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2000
Volume 21, Issue 5
  • ISSN: 1573-4072
  • E-ISSN: 1875-6646

Abstract

Alzheimer's disease (AD) stands as a pressing global health challenge with limited therapeutic options. In pursuit of alternative interventions, this review critically examines the potential of phytoconstituents in alleviating AD-related cognitive impairments through a comprehensive analysis of preclinical studies. The diverse and intricate pathogenesis of AD calls for multifaceted approaches, and phytoconstituents present a promising avenue due to their multifunctional properties. These natural compounds, derived from various plant sources, have been shown to possess anti-inflammatory, antioxidant, and neurogenesis-promoting activities, along with the ability to modulate amyloid-beta aggregation. A review of the literature highlights a broad spectrum of phytoconstituents, including polyphenols, alkaloids, flavonoids, and terpenoids, which have demonstrated neuroprotective effects in various animal models of AD. Despite the consistency in positive outcomes across studies, challenges emerge from the variability in dosages, administration routes, and extraction methods employed. The transition from preclinical findings to clinical applications demands a meticulous assessment of safety, pharmacokinetics, and dosing regimens, as well as consideration of individual patient characteristics. The review emphasizes the need for standardized protocols in future investigations to facilitate reliable comparisons and evidence-based conclusions. While promising, the translation of these preclinical successes to human trials necessitates a cautious approach guided by robust scientific inquiry. Collaboration between diverse disciplines, including botany, pharmacology, neurology, and clinical medicine, is pivotal for refining our understanding of phytoconstituent mechanisms, optimizing their delivery, and ultimately harnessing their potential for AD therapeutics.

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2025-09-28

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References

  1. VenkatesanR. JiE. KimS.Y. Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins: A comprehensive review.BioMed Res. Int.2015201512210.1155/2015/814068 26075266
     [Google Scholar]
  2. World Health Organization (WHO). Dementia.2023Available From: https://www.who.int/news-room/fact-sheets/detail/dementia
  3. Alzheimer’s Association International Conference® (AAIC®). Global Dementia Cases Forecasted to Triple by 2050. 2021Available From: https://alz.org/aaic/releases_2021/global-prevalence.asp
  4. Alzheimers Disease International. Dementia statistics.2024Available From: https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/
  5. RanjanJ.K. ChoudharyA. AsthanaH. Prevalence of dementia in India: A systematic review and meta-analysis.Indian J. Public Health202165215215810.4103/ijph.IJPH_1042_20 34135184
     [Google Scholar]
  6. Alzheimer’s Association Alzheimer’s and Dementia in India.2024Available From https://www.alz.org/in/dementia-alzheimers-en.asp
  7. TiwariS. AtluriV. KaushikA. YndartA. NairM. Alzheimer’s disease: Pathogenesis, diagnostics, and therapeutics.Int. J. Nanomedicine2019145541555410.2147/IJN.S200490 31410002
     [Google Scholar]
  8. OsorioC. KanukuntlaT. DiazE. JafriN. CummingsM. SferaA. The post-amyloid era in Alzheimer’s disease: Trust your gut feeling.Front. Aging Neurosci.201911JUN14310.3389/fnagi.2019.00143 31297054
     [Google Scholar]
  9. ChenX.Q. MobleyW.C. Alzheimer disease pathogenesis: Insights from molecular and cellular biology studies of oligomeric Aβ and tau species.Front. Neurosci.201913JUN65910.3389/fnins.2019.00659 31293377
     [Google Scholar]
  10. DeTureM.A. DicksonD.W. The neuropathological diagnosis of Alzheimer’s disease.Mol. Neurodegener.20191413210.1186/s13024‑019‑0333‑5 31375134
     [Google Scholar]
  11. Ardura-FabregatA. BoddekeE.W.G.M. Boza-SerranoA. BrioschiS. Castro-GomezS. CeyzériatK. DansokhoC. DierkesT. GeldersG. HenekaM.T. HoeijmakersL. HoffmannA. IaccarinoL. JahnertS. KuhbandnerK. LandrethG. LonnemannN. LöschmannP.A. McManusR.M. PaulusA. ReemstK. Sanchez-CaroJ.M. TiberiA. Van der PerrenA. VauthenyA. VenegasC. WebersA. WeydtP. WijasaT.S. XiangX. YangY. Targeting neuroinflammation to treat Alzheimer’s disease.CNS Drugs201731121057108210.1007/s40263‑017‑0483‑3 29260466
     [Google Scholar]
  12. KorolevI.O. Alzheimer’s disease: A clinical and basic science review.Med. Student Res. J.2014412433
     [Google Scholar]
  13. KmietowiczZ. Nice proposes to withdraw Alzheimer’s drugs from NHS.BMJ200533049510.1136/bmj.330.7490.495‑a
     [Google Scholar]
  14. FlickerL. Grimley EvansJ. Piracetam for dementia or cognitive impairment.Cochrane Libr.20042CD00101110.1002/14651858.CD001011 11405971
     [Google Scholar]
  15. CummingsJ. LeeG. RitterA. SabbaghM. ZhongK. Alzheimer’s disease drug development pipeline: 2019.Alzheimers Dement. (N. Y.)20195127229310.1016/j.trci.2019.05.008 31334330
     [Google Scholar]
  16. DrummondE. WisniewskiT. Alzheimer’s disease: Experimental models and reality.Acta Neuropathol.2017133215517510.1007/s00401‑016‑1662‑x 28025715
     [Google Scholar]
  17. KimM. KimS.H. YangW. Mechanisms of action of phytochemicals from medicinal herbs in the treatment of Alzheimer’s disease.Planta Med.201480151249125810.1055/s‑0034‑1383038 25210998
     [Google Scholar]
  18. KennedyD.O. WightmanE.L. Herbal extracts and phytochemicals: Plant secondary metabolites and the enhancement of human brain function.Adv. Nutr.201121325010.3945/an.110.000117 22211188
     [Google Scholar]
  19. DavinelliS. SapereN. ZellaD. BracaleR. IntrieriM. ScapagniniG. Pleiotropic protective effects of phytochemicals in Alzheimer’s disease.Oxid. Med. Cell. Longev.2012201211110.1155/2012/386527 22690271
     [Google Scholar]
  20. Abdull RazisA.F. IbrahimM.D. KntayyaS.B. Health benefits of Moringa oleifera.Asian Pac. J. Cancer Prev.201415208571857610.7314/APJCP.2014.15.20.8571 25374169
     [Google Scholar]
  21. BennettR.N. MellonF.A. FoidlN. PrattJ.H. DupontM.S. PerkinsL. KroonP.A. Profiling glucosinolates and phenolics in vegetative and reproductive tissues of the multi-purpose trees Moringa oleifera L. (horseradish tree) and Moringa stenopetala L.J. Agric. Food Chem.200351123546355310.1021/jf0211480 12769522
     [Google Scholar]
  22. GaluppoM. GiacoppoS. De NicolaG.R. IoriR. NavarraM. LombardoG.E. BramantiP. MazzonE. Antiinflammatory activity of glucomoringin isothiocyanate in a mouse model of experimental autoimmune encephalomyelitis.Fitoterapia20149516017410.1016/j.fitote.2014.03.018 24685508
     [Google Scholar]
  23. SutalangkaC. WattanathornJ. MuchimapuraS. Thukham-meeW. Moringa oleifera mitigates memory impairment and neurodegeneration in animal model of age-related dementia.Oxid. Med. Cell. Longev.201320131910.1155/2013/695936 24454988
     [Google Scholar]
  24. GangulyR. GuhaD. Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer’s disease & protection by Moringa oleifera.Indian J. Med. Res.20081286744751 19246799
     [Google Scholar]
