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Therapeutic Potential of Polyphenols in Alzheimer’s Therapy: Broad-Spectrum and Minimal Side Effects as Key Aspects

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Autism Spectrum Disorder and Alzheimer's Disease

Abstract

Alzheimer’s disease (AD) is a degenerative brain disease that is the leading cause of dementia among the human population. AD is characterized by accumulating amyloid plaques which are insoluble deposits of a 4 kDa peptide of ~40–42 amino acids in length, known as amyloid-β (Aβ). The imbalance between Aβ generation and clearance in the brain leads to the progression of AD. AD pathology is characterized by the deposition of oligomeric and fibrillar forms of amyloid-β (Aβ) in the neuropil and cerebral vessel walls. Neurofibrillary tangles are composed mainly of hyperphosphorylated tau and neurodegeneration. Polyphenols are the most abundant antioxidants in the diet. More than 8000 naturally occurring polyphenols exist.

Numerous studies have indicated that high consumption of fruits and vegetables rich in flavonoids and other polyphenols reduces the risk/incidence of age-related neurodegenerative disorders, highlighting the importance of these polyphenols as neuroprotective agents. Due to polyphenols’ ability to influence and modulate multiple targets in the cascade of the pathogenesis of neurodegenerative diseases, they are considered a candidate with a promising result against neurodegeneration, halting the progression of the disease. There is now substantial evidence indicating that oxidative damage to the brain is an early AD pathogenesis event. Oxidative stress and damage to brain macromolecules are vital processes in neurodegenerative diseases. The antioxidant properties of many polyphenols are purported to provide neuroprotection. There are pieces of evidence that some of the polyphenols can easily cross the blood-brain barrier (BBB). This chapter will provide deeper insights into various polyphenols that play a pivotal role in AD and shed light on the roles of these in the context of AD therapeutics.

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References

  • Abdalla FH, Cardoso AM et al (2013) Neuroprotective effect of quercetin in ectoenzymes and acetylcholinesterase activities in cerebral cortex synaptosomes of cadmium-exposed rats. Mol Cell Biochem 381(1–2):1–8

    Article  CAS  PubMed  Google Scholar 

  • Abdalla FH, Schmatz R et al (2014) Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: possible involvement of the acetylcholinesterase and Na+, K+-ATPase activities. Physiol Behav 135:152–167

    Article  CAS  PubMed  Google Scholar 

  • Adlercreutz H, Mazur W (1997) Phyto-oestrogens and Western diseases. Ann Med 29(2):95–120

    Article  CAS  PubMed  Google Scholar 

  • Akiyama S, Katsumata S-I et al (2009) Dietary hesperidin exerts hypoglycemic and hypolipidemic effects in streptozotocin-induced marginal type 1 diabetic rats. J Clin Biochem Nutr 46(1):87–92

    Article  PubMed  PubMed Central  Google Scholar 

  • Alok S, Jain SK et al (2014) Herbal antioxidant in clinical practice: a review. Asian Pac J Trop Biomed 4(1):78–84

    Article  PubMed  PubMed Central  Google Scholar 

  • Anwar S, Shamsi A et al (2020) Rosmarinic acid exhibits anticancer effects via MARK4 inhibition. Sci Rep 10(1):1–13

    Article  Google Scholar 

  • Aquilano K, Baldelli S et al (2008) Role of nitric oxide synthases in Parkinson’s disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem Res 33(12):2416–2426

    Article  CAS  PubMed  Google Scholar 

  • Arent SM, Senso M et al (2010) The effects of theaflavin-enriched black tea extract on muscle soreness, oxidative stress, inflammation, and endocrine responses to acute anaerobic interval training: a randomized, double-blind, crossover study. J Int Soc Sports Nutr 7(1):1–10

    Article  Google Scholar 

  • Bahadoran Z, Mirmiran P et al (2013) Dietary polyphenols as potential nutraceuticals in management of diabetes: a review. J Diabetes Metab Disord 12(1):43

    Article  PubMed  PubMed Central  Google Scholar 

  • Bate-Smith E, Swain T et al (1962) Comparative biochemistry. In: Mason HS, Florkin M (eds) vol 3, p 764

    Google Scholar 

  • Baum L, Ng A (2004) Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimers Dis 6(4):367–377

    Article  CAS  PubMed  Google Scholar 

  • Baur JA, Pearson KJ et al (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444(7117):337–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bieschke J, Russ J et al (2010) EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity. Proc Natl Acad Sci 107(17):7710–7715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bogdanski P, Suliburska J et al (2012) Green tea extract reduces blood pressure, inflammatory biomarkers, and oxidative stress and improves parameters associated with insulin resistance in obese, hypertensive patients. Nutr Res 32(6):421–427

