330
Views
14
CrossRef citations to date
0
Altmetric
Review

Nutraceuticals-based therapeutic approach: recent advances to combat pathogenesis of Alzheimer’s disease

, , , , ORCID Icon, , & show all
Pages 625-642 | Received 03 Dec 2020, Accepted 26 Apr 2021, Published online: 16 May 2021

References

  • Niculescu AB, Le-Niculescu H, Roseberry K, et al. Blood biomarkers for memory: toward early detection of risk for Alzheimer disease, pharmacogenomics, and repurposed drugs. Mol Psychiatry. 2020;25(8):1651–1672. 2020/08/01.
  • Winblad B, Amouyel P, Andrieu S, et al. Defeating Alzheimer’s disease and other dementias: a priority for European science and society. Lancet Neurol. 2016;15(5):455–532.
  • Weidner WS, Barbarino P. THE STATE OF THE ART OF DEMENTIA RESEARCH: NEW FRONTIERS. Alzheimers Dement. 2019;15:1473.
  • Ravi SK, Narasingappa RB, Vincent B. Neuro-nutrients as anti-alzheimer’s disease agents: a critical review. Crit Rev Food Sci Nutr. 2019;59(18):2999–3018. 2019/10/11.
  • McClam TD, Marano CM, Rosenberg PB, et al. Interventions for Neuropsychiatric Symptoms in Neurocognitive Impairment Due to Alzheimer’s Disease: a Review of the Literature. Harv Rev Psychiatry. 2015 Sep-Oct;23(5):377–393.
  • Riedel WJ. Preventing cognitive decline in preclinical Alzheimer’s disease. Curr Opin Pharmacol. 2014 Feb;14:18–22.
  • Olasehinde TA, Olaniran AO, Okoh AI. Cholinesterase inhibitory activity, antioxidant properties, and phytochemical composition of Chlorococcum sp. extracts. Journal of Food Biochemistry. 2020 Jul;27:e13395.
  • Association As. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016;12(4):459–509.
  • Hosseinkhani A, Sahragard A, Namdari A, et al. Botanical Sources for Alzheimer’s: a review on reports from traditional Persian medicine. Am J Alzheimer S Disease Other Dementias. 2017;32(7):429–437. 07/07.
  • Uddin MS, Kabir MT, Niaz K, et al. Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease. Molecules. 2020;25:1–30, 03/11
  • Anand A, Patience AA, Sharma N, et al. The present and future of pharmacotherapy of Alzheimer’s disease: a comprehensive review. Eur J Pharmacol. 2017 Nov 15;815:364–375.
  • Adefegha SA. Functional foods and nutraceuticals as dietary intervention in Chronic Diseases; novel perspectives for health promotion and disease prevention. J Diet Suppl. 2018 Nov 2;15(6):977–1009.
  • Witter S, Witter R, Vilu R, et al. Medical Plants and Nutraceuticals for Amyloid-β Fibrillation Inhibition. J Alzheimer’s Dis Reports. 2018 Dec 24;2(1):239–252.
  • Solfrizzi V, Agosti P, Lozupone M, et al. Nutritional intervention as a preventive approach for Cognitive-Related outcomes in cognitively healthy older adults: a systematic review. J Alzheimers Dis. 2018;64(s1):S229–S254.
  • Scholey A. Nutrients for neurocognition in health and disease: measures, methodologies and mechanisms. The Proceedings of the Nutrition Society. 2018 Feb;77( 1):73–83.
  • Kim HG, Oh MS. Nutraceuticals and prevention of neurodegeneration herbal medicines for the prevention and treatment of Alzheimer’s Disease. Curr Pharm Des. 2012 Jan 1;77(1):73–83.
  • Raji CA, Lopez OL, Kuller LH, et al. Age, Alzheimer disease, and brain structure. Neurology. 2009;73(22):1899–1905.
  • Van Cauwenberghe C, Van Broeckhoven C, Sleegers K. The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med. 2016;18(5):421–430. 2016/05/01.
  • Kivipelto M, Mangialasche F, Ngandu T. Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease. Nat Rev Neurol. 2018;14(11):653–666. 2018/11/01.
  • Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front Cell Neurosci. 2015;9:124.
  • Tiwari S, Atluri V, Kaushik A, et al. Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine. 2019;14:5541–5554.
  • Cioffi F, Adam RHI, Broersen K. Molecular mechanisms and genetics of oxidative stress in Alzheimer’s Disease. J Alzheimers Dis. 2019;72(4):981–1017.
  • Huang W-J, Zhang X, Chen -W-W. Role of oxidative stress in Alzheimer’s disease. Biomed Rep. 2016;4(5):519–522.
  • Talebi M, Talebi M, Farkhondeh T, et al. Molecular mechanism-based therapeutic properties of honey. Biomed Pharmacother. 2020/10/01/ 2020;130: 110590.
  • Farkhondeh T, Samarghandian S. Antidotal Effects of Curcumin Against Agents-Induced Cardiovascular Toxicity. Cardiovasc Hematol Disord Drug Targets. 2016;16(1):30–37.
  • Samarghandian S, Azimi‐Nezhad M, Borji A, Farkhondeh T. Effect of crocin on aged rat kidney through inhibition of oxidative stress and proinflammatory state.Phytotherapy research. 2016;30(8):1345–1353.
  • Samarghandian S, Borji A, Tabasi SH. Effects of Cichorium intybus linn on blood glucose, lipid constituents and selected oxidative stress parameters in streptozotocin-induced diabetic rats. Cardiovasc Hematol Disord Drug Targets. 2013 Dec;13(3):231–236.
  • Uddin MS, Hossain M, Mamun A, et al. Exploring the multimodal role of Phytochemicals in the modulation of cellular signaling pathways to Combat Age-Related neurodegeneration. SciTotal Environ. 07/10 2020;725: 138313.