  25. Cheng-Chung WeiJ. HuangH.C. ChenW.J. HuangC.N. PengC.H. LinC.L. Epigallocatechin gallate attenuates amyloid β-induced inflammation and neurotoxicity in EOC 13.31 microglia.Eur. J. Pharmacol.2016770162410.1016/j.ejphar.2015.11.048 26643169
     [Google Scholar]
  26. DragicevicN. SmithA. LinX. YuanF. CopesN. DelicV. TanJ. CaoC. ShytleR.D. BradshawP.C. Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer’s amyloid-induced mitochondrial dysfunction.J. Alzheimers Dis.201126350752110.3233/JAD‑2011‑101629 21694462
     [Google Scholar]
  27. BiasibettiR. TramontinaA.C. CostaA.P. DutraM.F. Quincozes-SantosA. NardinP. BernardiC.L. WartchowK.M. LunardiP.S. GonçalvesC.A. Green tea (−)epigallocatechin-3-gallate reverses oxidative stress and reduces acetylcholinesterase activity in a streptozotocin-induced model of dementia.Behav. Brain Res.2013236118619310.1016/j.bbr.2012.08.039 22964138
     [Google Scholar]
  28. ZhaoB. ZhaoB. Natural antioxidants in prevention and management of Alzheimer s disease.Front. Biosci. (Elite Ed.)2012E4379480810.2741/e419 22201914
     [Google Scholar]
  29. LiuM. ChenF. ShaL. WangS. TaoL. YaoL. HeM. YaoZ. LiuH. ZhuZ. ZhangZ. ZhengZ. ShaX. WeiM. (-)-Epigallocatechin-3-gallate ameliorates learning and memory deficits by adjusting the balance of TrkA/p75NTR signaling in APP/PS1 transgenic mice.Mol. Neurobiol.20144931350136310.1007/s12035‑013‑8608‑2 24356899
     [Google Scholar]
  30. ChoiS.S. ParkH.R. LeeK.A. A comparative study of rutin and rutin glycoside: Antioxidant activity, anti-inflammatory effect, effect on platelet aggregation and blood coagulation.Antioxidants20211011169610.3390/antiox10111696 34829567
     [Google Scholar]
  31. NegahdariR. BohlouliS. SharifiS. Maleki DizajS. Rahbar SaadatY. KhezriK. JafariS. AhmadianE. Gorbani JahandiziN. RaeesiS. Therapeutic benefits of rutin and its nanoformulations.Phytother. Res.20213541719173810.1002/ptr.6904 33058407
     [Google Scholar]
  32. BudzynskaB. FaggioC. Kruk-SlomkaM. SamecD. NabaviS.F. SuredaA. DeviK.P. NabaviS.M. Rutin as neuroprotective agent: From bench to bedside.Curr. Med. Chem.201926275152516410.2174/0929867324666171003114154 28971760
     [Google Scholar]
  33. XuP. WangS. YuX. SuY. WangT. ZhouW. ZhangH. WangY. LiuR. Rutin improves spatial memory in Alzheimer’s disease transgenic mice by reducing Aβ oligomer level and attenuating oxidative stress and neuroinflammation.Behav. Brain Res.201426417318010.1016/j.bbr.2014.02.002 24512768
     [Google Scholar]
  34. AbuznaitA.H. QosaH. BusnenaB.A. El SayedK.A. KaddoumiA. Olive-oil-derived oleocanthal enhances β-amyloid clearance as a potential neuroprotective mechanism against Alzheimer’s disease: In vitro and in vivo studies.ACS Chem. Neurosci.20134697398210.1021/cn400024q 23414128
     [Google Scholar]
  35. LiW. SperryJ.B. CroweA. TrojanowskiJ.Q. SmithA.B.III LeeV.M.Y. Inhibition of tau fibrillization by oleocanthal via reaction with the amino groups of tau.J. Neurochem.200911041339135110.1111/j.1471‑4159.2009.06224.x 19549281
     [Google Scholar]
  36. CalfioC. GonzalezA. SinghS.K. RojoL.E. MaccioniR.B. The emerging role of nutraceuticals and phytochemicals in the prevention and treatment of Alzheimer’s disease.J. Alzheimers Dis.2020771335110.3233/JAD‑200443 32651325
     [Google Scholar]
  37. LuoS. LanT. LiaoW. ZhaoM. YangH. Genistein inhibits Aβ25-35-induced neurotoxicity in PC12 cells via PKC signaling pathway.Neurochem. Res.201237122787279410.1007/s11064‑012‑0872‑4 22949092
     [Google Scholar]
  38. BagheriM. RoghaniM. JoghataeiM.T. MohseniS. Genistein inhibits aggregation of exogenous amyloid-beta1–40 and alleviates astrogliosis in the hippocampus of rats.Brain Res.2012142914515410.1016/j.brainres.2011.10.020 22079317
     [Google Scholar]
  39. BagheriM. JoghataeiM.T. MohseniS. RoghaniM. Genistein ameliorates learning and memory deficits in amyloid β(1–40) rat model of Alzheimer’s disease.Neurobiol. Learn. Mem.201195327027610.1016/j.nlm.2010.12.001 21144907
     [Google Scholar]
  40. MaW. DingB. YuH. YuanL. XiY. XiaoR. Genistein alleviates β-amyloid-induced inflammatory damage through regulating Toll-like receptor 4/nuclear factor κB.J. Med. Food201518327327910.1089/jmf.2014.3150 25384233
     [Google Scholar]
  41. WuY. ZhongL. YuZ. QiJ. Anti‐neuroinflammatory effects of tannic acid against lipopolysaccharide‐induced BV2 microglial cells via inhibition of NF‐κB activation.Drug Dev. Res.201980226226810.1002/ddr.21490 30724376
     [Google Scholar]
  42. MoriT. Rezai-ZadehK. KoyamaN. ArendashG.W. YamaguchiH. KakudaN. Horikoshi-SakurabaY. TanJ. TownT. Tannic acid is a natural β-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice.J. Biol. Chem.201228796912692710.1074/jbc.M111.294025 22219198
     [Google Scholar]
  43. MatiasM. SilvestreS. FalcãoA. AlvesG. Gastrodia elata and epilepsy: Rationale and therapeutic potential.Phytomedicine201623121511152610.1016/j.phymed.2016.09.001 27765372
     [Google Scholar]
  44. LiuX. WangM. Gastrodin improves learning behavior in a rat model of Alzheimer’s disease induced by intra-hippocampal Aβ 1-40 injection.Mol. Neurodegener.20127Suppl. 1S1510.1186/1750‑1326‑7‑S1‑S15
     [Google Scholar]
  45. LiuB. GaoJ.M. LiF. GongQ.H. ShiJ.S. Gastrodin attenuates bilateral common carotid artery occlusion-induced cognitive deficits via regulating Aβ-related proteins and reducing autophagy and apoptosis in rats.Front. Pharmacol.2018940510.3389/fphar.2018.00405 29755351
     [Google Scholar]
  46. AsaiM. IwataN. YoshikawaA. AizakiY. IshiuraS. SaidoT.C. MaruyamaK. Berberine alters the processing of Alzheimer’s amyloid precursor protein to decrease Aβ secretion.Biochem. Biophys. Res. Commun.2007352249850210.1016/j.bbrc.2006.11.043 17125739
     [Google Scholar]
  47. HuJ.P. NishishitaK. SakaiE. YoshidaH. KatoY. TsukubaT. OkamotoK. Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-κB and Akt pathways.Eur. J. Pharmacol.20085801-2707910.1016/j.ejphar.2007.11.013 18083161
     [Google Scholar]
  48. JiaL. LiuJ. SongZ. PanX. ChenL. CuiX. WangM. Berberine suppresses amyloid-beta-induced inflammatory response in microglia by inhibiting nuclear factor-kappaB and mitogen-activated protein kinase signalling pathways.J. Pharm. Pharmacol.201264101510152110.1111/j.2042‑7158.2012.01529.x 22943182
     [Google Scholar]
  49. DurairajanS.S.K. LiuL.F. LuJ.H. ChenL.L. YuanQ. ChungS.K. HuangL. LiX.S. HuangJ.D. LiM. Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer’s disease transgenic mouse model.Neurobiol. Aging201233122903291910.1016/j.neurobiolaging.2012.02.016 22459600
     [Google Scholar]
  50. LaraC.O. MurathP. MuñozB. MarileoA.M. MartínL.S. San MartínV.P. BurgosC.F. MariqueoT.A. AguayoL.G. FuentealbaJ. GodoyP. GuzmanL. YévenesG.E. Functional modulation of glycine receptors by the alkaloid gelsemine.Br. J. Pharmacol.2016173142263227710.1111/bph.13507 27128379
     [Google Scholar]
  51. WuY. LiY. LuoY. WangT. WangH. ChenS. QuW. HuangZ. Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice.Acta Pharmacol. Sin.201536111308131710.1038/aps.2015.86 26388157
     [Google Scholar]