    Article  CAS  PubMed  Google Scholar 

  • Braak H, Braak E et al (1996) Pattern of brain destruction in Parkinson’s and Alzheimer’s diseases. J Neural Transm 103(4):455–490

    Article  CAS  PubMed  Google Scholar 

  • Brettschneider J, Del Tredici K et al (2015) Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci 16(2):109–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruno RS, Bomser JA et al (2014) Antioxidant capacity of green tea (Camellia sinensis). Processing and impact on antioxidants in beverages. Elsevier, pp 33–39

    Book  Google Scholar 

  • Bugg CW, Isas JM et al (2012) Structural features and domain organization of huntingtin fibrils. J Biol Chem 287(38):31739–31746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caruana M, Cauchi R et al (2016) Putative role of red wine polyphenols against brain pathology in Alzheimer’s and Parkinson’s disease. Front Nutr 3:31

    Article  PubMed  PubMed Central  Google Scholar 

  • Cassidy A, Hanley B et al (2000) Isoflavones, lignans and stilbenes–origins, metabolism and potential importance to human health. J Sci Food Agric 80(7):1044–1062

    Article  CAS  Google Scholar 

  • Cheynier V, Comte G et al (2013) Plant phenolics: recent advances on their biosynthesis, genetics, and ecophysiology. Plant Physiol Biochem 72:1–20

    Article  CAS  PubMed  Google Scholar 

  • Choi Y-T, Jung C-H et al (2001) The green tea polyphenol (−)-epigallocatechin gallate attenuates β-amyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci 70(5):603–614

    Article  CAS  PubMed  Google Scholar 

  • Cornejo A, Aguilar Sandoval F et al (2017) Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer’s disease. J Enzyme Inhib Med Chem 32(1):945–953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Costa LG, Garrick JM et al (2016) Mechanisms of neuroprotection by quercetin: counteracting oxidative stress and more. Oxidative Med Cell Longev 2016

    Google Scholar 

  • da Silva Pinto M (2013) Tea: a new perspective on health benefits. Food Res Int 53(2):558–567

    Article  Google Scholar 

  • Dahiya R, Mohammad T et al (2019a) Molecular interaction studies on ellagic acid for its anticancer potential targeting pyruvate dehydrogenase kinase 3. RSC Adv 9(40):23302–23315

    Article  CAS  Google Scholar 

  • Dahiya R, Mohammad T et al (2019b) Investigation of inhibitory potential of quercetin to the pyruvate dehydrogenase kinase 3: towards implications in anticancer therapy. Int J Biol Macromol 136:1076–1085

    Article  CAS  PubMed  Google Scholar 

  • Daniel S, Limson JL et al (2004) Through metal binding, curcumin protects against lead-and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J Inorg Biochem 98(2):266–275

    Article  CAS  PubMed  Google Scholar 

  • Das J, Ramani R et al (2016) Polyphenol compounds and PKC signaling. Biochim Biophys Acta (BBA) Gen Subjects 1860(10):2107–2121

    Article  CAS  Google Scholar 

  • Eid HM, Martineau LC et al (2010) Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea. Mol Nutr Food Res 54(7):991–1003

    Article  CAS  PubMed  Google Scholar 

  • Fiala M, Liu PT et al (2007) Innate immunity and transcription of MGAT-III and toll-like receptors in Alzheimer’s disease patients are improved by bisdemethoxycurcumin. Proc Natl Acad Sci U S A 104(31):12849–12854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Figueira I, Garcia G et al (2017) Polyphenols journey through blood-brain barrier towards neuronal protection. Sci Rep 7(1):1–16

    Article  CAS  Google Scholar 

  • Ganguli M, Chandra V et al (2000) Apolipoprotein E polymorphism and Alzheimer disease: the Indo-US cross-national dementia study. Arch Neurol 57(6):824–830

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Alloza M, Borrelli L et al (2007) Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem 102(4):1095–1104

    Article  CAS  PubMed  Google Scholar 

  • Griffioen G, Duhamel H et al (2006) A yeast-based model of α-synucleinopathy identifies compounds with therapeutic potential. Biochim Biophys Acta (BBA) Mol Basis Dis 1762(3):312–318

    Article  CAS  Google Scholar 

  • Guo S, Bezard E et al (2005) Protective effect of green tea polyphenols on the SH-SY5Y cells against 6-OHDA induced apoptosis through ROS–NO pathway. Free Radic Biol Med 39(5):682–695

    Article  CAS  PubMed  Google Scholar 

  • Gupta A, Vij G et al (2009) Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model. Immunobiology 214(1):33–39