  • Abe M, Bonini NM. MicroRNAs and neurodegeneration: role and impact. Trends Cell Biol. 2013 Jan;23(1):30–36.
  • Devi L, Prabhu BM, Galati DF, et al. Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer’s disease brain is associated with mitochondrial dysfunction. J Neurosci. 2006 Aug 30;26(35):9057–9068.
  • Manczak M, Anekonda TS, Henson E, et al. Mitochondria are a direct site of A beta accumulation in Alzheimer’s disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet. 2006 May 1;15(9):1437–1449.
  • Takuma K, Yao J, Huang J, et al. ABAD enhances Abeta-induced cell stress via mitochondrial dysfunction. Faseb J. 2005 Apr;19(6):597–598.
  • Casley CS, Canevari L, Land JM, et al. Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities. J Neurochem. 2002 Jan;80(1):91–100.
  • Perez Ortiz JM, Swerdlow RH. Mitochondrial dysfunction in Alzheimer’s disease: role in pathogenesis and novel therapeutic opportunities. Br J Pharmacol. 2019 Sep;176(18):3489–3507.
  • Sawikr Y, Yarla NS, Peluso I, et al. Neuroinflammation in Alzheimer’s Disease: the preventive and therapeutic potential of Polyphenolic Nutraceuticals. Adv Protein Chem Struct Biol. 2017;108:33–57.
  • Morales I, Guzmán-Martínez L, Cerda-Troncoso C, et al. Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Frontiers in Cellular Neuroscience. 2014;8:112.
  • Rangarajan P, Karthikeyan A, Dheen ST. Role of dietary phenols in mitigating microglia-mediated neuroinflammation. Neuromolecular Med. 2016 Sep;18(3):453–464.
  • Iqbal K, Liu F, Gong CX, et al. Tau in Alzheimer disease and related tauopathies. Curr Alzheimer Res. 2010 Dec;7(8):656–664.
  • Manoharan S, Guillemin GJ, Abiramasundari RS, et al. The role of reactive oxygen species in the pathogenesis of Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease: a Mini review. Oxid Med Cell Longev. 2016;2016:8590578.
  • Querfurth HW, LaFerla FM. Alzheimer’s Disease. N Engl J Med. 2010;362(4):329–344. 2010/01/28.
  • Du S, Readel E, Wey M, et al. Complete identification of all 20 relevant epimeric peptides in β-amyloid: a new HPLC-MS based analytical strategy for Alzheimer’s research. Chem Comm. 2020 January 10;56(10):1537–1540.
  • Lanoiselée HM, Nicolas G, Wallon D, et al. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: a genetic screening study of familial and sporadic cases. PLoS Med. 2017 Mar;14(3):e1002270.
  • Scheltens P, Blennow K, Breteler MMB, et al. Alzheimer’s disease. Lancet. 2016;388(10043):505–517.
  • O’Brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci. 2011;34(1):185–204.
  • Matsui T, Ingelsson M, Fukumoto H, et al. Expression of APP pathway mRNAs and proteins in Alzheimer’s disease. Brain Res. 2007;1161:116–123.
  • Li P, Marshall L, Oh G, et al. Epigenetic dysregulation of enhancers in neurons is associated with Alzheimer’s disease pathology and cognitive symptoms. Nat Commun. 2019 May 21;10(1):2246.
  • Guo T, Zhang D, Zeng Y, et al. Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease. Mol Neurodegener. 2020;15(1):40. 2020/07/16.
  • Zhao Y, Zhao B. Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid Med Cell Longev. 2013;2013:316523.
  • Crews L, Masliah E. Molecular mechanisms of neurodegeneration in Alzheimer’s disease. Hum Mol Genet. 2010;19(R1):R12–R20.
  • Kobayashi K, Nakano H, Hayashi M, et al. Association of phosphorylation site of tau protein with neuronal apoptosis in Alzheimer’s disease. J Neurol Sci. 2003;208(1):17–24. 2003/04/15.
  • Petrella C, Di Certo MG, Barbato C, et al. Neuropeptides in Alzheimer’s Disease: an update. Curr Alzheimer Res. 2019;16(6):544–558.
  • Long JM, Holtzman DM. Alzheimer Disease: an Update on Pathobiology and Treatment Strategies. Cell. 2019;179(2):312–339.
  • Agnihotri A, Aruoma OI. Alzheimer’s Disease and Parkinson’s Disease: a nutritional toxicology perspective of the impact of oxidative stress, Mitochondrial Dysfunction, nutrigenomics and environmental chemicals. J Am Coll Nutr. 2020 Jan;39(1):16–27.
  • Iqbal K, Liu F, Gong C-X. Tau and neurodegenerative disease: the story so far. Nat Rev Neurol. 2016;12(1):15.
  • Olajide O, Sarker S. Alzheimer’s disease: natural products as inhibitors of neuroinflammation. Inflammopharmacology. 2020;28(6):1439–1455. 09/15.
  • Magrone T, Magrone M, Russo MA, et al. Peripheral immunosenescence and central neuroinflammation: a dangerous Liaison. A dietary approach. Endocr Metab Immune Disord Drug Targets. 2020 Apr 6;20(9):1391–1411.
  • Mattson MP. Pathways towards and away from Alzheimer’s disease. Nature. 2004 Aug 5;430(7000):631–639.
  • Yamazaki Y, Zhao N, Caulfield TR, et al. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat Rev Neurol. 2019 Sep;15(9):501–518.
  • Van Der Lee SJ, Wolters FJ, Ikram MK, et al. The effect of APOE and other common genetic variants on the onset of Alzheimer’s disease and dementia: a community-based cohort study. Lancet Neurol. 2018;17(5):434–444.