  52. KonrathE.L. PassosC.S. Klein-JúniorL.C. HenriquesA.T. Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer’s disease.J. Pharm. Pharmacol.201365121701172510.1111/jphp.12090 24236981
     [Google Scholar]
  53. MehtaM. AdemA. SabbaghM. New acetylcholinesterase inhibitors for Alzheimer’s disease.Int. J. Alzheimers Dis.201220121810.1155/2012/728983 22216416
     [Google Scholar]
  54. KurzA. FarlowM. LefèvreG. Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer’s disease: A review.Int. J. Clin. Pract.200963579980510.1111/j.1742‑1241.2009.02052.x 19392927
     [Google Scholar]
  55. CummingsJ. WinbladB. A rivastigmine patch for the treatment of Alzheimer’s disease and Parkinson’s disease dementia.Expert Rev. Neurother.20077111457146310.1586/14737175.7.11.1457 17997695
     [Google Scholar]
  56. BirksJ.S. EvansJ.G. Rivastigmine for Alzheimer’s disease.Cochrane Database Syst. Rev.2015410.1002/14651858.CD001191
     [Google Scholar]
  57. MatsuzonoK. SatoK. KonoS. HishikawaN. OhtaY. YamashitaT. DeguchiK. NakanoY. AbeK. Clinical benefits of rivastigmine in the real world dementia clinics of the Okayama Rivastigmine Study (ORS).J. Alzheimers Dis.201548375776310.3233/JAD‑150518 26402119
     [Google Scholar]
  58. LibroR. GiacoppoS. Soundara RajanT. BramantiP. MazzonE. Natural phytochemicals in the treatment and prevention of dementia: An overview.Molecules201621451810.3390/molecules21040518 27110749
     [Google Scholar]
  59. ChungH.S. LeeY.C. Kyung RheeY. LeeS.Y. Consumer acceptance of ginseng food products.J. Food Sci.2011769S516S52210.1111/j.1750‑3841.2011.02399.x 22416723
     [Google Scholar]
  60. JooS.S. YooY.M. AhnB.W. NamS.Y. KimY.B. HwangK.W. LeeD.I. Prevention of inflammation-mediated neurotoxicity by Rg3 and its role in microglial activation.Biol. Pharm. Bull.20083171392139610.1248/bpb.31.1392 18591781
     [Google Scholar]
  61. KangK.A. KangJ.H. YangM.P. Ginseng total saponin enhances the phagocytic capacity of canine peripheral blood phagocytes in vitro.Am. J. Chin. Med.200836232934110.1142/S0192415X08005801 18457364
     [Google Scholar]
  62. BuY. RhoS. KimJ. KimM.Y. LeeD.H. KimS.Y. ChoiH. KimH. Neuroprotective effect of tyrosol on transient focal cerebral ischemia in rats.Neurosci. Lett.2007414321822110.1016/j.neulet.2006.08.094 17316989
     [Google Scholar]
  63. St-Laurent-ThibaultC. ArseneaultM. LongpréF. RamassamyC. Tyrosol and hydroxytyrosol, two main components of olive oil, protect N2a cells against amyloid-β-induced toxicity. Involvement of the NF-κB signaling.Curr. Alzheimer Res.20118554355110.2174/156720511796391845 21605049
     [Google Scholar]
  64. ImranM. ArshadM.S. ButtM.S. KwonJ.H. ArshadM.U. SultanM.T. Mangiferin: A natural miracle bioactive compound against lifestyle related disorders.Lipids Health Dis.20171618410.1186/s12944‑017‑0449‑y 28464819
     [Google Scholar]
  65. DuZ. FanshiF. LaiY.H. ChenJ.R. HaoE. DengJ. HsiaoC.D. Mechanism of anti-dementia effects of mangiferin in a senescence accelerated mouse (SAMP8) model.Biosci. Rep.2019399BSR2019048810.1042/BSR20190488 31484797
     [Google Scholar]
  66. Pardo AndreuG.L. MaurmannN. ReolonG.K. de FariasC.B. SchwartsmannG. DelgadoR. RoeslerR. Mangiferin, a naturally occurring glucoxilxanthone improves long-term object recognition memory in rats.Eur. J. Pharmacol.20106351-312412810.1016/j.ejphar.2010.03.011 20303935
     [Google Scholar]
  67. BiradarS.M. JoshiH. ChhedaT.K. Neuropharmacological effect of Mangiferin on brain cholinesterase and brain biogenic amines in the management of Alzheimer’s disease.Eur. J. Pharmacol.20126831-314014710.1016/j.ejphar.2012.02.042 22426032
     [Google Scholar]
  68. GongE.J. ParkH.R. KimM.E. PiaoS. LeeE. JoD.G. ChungH.Y. HaN.C. MattsonM.P. LeeJ. Morin attenuates tau hyperphosphorylation by inhibiting GSK3β.Neurobiol. Dis.201144222323010.1016/j.nbd.2011.07.005 21782947
     [Google Scholar]
  69. DuY. QuJ. ZhangW. BaiM. ZhouQ. ZhangZ. LiZ. MiaoJ. Morin reverses neuropathological and cognitive impairments in APPswe/PS1dE9 mice by targeting multiple pathogenic mechanisms.Neuropharmacology201610811310.1016/j.neuropharm.2016.04.008 27067919
     [Google Scholar]
  70. AnekondaT.S. ReddyP.H. Neuronal protection by sirtuins in Alzheimer’s disease.J. Neurochem.200696230531310.1111/j.1471‑4159.2005.03492.x 16219030
     [Google Scholar]
  71. YuK.C. KwanP. CheungS.K.K. HoA. BaumL. Effects of resveratrol and morin on insoluble tau in tau transgenic mice.Transl. Neurosci.201891546010.1515/tnsci‑2018‑0010 30479844
     [Google Scholar]
  72. SunX.Y. DongQ.X. ZhuJ. SunX. ZhangL.F. QiuM. YuX.L. LiuR.T. Resveratrol rescues tau-induced cognitive deficits and neuropathology in a mouse model of tauopathy.Curr. Alzheimer Res.201916871072210.2174/1567205016666190801153751 31368873
     [Google Scholar]
  73. SchweigerS. MatthesF. PoseyK. KicksteinE. WeberS. HettichM.M. PfurtschellerS. EhningerD. SchneiderR. KraußS. Resveratrol induces dephosphorylation of Tau by interfering with the MID1-PP2A complex.Sci. Rep.2017711375310.1038/s41598‑017‑12974‑4 29062069
     [Google Scholar]
  74. BuiT.T. NguyenT.H. Natural product for the treatment of Alzheimer’s disease.J. Basic Clin. Physiol. Pharmacol.201728541342310.1515/jbcpp‑2016‑0147 28708573
     [Google Scholar]
  75. El OmriA. HanJ. YamadaP. KawadaK. AbdrabbahM.B. IsodaH. Rosmarinus officinalis polyphenols activate cholinergic activities in PC12 cells through phosphorylation of ERK1/2.J. Ethnopharmacol.2010131245145810.1016/j.jep.2010.07.006 20633629
     [Google Scholar]
  76. YooD.Y. ChoiJ.H. KimW. YooK.Y. LeeC.H. YoonY.S. WonM.H. HwangI.K. Effects of Melissa officinalis L. (lemon balm) extract on neurogenesis associated with serum corticosterone and GABA in the mouse dentate gyrus.Neurochem. Res.201136225025710.1007/s11064‑010‑0312‑2 21076869
     [Google Scholar]
  77. Nurzyńska-WierdakR. Bogucka-KockaA. SzymczakG. Volatile constituents of Melissa officinalis leaves determined by plant age.Nat. Prod. Commun.2014951934578X140090010.1177/1934578X1400900531 25026727
     [Google Scholar]
  78. BayatM. Azami TamehA. Hossein GhahremaniM. AkbariM. MehrS.E. KhanaviM. HassanzadehG. Neuroprotective properties of Melissa officinalis after hypoxic-ischemic injury both in vitro and in vivo.Daru20122014210.1186/2008‑2231‑20‑42 23351182
     [Google Scholar]
  79. WangX. GongG. YangW. LiY. JiangM. LiL. Antifibrotic activity of galangin, a novel function evaluated in animal liver fibrosis model.Environ. Toxicol. Pharmacol.201336228829510.1016/j.etap.2013.04.004 23686009
     [Google Scholar]
  80. HuhJ.E. JungI.T. ChoiJ. BaekY.H. LeeJ.D. ParkD.S. ChoiD.Y. The natural flavonoid galangin inhibits osteoclastic bone destruction and osteoclastogenesis by suppressing NF-κB in collagen-induced arthritis and bone marrow-derived macrophages.Eur. J. Pharmacol.20136981-3576610.1016/j.ejphar.2012.08.013 22985747
     [Google Scholar]
  81. ZengH. HuangP. WangX. WuJ. WuM. HuangJ. Galangin-induced down-regulation of BACE1 by epigenetic mechanisms in SH-SY5Y cells.Neuroscience201529417218110.1016/j.neuroscience.2015.02.054 25779965
     [Google Scholar]