    Article  CAS  PubMed  Google Scholar 

  • Gupta P, Mohammad T et al (2019a) Evaluation of binding and inhibition mechanism of dietary phytochemicals with sphingosine kinase 1: towards targeted anticancer therapy. Sci Rep 9(1):1–15

    Article  Google Scholar 

  • Gupta P, Mohammad T et al (2019b) Evaluation of ellagic acid as an inhibitor of sphingosine kinase 1: a targeted approach towards anticancer therapy. Biomed Pharmacother 118:109245

    Article  CAS  PubMed  Google Scholar 

  • Han X, Shen T et al (2007) Dietary polyphenols and their biological significance. Int J Mol Sci 8(9):950–988

    Article  CAS  PubMed Central  Google Scholar 

  • Haque AM, Hashimoto M et al (2006) Long-term administration of green tea catechins improves spatial cognition learning ability in rats. J Nutr 136(4):1043–1047

    Article  CAS  PubMed  Google Scholar 

  • Hartman RE, Shah A et al (2006) Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer’s disease. Neurobiol Dis 24(3):506–515

    Article  CAS  PubMed  Google Scholar 

  • Hase T, Shishido S et al (2019) Rosmarinic acid suppresses Alzheimer’s disease development by reducing amyloid β aggregation by increasing monoamine secretion. Sci Rep 9(1):1–13

    Article  CAS  Google Scholar 

  • Hashemzaei M, Delarami Far A et al (2017) Anticancer and apoptosis-inducing effects of quercetin in vitro and in vivo. Oncol Rep 38(2):819–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hewlings SJ, Kalman DS (2017) Curcumin: a review of its’ effects on human health. Foods 6(10):92

    Article  PubMed Central  Google Scholar 

  • Ho L, Chen LH et al (2009) Heterogeneity in red wine polyphenolic contents differentially influences Alzheimer’s disease-type neuropathology and cognitive deterioration. J Alzheimers Dis 16(1):59–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu N, Yu J-T et al (2013) Nutrition and the risk of Alzheimer’s disease. BioMed Res Int 2013:524820

    Article  PubMed  PubMed Central  Google Scholar 

  • Imran A, Arshad MU et al (2018) Lipid peroxidation diminishing perspective of isolated theaflavins and thearubigins from black tea in arginine induced renal malfunctional rats. Lipids Health Dis 17(1):157

    Article  PubMed  PubMed Central  Google Scholar 

  • Iuvone T, De Filippis D et al (2006) The spice sage and its active ingredient rosmarinic acid protect PC12 cells from amyloid-β peptide-induced neurotoxicity. J Pharmacol Exp Ther 317(3):1143–1149

    Article  CAS  PubMed  Google Scholar 

  • Jalel A, Soumaya GS et al (2009) Vitiligo treatment with vitamins, minerals and polyphenol supplementation. Indian J Dermatol 54(4):357

    Article  PubMed  PubMed Central  Google Scholar 

  • Jantan I, Ahmad W et al (2015) Plant-derived immunomodulators: an insight on their preclinical evaluation and clinical trials. Front Plant Sci 6:655

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang W, Luo T et al (2016) Quercetin protects against okadaic acid-induced injury via MAPK and PI3K/Akt/GSK3β signaling pathways in HT22 hippocampal neurons. PLoS One 11(4):e0152371

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiménez-Flores LM, López-Briones S et al (2014) A PPARγ, NF-κB and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver. Molecules 19(6):8289–8302

    Article  PubMed  PubMed Central  Google Scholar 

  • Johnston K, Sharp P et al (2005) Dietary polyphenols decrease glucose uptake by human intestinal Caco-2 cells. FEBS Lett 579(7):1653–1657

    Article  CAS  PubMed  Google Scholar 

  • Joseph JA, Shukitt-Hale B et al (2005) Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr 81(1):313S–316S

    Article  CAS  PubMed  Google Scholar 

  • Kalfon L, Youdim MB et al (2007) Green tea polyphenol (-)-epigallocatechin-3-gallate promotes the rapid protein kinase C-and proteasome-mediated degradation of bad: implications for neuroprotection. J Neurochem 100(4):992–1002

    Article  CAS  PubMed  Google Scholar 

  • Kaltschmidt B, Uherek M et al (1997) Transcription factor NF-κB is activated in primary neurons by amyloid β peptides and in neurons surrounding early plaques from patients with Alzheimer disease. Proc Natl Acad Sci 94(6):2642–2647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaltschmidt B, Uherek M et al (1999) Inhibition of NF-κB potentiates amyloid β-mediated neuronal apoptosis. Proc Natl Acad Sci 96(16):9409–9414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaulmann A, Bohn T (2016) Bioactivity of polyphenols: preventive and adjuvant strategies toward reducing inflammatory bowel diseases—promises, perspectives, and pitfalls. Oxidative Med Cell Longev 2016