  • Soares HD, Potter WZ, Pickering E, et al. Plasma biomarkers associated with the Apolipoprotein E Genotype and Alzheimer Disease. Arch Neurol. 2012;69(10):1310–1317.
  • Phillips MC. Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB Life. 2014 Sep;66(9):616–623.
  • Pardeshi R, Bolshette N, Gadhave K, et al. Insulin signaling: an opportunistic target to minify the risk of Alzheimer’s disease. Psychoneuroendocrinology. 2017 Sep;83:159–171.
  • Sanabria-Castro A, Alvarado-Echeverría I, Monge-Bonilla C. Molecular pathogenesis of Alzheimer’s Disease: an update. Ann Neurosci. 2017;24(1):46–54.
  • Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci. 2011 Nov 3;12(12):723–738.
  • Zhao Z, Nelson AR, Betsholtz C, et al. Establishment and Dysfunction of the Blood-Brain Barrier. Cell. 2015 Nov 19;163(5):1064–1078.
  • Andrade S, Ramalho MJ, Loureiro JA, Pereira MDC. Natural Compounds for Alzheimer's Disease Therapy: A Systematic Review of Preclinical and Clinical Studies. Int J Mol Sci. 2019 May 10;20(9):2313.
  • Yazdani E, Talebi M, Zarshenas MM, et al. Evaluation of possible antioxidant activities of barberry solid formulation, a selected formulation from traditional Persian medicine (TPM) via various procedures [Article]. Biointerf Res Appl Chem. 2019;9(6): 4517–1521.
  • defelice SL. The nutraceutical revolution: its impact on food industry R&D. Trends Food SciTechnol. 1995;6(2):59–61. 1995/02/01.
  • Makkar R, Behl T, Bungau S, et al. Nutraceuticals in neurological disorders. Int J Mol Sci. 2020;21(12):4424.
  • Ali A, Ahmad U, Akhtar J, et al. Engineered nano scale formulation strategies to augment efficiency of nutraceuticals. J Funct Foods. 2019/11/01/ 2019;62: 103554.
  • Gupta S, Parvez N, Sharma P. Nutraceuticals as functional foods. J Nutrit Therap. 2015;4(2):64–72.
  • Singh J, Sinha S. Classification, regulatory acts and applications of nutraceuticals for health. Int J Pharm Biol Sci. 2012;2: 177–187. 01/01.
  • Sullivan A, Nord CE. Probiotics and gastrointestinal diseases. J Intern Med. 2005 Jan;257(1):78–92.
  • Pan SJ, Kuo CH, Lam KP, et al. Probiotics and allergy in children–an update review. Pediatr Allergy Immunol. 2010 Jun;21(4 Pt 2):e659–66.
  • Gul K, Singh AK, Jabeen R. Nutraceuticals and Functional Foods: The Foods for the Future World. Crit Rev Food Sci Nutr. 2016 Dec 9;56(16):2617–27.
  • Poddar J, Pradhan M, Ganguly G, et al. Biochemical deficits and cognitive decline in brain aging: intervention by dietary supplements. J Chem Neuroanat. 2019 Jan;95:70–80.
  • Frank J, Fukagawa NK, Bilia AR, et al. Terms and nomenclature used for plant-derived components in nutrition and related research: efforts toward harmonization. Nutr Rev. 2020;78(6):451–458.
  • Erb M, Huber M, Robert CAM, et al. Chapter Two - The role of plant primary and secondary metabolites in Root-Herbivore behaviour, nutrition and physiology. In: Johnson SN, Hiltpold I, Turlings TCJ, editors Advances in insect physiology. Vol. 45, Academic Press; 2013. p. 53–95.
  • Brady RO, Schiffmann R. Enzyme-replacement therapy for metabolic storage disorders. Lancet Neurol. 2004 Dec;3(12):752–756.
  • Pandareesh MD, Kandikattu HK, Razack S, et al. Nutrition and nutraceuticals in neuroinflammatory and brain metabolic stress: implications for neurodegenerative disorders. CNS Neurol Disord Drug Targets. 2018;17(9):680–688.
  • Osadebe P, Odoh U, Uzor P. Natural products as potential sources of antidiabetic drugs. Br J Pharm Res. 2014;4(17):2075–2095. 01/10.
  • Patel DK, Prasad SK, Kumar R, et al. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Tropical Biomedicine. 2012 Apr;2(4):320–330.
  • Pitsikas N, Zisopoulou S, Tarantilis PA, et al. Effects of the active constituents of Crocus sativus L., crocins on recognition and spatial rats’ memory. Behav Brain Res. 2007 Nov 2;183(2):141–146.
  • Kennedy DO, Wightman EL. Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Advances in Nutrition (Bethesda, Md). 2011 Jan;2(1):32–50.
  • Rodríguez-García C, Sánchez-Quesada C, Gaforio J, J. Dietary Flavonoids as Cancer Chemopreventive Agents: an updated review of human studies. Antioxidants (Basel). 2019;8(5):137.
  • Soobrattee MA, Neergheen VS, Luximon-Ramma A, et al. Phenolics as potential antioxidant therapeutic agents: mechanism and actions. Mutat Res. 2005;579(1):200–213. 2005/11/11.
  • Pérez-Gálvez A, Jarén-Galán M, Garrido-Fernández J, et al. Activities, bioavailability, and metabolism of lipids from structural membranes and oils: promising research on mild cognitive impairment. Pharmacol Res. 2018 Aug;134:299–304.
  • Lange KW, Guo J, Kanaya S, et al. Medical foods in Alzheimer’s disease. Food Sci Human Wellness. 2019;8(1):1–7. 2019/03/01.
  • Dadhania VP, Trivedi PP, Vikram A, et al. Nutraceuticals against Neurodegeneration: a mechanistic insight. Curr Neuropharmacol. 2016;14(6):627–640.