  82. DhouafliZ. Cuanalo-ContrerasK. HayouniE.A. MaysC.E. SotoC. Moreno-GonzalezI. Inhibition of protein misfolding and aggregation by natural phenolic compounds.Cell. Mol. Life Sci.201875193521353810.1007/s00018‑018‑2872‑2 30030591
     [Google Scholar]
  83. JiangW. LuoT. LiS. ZhouY. ShenX.Y. HeF. XuJ. WangH.Q. Quercetin protects against okadaic acid-induced injury via MAPK and PI3K/Akt/GSK3β signaling pathways in HT22 hippocampal neurons.PLoS One2016114e015237110.1371/journal.pone.0152371 27050422
     [Google Scholar]
  84. Sabogal-GuáquetaA.M. Muñoz-MancoJ.I. Ramírez-PinedaJ.R. Lamprea-RodriguezM. OsorioE. Cardona-GómezG.P. The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice.Neuropharmacology20159313414510.1016/j.neuropharm.2015.01.027 25666032
     [Google Scholar]
  85. NgY.P. OrT.C.T. IpN.Y. Plant alkaloids as drug leads for Alzheimer’s disease.Neurochem. Int.20158926027010.1016/j.neuint.2015.07.018 26220901
     [Google Scholar]
  86. HeinrichM. Lee TeohH. Galanthamine from snowdrop-the development of a modern drug against Alzheimer’s disease from local Caucasian knowledge.J. Ethnopharmacol.2004922-314716210.1016/j.jep.2004.02.012 15137996
     [Google Scholar]
  87. LiT. WongV.K.W. YiX.Q. WongY.F. ZhouH. LiuL. Matrine induces cell anergy in human Jurkat T cells through modulation of mitogen-activated protein kinases and nuclear factor of activated T-cells signaling with concomitant up-regulation of anergy-associated genes expression.Biol. Pharm. Bull.2010331404610.1248/bpb.33.40 20045933
     [Google Scholar]
  88. ZhangY. WangS. LiY. XiaoZ. HuZ. ZhangJ. Sophocarpine and matrine inhibit the production of TNF-α and IL-6 in murine macrophages and prevent cachexia-related symptoms induced by colon26 adenocarcinoma in mice.Int. Immunopharmacol.2008813-141767177210.1016/j.intimp.2008.08.008 18775799
     [Google Scholar]
  89. MaoY.M. ZengM.D. LuL.G. WanM.B. LiC.Z. ChenC.W. FuQ.C. WangJ.Y. SheW.M. CaiX. YeJ. ZhouX.Q. WangH. WuS.M. TangM.F. ZhuJ.S. ChenW.X. ZhangH.Q. Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis: A randomized, double blind, placebo-controlled, multicenter clinical study.World J. Gastroenterol.200410223269327310.3748/wjg.v10.i22.3269 15484298
     [Google Scholar]
  90. CuiL. CaiY. ChengW. LiuG. ZhaoJ. CaoH. TaoH. WangY. YinM. LiuT. LiuY. HuangP. LiuZ. LiK. ZhaoB. A novel, multi-target natural drug candidate, matrine, improves cognitive deficits in Alzheimer’s disease transgenic mice by inhibiting Aβ aggregation and blocking the RAGE/Aβ axis.Mol. Neurobiol.20175431939195210.1007/s12035‑016‑9783‑8 26899576
     [Google Scholar]
  91. ZhaoZ. FangM. XiaoD. LiuM. FefelovaN. HuangC. ZangW.J. XieL.H. Potential antiarrhythmic effect of methyl 3,4,5-trimethoxycinnamate, a bioactive substance from roots of polygalae radix: Suppression of triggered activities in rabbit myocytes.Biol. Pharm. Bull.201336223824410.1248/bpb.b12‑00654 23196428
     [Google Scholar]
  92. WuA.G. WongV. XuS.W. ChanW.K. NgC.I. LiuL. LawB. Onjisaponin B derived from radix polygalae enhances autophagy and accelerates the degradation of mutant α-synuclein and huntingtin in PC-12 cells.Int. J. Mol. Sci.20131411226182264110.3390/ijms141122618 24248062
     [Google Scholar]
  93. LiX. CuiJ. YuY. LiW. HouY. WangX. QinD. ZhaoC. YaoX. ZhaoJ. PeiG. Traditional chinese nootropic medicine radix polygalae and its active constituent onjisaponin B reduce β-amyloid production and improve cognitive impairments.PLoS One2016113e015114710.1371/journal.pone.0151147 26954017
     [Google Scholar]
  94. HaniadkaR. RajeevA.G. PalattyP.L. AroraR. BaligaM.S. Zingiber officinale (ginger) as an anti-emetic in cancer chemotherapy: A review.J. Altern. Complement. Med.201218544044410.1089/acm.2010.0737 22540971
     [Google Scholar]
  95. PanM.H. HsiehM.C. HsuP.C. HoS.Y. LaiC.S. WuH. SangS. HoC.T. 6‐Shogaol suppressed lipopolysaccharide‐induced up‐expression of iNOS and COX‐2 in murine macrophages.Mol. Nutr. Food Res.200852121467147710.1002/mnfr.200700515 18683823
     [Google Scholar]
  96. MoonM. KimH.G. ChoiJ.G. OhH. LeeP.K. HaS.K. KimS.Y. ParkY. HuhY. OhM.S. 6-Shogaol, an active constituent of ginger, attenuates neuroinflammation and cognitive deficits in animal models of dementia.Biochem. Biophys. Res. Commun.20144491813
     [Google Scholar]
  97. KimS. KwonJ. [6]-shogaol attenuates neuronal apoptosis in hydrogen peroxide-treated astrocytes through the up-regulation of neurotrophic factors.Phytother. Res.201327121795179910.1002/ptr.4946 23401228
     [Google Scholar]
  98. ShimS. KwonJ. Effects of [6]-shogaol on cholinergic signaling in HT22 cells following neuronal damage induced by hydrogen peroxide.Food Chem. Toxicol.20125051454145910.1016/j.fct.2012.02.014 22381256
     [Google Scholar]
  99. ZhouL. TanS. ShanY. WangY.G. CaiW. HuangX. LiaoX. LiH. ZhangL. ZhangB. LuZ. Baicalein improves behavioral dysfunction induced by Alzheimer’s disease in rats.Neuropsychiatr. Dis. Treat.2016123145315210.2147/NDT.S117469 28003750
     [Google Scholar]
  100. LuJ.H. ArdahM.T. DurairajanS.S.K. LiuL.F. XieL.X. FongW.F.D. HasanM.Y. HuangJ.D. El-AgnafO.M.A. LiM. Baicalein inhibits formation of α-synuclein oligomers within living cells and prevents Aβ peptide fibrillation and oligomerisation.ChemBioChem201112461562410.1002/cbic.201000604 21271629
     [Google Scholar]
  101. GuX.H. XuL.J. LiuZ.Q. WeiB. YangY.J. XuG.G. YinX.P. WangW. The flavonoid baicalein rescues synaptic plasticity and memory deficits in a mouse model of Alzheimer’s disease.Behav. Brain Res.201631130932110.1016/j.bbr.2016.05.052 27233830
     [Google Scholar]
  102. MakarovaM.N. PozharitskayaO.N. ShikovA.N. TesakovaS.V. MakarovV.G. TikhonovV.P. Effect of lipid-based suspension of Epimedium koreanum Nakai extract on sexual behavior in rats.J. Ethnopharmacol.2007114341241610.1016/j.jep.2007.08.021 17890032
     [Google Scholar]
  103. LiC. LiQ. MeiQ. LuT. Pharmacological effects and pharmacokinetic properties of icariin, the major bioactive component in Herba Epimedii.Life Sci.2015126576810.1016/j.lfs.2015.01.006 25634110
     [Google Scholar]
  104. NieJ. LuoY. HuangX.N. GongQ.H. WuQ. ShiJ.S. Icariin inhibits beta-amyloid peptide segment 25–35 induced expression of β-secretase in rat hippocampus.Eur. J. Pharmacol.20106262-321321810.1016/j.ejphar.2009.09.039 19782061
     [Google Scholar]
  105. ZhangZ. ZhangT. DongK. Icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels in the hippocampus of the senescence-accelerated mouse.Neural Regen. Res.201271288589010.3969/j.issn.1673‑5374.2012.12.001 25722670
     [Google Scholar]
  106. FuX. ZhangJ. GuoL. XuY. SunL. WangS. FengY. GouL. ZhangL. LiuY. Protective role of luteolin against cognitive dysfunction induced by chronic cerebral hypoperfusion in rats.Pharmacol. Biochem. Behav.201412612213010.1016/j.pbb.2014.09.005 25220684
     [Google Scholar]
  107. LiuY. FuX. LanN. LiS. ZhangJ. WangS. LiC. ShangY. HuangT. ZhangL. Luteolin protects against high fat diet-induced cognitive deficits in obesity mice.Behav. Brain Res.201426717818810.1016/j.bbr.2014.02.040 24667364
     [Google Scholar]
