenously Administered, Retinoid Activating Nanoparticles Increase Lifespan and Reduce Neurodegeneration in the SOD1(G93A) Mouse Model of ALS. Front. Bioeng. Biotechnol. 2020, 8, 224. [Google Scholar] [CrossRef]
- Mauricio, M.D.; Guerra-Ojeda, S.; Marchio, P.; Valles, S.L.; Aldasoro, M.; Escribano-Lopez, I.; Herance, J.R.; Rocha, M.; Vila, J.M.; Victor, V.M. Nanoparticles in Medicine: A Focus on Vascular Oxidative Stress. Oxid. Med. Cell Longev. 2018, 2018, 6231482. [Google Scholar] [CrossRef] [Green Version]
- Mei, T.; Kim, A.; Vong, L.B.; Marushima, A.; Puentes, S.; Matsumaru, Y.; Matsumura, A.; Nagasaki, Y. Encapsulation of tissue plasminogen activator in pH-sensitive self-assembled antioxidant nanoparticles for ischemic stroke treatment—Synergistic effect of thrombolysis and antioxidant. Biomaterials 2019, 215, 119209. [Google Scholar] [CrossRef]
- Marques, M.S.; Cordeiro, M.F.; Marinho, M.A.G.; Vian, C.O.; Vaz, G.R.; Alves, B.S.; Jardim, R.D.; Hort, M.A.; Dora, C.L.; Horn, A.P. Curcumin-loaded nanoemulsion improves haemorrhagic stroke recovery in wistar rats. Brain Res. 2020, 1746, 147007. [Google Scholar] [CrossRef]
- Chen, W.; Zhao, Z.; Zhao, S.; Zhang, L.; Song, Q. Resveratrol and Puerarin loaded polymeric nanoparticles to enhance the chemotherapeutic efficacy in spinal cord injury. Biomed. Microdevices 2020, 22, 69. [Google Scholar] [CrossRef] [PubMed]
- Luan, X.; Sansanaphongpricha, K.; Myers, I.; Chen, H.; Yuan, H.; Sun, D. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol. Sin. 2017, 38, 754–763. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bao, Q.; Hu, P.; Xu, Y.; Cheng, T.; Wei, C.; Pan, L.; Shi, J. Simultaneous Blood-Brain Barrier Crossing and Protection for Stroke Treatment Based on Edaravone-Loaded Ceria Nanoparticles. ACS Nano 2018, 12, 6794–6805. [Google Scholar] [CrossRef]
- Jin, Q.; Cai, Y.; Li, S.; Liu, H.; Zhou, X.; Lu, C.; Gao, X.; Qian, J.; Zhang, J.; Ju, S.; et al. Edaravone-Encapsulated Agonistic Micelles Rescue Ischemic Brain Tissue by Tuning Blood-Brain Barrier Permeability. Theranostics 2017, 7, 884–898. [Google Scholar] [CrossRef] [Green Version]
- Wang, G.Y.; Rayner, S.L.; Chung, R.; Shi, B.Y.; Liang, X.J. Advances in nanotechnology-based strategies for the treatments of amyotrophic lateral sclerosis. Mater. Today Bio 2020, 6, 100055. [Google Scholar] [CrossRef] [PubMed]
- Alkadi, H. A Review on Free Radicals and Antioxidants. Infect. Disord. Drug Targets 2020, 20, 16–26. [Google Scholar] [CrossRef]
- Beckman, J.S.; Minor, R.L., Jr.; White, C.W.; Repine, J.E.; Rosen, G.M.; Freeman, B.A. Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance. J. Biol. Chem. 1988, 263, 6884–6892. [Google Scholar] [CrossRef]
- Tsubokawa, T.; Jadhav, V.; Solaroglu, I.; Shiokawa, Y.; Konishi, Y.; Zhang, J.H. Lecithinized superoxide dismutase improves outcomes and attenuates focal cerebral ischemic injury via antiapoptotic mechanisms in rats. Stroke 2007, 38, 1057–1062. [Google Scholar] [CrossRef] [Green Version]
- Kim, D.W.; Eum, W.S.; Jang, S.H.; Kim, S.Y.; Choi, H.S.; Choi, S.H.; An, J.J.; Lee, S.H.; Lee, K.S.; Han, K.; et al. Transduced Tat-SOD fusion protein protects against ischemic brain injury. Mol. Cells 2005, 19, 88–96. [Google Scholar]
- Veronese, F.M.; Caliceti, P.; Schiavon, O.; Sergi, M. Polyethylene glycol-superoxide dismutase, a conjugate in search of exploitation. Adv. Drug Deliv. Rev. 2002, 54, 587–606. [Google Scholar] [CrossRef]
- Morris, M.C.; Depollier, J.; Mery, J.; Heitz, F.; Divita, G. A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat. Biotech. 2001, 19, 1173–1176. [Google Scholar] [CrossRef]
- Francis, J.W.; Ren, J.; Warren, L.; Brown, R.H., Jr.; Finklestein, S.P. Postischemic infusion of Cu/Zn superoxide dismutase or SOD:Tet451 reduces cerebral infarction following focal ischemia/reperfusion in rats. Exp. Neurol. 1997, 146, 435–443. [Google Scholar] [CrossRef] [PubMed]