  • Chiu HF, Venkatakrishnan K, Wang CK. The role of nutraceuticals as a complementary therapy against various neurodegenerative diseases: a mini-review. J Tradit Complement Med. 2020 Sep;10(5):434–439.
  • Witter S, Samoson A, Vilu R, et al. Screening of Nutraceuticals and Plant Extracts for Inhibition of Amyloid-β Fibrillation. J Alzheimers Dis. 2020;73(3):1003–1012.
  • Rigacci S, Stefani M. Nutraceuticals and amyloid neurodegenerative diseases: a focus on natural phenols. Expert Rev Neurother. 2015 Jan;15(1):41–52.
  • Murray F. Can Alzheimer’s disease be prevented? Intractable Rare Dis Res. 2013 Nov;2(4):136–138.
  • Agosti P, Custodero C, Schilardi A, et al. Nutritional interventions in patients with Alzheimer’s disease and other late-life cognitive disorders. J Gerontol Geriatrics. 2018;66:101–118, 01/01
  • Andrade V, Guzman-Martinez L, Cortés N, et al. The emergency of nutraceutical compounds in the preventive medicine scenario. Potential TreatAlzheimer’s Disease Other Chronic Disord. 2018 November 25;8:100–118.
  • Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016;5:e47–e47.
  • Waheed Janabi AH, Kamboh AA, Saeed M, et al. Flavonoid-rich foods (FRF): a promising nutraceutical approach against lifespan-shortening diseases. Iran J Basic Med Sci. 2020 Feb;23(2):140–153.
  • Cazarolli LH, Zanatta L, Alberton EH, et al. Flavonoids: prospective drug candidates. Mini Rev Med Chem. 2008 Nov;8(13):1429–1440.
  • Talebi M, Zarshenas M, Yazdani E, et al. Preparation and evaluation of possible antioxidant activities of Rose traditional tablet”[Qurs-e-Vard]” a selected Traditional Persian Medicine [TPM] formulation via various procedures. Curr Drug Discov Technol. 2020 Sep 29;17. DOI:10.2174/1570163817666200929114517
  • Pietta P-G. Flavonoids as Antioxidants. J Nat Prod. 2000;63(7):1035–1042. 2000/07/01.
  • Jung UJ, Kim SR. Beneficial Effects of Flavonoids Against Parkinson’s Disease. J Med Food. 2018 May;21(5):421–432.
  • Mozaffarian D, Wu JHY. Flavonoids, dairy foods, and Cardiovascular and Metabolic Health: a review of emerging biologic pathways. Circ Res. 2018 Jan 19;122(2):369–384.
  • Schroeter H, Boyd C, Spencer JP, et al. MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide. Neurobiol Aging. 2002 Sep-Oct;23(5):861–880.
  • Spencer JPE, Kuhnle GGC, Williams RJ, et al. Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites. Biochem J. 2003;372(Pt 1):173–181.
  • Ayaz M, Sadiq A, Junaid M, et al. Flavonoids as prospective neuroprotectants and their therapeutic propensity in aging associated neurological disorders. Front Aging Neurosci. 2019;11:155.
  • Hussain G, Zhang L, Rasul A, et al. Role of Plant-Derived Flavonoids and their mechanism in attenuation of Alzheimer’s and Parkinson’s Diseases: an update of recent data. Molecules. 2018 Apr 2;23(4):814.
  • Youdim KA, Dobbie MS, Kuhnle G, et al. Interaction between flavonoids and the blood–brain barrier: in vitro studies. J Neurochem. 2003;85(1):180–192. 2003/04/01.
  • Sonee M, Sum T, Wang C, et al. The Soy Isoflavone, Genistein, Protects Human Cortical Neuronal Cells from Oxidative Stress. NeuroToxicology. 2004;25(5):885–891. 2004/09/01.
  • Wang R, Tu J, Zhang Q, et al. Genistein attenuates ischemic oxidative damage and behavioral deficits via eNOS/Nrf2/HO-1 signaling. Hippocampus. 2013 Jul;23(7):634–647.
  • Kim H, Bang OY, Jung MW, et al. Neuroprotective effects of estrogen against beta-amyloid toxicity are mediated by estrogen receptors in cultured neuronal cells. Neurosci Lett. 2001 Apr 13;302(1):58–62.
  • Kwon Y. Luteolin as a potential preventive and therapeutic candidate for Alzheimer’s disease. Exp Gerontol. 2017 Sep;95:39–43.
  • Sawmiller D, Habib A, Li S, et al. Diosmin reduces cerebral Aβ levels, tau hyperphosphorylation, neuroinflammation, and cognitive impairment in the 3xTg-AD mice. J Neuroimmunol. 2016;299:98–106.
  • Sachdeva AK, Kuhad A, Chopra K. Naringin ameliorates memory deficits in experimental paradigm of Alzheimer’s disease by attenuating mitochondrial dysfunction. Pharmacol Biochem Behav. 2014;127:101–110. [ 2014/12/01].
  • Ghofrani S, Joghataei M-T, Mohseni S, et al. Naringenin improves learning and memory in an Alzheimer’s disease rat model: insights into the underlying mechanisms. Eur J Pharmacol. 2015/10/05 2015;764: 195–201.
  • Braidy N, Behzad S, Habtemariam S, et al. Neuroprotective effects of citrus Fruit-Derived Flavonoids, Nobiletin and Tangeretin in Alzheimer’s and Parkinson’s Disease. CNS Neurol Disord Drug Targets. 2017;16(4):387–397.
  • Wang X, Wang W, Li L, et al. Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta. 2014 Aug;1842(8):1240–1247.