  108. Rezai-ZadehK. Douglas ShytleR. BaiY. TianJ. HouH. MoriT. ZengJ. ObregonD. TownT. TanJ. Flavonoid‐mediated presenilin‐1 phosphorylation reduces Alzheimer’s disease β‐amyloid production.J. Cell. Mol. Med.200913357458810.1111/j.1582‑4934.2008.00344.x 18410522
     [Google Scholar]
  109. ZhouF. ChenS. XiongJ. LiY. QuL. Luteolin reduces zinc-induced tau phosphorylation at Ser262/356 in an ROS-dependent manner in SH-SY5Y cells.Biol. Trace Elem. Res.2012149227327910.1007/s12011‑012‑9411‑z 22528780
     [Google Scholar]
  110. SawmillerD. LiS. ShahaduzzamanM. SmithA. ObregonD. GiuntaB. BorlonganC. SanbergP. TanJ. Luteolin reduces Alzheimer’s disease pathologies induced by traumatic brain injury.Int. J. Mol. Sci.201415189590410.3390/ijms15010895 24413756
     [Google Scholar]
  111. Colín-GonzálezA.L. AliS.F. TúnezI. SantamaríaA. On the antioxidant, neuroprotective and anti-inflammatory properties of S-allyl cysteine: An update.Neurochem. Int.201589839110.1016/j.neuint.2015.06.011 26122973
     [Google Scholar]
  112. ZarezadehM. BaluchnejadmojaradT. KiasalariZ. Afshin-MajdS. RoghaniM. Garlic active constituent s-allyl cysteine protects against lipopolysaccharide-induced cognitive deficits in the rat: Possible involved mechanisms.Eur. J. Pharmacol.2017795132110.1016/j.ejphar.2016.11.051 27915041
     [Google Scholar]
  113. KangK.A. WangZ.H. ZhangR. PiaoM.J. KimK.C. KangS.S. KimY.W. LeeJ. ParkD. HyunJ.W. Myricetin protects cells against oxidative stress-induced apoptosis via regulation of PI3K/Akt and MAPK signaling pathways.Int. J. Mol. Sci.201011114348436010.3390/ijms11114348 21151442
     [Google Scholar]
  114. YaoY. LinG. XieY. MaP. LiG. MengQ. WuT. Preformulation studies of myricetin: A natural antioxidant flavonoid.Pharmazie20146911926 24601218
     [Google Scholar]
  115. MaZ. WangG. CuiL. WangQ. Myricetin attenuates depressant-like behavior in mice subjected to repeated restraint stress.Int. J. Mol. Sci.20151612283772838510.3390/ijms161226102 26633366
     [Google Scholar]
  116. ShimmyoY. KiharaT. AkaikeA. NiidomeT. SugimotoH. Multifunction of myricetin on Aβ: Neuroprotection via a conformational change of Aβ and reduction of Aβ via the interference of secretases.J. Neurosci. Res.200886236837710.1002/jnr.21476 17722071
     [Google Scholar]
  117. RiveraD.S. LindsayC. CodocedoJ.F. MorelI. PintoC. CisternasP. BozinovicF. InestrosaN.C. Andrographolide recovers cognitive impairment in a natural model of Alzheimer’s disease (Octodon degus).Neurobiol. Aging20164620422010.1016/j.neurobiolaging.2016.06.021 27505720
     [Google Scholar]
  118. SerranoF.G. Tapia-RojasC. CarvajalF.J. HanckeJ. CerpaW. InestrosaN.C. Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice.Mol. Neurodegener.2014916110.1186/1750‑1326‑9‑61 25524173
     [Google Scholar]
  119. GazákR. WalterováD. KrenV. Silybin and silymarin-new and emerging applications in medicine.Curr. Med. Chem.200714331533810.2174/092986707779941159 17305535
     [Google Scholar]
  120. YinF. LiuJ. JiX. WangY. ZidichouskiJ. ZhangJ. Silibinin: A novel inhibitor of Aβ aggregation.Neurochem. Int.201158339940310.1016/j.neuint.2010.12.017 21185897
     [Google Scholar]
  121. LuP. MamiyaT. LuL.L. MouriA. ZouL.B. NagaiT. HiramatsuM. IkejimaT. NabeshimaT. Silibinin prevents amyloid β peptide‐induced memory impairment and oxidative stress in mice.Br. J. Pharmacol.200915771270127710.1111/j.1476‑5381.2009.00295.x 19552690
     [Google Scholar]
  122. LuP. MamiyaT. LuL.L. MouriA. NiwaM. HiramatsuM. ZouL.B. NagaiT. IkejimaT. NabeshimaT. Silibinin attenuates amyloid β(25-35) peptide-induced memory impairments: Implication of inducible nitric-oxide synthase and tumor necrosis factor-α in mice.J. Pharmacol. Exp. Ther.2009331131932610.1124/jpet.109.155069 19638571
     [Google Scholar]
  123. De NicolaG. RollinP. MazzonE. IoriR. Novel gram-scale production of enantiopure R-sulforaphane from Tuscan black kale seeds.Molecules20141966975698610.3390/molecules19066975 24871574
     [Google Scholar]
  124. GarberK. Biochemistry: A radical treatment.Nature20124897417S4S610.1038/489S4a 23013714
     [Google Scholar]
  125. AlfieriA. SrivastavaS. SiowR.C.M. CashD. ModoM. DuchenM.R. FraserP.A. WilliamsS.C.R. MannG.E. Sulforaphane preconditioning of the Nrf2/HO-1 defense pathway protects the cerebral vasculature against blood–brain barrier disruption and neurological deficits in stroke.Free Radic. Biol. Med.2013651012102210.1016/j.freeradbiomed.2013.08.190 24017972
     [Google Scholar]
  126. LeeC. ParkG.H. LeeS.R. JangJ.H. Attenuation of β-amyloid-induced oxidative cell death by sulforaphane via activation of NF-E2-related factor 2.Oxid. Med. Cell. Longev.2013201311210.1155/2013/313510 23864927
     [Google Scholar]
  127. KimH.V. KimH.Y. EhrlichH.Y. ChoiS.Y. KimD.J. KimY. Amelioration of Alzheimer’s disease by neuroprotective effect of sulforaphane in animal model.Amyloid201320171210.3109/13506129.2012.751367 23253046
     [Google Scholar]
  128. GiacoppoS. GaluppoM. IoriR. De NicolaG.R. BramantiP. MazzonE. The protective effects of bioactive (RS)-glucoraphanin on the permeability of the mice blood-brain barrier following experimental autoimmune encephalomyelitis.Eur. Rev. Med. Pharmacol. Sci.2014182194204 24488908
     [Google Scholar]
  129. RitchieK. CarrièreI. de MendonçaA. PortetF. DartiguesJ.F. RouaudO. Barberger-GateauP. AncelinM.L. The neuroprotective effects of caffeine.Neurology200769653654510.1212/01.wnl.0000266670.35219.0c 17679672
     [Google Scholar]
  130. CaoC. LoewensteinD.A. LinX. ZhangC. WangL. DuaraR. WuY. GianniniA. BaiG. CaiJ. GreigM. SchofieldE. AshokR. SmallB. PotterH. ArendashG.W. High blood caffeine levels in MCI linked to lack of progression to dementia.J. Alzheimers Dis.201230355957210.3233/JAD‑2012‑111781 22430531
     [Google Scholar]
  131. ArendashG.W. MoriT. CaoC. MamcarzM. RunfeldtM. DicksonA. Rezai-ZadehK. TanJ. CitronB.A. LinX. EcheverriaV. PotterH. Caffeine reverses cognitive impairment and decreases brain amyloid-β levels in aged Alzheimer’s disease mice.J. Alzheimers Dis.200917366168010.3233/JAD‑2009‑1087 19581722
     [Google Scholar]
  132. LublinA. IsodaF. PatelH. YenK. NguyenL. HajjeD. SchwartzM. MobbsC. FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.PLoS One2011611e2776210.1371/journal.pone.0027762 22114686
     [Google Scholar]
  133. Dall’IgnaO.P. FettP. GomesM.W. SouzaD.O. CunhaR.A. LaraD.R. Caffeine and adenosine A2a receptor antagonists prevent β-amyloid (25–35)-induced cognitive deficits in mice.Exp. Neurol.2007203124124510.1016/j.expneurol.2006.08.008 17007839
     [Google Scholar]
  134. FengX. WangX. LiuY. DiX. Linarin inhibits the acetylcholinesterase activity in-vitro and ex-vivo.Iran. J. Pharm. Res.2015143949954 26330885
     [Google Scholar]
  135. PanH. ZhangQ. CuiK. ChenG. LiuX. WangL. Optimization of extraction of linarin from Flos chrysanthemi indici by response surface methodology and artificial neural network.J. Sep. Sci.20174092062207010.1002/jssc.201601259 28319649
     [Google Scholar]
  136. FanP. HayA.E. MarstonA. HostettmannK. Acetylcholinesterase-inhibitory activity of linarin from Buddleja davidii, structure-activity relationships of related flavonoids, and chemical investigation of Buddleja nitida.Pharm. Biol.200846959660110.1080/13880200802179592