- Imaizumi, S.; Woolworth, V.; Fishman, R.A.; Chan, P.H. Liposome-entrapped superoxide dismutase reduces cerebral infarction in cerebral ischemia in rats. Stroke 1990, 21, 1312–1317. [Google Scholar] [CrossRef] [Green Version]
- Sinha, J.; Das, N.; Basu, M.K. Liposomal antioxidants in combating ischemia-reperfusion injury in rat brain. Biomed. Pharmacother. 2001, 55, 264–271. [Google Scholar] [CrossRef]
- Klyachko, N.L.; Manickam, D.S.; Brynskikh, A.M.; Uglanova, S.V.; Li, S.; Higginbotham, S.M.; Bronich, T.K.; Batrakova, E.V.; Kabanov, A.V. Cross-linked antioxidant nanozymes for improved delivery to CNS. Nanomedicine 2012, 8, 119–129. [Google Scholar] [CrossRef] [Green Version]
- Manickam, D.S.; Brynskikh, A.M.; Kopanic, J.L.; Sorgen, P.L.; Klyachko, N.L.; Batrakova, E.V.; Bronich, T.K.; Kabanov, A.V. Well-defined cross-linked antioxidant nanozymes for treatment of ischemic brain injury. J. Control. Release 2012, 162, 636–645. [Google Scholar] [CrossRef] [Green Version]
- Nukolova, N.V.; Aleksashkin, A.D.; Abakumova, T.O.; Morozova, A.Y.; Gubskiy, I.L.; Kirzhanova capital Ie, C.A.C.; Abakumov, M.A.; Chekhonin, V.P.; Klyachko, N.L.; Kabanov, A.V. Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute spinal cord injury. J. Control. Release 2018, 270, 226–236. [Google Scholar] [CrossRef]
- Hood, E.; Simone, E.; Wattamwar, P.; Dziubla, T.; Muzykantov, V. Nanocarriers for vascular delivery of antioxidants. Nanomedicine 2011, 6, 1257–1272. [Google Scholar] [CrossRef] [Green Version]
- Reddy, M.K.; Wu, L.; Kou, W.; Ghorpade, A.; Labhasetwar, V. Superoxide dismutase-loaded PLGA nanoparticles protect cultured human neurons under oxidative stress. Appl. Biochem. Biotechnol. 2008, 151, 565–577. [Google Scholar] [CrossRef] [Green Version]
- Singhal, A.; Morris, V.B.; Labhasetwar, V.; Ghorpade, A. Nanoparticle-mediated catalase delivery protects human neurons from oxidative stress. Cell Death Dis. 2013, 4, e903. [Google Scholar] [CrossRef] [Green Version]
- Reddy, M.K.; Labhasetwar, V. Nanoparticle-mediated delivery of superoxide dismutase to the brain: An effective strategy to reduce ischemia-reperfusion injury. FASEB J. 2009, 23, 1384–1395. [Google Scholar] [CrossRef] [PubMed]
- Petro, M.; Jaffer, H.; Yang, J.; Kabu, S.; Morris, V.B.; Labhasetwar, V. Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain. Biomaterials 2016, 81, 169–180. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jaffer, H.; Adjei, I.M.; Labhasetwar, V. Optical imaging to map blood-brain barrier leakage. Sci. Rep. 2013, 3, 3117. [Google Scholar] [CrossRef] [Green Version]
- Andrabi, S.S.; Yang, J.; Gao, Y.; Kuang, Y.; Labhasetwar, V. Nanoparticles with antioxidant enzymes protect injured spinal cord from neuronal cell apoptosis by attenuating mitochondrial dysfunction. J. Control. Release 2020, 317, 300–311. [Google Scholar] [CrossRef]
- Gao, Y.; Vijayaraghavalu, S.; Stees, M.; Kwon, B.K.; Labhasetwar, V. Evaluating accessibility of intravenously administered nanoparticles at the lesion site in rat and pig contusion models of spinal cord injury. J. Control. Release 2019, 302, 160–168. [Google Scholar] [CrossRef]
Antioxidants | Route | Disease Patients | Dosage | Follow Up Period | No. of Patients | Outcome | References |
---|---|---|---|---|---|---|---|
Curcumin | Oral | AD ALS | 1.5 g/d 100 mg/d | 6 months 9 months | 34 42 | Reduced cognitive deterioration Slowdown in disease progression | [251,252] |
Resveratrol | Oral | AD | 1 g/d | 52 weeks | 119 | Decreased Aβ1–40 and MMP-9 levels in CSF Slowed cognitive decline | [253] |
