{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T09:43:51Z","timestamp":1770457431573,"version":"3.49.0"},"reference-count":124,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004515","name":"Universiti Kebangsaan Malaysia","doi-asserted-by":"publisher","award":["FF-2019-125"],"award-info":[{"award-number":["FF-2019-125"]}],"id":[{"id":"10.13039\/501100004515","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Neurodegenerative diseases (ND) can be characterized by degradation and subsequent loss of neurons. ND has been identified as the leading cause of disability-adjusted life years (DALYs) worldwide and is associated with various risk factors such as ageing, certain genetic polymorphisms, inflammation, immune and metabolic conditions that may induce elevated reactive oxygen species (ROS) release and subsequent oxidative stress. Presently, no specific cure or prevention is available for ND patients; the symptoms can be only alleviated via drug treatment or surgery. The existing pharmacological treatments are only available for partial treatment of the symptoms. A natural product known as oil palm phenolics (OPP), which is high in antioxidant, could become a potential supplementary antioxidant for neurodegenerative health. OPP is a water-soluble extract from palm fruit that demonstrated medicinal properties including anti-tumor, anti-diabetic and neuroprotective effects. In this review, OPP was proposed for its neuroprotective effects via several mechanisms including antioxidant and anti-inflammatory properties. Besides, OPP has been found to modulate the genes involved in neurotrophic activity. The evidence and proposed mechanism of OPP on the neuroprotective health may provide a comprehensive natural medicine approach to alleviate the symptoms of neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/molecules25215159","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T19:38:41Z","timestamp":1604605121000},"page":"5159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Potential Mechanisms of the Neuroprotective Actions of Oil Palm Phenolics: Implications for Neurodegenerative Diseases"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2486-9486","authenticated-orcid":false,"given":"Nurul \u2018Izzah","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Pharmacoepidemiology and Drug Safety Unit, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8065-8117","authenticated-orcid":false,"given":"Nur Balqis","family":"Muhammad Ismail Tadj","sequence":"additional","affiliation":[{"name":"Pharmacoepidemiology and Drug Safety Unit, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9795-0608","authenticated-orcid":false,"given":"Md. Moklesur","family":"Rahman Sarker","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, State University of Bangladesh, 77 Satmasjid Road, Dhanmondi, Dhaka 1205, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isa","family":"Naina Mohamed","sequence":"additional","affiliation":[{"name":"Pharmacoepidemiology and Drug Safety Unit, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/428010","article-title":"Mechanism of oxidative stress in neurodegeneration","volume":"2012","author":"Gandhi","year":"2012","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"325","DOI":"10.5607\/en.2015.24.4.325","article-title":"The role of oxidative stress in neurodegenerative diseases","volume":"24","author":"Kim","year":"2015","journal-title":"Exp. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000495197","article-title":"Global burden of neurological disorders: From global burden of disease estimates to actions","volume":"52","author":"Feigin","year":"2018","journal-title":"Neuroepidemiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1289\/ehp.7567","article-title":"Neurodegenerative diseases: An overview of environmental risk factors","volume":"113","author":"Brown","year":"2005","journal-title":"Environ. Heal. Perspect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S36","DOI":"10.1016\/j.arr.2010.08.006","article-title":"Ageing and neurodegenerative diseases","volume":"9","author":"Hung","year":"2010","journal-title":"Ageing Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pohl, F., and Lin, P.K.T. (2018). The potential use of plant natural products and plant extracts with antioxidant properties for the prevention\/treatment of neurodegenerative diseases: In Vitro, In Vivo and clinical trials. Moecules, 23.","DOI":"10.3390\/molecules23123283"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.mad.2008.09.017","article-title":"The age-related decrease in catecholamine sensitivity is mediated by beta(1)-adrenergic receptors linked to a decrease in adenylate cyclase activity in ventricular myocytes from male Fischer 344 rats","volume":"129","author":"Farrell","year":"2008","journal-title":"Mech. Ageing Dev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2010.12.017","article-title":"Tyrosine hydroxylase and regulation of dopamine synthesis","volume":"508","author":"Daubner","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJM198207223070401","article-title":"Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts","volume":"307","author":"Bristow","year":"1982","journal-title":"N. Engl. J. Med."