     [Google Scholar]
  137. LouH. FanP. PerezR.G. LouH. Neuroprotective effects of linarin through activation of the PI3K/Akt pathway in amyloid-β-induced neuronal cell death.Bioorg. Med. Chem.201119134021402710.1016/j.bmc.2011.05.021 21652214
     [Google Scholar]
  138. FanL.L. SunL.H. LiJ. YueX.H. YuH.X. WangS.Y. The protective effect of puerarin against myocardial reperfusion injury. Study on cardiac function.Chin. Med. J. (Engl.)199210511117 1576864
     [Google Scholar]
  139. ZouY. HongB. FanL. ZhouL. LiuY. WuQ. ZhangX. DongM. Protective effect of puerarin against beta-amyloid-induced oxidative stress in neuronal cultures from rat hippocampus: Involvement of the GSK-3β/Nrf2 signaling pathway.Free Radic. Res.2013471556310.3109/10715762.2012.742518 23088308
     [Google Scholar]
  140. ZhangH.Y. LiuY.H. WangH.Q. XuJ.H. HuH.T. Puerarin protects PC12 cells against β‐amyloid‐induced cell injury.Cell Biol. Int.200832101230123710.1016/j.cellbi.2008.07.006 18675923
     [Google Scholar]
  141. ZhangH. LiuY. LaoM. MaZ. YiX. Puerarin protects Alzheimer’s disease neuronal cybrids from oxidant-stress induced apoptosis by inhibiting pro-death signaling pathways.Exp. Gerontol.2011461303710.1016/j.exger.2010.09.013 20933077
     [Google Scholar]
  142. LiJ. WangG. LiuJ. ZhouL. DongM. WangR. LiX. LiX. LinC. NiuY. Puerarin attenuates amyloid-beta-induced cognitive impairment through suppression of apoptosis in rat hippocampus in vivo.Eur. J. Pharmacol.20106491-319520110.1016/j.ejphar.2010.09.045 20868658
     [Google Scholar]
  143. BoozG.W. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress.Free Radic. Biol. Med.20115151054106110.1016/j.freeradbiomed.2011.01.007 21238581
     [Google Scholar]
  144. EspositoG. De FilippisD. CarnuccioR. IzzoA.A. IuvoneT. The marijuana component cannabidiol inhibits β-amyloid-induced tau protein hyperphosphorylation through Wnt/β-catenin pathway rescue in PC12 cells.J. Mol. Med. (Berl.)200684325325810.1007/s00109‑005‑0025‑1 16389547
     [Google Scholar]
  145. AsoE. Sánchez-PlaA. Vegas-LozanoE. MaldonadoR. FerrerI. Cannabis-based medicine reduces multiple pathological processes in AβPP/PS1 mice.J. Alzheimers Dis.201443397799110.3233/JAD‑141014 25125475
     [Google Scholar]
  146. DurairajanS.S.K. YuanQ. XieL. ChanW.S. KumW.F. KooI. LiuC. SongY. HuangJ.D. KleinW.L. LiM. Salvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty.Neurochem. Int.2008524-574175010.1016/j.neuint.2007.09.006 17964692
     [Google Scholar]
  147. WangS.X. HuL.M. GaoX.M. GuoH. FanG.W. Anti-inflammatory activity of salvianolic acid B in microglia contributes to its neuroprotective effect.Neurochem. Res.20103571029103710.1007/s11064‑010‑0151‑1 20238162
     [Google Scholar]
  148. KimD.H. ParkS.J. KimJ.M. JeonS.J. KimD.H. ChoY.W. SonK.H. LeeH.J. MoonJ.H. CheongJ.H. KoK.H. RyuJ.H. Cognitive dysfunctions induced by a cholinergic blockade and Aβ25–35 peptide are attenuated by salvianolic acid B.Neuropharmacology20116181432144010.1016/j.neuropharm.2011.08.038 21903108
     [Google Scholar]
  149. LeeY.W. KimD.H. JeonS.J. ParkS.J. KimJ.M. JungJ.M. LeeH.E. BaeS.G. OhH.K. Ho SonK.H. RyuJ.H. Neuroprotective effects of salvianolic acid B on an Aβ25–35 peptide-induced mouse model of Alzheimer’s disease.Eur. J. Pharmacol.20137041-3707710.1016/j.ejphar.2013.02.015 23461850
     [Google Scholar]
  150. MoriT. KoyamaN. Guillot-SestierM.V. TanJ. TownT. Ferulic acid is a nutraceutical β-secretase modulator that improves behavioral impairment and alzheimer-like pathology in transgenic mice.PLoS One201382e5577410.1371/journal.pone.0055774 23409038
     [Google Scholar]
  151. SrinivasanM. SudheerA.R. MenonV.P. Ferulic Acid: Therapeutic potential through its antioxidant property.J. Clin. Biochem. Nutr.20074029210010.3164/jcbn.40.92 18188410
     [Google Scholar]
  152. YanJ.J. JungJ.S. KimT.K. HasanM.A. HongC.W. NamJ.S. SongD.K. Protective effects of ferulic acid in amyloid precursor protein plus presenilin-1 transgenic mouse model of Alzheimer disease.Biol. Pharm. Bull.201336114014310.1248/bpb.b12‑00798 23075678
     [Google Scholar]
  153. HuangS.L. YuR.T. GongJ. FengY. DaiY.L. HuF. HuY.H. TaoY.D. LengY. Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice.Diabetologia20125551469148110.1007/s00125‑011‑2366‑3 22095235
     [Google Scholar]
  154. ZhuZ. YanJ. JiangW. YaoX. ChenJ. ChenL. LiC. HuL. JiangH. ShenX. Arctigenin effectively ameliorates memory impairment in Alzheimer’s disease model mice targeting both β-amyloid production and clearance.J. Neurosci.20133332131381314910.1523/JNEUROSCI.4790‑12.2013 23926267
     [Google Scholar]
  155. BarbosaP.R. ValvassoriS.S. BordignonC.L.Jr KappelV.D. MartinsM.R. GavioliE.C. QuevedoJ. ReginattoF.H. The aqueous extracts of Passiflora alata and Passiflora edulis reduce anxiety-related behaviors without affecting memory process in rats.J. Med. Food200811228228810.1089/jmf.2007.722 18598170
     [Google Scholar]
  156. NabaviS. HabtemariamS. DagliaM. NabaviS. Apigenin and breast cancers: From chemistry to medicine.Anticancer. Agents Med. Chem.201515672873510.2174/1871520615666150304120643 25738871
     [Google Scholar]
  157. ZhaoL. WangJ.L. LiuR. LiX.X. LiJ.F. ZhangL. Neuroprotective, anti-amyloidogenic and neurotrophic effects of apigenin in an Alzheimer’s disease mouse model.Molecules20131889949996510.3390/molecules18089949 23966081
     [Google Scholar]
  158. XuF. WangC. YangL. LuoH. FanW. ZiC. DongF. HuJ. ZhouJ. C-dideoxyhexosyl flavones from the stems and leaves of Passiflora edulis Sims.Food Chem.20131361949910.1016/j.foodchem.2012.07.101 23017397
     [Google Scholar]
  159. ZhuX.Z. LiX.Y. LiuJ. Recent pharmacological studies on natural products in China.Eur. J. Pharmacol.20045001-322123010.1016/j.ejphar.2004.07.027 15464035
     [Google Scholar]
  160. ZhangH.Y. TangX.C. Neuroprotective effects of huperzine A: New therapeutic targets for neurodegenerative disease.Trends Pharmacol. Sci.2006271261962510.1016/j.tips.2006.10.004 17056129
     [Google Scholar]
  161. WangZ. TangL. YanH. WangY. TangX. Effects of huperzine A on memory deficits and neurotrophic factors production after transient cerebral ischemia and reperfusion in mice.Pharmacol. Biochem. Behav.200683460361110.1016/j.pbb.2006.03.027 16687166
     [Google Scholar]
  162. TangL.L. WangR. TangX.C. Huperzine A protects SHSY5Y neuroblastoma cells against oxidative stress damage via nerve growth factor production.Eur. J. Pharmacol.20055191-291510.1016/j.ejphar.2005.06.026 16111675
     [Google Scholar]
  163. TangL. WangR. TangX. Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells.Acta Pharmacol. Sin.200526667367810.1111/j.1745‑7254.2005.00130.x 15916732
     [Google Scholar]
  164. MaoX.Y. CaoD.F. LiX. YinJ.Y. WangZ.B. ZhangY. MaoC.X. ZhouH.H. LiuZ.Q. Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats.Int. J. Mol. Sci.20141557667768310.3390/ijms15057667 24857910
     [Google Scholar]