    Google Scholar 

  • Kaur T, Hussain K et al (2013) Evaluation of nutritional and antioxidant status of Lepidium latifolium Linn.: a novel phytofood from Ladakh. PLoS One 8(8):e69112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kennedy MA, Moffat TC et al (2016) A signaling lipid associated with Alzheimer’s disease promotes mitochondrial dysfunction. Sci Rep 6:19332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan N, Afaq F et al (2006) Targeting multiple signaling pathways by green tea polyphenol (−)-epigallocatechin-3-gallate. Cancer Res 66(5):2500–2505

    Article  CAS  PubMed  Google Scholar 

  • Khan P, Rahman S et al (2017) Elucidation of dietary polyphenolics as potential inhibitor of microtubule affinity regulating kinase 4: in silico and in vitro studies. Sci Rep 7(1):1–15

    Article  Google Scholar 

  • Khokhar S, Magnusdottir S (2002) Total phenol, catechin, and caffeine contents of teas commonly consumed in the United Kingdom. J Agric Food Chem 50(3):565–570

    Article  CAS  PubMed  Google Scholar 

  • Kim G-Y, Kim K-H et al (2005) Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-κB as potential targets. J Immunol 174(12):8116–8124

    Article  CAS  PubMed  Google Scholar 

  • Kim D, Nguyen MD et al (2007) SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J 26(13):3169–3179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kimura Y, Ito H et al (2010) Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity. Food Chem Toxicol 48(1):429–435

    Article  CAS  PubMed  Google Scholar 

  • Krikorian R, Nash TA et al (2010) Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr 103(5):730–734

    Article  CAS  PubMed  Google Scholar 

  • Kukula-Koch W, Aligiannis N et al (2013) Influence of extraction procedures on phenolic content and antioxidant activity of Cretan barberry herb. Food Chem 138(1):406–413

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Pandey AK (2013) Chemistry and biological activities of flavonoids: an overview. Sci World J 2013

    Google Scholar 

  • Kumar A, Nisha CM et al (2016) Current and novel therapeutic molecules and targets in Alzheimer’s disease. J Formos Med Assoc 115(1):3–10

    Article  CAS  PubMed  Google Scholar 

  • Kunnumakkara AB, Bordoloi D et al (2017) Curcumin mediates anticancer effects by modulating multiple cell signaling pathways. Clin Sci 131(15):1781–1799

    Article  CAS  Google Scholar 

  • Kwiatkowski TJ, Bosco D et al (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323(5918):1205–1208

    Article  CAS  PubMed  Google Scholar 

  • Lagouge M, Argmann C et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell 127(6):1109–1122

    Article  CAS  PubMed  Google Scholar 

  • Lakhanpal P, Rai DK (2007) Quercetin: a versatile flavonoid. Int J Med Update 2(2):22–37

    Google Scholar 

  • Lambert JD, Elias RJ (2010) The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. Arch Biochem Biophys 501(1):65–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee M-J, Wang Z-Y et al (1995) Analysis of plasma and urinary tea polyphenols in human subjects. Cancer Epidemiol Prevent Biomark 4(4):393–399

    CAS  Google Scholar 

  • Lee CJ, Wilson L et al (2010) Hesperidin suppressed proliferations of both human breast cancer and androgen-dependent prostate cancer cells. Phytother Res 24(S1):S15–S19

    Article  PubMed  Google Scholar 

  • Lee AY, Hwang BR et al (2016) Perilla frutescens var. japonica and rosmarinic acid improve amyloid-β25-35 induced impairment of cognition and memory function. Nutr Res Pract 10(3):274–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lees AJ (2007) Unresolved issues relating to the shaking palsy on the celebration of James Parkinson’s 250th birthday. Mov Disord 22(S17):S327–S334

    Article  PubMed  Google Scholar 

  • Levites Y, Amit T et al (2003) Neuroprotection and neurorescue against Aβ toxicity and PKC-dependent release of non-amyloidogenic soluble precursor protein by green tea polyphenol (-)-epigallocatechin-3-gallate. FASEB J 17(8):1–23

    Article  Google Scholar 

  • Lewandowska H, Kalinowska M et al (2016) The role of natural polyphenols in cell signaling and cytoprotection against cancer development. J Nutr Biochem 32:1–19

    Article  CAS  PubMed  Google Scholar 

  • Lim HJ, Shim SB et al (2013) Green tea catechin leads to global improvement among Alzheimer’s disease-related phenotypes in NSE/hAPP-C105 Tg mice. J Nutr Biochem 24(7):1302–1313