  • Katalinić M, Rusak G, Domaćinović Barović J, et al. Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase. Eur J Med Chem. 2010 Jan;45(1):186–192.
  • Farkhondeh T, Pourbagher-Shahri A, Ashrafizadeh M, et al. Green tea catechins inhibit microglial activation which prevents the development of neurological disorders [Review]. Neural Regen Res. 2020 October 1;15(10):1792–1798. 2020.
  • Shimmyo Y, Kihara T, Akaike A, et al. Epigallocatechin-3-gallate and curcumin suppress amyloid beta-induced beta-site APP cleaving enzyme-1 upregulation. Neuroreport. 2008 Aug 27;19(13):1329–1333.
  • Rezai-Zadeh K, Arendash GW, Hou H, et al. Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res. 2008 Jun 12;1214:177–187.
  • Willem M, Tahirovic S, Busche MA, et al. η-Secretase processing of APP inhibits neuronal activity in the hippocampus. Nature. 2015 Oct 15;526(7573):443–447.
  • Calfio C, Gonzalez A, Singh SK, et al. The emerging role of nutraceuticals and phytochemicals in the prevention and treatment of Alzheimer’s Disease. J Alzheimers Dis. 2020;77(1):33–51.
  • Zhao S, Zhang L, Yang C, et al. Procyanidins and Alzheimer’s Disease. Mol Neurobiol. 2019 Aug;56(8):5556–5567.
  • Löffler T, Flunkert S, Temmel M, et al. Decreased Plasma Aβ in Hyperlipidemic APPSL Transgenic mice is associated with BBB Dysfunction. Front Neurosci. 2016;10:232.
  • Yang X, Dai G, Li G, et al. Coenzyme Q10 reduces beta-amyloid plaque in an APP/PS1 transgenic mouse model of Alzheimer’s disease. J Mol Neurosci. 2010 May;41(1):110–113.
  • Guo H, Cao H, Cui X, et al. Silymarin’s inhibition and treatment effects for Alzheimer’s Disease. Molecules. 2019;24(9):1748.
  • Kouhestani S, Jafari A, Babaei P. Kaempferol attenuates cognitive deficit via regulating oxidative stress and neuroinflammation in an ovariectomized rat model of sporadic dementia. Neural Regen Res. 2018;13(10):1827–1832.
  • Omar SH. Biophenols pharmacology against the amyloidogenic activity in Alzheimer’s disease. Biomed Pharmacothe. 2017 May;89:396–413.
  • Sadhukhan P, Saha S, Dutta S, et al. Nutraceuticals: an emerging therapeutic approach against the pathogenesis of Alzheimer’s disease. Pharmacol Res. 2018 Mar;129:100–114.
  • Mecocci P, Tinarelli C, Schulz RJ, et al. Nutraceuticals in cognitive impairment and Alzheimer’s disease. Front Pharmacol. 2014;5:147.
  • Mori T, Koyama N, Tan J, et al. Combined treatment with the phenolics (-)-epigallocatechin-3-gallate and ferulic acid improves cognition and reduces Alzheimer-like pathology in mice. J Biol Chem. 2019 Feb 22;294(8):2714–2731.
  • Berman AY, Motechin RA, Wiesenfeld MY, et al. The therapeutic potential of resveratrol: a review of clinical trials. NPJ Precis Oncol. 2017;1(1):35. 2017/09/25.
  • Meng X, Zhou J, Zhao CN, et al. Health benefits and molecular mechanisms of Resveratrol: a narrative review. Foods. 2020 Mar 14;9(3). DOI:10.3390/foods9030340.
  • Virmani A, Pinto L, Binienda Z, et al. Food, nutrigenomics, and neurodegeneration–neuroprotection by what you eat! Mol Neurobiol. 2013 Oct;48(2):353–362.
  • Kocaadam B, Şanlier N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit Rev Food Sci Nutr. 2017 Sep 2;57(13):2889–2895.
  • Hewlings SJ, Kalman DS. Curcumin: a Review of Its Effects on Human Health. Foods. 2017;6(10):92.
  • Pagano E, Romano B, Izzo AA, et al. The clinical efficacy of curcumin-containing nutraceuticals: an overview of systematic reviews. Pharmacol Res. 2018 Aug;134:79–91.
  • Giri RK, Rajagopal V, Kalra VK. Curcumin, the active constituent of turmeric, inhibits amyloid peptide-induced cytochemokine gene expression and CCR5-mediated chemotaxis of THP-1 monocytes by modulating early growth response-1 transcription factor. J Neurochem. 2004 Dec;91(5):1199–1210.
  • Qin X, Wang Y, Paudel HK. Inhibition of Early Growth Response 1 in the Hippocampus Alleviates Neuropathology and improves cognition in an Alzheimer Model with Plaques and Tangles. Am J Pathol. 2017 Aug;187(8):1828–1847.
  • Lim GP, Chu T, Yang F, et al. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001 Nov 1;21(21):8370–8377.
  • Serafini MM, Catanzaro M, Rosini M, et al. Curcumin in Alzheimer’s disease: can we think to new strategies and perspectives for this molecule? Pharmacol Res. 2017 Oct;124:146–155.
  • Murphy MP. Amyloid-Beta Solubility in the treatment of Alzheimer’s Disease. N Engl J Med. 2018;378(4):391–392. 2018/01/25.
  • Sikora E, Scapagnini G, Barbagallo M. Curcumin, inflammation, ageing and age-related diseases. Immun Ageing. 2010 Jan 17;7(1):1.
  • Sikora E, Bielak-Zmijewska A, Mosieniak G, et al. The promise of slow down ageing may come from curcumin. Curr Pharm Des. 2010;16(7):884–892.
  • Craft NE, Haitema TB, Garnett KM, et al. Carotenoid, tocopherol, and retinol concentrations in elderly human brain. J Nutr Health Aging. 2004;8(3):156–162.