  165. SalgaS.M. AliH.M. AbdullahM.A. AbdelwahabS.I. WaiL.K. BuckleM.J.C. SukumaranS.D. HadiA.H.A. Synthesis, characterization, acetylcholinesterase inhibition, molecular modeling and antioxidant activities of some novel Schiff bases derived from 1-(2-ketoiminoethyl)piperazines.Molecules201116119316933010.3390/molecules16119316 22064271
     [Google Scholar]
  166. TsengY.T. HsuY.Y. ShihY.T. LoY.C. Paeonol attenuates microglia-mediated inflammation and oxidative stress-induced neurotoxicity in rat primary microglia and cortical neurons.Shock201237331231810.1097/SHK.0b013e31823fe939 22089194
     [Google Scholar]
  167. ZhouJ. ZhouL. HouD. TangJ. SunJ. BondyS.C. Paeonol increases levels of cortical cytochrome oxidase and vascular actin and improves behavior in a rat model of Alzheimer’s disease.Brain Res.2011138814114710.1016/j.brainres.2011.02.064 21377451
     [Google Scholar]
  168. SchugS.A. ZechD. DörrU. Cancer pain management according to WHO analgesic guidelines.J. Pain Symptom Manage.199051273210.1016/S0885‑3924(05)80006‑5 2324558
     [Google Scholar]
  169. CuiJ. WangY. DongQ. WuS. XiaoX. HuJ. ChaiZ. ZhangY. Morphine protects against intracellular amyloid toxicity by inducing estradiol release and upregulation of Hsp70.J. Neurosci.20113145162271624010.1523/JNEUROSCI.3915‑11.2011 22072674
     [Google Scholar]
  170. WangY. WangY.X. LiuT. LawP.Y. LohH.H. QiuY. ChenH.Z. μ-Opioid receptor attenuates Aβ oligomers-induced neurotoxicity through mTOR signaling.CNS Neurosci. Ther.201521181410.1111/cns.12316 25146548
     [Google Scholar]
  171. SwiechL. PeryczM. MalikA. JaworskiJ. Role of mTOR in physiology and pathology of the nervous system.Biochim. Biophys. Acta. Proteins Proteomics20081784111613210.1016/j.bbapap.2007.08.015 17913600
     [Google Scholar]
  172. ZhuZ. LiC. WangX. YangZ. ChenJ. HuL. JiangH. ShenX. 2,2′,4′‐Trihydroxychalcone from Glycyrrhiza glabra as a new specific BACE1 inhibitor efficiently ameliorates memory impairment in mice.J. Neurochem.2010114237438510.1111/j.1471‑4159.2010.06751.x 20412384
     [Google Scholar]
  173. SabzevariO. GalatiG. MoridaniM.Y. SirakiA. O’BrienP.J. Molecular cytotoxic mechanisms of anticancer hydroxychalcones.Chem. Biol. Interact.20041481-2576710.1016/j.cbi.2004.04.004 15223357
     [Google Scholar]
  174. MeiZ. ZhangF. TaoL. ZhengW. CaoY. WangZ. TangS. LeK. ChenS. PiR. LiuP. Cryptotanshinone, a compound from Salvia miltiorrhiza modulates amyloid precursor protein metabolism and attenuates β-amyloid deposition through upregulating α-secretase in vivo and in vitro.Neurosci. Lett.20094522909510.1016/j.neulet.2009.01.013 19154776
     [Google Scholar]
  175. KimH.S. SulD. LimJ.Y. LeeD. JooS.S. HwangK.W. ParkS.Y. Delphinidin ameliorates beta-amyloid-induced neurotoxicity by inhibiting calcium influx and tau hyperphosphorylation.Biosci. Biotechnol. Biochem.20097371685168910.1271/bbb.90032 19584523
     [Google Scholar]
  176. ChenB. MaY. LiH. ChenX. ZhangC. WangH. DengZ. The antioxidant activity and active sites of delphinidin and petunidin measured by DFT, in vitro chemical‐based and cell‐based assays.J. Food Biochem.2019439e1296810.1111/jfbc.12968 31489675
     [Google Scholar]
  177. HaseebA. ChenD. HaqqiT.M. Delphinidin inhibits IL-1-induced activation of NF- B by modulating the phosphorylation of IRAK-1Ser376 in human articular chondrocytes.Rheumatology (Oxford)2013526998100810.1093/rheumatology/kes363 23392593
     [Google Scholar]
  178. NagaseH. YamakuniT. MatsuzakiK. MaruyamaY. KasaharaJ. HinoharaY. KondoS. MimakiY. SashidaY. TankA.W. FukunagaK. OhizumiY. Mechanism of neurotrophic action of nobiletin in PC12D cells.Biochemistry20054442136831369110.1021/bi050643x 16229458
     [Google Scholar]
  179. MatsuzakiK. YamakuniT. HashimotoM. HaqueA.M. ShidoO. MimakiY. SashidaY. OhizumiY. Nobiletin restoring β-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer’s disease model rats.Neurosci. Lett.2006400323023410.1016/j.neulet.2006.02.077 16581185
     [Google Scholar]
  180. NakajimaA. YamakuniT. HaraguchiM. OmaeN. SongS.Y. KatoC. NakagawasaiO. TadanoT. YokosukaA. MimakiY. SashidaY. OhizumiY. Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice.J. Pharmacol. Sci.2007105112212610.1254/jphs.SC0070155 17895593
     [Google Scholar]
  181. Sadigh-EteghadS. SabermaroufB. MajdiA. TalebiM. FarhoudiM. MahmoudiJ. Amyloid-beta: A crucial factor in Alzheimer’s disease.Med. Princ. Pract.201524111010.1159/000369101 25471398
     [Google Scholar]
  182. MajdiA. KamariF. VafaeeM.S. Sadigh-EteghadS. Revisiting nicotine’s role in the ageing brain and cognitive impairment.Rev. Neurosci.201728776778110.1515/revneuro‑2017‑0008 28586306
     [Google Scholar]
  183. CormierA. MorinC. ZiniR. TillementJ.P. LagrueG. Nicotine protects rat brain mitochondria against experimental injuries.Neuropharmacology200344564265210.1016/S0028‑3908(03)00041‑8 12668050
     [Google Scholar]
  184. MyersC.S. TaylorR.C. MoolchanE.T. HeishmanS.J. Dose-related enhancement of mood and cognition in smokers administered nicotine nasal spray.Neuropsychopharmacology200833358859810.1038/sj.npp.1301425 17443125
     [Google Scholar]
  185. WanningerS. LorenzV. SubhanA. EdelmannF.T. Metal complexes of curcumin – synthetic strategies, structures and medicinal applications.Chem. Soc. Rev.201544154986500210.1039/C5CS00088B 25964104
     [Google Scholar]
  186. ZhangK. ChenM. DuZ-Y. ZhengX. LiD-L. ZhouR-P. Use of curcumin in diagnosis, prevention, and treatment of Alzheimer’s disease.Neural Regen. Res.201813474275210.4103/1673‑5374.230303 29722330
     [Google Scholar]
  187. SilvestroS. ChiricostaL. GugliandoloA. IoriR. RollinP. PerenzoniD. MattiviF. BramantiP. MazzonE. The Moringin/α-CD pretreatment induces neuroprotection in an in vitro model of Alzheimer’s disease: A transcriptomic study.Curr. Issues Mol. Biol.202143119721410.3390/cimb43010017 34073287
     [Google Scholar]
  188. NanS. WangP. ZhangY. FanJ. Epigallocatechin-3-gallate provides protection against Alzheimer’s disease-induced learning and memory impairments in rats.Drug Des. Devel. Ther.2021152013202410.2147/DDDT.S289473 34012254
     [Google Scholar]
  189. SunX. LiL. DongQ.X. ZhuJ. HuangY. HouS. YuX. LiuR. Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer’s disease.J. Neuroinflammation202118113110.1186/s12974‑021‑02182‑3 34116706
     [Google Scholar]
  190. TajmimA. Cuevas-OcampoA.K. SiddiqueA.B. QusaM.H. KingJ.A. AbdelwahedK.A. SonjuJ.J. El SayedK.A. (-)-Oleocanthal nutraceuticals for Alzheimer’s disease amyloid pathology: Novel oral formulations, therapeutic, and molecular insights in 5xFAD transgenic mice model.Nutrients2021135170210.3390/nu13051702 34069842
     [Google Scholar]
  191. WangY. XiaZ. JiangX. LiL. WangH. AnD. LiuY. Genistein inhibits amyloid peptide 25-35-induced neuronal death by modulating estrogen receptors, choline acetyltransferase and glutamate receptors.Arch. Biochem. Biophys.202069310856110.1016/j.abb.2020.108561 32857999
     [Google Scholar]
  192. GerzsonM.F.B. BonaN.P. SoaresM.S.P. TeixeiraF.C. RahmeierF.L. CarvalhoF.B. da Cruz FernandesM. OnziG. LenzG. GonçalesR.A. SpanevelloR.M. StefanelloF.M. Tannic acid ameliorates STZ-induced Alzheimer’s disease-like impairment of memory, neuroinflammation, neuronal death and modulates Akt expression.Neurotox. Res.20203741009101710.1007/s12640‑020‑00167‑3 31997154