    Article  CAS  PubMed  Google Scholar 

  • Longpré F, Garneau P et al (2006) Protection by EGb 761 against β-amyloid-induced neurotoxicity: involvement of NF-κB, SIRT1, and MAPKs pathways and inhibition of amyloid fibril formation. Free Radic Biol Med 41(12):1781–1794

    Article  PubMed  Google Scholar 

  • Maher P, Dargusch R et al (2011) ERK activation by the polyphenols fisetin and resveratrol provides neuroprotection in multiple models of Huntington’s disease. Hum Mol Genet 20(2):261–270

    Article  CAS  PubMed  Google Scholar 

  • Manach C, Scalbert A et al (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79(5):727–747

    Article  CAS  PubMed  Google Scholar 

  • Mandel S, Youdim MB (2004) Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radic Biol Med 37(3):304–317

    Article  CAS  PubMed  Google Scholar 

  • Mandel SA, Avramovich-Tirosh Y et al (2005) Multifunctional activities of green tea catechins in neuroprotection. Neurosignals 14(1–2):46–60

    Article  CAS  PubMed  Google Scholar 

  • Martin JB, Gusella JF (1986) Huntington’s disease. N Engl J Med 315(20):1267–1276

    Article  CAS  PubMed  Google Scholar 

  • Masuda M, Suzuki N et al (2006) Small molecule inhibitors of α-synuclein filament assembly. Biochemistry 45(19):6085–6094

    Article  CAS  PubMed  Google Scholar 

  • Mazzolani F, Togni S (2013) Oral administration of a curcumin-phospholipid delivery system for the treatment of central serous chorioretinopathy: a 12-month follow-up study. Clin Ophthalmol 7:939

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mishra S, Palanivelu K (2008) The effect of curcumin (turmeric) on Alzheimer’s disease: an overview. Ann Indian Acad Neurol 11(1):13

    Article  PubMed  PubMed Central  Google Scholar 

  • Mishra A, Kumar S et al (2013) Scientific validation of the medicinal efficacy of Tinospora cordifolia. Sci World J 2013

    Google Scholar 

  • Nanjo F, Goto K et al (1996) Scavenging effects of tea catechins and their derivatives on 1, 1-diphenyl-2-picrylhydrazyl radical. Free Radic Biol Med 21(6):895–902

    Article  CAS  PubMed  Google Scholar 

  • Narlawar R, Pickhardt M et al (2008) Curcumin-derived pyrazoles and isoxazoles: Swiss army knives or blunt tools for Alzheimer’s disease? ChemMedChem 3(1):165–172

    Article  CAS  PubMed  Google Scholar 

  • Ng T-P, Chiam P-C et al (2006) Curry consumption and cognitive function in the elderly. Am J Epidemiol 164(9):898–906

    Article  PubMed  Google Scholar 

  • Nie G, Cao Y et al (2002) Protective effects of green tea polyphenols and their major component, (-)-epigallocatechin-3-gallate (EGCG), on 6-hydroxydopamine-induced apoptosis in PC12 cells. Redox Rep 7(3):171–177

    Article  CAS  PubMed  Google Scholar 

  • Nikfarjam BA, Adineh M et al (2017) Treatment with rutin-A therapeutic strategy for neutrophil-mediated inflammatory and autoimmune diseases-anti-inflammatory effects of rutin on neutrophils. J Pharm 20(1):52–56

    Google Scholar 

  • O’Brien RJ, Wong PC (2011) Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci 34:185–204

    Article  PubMed  PubMed Central  Google Scholar 

  • Okello EJ, Leylabi R et al (2012) Inhibition of acetylcholinesterase by green and white tea and their simulated intestinal metabolites. Food Funct 3(6):651–661

    Article  CAS  PubMed  Google Scholar 

  • Ono K, Yoshiike Y et al (2003) Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer’s disease. J Neurochem 87(1):172–181

    Article  CAS  PubMed  Google Scholar 

  • Ono K, Li L et al (2012) Phenolic compounds prevent amyloid β-protein oligomerization and synaptic dysfunction by site-specific binding. J Biol Chem 287(18):14631–14643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pae M, Wu D (2013) Immunomodulating effects of epigallocatechin-3-gallate from green tea: mechanisms and applications. Food Funct 4(9):1287–1303

    Article  CAS  PubMed  Google Scholar 

  • Pandey KB, Rizvi SI (2009) Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Med Cell Longev 2

    Google Scholar 

  • Paris D, Mathura V et al (2011) Flavonoids lower Alzheimer’s Aβ production via an NFκB dependent mechanism. Bioinformation 6(6):229

    Article  PubMed  PubMed Central  Google Scholar 

  • Park S-Y, Kim DS (2002) Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult: a drug discovery effort against Alzheimer’s disease. J Nat Prod 65(9):1227–1231