},{"key":"ref_11","first-page":"520","article-title":"Linking functional decline of telomeres, mitochondria and stem cells during ageing","volume":"464","author":"Sahin","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_12","first-page":"376","article-title":"Oxidative stress in neurodegenerative diseases","volume":"7","author":"Chen","year":"2012","journal-title":"Neural Regen. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/2525967","article-title":"Oxidative stress in neurodegenerative diseases: From molecular mechanisms to clinical applications","volume":"2017","author":"Liu","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/apha.12515","article-title":"Biological and physiological role of reactive oxygen species-The good, the bad and the ugly","volume":"214","author":"Zuo","year":"2015","journal-title":"Acta Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2174\/157015909787602823","article-title":"Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options","volume":"7","author":"Uttara","year":"2009","journal-title":"Curr. Neuropharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"477","DOI":"10.3389\/fphys.2018.00477","article-title":"Role of ROS and nutritional antioxidants in human diseases","volume":"9","author":"Liu","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rafii, M., and Aisen, P.S. (2009). Recent developments in Alzheimer\u2019s disease therapeutics. BMC Med., 7.","DOI":"10.1186\/1741-7015-7-7"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1001\/archneur.61.1.82","article-title":"Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements","volume":"61","author":"Zandi","year":"2004","journal-title":"Arch. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1017\/S0007114511002121","article-title":"Oil palm vegetation liquor: A new source of phenolic bioactives","volume":"106","author":"Sambanthamurthi","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"711","DOI":"10.7150\/ijms.29934","article-title":"The pharmacological potential of Oil Palm Phenolics (OPP) individual components","volume":"16","author":"Zulfarina","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_21","unstructured":"Sambanthamurthi, R., Rha, C., Sinskey, A., Tan, Y.A., and Wahid, M.B. (2010). Oil palm phenolics as a source of shikimic acid-An MPOB and MIT collaboration. MPOB Inf. Ser., 506. Available online: http:\/\/palmoilis.mpob.gov.my\/publications\/TOT\/TT-450.pdf."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12154-011-0064-8","article-title":"Shikimic acid: Review of its analytical, isolation, and purification techniques from plant and microbial sources","volume":"5","author":"Bochkov","year":"2012","journal-title":"J. Chem. Biol."},{"key":"ref_23","first-page":"1672","article-title":"Shikimic acid: A highly prospective molecule in pharmaceutical industry","volume":"109","author":"Borah","year":"2015","journal-title":"Curr. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.fct.2005.01.020","article-title":"Safety assessment of esters of p-hydroxybenzoic acid (parabens)","volume":"43","author":"Soni","year":"2005","journal-title":"Food Chem. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1080\/14786419.2016.1222386","article-title":"An insight into anti-biofilm and anti-quorum sensing activities of the selected anthocyanidins: The case study of Pseudomonas aeruginosa PAO1","volume":"31","author":"Pejin","year":"2016","journal-title":"Nat. Prod. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2174\/1389201016666150505121951","article-title":"Quercetin potently reduces biofilm formation of the strain Pseudomonas aeruginosa PAO1 in vitro","volume":"16","author":"Pejin","year":"2015","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0378-8741(98)00061-0","article-title":"4-Hydroxybenzoic acid: A hypoglycemic constituent of aqueous extract of Pandanus odorus root","volume":"62","author":"Peungvicha","year":"1998","journal-title":"J. Ethnopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1254\/jjp.78.395","article-title":"Possible mechanism of hypoglycemic effect of 4-hydroxybenzoic acid, a constituent of Pandanus odorus root","volume":"78","author":"Peungvicha","year":"1998","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.2337\/db10-1461","article-title":"Cyanidin-3-O-\u03b2-glucoside and protocatechuic acid exert insulin-like effects by upregulating PPAR\u03b3 activity in human omental adipocytes","volume":"60","author":"Scazzocchio","year":"2011","journal-title":"Diabetes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6661","DOI":"10.1021\/jf9015202","article-title":"Anticoagulatory, antiinflammatory, and antioxidative effects of protocatechuic acid in diabetic mice","volume":"57","author":"Lin","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1515\/JBCPP.2010.21.1.79","article-title":"Antihyperglycemic effect of protocatechuic acid on streptozotocin-diabetic rats","volume":"21","author":"Harini","year":"2010","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.bcp.2011.04.007","article-title":"Cyanidin-3-O-\u03b2-glucoside with the aid of its metabolite protocatechuic acid, reduces monocyte infiltration in apolipoprotein E-deficient mice","volume":"82","author":"Wang","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_33","first-page":"456","article-title":"Antihyperlipidemic effect of protocatechuic acid in fructose induced hyperlipidemia in rats","volume":"2","author":"Borate","year":"2011","journal-title":"Int. J. Pharma Bio Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.fct.2010.10.014","article-title":"Hydroxytyrosol rich extract from olive leaves modulates cell cycle progression in MCF-7 human breast cancer cells","volume":"49","author":"Bouallagui","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s10616-009-9191-2","article-title":"Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells","volume":"59","author":"Han","year":"2009","journal-title":"Cytotechnology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1097\/00008469-200208000-00006","article-title":"Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis","volume":"11","author":"FabianiMaria","year":"2002","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.neulet.2008.09.022","article-title":"Neuroprotective effect of hydroxytyrosol and hydroxytyrosol acetate in rat brain slices subjected to hypoxia\u2013reoxygenation","volume":"446","author":"Navas","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"333","DOI":"10.7326\/0003-4819-145-5-200609050-00006","article-title":"The effect of polyphenols in olive oil on heart disease risk factors","volume":"145","author":"Covas","year":"2006","journal-title":"Ann. Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5043","DOI":"10.1021\/jf0703710","article-title":"Hydroxytyrosol-rich olive mill wastewater extract protects brain cells in vitro and ex vivo","volume":"55","author":"Schaffer","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1017\/S0007114511002133","article-title":"Positive outcomes of oil palm phenolics on degenerative diseases in animal models","volume":"106","author":"Sambanthamurthi","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ibrahim, N.I., Fairus, S., and Mohamed, I.N. (2020). The effects and potential mechanism of oil palm phenolics in cardiovascular health: Ace. Nutrients, 12.","DOI":"10.3390\/nu12072055"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1179\/1476830512Y.0000000047","article-title":"Oil palm phenolics confer neuroprotective effects involving cognitive and motor functions in mice","volume":"16","author":"Leow","year":"2013","journal-title":"Nutr. Neurosci."},{"key":"ref_43","unstructured":"Yan, W. (2017). The in vivo effect of oil palm phenolics (opp) In Atherogenic Diet Induced Rats Model of Alzheimer\u2019s Disease (ad). Nutrition and Food Science, Wayne State University."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jep.2010.06.023","article-title":"Neuroprotective effects of water-soluble Ganoderma lucidum polysaccharides on cerebral ischemic injury in rats","volume":"131","author":"Zhou","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1002\/ptr.2797","article-title":"Neuroprotective effects of Brazilian green propolis and its main constituents against oxygen-glucose deprivation Stress, with a gene-expression analysis","volume":"23","author":"Nakajima","year":"2009","journal-title":"Phytotherapy Res."},{"key":"ref_46","unstructured":"Michelle, G.L. (2012). The Effects of Oil Palm Phenolics on Inflammation and Oxidative Stress in Relation to Amyloid Beta Plaques in Fad-Mutant and Wild Type B103 Cells. [Master\u2019s Thesis, Wayne State University]."