  • Ding Y, Qiao A, Wang Z, et al. Retinoic acid attenuates beta-amyloid deposition and rescues memory deficits in an Alzheimer’s disease transgenic mouse model. J Neurosci. 2008 Nov 5;28(45):11622–11634.
  • Dheen ST, Jun Y, Yan Z, et al. Retinoic acid inhibits expression of TNF-alpha and iNOS in activated rat microglia. Glia. 2005 Apr 1;50(1):21–31.
  • Sachdeva AK, Chopra K. Lycopene abrogates Aβ(1-42)-mediated neuroinflammatory cascade in an experimental model of Alzheimer’s disease. J Nutr Biochem. 2015 Jul;26(7):736–744.
  • Qu M, Jiang Z, Liao Y, et al. Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative stress and dysfunctions in cultured rat cortical neurons. Neurochem Res. 2016 Jun;41(6):1354–1364.
  • Talebi M, Talebi M, Samarghandian S. Association of Crocus sativus with Cognitive Dysfunctions and Alzheimer’s Disease: a systematic review. Biointerf Res Appl Chem. 2021;11(1):7468–7492.
  • Tarantilis PA, Tsoupras G, Polissiou M. Determination of saffron (Crocus sativus L.) components in crude plant extract using high-performance liquid chromatography-UV-visible photodiode-array detection-mass spectrometry. J Chromatogr A. 1995 May 5;699(1–2):107–118.
  • Hatziagapiou K, Kakouri E, Lambrou GI, et al. Antioxidant properties of Crocus Sativus L. and its constituents and relevance to neurodegenerative diseases; focus on Alzheimer’s and Parkinson’s disease. Curr Neuropharmacol. 2019;17(4):377–402.
  • Ahn JH, Hu Y, Hernandez M, et al. Crocetin inhibits beta-amyloid fibrillization and stabilizes beta-amyloid oligomers. Biochem Biophys Res Commun. 2011 Oct 14;414(1):79–83.
  • Hook V, Yoon M, Mosier C, et al. Cathepsin B in neurodegeneration of Alzheimer’s disease, traumatic brain injury, and related brain disorders. Biochimica Et Biophysica Acta Proteins and Proteomics. 2020 Aug;1868(8):140428.
  • Tiribuzi R, Crispoltoni L, Chiurchiù V, et al. Trans-crocetin improves amyloid-β degradation in monocytes from Alzheimer’s Disease patients. J Neurol Sci. 2017 Jan;15(372):408–412.
  • Zhang J, Wang Y, Dong X, et al. Crocetin attenuates inflammation and amyloid-β accumulation in APPsw transgenic mice. Immunity Ageing. 2018;15(1):24. 2018/10/30.
  • Chalatsa I, Arvanitis DA, Koulakiotis NS, et al. The Crocus sativus Compounds trans-Crocin 4 and trans-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models. Front Neurosci. 2019;13:249.
  • Ghahghaei A, Bathaie SZ, Kheirkhah H, et al. The protective effect of crocin on the amyloid fibril formation of Aβ42 peptide in vitro. Cell Mol Biol Lett. 2013 Sep;18(3):328–339.
  • Akhondzadeh S, Shafiee Sabet M, Harirchian MH, et al. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacology (Berl). 2010 Jan;207(4):637–643.
  • Asadi F, Jamshidi AH, Khodagholi F, et al. Reversal effects of crocin on amyloid β-induced memory deficit: modification of autophagy or apoptosis markers. Pharmacol Biochem Behav. 2015/12/01 2015;139: 47–58.
  • Karakani AM, Riazi G, Mahmood Ghaffari S, et al. Inhibitory effect of corcin on aggregation of 1N/4R human tau protein in vitro. Iran J Basic Med Sci. 2015 May;18(5):485–492.
  • Papandreou MA, Kanakis CD, Polissiou MG, et al. Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem. 2006 Nov 15;54(23):8762–8768.
  • Shaterzadeh-Yazdi H, Samarghandian S, Farkhondeh T. Effects of Crocins in the management of neurodegenerative pathologies: a review. Neurophysiology. 2018;50(4):302–308. 2018/08/01.
  • Wang D, Dong X, Wang B, et al. Geraniin Attenuates Lipopolysaccharide-Induced cognitive impairment in mice by inhibiting Toll-Like receptor 4 activation. J Agric Food Chem. 2019;67(36):10079–10088. 2019/09/11.
  • Braidy N, Jugder BE, Poljak A, et al. Molecular targets of Tannic Acid in Alzheimer’s disease. Curr Alzheimer Res. 2017;14(8):861–869.
  • Egea J, Martín-de-Saavedra MD, Parada E, et al. Galantamine elicits neuroprotection by inhibiting iNOS, NADPH oxidase and ROS in hippocampal slices stressed with anoxia/reoxygenation. Neuropharmacology. 2012 Feb;62(2):1082–90.
  • Scott LJ, Goa KL. Galantamine: a review of its use in Alzheimer’s disease. Drugs. 2000 Nov;60(5):1095–1122.
  • Egea J, Martín-de-saavedra MD, Parada E, et al. Galantamine elicits neuroprotection by inhibiting iNOS, NADPH oxidase and ROS in hippocampal slices stressed with anoxia/reoxygenation. Neuropharmacology. 2012;62(2):1082–1090. 2012/02/01.
  • Wang R, Yan H, Tang X-C. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin. 2006;27(1):1–26. 2006/01/01.
  • Tao L-X, Huang X-T, Chen Y-T, et al. Acetylcholinesterase-independent protective effects of huperzine A against iron overload-induced oxidative damage and aberrant iron metabolism signaling in rat cortical neurons. Acta Pharmacol Sin. 2016;37(11):1391–1400. 2016/11/01.