    Article  CAS  PubMed  Google Scholar 

  • Parker-Athill E, Luo D et al (2009) Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism. J Neuroimmunol 217(1–2):20–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pasinetti GM, Wang J et al (2015) Roles of resveratrol and other grape-derived polyphenols in Alzheimer’s disease prevention and treatment. Biochim Biophys Acta (BBA) Mol Basis Dis 1852(6):1202–1208

    Article  CAS  Google Scholar 

  • Pérez-Jiménez J, Neveu V et al (2010) Identification of the 100 richest dietary sources of polyphenols: an application of the phenol-explorer database. Eur J Clin Nutr 64(3):S112–S120

    Article  PubMed  Google Scholar 

  • Perez-Vizcaino F, Duarte J et al (2006) Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols. Free Radic Res 40(10):1054–1065

    Article  CAS  PubMed  Google Scholar 

  • Pimpão R (2014) Exploring the bioavailability of (poly) phenols from berries and their potential activities in humans

    Google Scholar 

  • Potenza MA, Marasciulo FL et al (2007) EGCG, a green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR. Am J Physiol Endocrinol Metab 292(5):E1378–E1387

    Article  CAS  PubMed  Google Scholar 

  • Prince PSM, Kamalakkannan N (2006) Rutin improves glucose homeostasis in streptozotocin diabetic tissues by altering glycolytic and gluconeogenic enzymes. J Biochem Mol Toxicol 20(2):96–102

    Article  Google Scholar 

  • Pu P, Gao D-M et al (2012) Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet. Arch Biochem Biophys 518(1):61–70

    Article  CAS  PubMed  Google Scholar 

  • Qin X-Y, Cheng Y et al (2012) Potential protection of green tea polyphenols against intracellular amyloid beta-induced toxicity on primary cultured prefrontal cortical neurons of rats. Neurosci Lett 513(2):170–173

    Article  CAS  PubMed  Google Scholar 

  • Queen BL, Tollefsbol TO (2010) Polyphenols and aging. Curr Aging Sci 3(1):34–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quist A, Doudevski I et al (2005) Amyloid ion channels: a common structural link for protein-misfolding disease. Proc Natl Acad Sci U S A 102(30):10427–10432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramassamy C (2006) Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 545(1):51–64

    Article  CAS  PubMed  Google Scholar 

  • Ramazzotti M, Melani F et al (2016) Mechanisms for the inhibition of amyloid aggregation by small ligands. Biosci Rep 36(5)

    Google Scholar 

  • Ranney A, Petro MS (2009) Resveratrol protects spatial learning in middle-aged C57BL/6 mice from effects of ethanol. Behav Pharmacol 20(4):330–336

    Article  CAS  PubMed  Google Scholar 

  • Regitz C, Wenzel U (2014) Amyloid-beta (Aβ1–42)-induced paralysis in Caenorhabditis elegans is reduced by restricted cholesterol supply. Neurosci Lett 576:93–96

    Article  CAS  PubMed  Google Scholar 

  • Rezai-Zadeh K, Shytle D et al (2005) Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci 25(38):8807–8814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rezai-Zadeh K, Arendash GW et al (2008) Green tea epigallocatechin-3-gallate (EGCG) reduces β-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res 1214:177–187

    Article  CAS  PubMed  Google Scholar 

  • Rimando AM, Kalt W et al (2004) Resveratrol, pterostilbene, and piceatannol in vaccinium berries. J Agric Food Chem 52(15):4713–4719

    Article  CAS  PubMed  Google Scholar 

  • Rocha-González HI, Ambriz-Tututi M et al (2008) Resveratrol: a natural compound with pharmacological potential in neurodegenerative diseases. CNS Neurosci Ther 14(3):234–247

    Article  PubMed  PubMed Central  Google Scholar 

  • Rosen DR, Siddique T et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362(6415):59–62

    Article  CAS  PubMed  Google Scholar 

  • Sabogal-Guáqueta AM, Munoz-Manco JI et al (2015) The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology 93:134–145

    Article  PubMed  Google Scholar 

  • Sanders TH, McMichael RW et al (2000) Occurrence of resveratrol in edible peanuts. J Agric Food Chem 48(4):1243–1246

    Article  CAS  PubMed  Google Scholar 

  • Scalbert A, Williamson G (2000) Dietary intake and bioavailability of polyphenols. J Nutr 130(8):2073S–2085S

    Article  CAS  PubMed  Google Scholar 

  • Schaffer S, Asseburg H et al (2012) Effects of polyphenols on brain ageing and Alzheimer’s disease: focus on mitochondria. Mol Neurobiol 46(1):161–178