     [Google Scholar]
  193. ShiR. ZhengC. WangH. RaoQ. DuT. BaiC. XiaoC. DaiZ. ZhangC. ChenC. LiX. TianM. YuX. JiB. WengZ. YangW. Gastrodin alleviates vascular dementia in a 2-VO-vascular dementia rat model by altering amyloid and tau levels.Pharmacology20201057-838639610.1159/000504056 31752010
     [Google Scholar]
  194. ChenL. PanH. BaiY. LiH. YangW. LinZ.X. CuiW. XianY.F. Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aβ oligomer-treated mice.Psychopharmacology (Berl.)202023772111212410.1007/s00213‑020‑05522‑y 32363440
     [Google Scholar]
  195. RayB. MaloneyB. SambamurtiK. KarnatiH.K. NelsonP.T. GreigN.H. LahiriD.K. Rivastigmine modifies the α-secretase pathway and potentially early Alzheimer’s disease.Transl. Psychiatry20201014710.1038/s41398‑020‑0709‑x 32066688
     [Google Scholar]
  196. ChenY. ChenY. LiangY. ChenH. JiX. HuangM. Berberine mitigates cognitive decline in an Alzheimer’s disease mouse model by targeting both tau hyperphosphorylation and autophagic clearance.Biomed. Pharmacother.202012110967010.1016/j.biopha.2019.109670 31810131
     [Google Scholar]
  197. ZhangY. YangX. WangS. SongS. Ginsenoside Rg3 prevents cognitive impairment by improving mitochondrial dysfunction in the rat model of Alzheimer’s disease.J. Agric. Food Chem.20196736100481005810.1021/acs.jafc.9b03793 31422666
     [Google Scholar]
  198. TaniguchiK. YamamotoF. AraiT. YangJ. SakaiY. ItohM. MamadaN. SekiguchiM. YamadaD. SaitohA. KametaniF. TamaokaA. ArakiY.M. WadaK. MizusawaH. ArakiW. Tyrosol reduces amyloid-β oligomer neurotoxicity and alleviates synaptic, oxidative, and cognitive disturbances in Alzheimer’s disease model mice.J. Alzheimers Dis.201970393795210.3233/JAD‑190098 31227651
     [Google Scholar]
  199. HaseT. ShishidoS. YamamotoS. YamashitaR. NukimaH. TairaS. ToyodaT. AbeK. HamaguchiT. OnoK. Noguchi-ShinoharaM. YamadaM. KobayashiS. Rosmarinic acid suppresses Alzheimer’s disease development by reducing amyloid β aggregation by increasing monoamine secretion.Sci. Rep.201991871110.1038/s41598‑019‑45168‑1 31213631
     [Google Scholar]
  200. HuangL. LinM. ZhongX. YangH. DengM. Galangin decreases p tau, Aβ42 and β secretase levels, and suppresses autophagy in okadaic acid induced PC12 cells via an Akt/GSK3β/mTOR signaling dependent mechanism.Mol. Med. Rep.20191931767177410.3892/mmr.2019.9824 30628698
     [Google Scholar]
  201. KhanA. AliT. RehmanS.U. KhanM.S. AlamS.I. IkramM. MuhammadT. SaeedK. BadshahH. KimM.O. Neuroprotective effect of quercetin against the detrimental effects of LPS in the adult mouse brain.Front. Pharmacol.20189138310.3389/fphar.2018.01383
     [Google Scholar]
  202. LiuY. ZhangY. ZhengX. FangT. YangX. LuoX. GuoA. NewellK.A. HuangX.F. YuY. Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice.J. Neuroinflammation201815111210.1186/s12974‑018‑1141‑5 29669582
     [Google Scholar]
  203. NaJ.Y. SongK. LeeJ.W. KimS. KwonJ. 6-Shogaol has anti-amyloidogenic activity and ameliorates Alzheimer’s disease via CysLT1R-mediated inhibition of cathepsin B.Biochem. Biophys. Res. Commun.201647719610210.1016/j.bbrc.2016.06.026 27286707
     [Google Scholar]
  204. ZongN. LiF. DengY. ShiJ. JinF. GongQ. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus.Behav. Brain Res.201631311111910.1016/j.bbr.2016.06.055 27368415
     [Google Scholar]
  205. WangH. WangH. ChengH. CheZ. Ameliorating effect of luteolin on memory impairment in an Alzheimer’s disease model.Mol. Med. Rep.20161354215422010.3892/mmr.2016.5052 27035793
     [Google Scholar]
  206. RamezaniM. DarbandiN. KhodagholiF. HashemiA. Myricetin protects hippocampal CA3 pyramidal neurons and improves learning and memory impairments in rats with Alzheimer’s disease.Neural Regen. Res.201611121976198010.4103/1673‑5374.197141 28197195
     [Google Scholar]
  207. DuanS. GuanX. LinR. LiuX. YanY. LinR. ZhangT. ChenX. HuangJ. SunX. LiQ. FangS. XuJ. YaoZ. GuH. Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: A dual-target drug for the treatment of Alzheimer’s disease.Neurobiol. Aging20153651792180710.1016/j.neurobiolaging.2015.02.002 25771396
     [Google Scholar]
  208. ZhangR. MiaoQ.W. ZhuC.X. ZhaoY. LiuL. YangJ. AnL. Sulforaphane ameliorates neurobehavioral deficits and protects the brain from amyloid β deposits and peroxidation in mice with Alzheimer-like lesions.Am. J. Alzheimers Dis. Other Demen.201530218319110.1177/1533317514542645 25024455
     [Google Scholar]
  209. LaurentC. EddarkaouiS. DerisbourgM. LeboucherA. DemeyerD. CarrierS. SchneiderM. HamdaneM. MüllerC.E. BuéeL. BlumD. Beneficial effects of caffeine in a transgenic model of Alzheimer’s disease-like tau pathology.Neurobiol. Aging20143592079209010.1016/j.neurobiolaging.2014.03.027 24780254
     [Google Scholar]
  210. ZhouY. XieN. LiL. ZouY. ZhangX. DongM. Puerarin alleviates cognitive impairment and oxidative stress in APP/PS1 transgenic mice.Int. J. Neuropsychopharmacol.201417463564410.1017/S146114571300148X 24345484
     [Google Scholar]
  211. ChengD. SpiroA.S. JennerA.M. GarnerB. KarlT. Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer’s disease transgenic mice.J. Alzheimers Dis.20144241383139610.3233/JAD‑140921 25024347
     [Google Scholar]
  212. WangC.Y. ZhengW. WangT. XieJ.W. WangS.L. ZhaoB.L. TengW.P. WangZ.Y. Huperzine A activates Wnt/β-catenin signaling and enhances the nonamyloidogenic pathway in an Alzheimer transgenic mouse model.Neuropsychopharmacology20113651073108910.1038/npp.2010.245 21289607
     [Google Scholar]
  213. OnozukaH. NakajimaA. MatsuzakiK. ShinR.W. OginoK. SaigusaD. TetsuN. YokosukaA. SashidaY. MimakiY. YamakuniT. Nobiletin, a citrus flavonoid, improves memory impairment and Aβ pathology in a transgenic mouse model of Alzheimer’s disease.J. Pharmacol. Exp. Ther.2008326373974410.1124/jpet.108.140293
     [Google Scholar]
  214. NordbergA. Hellström-LindahlE. LeeM. JohnsonM. MousaviM. HallR. PerryE. BednarI. CourtJ. Chronic nicotine treatment reduces β‐amyloidosis in the brain of a mouse model of Alzheimer’s disease (APPsw).J. Neurochem.200281365565810.1046/j.1471‑4159.2002.00874.x 12065674
     [Google Scholar]
  215. LimG.P. ChuT. YangF. BeechW. FrautschyS.A. ColeG.M. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse.J. Neurosci.200121218370837710.1523/JNEUROSCI.21‑21‑08370.2001 11606625
     [Google Scholar]
/content/journals/cbc/10.2174/0115734072309710240603065813
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Phytoconstituents Ameliorates Alzheimer's Disease and Cognitive Impairments: A Review of Preclinical Studies
Curr. Bioact. Compd. 21, E140624231042 (2025); https://doi.org/10.2174/0115734072309710240603065813
/content/journals/cbc/10.2174/0115734072309710240603065813
/content/journals/cbc/10.2174/0115734072309710240603065813
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  • Article Type:     Review Article
Keyword(s): Alzheimer's disease; amyloid-beta; cognitive dysfunction; learning and memory; neuroprotective; phytochemicals; phytoconstituents; τ-protein

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