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nprot.2006.116","article-title":"Morris water maze: Procedures for assessing spatial and related forms of learning and memory","volume":"1","author":"Vorhees","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6983","DOI":"10.1038\/s41598-018-25529-y","article-title":"Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients","volume":"8","author":"Kao","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1385\/NMM:4:1-2:49","article-title":"Interactions of amyloidogenic proteins","volume":"4","author":"Giasson","year":"2003","journal-title":"NeuroMolecular Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/7608038","article-title":"Oil palm phenolics inhibit the in vitro aggregation of \u03b2 -amyloid peptide into oligomeric complexes","volume":"2018","author":"Weinberg","year":"2018","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/aps.2017.28","article-title":"Amyloid beta: Structure, biology and structure-based therapeutic development","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jneumeth.2006.09.013","article-title":"Linear quantitation of A\u03b2 aggregation using Thioflavin T: Reduction in fibril formation by colostrinin","volume":"160","author":"Bourhim","year":"2007","journal-title":"J. Neurosci. Methods"},{"key":"ref_53","unstructured":"Monplaisir, K.M. (2016). Effect of Oil Palm Phenolics on Beta Amyloid Deposition in Cholesterol Induced Rat Model. of Alzheimer\u2019s Disease: Histological Evidence. [Master\u2019s Thesis, Wayne State University]."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.mcn.2010.08.001","article-title":"Hypercholesterolemia in rats impairs the cholinergic system and leads to memory deficits","volume":"45","author":"Ullrich","year":"2010","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_55","unstructured":"Sundaresan, A.M. (2013). Oil Palm Phenolics Suppresses Oxidative Stress and Inflammation. [Master\u2019s Thesis, Massachusetts Institute of Technology]."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"16423","DOI":"10.1038\/s41598-018-34763-3","article-title":"Palm fruit bioactives modulate human astrocyte activity in vitro altering the cytokine secretome reducing levels of TNF\u03b1, RANTES and IP-10","volume":"8","author":"Weinberg","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/mnfr.201000225","article-title":"Chemopreventive effect of dietary curcumin on inflammation-induced colorectal carcinogenesis in mice","volume":"55","author":"Villegas","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0896-6273(94)90458-8","article-title":"Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: Evidence that an initially deposited species is A beta 42(43)","volume":"13","author":"Iwatsubo","year":"1994","journal-title":"Neuron"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1161\/CIRCULATIONAHA.115.017545","article-title":"Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure","volume":"133","author":"Bedi","year":"2016","journal-title":"Circulation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"505","DOI":"10.2217\/17460875.3.5.505","article-title":"Apolipoprotein E and cholesterol in aging and disease in the brain","volume":"3","author":"Narayanaswami","year":"2008","journal-title":"Future Lipidol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11706","DOI":"10.1523\/JNEUROSCI.0730-12.2012","article-title":"Lipopolysaccharide-induced microglial activation and neuroprotection against experimental brain injury is independent of hematogenous TLR4","volume":"32","author":"Chen","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/S0002-9343(00)00412-5","article-title":"The evolution of free radicals and oxidative stress","volume":"108","author":"Mccord","year":"2000","journal-title":"Am. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/391914","article-title":"Nitric oxide inactivation mechanisms in the brain: Role in bioenergetics and neurodegeneration","volume":"2012","author":"Santos","year":"2012","journal-title":"Int. J. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1111\/j.1460-9568.2008.06285.x","article-title":"Concepts of neural nitric oxide-mediated transmission","volume":"27","author":"Garthwaite","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_65","first-page":"435","article-title":"Nitric oxide signaling in brain function, dysfunction, and dementia","volume":"16","author":"Steinert","year":"2010","journal-title":"Neuroscience"},{"key":"ref_66","first-page":"71","article-title":"Role of oxidative DNA damage in cancer initiation and promotion","volume":"7","author":"Poulsen","year":"1998","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_67","first-page":"872","article-title":"Free radicals, antioxidants, and nutrition","volume":"18","author":"Fang","year":"2002","journal-title":"Nutrients"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12937-016-0186-5","article-title":"The importance of antioxidants which play the role in cellular response against oxidative\/nitrosative stress: Current state","volume":"15","author":"Kurutas","year":"2015","journal-title":"Nutr. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1152\/physrev.00047.2006","article-title":"Life and death: Metabolic rate, membrane composition, and life span of animals","volume":"87","author":"Hulbert","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1007\/s11064-008-9697-6","article-title":"Role of nitric oxide synthases in Parkinson\u2019s disease: A review on the antioxidant and anti-inflammatory activity of polyphenols","volume":"33","author":"Aquilano","year":"2008","journal-title":"Neurochem. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nrn1886","article-title":"Ageing and neuronal vulnerability","volume":"7","author":"Mattson","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"982","DOI":"10.7150\/ijbs.12096","article-title":"Significance of antioxidant potential of plants and its relevance to therapeutic applications","volume":"11","author":"Kasote","year":"2015","journal-title":"Int. J. Biol. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/0891-5849(95)02227-9","article-title":"Structure-antioxidant activity relationships of flavonoids and phenolic acids","volume":"20","author":"Miller","year":"1996","journal-title":"Free Radic. Biol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"685","DOI":"10.2165\/00002512-200118090-00004","article-title":"Role of free radicals in the neurodegenerative diseases","volume":"18","author":"Halliwell","year":"2001","journal-title":"Drugs Aging"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s12640-012-9335-6","article-title":"Oxidative stress biomarkers in some rat brain structures and peripheral organs underwent cocaine","volume":"23","author":"Moniczewski","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1749-6632.1996.tb39064.x","article-title":"Oxidative stress and Parkinson\u2019s disease","volume":"786","author":"Owen","year":"1996","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref_77","first-page":"581","article-title":"Free radicals, lipid peroxidation and antioxidants in apoptosis: Implications in cancer, cardiovascular and neurological diseases","volume":"55","author":"Ferrari","year":"2000","journal-title":"Biologia"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"271.8","DOI":"10.1096\/fasebj.29.1_supplement.271.8","article-title":"The in vivo effect of oil palm phenolics (OPP) in atherogenic diet induced rat model of Alzheimer\u2019s disease (AD)","volume":"29","author":"Wu","year":"2015","journal-title":"FASEB J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1590\/S0100-40422009000100032","article-title":"Importance of the lipid peroxidation biomarkers and methodological aspects FOR malondialdehyde quantification","volume":"32","author":"Grotto","year":"2009","journal-title":"Qu\u00edmica Nova"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev.pharmtox.010909.105600","article-title":"Mechanisms of cell protection by heme oxygenase-1","volume":"50","author":"Gozzelino","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Nitti, M., Piras, S., Brondolo, L., Marinari, U.M., Pronzato, M.A., and Furfaro, A.L. (2018). Heme oxygenase 1 in the nervous system: Does it favor neuronal cell survival or induce neurodegeneration?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082260"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"8919","DOI":"10.1074\/jbc.M309660200","article-title":"Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase\/akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol","volume":"279","author":"Martin","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_83","first-page":"165","article-title":"Curcumin induces heme oxygenase 1 through generation of reactive oxygen species, p38 activation and phosphatase inhibition","volume":"19","author":"McNally","year":"2007","journal-title":"Int. J. Mol. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1055\/s-0028-1088302","article-title":"Nrf2 as a Master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals","volume":"74","author":"Surh","year":"2008","journal-title":"Planta Medica"},{"key":"ref_85","first-page":"S84","article-title":"Molecular mechanisms of natural products in chemoprevention: Induction of cytoprotective enzymes by Nrf2","volume":"52","author":"Eggler","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"12731","DOI":"10.1073\/pnas.96.22.12731","article-title":"Nrf2 is essential for protection against acute pulmonary injury in mice","volume":"96","author":"Chan","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.redox.2018.05.002","article-title":"Antioxidant response elements: Discovery, classes, regulation and potential applications","volume":"17","author":"Raghunath","year":"2018","journal-title":"Redox Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cnr.2006.09.006","article-title":"Neuroinflammation, oxidative stress, and the pathogenesis of Parkinson\u2019s disease","volume":"6","author":"Mosley","year":"2006","journal-title":"Clin. Neurosci. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/mds.870130205","article-title":"Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson\u2019s disease","volume":"13","author":"Banati","year":"1998","journal-title":"Mov. Disord."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.neurobiolaging.2004.05.010","article-title":"Glia and their cytokines in progression of neurodegeneration","volume":"26","author":"Mrak","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ijdevneu.2005.11.001","article-title":"Neuroinflammation and regeneration in the early stages of Alzheimer\u2019s disease pathology","volume":"24","author":"Hoozemans","year":"2006","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative stress: Harms and benefits for human health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1146\/annurev.nu.16.070196.000341","article-title":"Antioxidants in human health and disease","volume":"16","author":"Halliwell","year":"1996","journal-title":"Annu. Rev. Nutr."},{"key":"ref_94","first-page":"86","article-title":"Stress-related diseases\u2014A potential role for nitric oxide","volume":"8","author":"Esch","year":"2002","journal-title":"Med. Sci. Monit."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.parkreldis.2004.01.005","article-title":"Inflammation and neurodegeneration in Parkinson\u2019s disease","volume":"10","author":"McGeer","year":"2004","journal-title":"Parkinsonism Rel. Disord."},{"key":"ref_96","first-page":"1","article-title":"Role of redox signaling in neuroinflammation and neurodegenerative diseases","volume":"2013","author":"Hsieh","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1097\/00001756-200310060-00011","article-title":"Effect of sesame antioxidants on LPS-induced NO production by BV2 microglial cells","volume":"14","author":"Hou","year":"2003","journal-title":"Neuroreport"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.jff.2009.05.001","article-title":"Attenuation of iNOS and COX2 by blueberry polyphenols is mediated through the suppression of NF-\u03baB activation","volume":"1","author":"Lau","year":"2009","journal-title":"J. Funct. Foods"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-9255-6-1","article-title":"Polyphenol-rich pomegranate fruit extract (POMx) suppresses PMACI-induced expression of pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-kappaB in human KU812 cells","volume":"6","author":"Rasheed","year":"2009","journal-title":"J. Inflamm. (Lond)"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fnmol.2015.00077","article-title":"NF-kappaB signaling pathways in neurological inflammation: A mini review","volume":"8","author":"Shih","year":"2015","journal-title":"Front. Mol. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.0105-2896.2006.00375.x","article-title":"Circuitry of nuclear factor kappaB signaling","volume":"210","author":"Hoffmann","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1080\/14767050701483298","article-title":"CXCL10\/IP-10: A missing link between inflammation and anti-angiogenesis in preeclampsia? The journal of maternal-fetal & neonatal medicine","volume":"20","author":"Gotsch","year":"2007","journal-title":"J. Matern. -Fetal Neonatal Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1046\/j.1365-2249.1999.00766.x","article-title":"Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE)","volume":"115","author":"Viallard","year":"1999","journal-title":"Clin. Exp. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neurobiolaging.2008.03.009","article-title":"RANTES upregulation in the Alzheimer\u2019s disease brain: A possible neuroprotective role","volume":"31","author":"Tripathy","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/S0166-2236(97)01139-9","article-title":"Reactive astrocytes: Cellular and molecular cues to biological function","volume":"20","author":"Ridet","year":"1997","journal-title":"Trends Neurosci."