    Article  CAS  PubMed  Google Scholar 

  • Shamsi A, Ahmed A et al (2020a) Understanding the binding between rosmarinic acid and serum albumin: in vitro and in silico insight. J Mol Liq 113348

    Google Scholar 

  • Shamsi A, Ahmed A et al (2020b) Rosmarinic acid restrains protein glycation and aggregation in human serum albumin: multi spectroscopic and microscopic insight-possible therapeutics targeting diseases. Int J Biol Macromol 161:187–193

    Article  CAS  PubMed  Google Scholar 

  • Shan Y, Wang D-D et al (2016) Aging as a precipitating factor in chronic restraint stress-induced tau aggregation pathology, and the protective effects of rosmarinic acid. J Alzheimers Dis 49(3):829–844

    Article  CAS  PubMed  Google Scholar 

  • Sharma V, Bhattacharya A et al (2007) Health benefits of tea consumption. Trop J Pharm Res 6(3):785–792

    Article  Google Scholar 

  • Shen L, Ji H-F (2012) The pharmacology of curcumin: is it the degradation products? Trends Mol Med 18(3):138–144

    Article  CAS  PubMed  Google Scholar 

  • Shimmyo Y, Kihara T et al (2008) Flavonols and flavones as BACE-1 inhibitors: structure–activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features. Biochim Biophys Acta (BBA) Gen Subjects 1780(5):819–825

    Article  CAS  Google Scholar 

  • Shishodia S, Sethi G et al (2005) Curcumin: getting back to the roots. Ann N Y Acad Sci 1056(1):206–217

    Article  CAS  PubMed  Google Scholar 

  • Shults CW (2006) Lewy bodies. Proc Natl Acad Sci U S A 103(6):1661–1668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silveira AC, Dias JP et al (2019) The action of polyphenols in diabetes mellitus and Alzheimer’s disease: a common agent for overlapping pathologies. Curr Neuropharmacol 17(7):590–613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh R, Akhtar N et al (2010) Green tea polyphenol epigallocatechi3-gallate: inflammation and arthritis. Life Sci 86(25–26):907–918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh NA, Mandal AKA et al (2015) Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). Nutr J 15(1):60

    Article  Google Scholar 

  • Skupień K, Oszmiański J et al (2006) In vitro antileukaemic activity of extracts from berry plant leaves against sensitive and multidrug resistant HL60 cells. Cancer Lett 236(2):282–291

    Article  PubMed  Google Scholar 

  • Song W, Zhao X et al (2017) Quercetin inhibits angiogenesis-mediated human retinoblastoma growth by targeting vascular endothelial growth factor receptor. Oncol Lett 14(3):3343–3348

    Article  PubMed  PubMed Central  Google Scholar 

  • Soto C (2003) Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci 4(1):49–60

    Article  CAS  PubMed  Google Scholar 

  • Spencer JP (2010) Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain. Proc Nutr Soc 69(2):244–260

    Article  CAS  PubMed  Google Scholar 

  • Spencer JP, Abd El Mohsen MM et al (2004) Cellular uptake and metabolism of flavonoids and their metabolites: implications for their bioactivity. Arch Biochem Biophys 423(1):148–161

    Article  CAS  PubMed  Google Scholar 

  • Spencer JP, Abd El Mohsen MM et al (2008) Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research. Br J Nutr 99(1):12–22

    Article  CAS  PubMed  Google Scholar 

  • Sreedharan J, Blair IP et al (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319(5870):1668–1672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Surh Y-J, Chun K-S et al (2001) Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-κB activation. Mutat Res 480:243–268

    Article  PubMed  Google Scholar 

  • Tsao R (2010) Chemistry and biochemistry of dietary polyphenols. Nutrients 2(12):1231–1246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tydlacka S, Wang C-E et al (2008) Differential activities of the ubiquitin–proteasome system in neurons versus glia may account for the preferential accumulation of misfolded proteins in neurons. J Neurosci 28(49):13285–13295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Um J-H, Park S-J et al (2010) AMP-activated protein kinase–deficient mice are resistant to the metabolic effects of resveratrol. Diabetes 59(3):554–563

    Article  CAS  PubMed  Google Scholar 

  • Unno K, Takabayashi F et al (2004) Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10). Exp Gerontol 39(7):1027–1034

    Article  CAS  PubMed  Google Scholar 

  • Unno K, Takabayashi F et al (2007) Daily consumption of green tea catechin delays memory regression in aged mice. Biogerontology 8(2):89–95

    Article  CAS  PubMed  Google Scholar 

  • Upadhyay S, Dixit M (2015) Role of polyphenols and other phytochemicals on molecular signaling. Oxidative Med Cell Longev 2015