GSH | Intranasal | PD | 300 mg/d or 600 mg/d thrice 100 mg/d or 200 mg/d thrice | 3 months | 30 45 | Safety and tolerability No significant differences between groups No effect on motor function | [256,257] |
CoQ10 | Oral | PD PD ALS | 400, 800, 1200, and 2400 mg/d 1200 mg/d or 2400 mg/d 1800 mg/d and 2700 mg/d | 10 weeks 16 months 9 months | 16 600 105 | Improved UPDRS, Reduced F2-isoprostanes No therapeutic benefit Decreased ALSFRSr No significant differences between groups at high dose | [258,259,260] |
Ginkgo biloba | Oral | AD | 120 mg/d twice | 8 years | 3069 | No improvement in cognition | [261] |
Edaravone (FDA Approved in 2017) | Intravenous | ALS | 60 mg/d | 24 Weeks | 137 | Decreased ALSFRSr | [262,263] |
Lipoic acid and, Omega-3 fatty acids | Oral | AD | 600 mg/d 675 mg docosahexaenoic acid (DHA) 975 mg eicosapentaenoic acid (EPA) | 12 months | 39 | Slowed cognitive and functional decline | [268] |
Vitamin E and, Memantine | Oral | AD | 2000 IU/d20 mg/d | 5 years | 613 | Slower functional deterioration in Vitamin E group | [269] |
Vitamin E, Vitamin C, ALA, and CoQ | Oral | AD | 800 IU/d 500 mg/d 900 mg/d 400 mg/d thrice | 16 weeks | 78 | No effect on amyloid or tau pathology biomarkers | [270] |
Omega-3 fatty acids and, Vitamin E | Oral | PD | 1000 mg 400 IU | 12 weeks | 60 | Improved UPDRS, TAC and GSH | [271] |
Nanocurcumin and, Riluzole | Oral | ALS | 80 mg/d 50 mg/d twice | 12 months | 54 | Safety and tolerability Increased survival probability of ALS patients | [272] |
Curcumin Formulation (Longvida) Solid-Lipid Curcumin | Oral | AD Control | 2000 mg–3000 mg/d 400 mg/d | 9 months 4 weeks | 26 60 | Not provided Improved cognition and mood | [273,274] |
Antioxidants | Route | Disease Patients | Dosage | Follow Up Period | No. of Patients | Outcome | References |
---|---|---|---|---|---|---|---|
Resveratrol | Oral/ Infusion | Stroke | 2.5 mg/kg | 0–2 h of stroke onset | 312 | Decreased MMP-9 and MMP-2 levels | [253,254] |
EGCG | Intravenous/ oral/ infusion | Stroke | 500 mg | 0–5 h of stroke onset | 371 | Decreased MMP-9 and MMP-2 levels | [255] |
Edaravone | Intravenous | Stroke | 30 mg 60 mg | 6 months 12–24 h of stroke onset | 40163 | Effective recovery Decreased MMP-9 levels | [264,265] |
Edaravone Dexborneol | Intravenous | Stroke Intracerebral Hemorrhage | 12.5 mg, 37.5 mg or 62.5 mg every 12 h for 14 days 37.5 mg every 12 h for 14 days | 3 months NA | 385390 (estimated) | Safe and well tolerated No Recruitment | [266,267] |
Nanoparticle-loaded Edaravone | Intravenous | Cerebral Hemorrhage | 25 mg | 3 weeks | 120 | Reduced edema Improved neurological function Reduced interleukin and tumor necrosis factor | [275] |
Ginkgo biloba and, Aspirin | Oral | Stroke | 450 mg 100 mg | 6 months | 348 | Alleviated cognitive and neurological impairment | [276] |
Omega-3 pill Vegetation Protein Powder InflanNox (curcumin) capsuleAnti-oxidant Network capsule Chlorella tablet | Oral | SCI | 500 mg/d EPA, 250 mg/d DHA, thrice 45 g/d 400 mg/d thrice 615 mg/d twice 1000 mg/d, 6 times | 3 months | 20 | Improvement in behavior Modification in neuroactive compounds Reduction in IL-1β | [277] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ashok, A.; Andrabi, S.S.; Mansoor, S.; Kuang, Y.; Kwon, B.K.; Labhasetwar, V. Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation. Antioxidants 2022, 11, 408. https://doi.org/10.3390/antiox11020408
Ashok A, Andrabi SS, Mansoor S, Kuang Y, Kwon BK, Labhasetwar V. Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation. Antioxidants. 2022; 11(2):408. https://doi.org/10.3390/antiox11020408
Chicago/Turabian StyleAshok, Anushruti, Syed Suhail Andrabi, Saffar Mansoor, Youzhi Kuang, Brian K. Kwon, and Vinod Labhasetwar. 2022. "Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation" Antioxidants 11, no. 2: 408. https://doi.org/10.3390/antiox11020408