  • Simunkova M, Alwasel SH, Alhazza IM, et al. Management of oxidative stress and other pathologies in Alzheimer’s disease. Arch Toxicol. 2019;93(9):2491–2513.
  • Xiao XQ, Zhang HY, Tang XC. Huperzine A attenuates amyloid beta-peptide fragment 25-35-induced apoptosis in rat cortical neurons via inhibiting reactive oxygen species formation and caspase-3 activation. J Neurosci Res. 2002 Jan 1;67(1):30–36.
  • Ma T, Gong K, Yan Y, et al. Huperzine A promotes hippocampal neurogenesis in vitro and in vivo. Brain Res. 2013 Apr 19;1506:35–43.
  • Yu G, Li Y, Tian Q, et al. Berberine attenuates calyculin A-induced cytotoxicity and Tau hyperphosphorylation in HEK293 cells. J Alzheimers Dis. 2011;24(3):525–535.
  • Roshanravan B, Yousefizadeh S, Apaydin Yildirim B, et al. The effects of Berberis vulgaris L. and Berberis aristata L. in metabolic syndrome patients: a systematic and meta-analysis study. Arch Physiol Biochem. 2020;1–12. Available from: https://doi.org/10.1080/13813455.2020.1828482.
  • Dall’Igna OP, Fett P, Gomes MW, et al. Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cognitive deficits in mice. Exp Neurol. 2007 Jan;203(1):241–245.
  • Cao C, Cirrito JR, Lin X, et al. Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer’s disease transgenic mice. J Alzheimers Dis. 2009;17(3):681–697.
  • Kim JW, Byun MS, Yi D, et al. Coffee intake and decreased amyloid pathology in human brain. Transl Psychiatry. 2019;9(1):270. 2019/10/22.
  • Howes MR, Perry NSL, Vásquez-Londoño C, et al. Role of phytochemicals as nutraceuticals for cognitive functions affected in ageing. Br J Pharmacol. 2020 Mar;177(6):1294–1315.
  • Oboh G, Adedayo BC, Adetola MB, et al. Characterization and neuroprotective properties of alkaloid extract of Vernonia amygdalina Delile in experimental models of Alzheimer’s disease. Drug Chem Toxicol. 2020 Jun;16:1–10.
  • Oboh G, Ademosun AO, Ogunsuyi OB, et al. In vitro anticholinesterase, antimonoamine oxidase and antioxidant properties of alkaloid extracts from kola nuts (Cola acuminata and Cola nitida). J Complement Integr Med. 2018 Jul 18;16(1). DOI:10.1515/jcim-2016-0155.
  • Talebi M, Talebi M, Farkhondeh T, et al. Biological and therapeutic activities of Thymoquinone: focus on the Nrf2 signaling pathway. Phytother Res. 2020;35(4):1739–1753.
  • Farkhondeh T, Samarghandian S, Shahri AMP, et al. The neuroprotective effects of Thymoquinone: a review. Dose-resp Publ Int Horm Soc. 2018 Apr-Jun;16(2):1559325818761455.
  • Cascella M, Bimonte S, Barbieri A, et al. Dissecting the potential roles of Nigella sativa and its constituent Thymoquinone on the prevention and on the progression of Alzheimer’s disease. Front Aging Neurosci. 2018;10:16.
  • Taram F, Ignowski E, Duval N, et al. Neuroprotection comparison of Rosmarinic Acid and Carnosic Acid in primary cultures of cerebellar granule neurons. Molecules. 2018 Nov 13;23(11):2956.
  • Bazinet RP, Layé S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci. 2014;15(12):771–785. 2014/12/01.
  • Bentsen H. Dietary polyunsaturated fatty acids, brain function and mental health. Microb Ecol Health Dis. 2017;28(sup1):1281916.
  • Young J, Wahle KW, Boyle SP. Cytoprotective effects of phenolic antioxidants and essential fatty acids in human blood monocyte and neuroblastoma cell lines: surrogates for neurological damage in vivo. Prostaglandins Leukot Essent Fatty Acids. 2008 Jan;78(1):45–59.
  • Dong Y, Xu M, Kalueff AV, et al. Dietary eicosapentaenoic acid normalizes hippocampal omega-3 and 6 polyunsaturated fatty acid profile, attenuates glial activation and regulates BDNF function in a rodent model of neuroinflammation induced by central interleukin-1β administration. Eur J Nutr. 2018 Aug;57(5):1781–1791.
  • Grimm MO, Kuchenbecker J, Grösgen S, et al. Docosahexaenoic acid reduces amyloid beta production via multiple pleiotropic mechanisms. J Biol Chem. 2011 Apr 22;286(16):14028–14039.
  • Oppedisano F, Maiuolo J, Gliozzi M, et al. The potential for natural antioxidant supplementation in the early stages of neurodegenerative disorders. Int J Mol Sci. 2020 Apr 9;21(7):2618.
  • Freund Levi Y, Vedin I, Cederholm T, et al. Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer’s disease: the OmegAD study. J Intern Med. 2014 Apr;275(4):428–436.
  • Arellanes IC, Choe N, Solomon V, et al. Brain delivery of supplemental docosahexaenoic acid (DHA): a randomized placebo-controlled clinical trial. EBioMedicine. 2020;59. DOI:10.1016/j.ebiom.2020.102883.
  • Casagrande D, Waib PH, Jordão Júnior AA. Mechanisms of action and effects of the administration of Coenzyme Q10 on metabolic syndrome. J Nutrit Intermed Metabol. 2018;13:26–32. [ 2018/09/01].
  • Ibrahim FG. Combination of Omega 3 and Coenzyme Q10 exerts neuroprotective potential against Hypercholesterolemia-Induced Alzheimer’s-Like disease in rats. Neurochem Res. 2020 May;45(5):1142–1155.