},{"key":"ref_107","first-page":"1","article-title":"Cytokines and chemokines at the crossroads of neuroinflammation, neurodegeneration, and neuropathic pain","volume":"2013","author":"Ramesh","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3233\/JAD-2011-102151","article-title":"The role of osteopontin in neurodegenerative diseases","volume":"25","author":"Carecchio","year":"2011","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1001\/archneur.64.3.366","article-title":"Novel panel of cerebrospinal fluid biomarkers for the prediction of progression to Alzheimer dementia in patients with mild cognitive impairment","volume":"64","author":"Simonsen","year":"2007","journal-title":"Arch. Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.4049\/jimmunol.163.4.2143","article-title":"Persistent expression of serum amyloid A during experimentally induced chronic inflammatory condition in rabbit involves differential activation of SAF, NF-kappa B, and C\/EBP transcription factors","volume":"163","author":"Ray","year":"1999","journal-title":"J. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Loerch, P.M., Lu, T., Dakin, K.A., Vann, J.M., Isaacs, A., Geula, C., Wang, J., Pan, Y., Gabuzda, D.H., and Li, C. (2008). Evolution of the aging brain transcriptome and synaptic regulation. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003329"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1385\/MN:26:2-3:369","article-title":"The neurobiology of apolipoproteins in psychiatric disorders","volume":"26","author":"Thomas","year":"2002","journal-title":"Mol. Neurobiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.neuropharm.2013.05.043","article-title":"Pre- and postsynaptic twists in BDNF secretion and action in synaptic plasticity","volume":"76","author":"Edelmann","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1007\/s12035-018-1283-6","article-title":"Brain-derived neurotrophic factor in brain disorders: Focus on neuroinflammation","volume":"56","author":"Giacobbo","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"331","DOI":"10.14336\/AD.2015.0825","article-title":"The involvement of BDNF, NGF and GDNF in aging and Alzheimer\u2019s disease","volume":"6","author":"Budni","year":"2015","journal-title":"Aging Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.parkreldis.2016.05.023","article-title":"Low BDNF is associated with cognitive impairments in patients with Parkinson\u2019s disease","volume":"29","author":"Wang","year":"2016","journal-title":"Park. Relat. Disord."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"7116","DOI":"10.1523\/JNEUROSCI.20-18-07116.2000","article-title":"Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats","volume":"20","author":"Mizuno","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1037\/0735-7044.112.4.1012","article-title":"Learning upregulates brain-derived neurotrophic factor messenger ribonucleic acid: A mechanism to facilitate encoding and circuit maintenance?","volume":"112","author":"Kesslak","year":"1998","journal-title":"Behav. Neurosci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1073\/pnas.042693699","article-title":"The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes","volume":"99","author":"Yin","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-016-0545-3","article-title":"A novel role for protein tyrosine phosphatase 1B as a positive regulator of neuroinflammation","volume":"13","author":"Song","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"6577","DOI":"10.1073\/pnas.111126298","article-title":"The in vivo neuromodulatory effects of the herbal medicine ginkgo biloba","volume":"98","author":"Watanabe","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Leung, H.-W., Foo, G.W.Q., and Vandongen, A. (2019). Arc regulates transcription of genes for plasticity, excitability and Alzheimer\u2019s disease. bioRxiv, 833988.","DOI":"10.1101\/833988"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13041-017-0324-9","article-title":"The DLGAP family: Neuronal expression, function and role in brain disorders","volume":"10","author":"Rasmussen","year":"2017","journal-title":"Mol. Brain"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fnins.2020.00188","article-title":"Acute sleep loss upregulates the synaptic scaffolding protein, Homer1a, in non-canonical sleep\/wake brain regions, claustrum, piriform and cingulate cortices","volume":"14","author":"Zhu","year":"2020","journal-title":"Front. Neurosci."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/21\/5159\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:29:54Z","timestamp":1760178594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/21\/5159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,5]]},"references-count":124,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["molecules25215159"],"URL":"https:\/\/doi.org\/10.3390\/molecules25215159","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,5]]}}}