    Google Scholar 

  • Vance C, Rogelj B et al (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323(5918):1208–1211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vinciguerra M, Fulco M et al (2010) SirT1 in muscle physiology and disease: lessons from mouse models. Dis Model Mech 3(5–6):298–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vingtdeux V, Dreses-Werringloer U et al (2008) Therapeutic potential of resveratrol in Alzheimer’s disease. BMC Neurosci 9(S2):S6

    Article  PubMed  PubMed Central  Google Scholar 

  • Vingtdeux V, Giliberto L et al (2010) AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-β peptide metabolism. J Biol Chem 285(12):9100–9113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vingtdeux V, Davies P et al (2011) AMPK is abnormally activated in tangle-and pre-tangle-bearing neurons in Alzheimer’s disease and other tauopathies. Acta Neuropathol 121(3):337–349

    Article  CAS  PubMed  Google Scholar 

  • Walker FO (2007) Huntington’s disease. Lancet 369(9557):218–228

    Article  CAS  PubMed  Google Scholar 

  • Wang LM, Wang YJ et al (2013) A dietary polyphenol resveratrol acts to provide neuroprotection in recurrent stroke models by regulating AMPK and SIRT 1 signaling, thereby reducing energy requirements during ischemia. Eur J Neurosci 37(10):1669–1681

    Article  PubMed  Google Scholar 

  • Wang D-M, Li S-Q et al (2014) Effects of long-term treatment with quercetin on cognition and mitochondrial function in a mouse model of Alzheimer’s disease. Neurochem Res 39(8):1533–1543

    Article  CAS  PubMed  Google Scholar 

  • Weinreb O, Mandel S et al (2004) Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s diseases. J Nutr Biochem 15(9):506–516

    Article  CAS  PubMed  Google Scholar 

  • Williams RJ, Spencer JP et al (2004) Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 36(7):838–849

    Article  CAS  PubMed  Google Scholar 

  • Wobst HJ, Sharma A et al (2015) The green tea polyphenol (−)-epigallocatechin gallate prevents the aggregation of tau protein into toxic oligomers at substoichiometric ratios. FEBS Lett 589(1):77–83

    Article  CAS  PubMed  Google Scholar 

  • World Health Organization (2018) Dementia. 2017. http://www.who.int/mediacentre/factsheets/fs362/en

  • Wu D (2016) Green tea EGCG, T-cell function, and T-cell-mediated autoimmune encephalomyelitis. J Investig Med 64(8):1213–1219

    Article  PubMed  Google Scholar 

  • Wu Y, Xia Z-Y et al (2017) (-)-Epigallocatechin-3-gallate attenuates myocardial injury induced by ischemia/reperfusion in diabetic rats and in H9c2 cells under hyperglycemic conditions. Int J Mol Med 40(2):389–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang F, Lim GP et al (2005) Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 280(7):5892–5901

    Article  CAS  PubMed  Google Scholar 

  • Youdim KA, Qaiser MZ et al (2004) Flavonoid permeability across an in situ model of the blood–brain barrier. Free Radic Biol Med 36(5):592–604

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Liu X et al (2016) Apigenin attenuates experimental autoimmune myocarditis by modulating Th1/Th2 cytokine balance in mice. Inflammation 39(2):678–686

    Article  PubMed  Google Scholar 

  • Zhao J, Li Y et al (2017) Hesperidin inhibits ovarian cancer cell viability through endoplasmic reticulum stress signaling pathways. Oncol Lett 14(5):5569–5574

    PubMed  PubMed Central  Google Scholar 

  • Zheng Q, Kebede MT et al (2019) Inhibition of the self-assembly of Aβ and of tau by polyphenols: mechanistic studies. Molecules 24(12):2316

    Article  CAS  PubMed Central  Google Scholar 

  • Zhou Y, Zheng J et al (2016) Natural polyphenols for prevention and treatment of cancer. Nutrients 8(8):515

    Article  PubMed Central  Google Scholar 

  • Zou J-G, Wang Z-R et al (2003) Effect of red wine and wine polyphenol resveratrol on endothelial function in hypercholesterolemic rabbits. Int J Mol Med 11(3):317–320

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors acknowledge the facilities provided by Jamia Millia Islamia, India, and Ajman University, UAE, for the successful accomplishment.

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Shamsi, A., Anwar, S., Mohammad, T., Shahwan, M., Hassan, M.I., Islam, A. (2021). Therapeutic Potential of Polyphenols in Alzheimer’s Therapy: Broad-Spectrum and Minimal Side Effects as Key Aspects. In: Md Ashraf, G., Alexiou, A. (eds) Autism Spectrum Disorder and Alzheimer's Disease . Springer, Singapore. https://doi.org/10.1007/978-981-16-4558-7_7

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