  • Dumont M, Kipiani K, Yu F, et al. Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis. 2011;27(1):211–223.
  • Sharman MJ, Gyengesi E, Liang H, et al. Assessment of diets containing curcumin, epigallocatechin-3-gallate, docosahexaenoic acid and α-lipoic acid on amyloid load and inflammation in a male transgenic mouse model of Alzheimer’s disease: are combinations more effective? Neurobiol Dis. 2019 Apr;124:505–519.
  • Hossain MF, Uddin MS, Uddin GMS, et al. Melatonin in Alzheimer’s Disease: a latent endogenous regulator of neurogenesis to mitigate Alzheimer’s Neuropathology. Mol Neurobiol. 2019;56(12):8255–8276. 2019/12/01.
  • Vincent B. Protective roles of melatonin against the amyloid-dependent development of Alzheimer’s disease: a critical review. Pharmacol Res. 2018;134:223–237. [ 2018/08/01s].
  • Mancuso C, Siciliano R, Barone E, et al. Natural substances and Alzheimer’s disease: from preclinical studies to evidence based medicine. Biochim Biophys Acta. 2012 May;1822(5):616–624.
  • Rehman MU, Wali AF, Ahmad A, et al. Neuroprotective strategies for neurological disorders by natural products: an update. Curr Neuropharmacol. 2019;17(3):247–267.
  • Li W, Guo J, Shen Y, et al. Probiotics, prebiotics, and synbiotics for the treatment of dementia: protocol for a systematic review. Medicine (Baltimore). 2020;99(5):e18608.
  • Castelli V, d’Angelo M, Quintiliani M, et al. The emerging role of probiotics in neurodegenerative diseases: new hope for Parkinson’s disease? Neural Regen Res. 2021 Apr;16(4):628–634.
  • Vasquez EC, Aires R, Ton AMM, et al. New insights on the beneficial effects of the probiotic Kefir on vascular dysfunction in cardiovascular and neurodegenerative diseases. Curr Pharm Des. 2020;26(30):3700–3710.
  • Serra D, Almeida LM, Dinis TCP. Polyphenols in the management of brain disorders: modulation of the microbiota-gut-brain axis. Adv Food Nutr Res. 2020;91:1–27.
  • Zhuang ZQ, Shen LL, Li WW, et al. Gut Microbiota is altered in patients with Alzheimer’s Disease. J Alzheimers Dis. 2018;63(4):1337–1346.
  • Pistollato F, Sumalla Cano S, Elio I, et al. Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease. Nutr Rev. 2016;74(10):624–634.
  • Liu S, Gao J, Zhu M, et al. Gut Microbiota and Dysbiosis in Alzheimer’s disease: implications for Pathogenesis and treatment. Mol Neurobiol. 2020;57(12):5026–5043. 2020/12/01.
  • Leblhuber F, Steiner K, Schuetz B, et al. Probiotic Supplementation in Patients with Alzheimer’s Dementia - An Explorative Intervention Study. Curr Alzheimer Res. 2018 August 13;15(12):1106–1113.
  • Pluta R, Ułamek-Kozioł M, Januszewski S, et al. Gut microbiota and pro/prebiotics in Alzheimer’s disease. Aging (Albany NY). 2020;12(6):5539–5550.
  • Ton AMM, Campagnaro BP, Alves GA, et al. Oxidative stress and dementia in Alzheimer’s Patients: effects of synbiotic supplementation. Oxid Med Cell Longev. 2020/01/13 2020;2020: 2638703.
  • Westfall S, Lomis N, Prakash S. A novel synbiotic delays Alzheimer’s disease onset via combinatorial gut-brain-axis signaling in Drosophila melanogaster. PloS One. 2019;14(4):e0214985.
  • Phan CW, David P, Sabaratnam V. Edible and medicinal mushrooms: emerging brain food for the mitigation of neurodegenerative diseases. J Med Food. 2017 Jan;20(1):1–10.
  • Olasehinde TA, Olaniran AO, Okoh AI. Aqueous-ethanol extracts of some South African seaweeds inhibit beta-amyloid aggregation, cholinesterases, and beta-secretase activities in vitro. Journal of Food Biochem. 2019 Jul;43(7):e12870.
  • Olasehinde TA, Olaniran AO, Okoh AI. Therapeutic Potentials of Microalgae in the Treatment of Alzheimer’s Disease. Molecules. 2017 Mar 18;22(3). DOI:10.3390/molecules22030480.
  • Liu K, Lin -H-H, Pi R, et al. Research and development of anti-Alzheimer’s disease drugs: an update from the perspective of technology flows. Expert Opin Ther Pat. 2018;28(4):341–350. 2018/04/03.
  • Mehta D, Jackson R, Paul G, et al. Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert Opin Investig Drugs. 2017;26(6):735–739.
  • Yiannopoulou KG, Papageorgiou SG. ElsevierElsevierte. J Cent Nerv Syst Dis. 2020;12:1179573520907397. [ 2020/01/01].
  • Rashid U, Ansari FL. Chapter 2 - Challenges in designing therapeutic agents for treating Alzheimer’s disease-from serendipity to rationality. In: Atta Ur R, Choudhary MI, editors. Drug Design and Discovery in Alzheimer’s Disease. Elsevier:Bentham Science Publishers. 2014. p. 40–141.
  • Cummings J, Aisen PS, DuBois B, et al. Drug development in Alzheimer’s disease: the path to 2025. Alzheimer’s Res Ther. 2016;8(1):39. 2016/09/20.
  • Cacabelos R. Have there been improvements in Alzheimer’s disease drug discovery over the past 5 years? Expert Opin Drug Discov. 2018;13(6):523–538. 2018/06/03.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.