CoChat
Sign Up
Cited by 82Alzheimer's disease research and treatmentsMedicinal Plants and NeuroprotectionAluminum toxicity and tolerance in plants and animals

Neuroprotective Effects of Phytochemicals against Aluminum Chloride-Induced Alzheimer’s Disease through ApoE4/LRP1, Wnt3/β-Catenin/GSK3β, and TLR4/NLRP3 Pathways with Physical and Mental Activities in a Rat Model

Open access
Hamdan, Ahmed Mohsen Elsaid, Alharthi, Fatimah Hussain J., Alanazi, Ahmed Hadi, El-Emam, Soad Z., Zaghlool, Sameh S., Metwally, Kamel, Albalawi, Sana Abdulaziz, Abdu, Yahia S. +4 more·2022·Pharmaceuticals
DOI 10.3390/ph15081008PMC PMC9416484
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that is associated with abnormal cognition. AD is aided in its initiation and progression by hereditary and environmental factors. Aluminum (Al) is a neurotoxic agent that causes oxidative stress, which is linked to AD progression. Additionally, Nrf2/HO-1, APOE4/LRP1, Wnt3/β-catenin, and TLR4/NLRP3 are the main signaling pathways involved in AD pathogenesis. Several phytochemicals are promising options in delaying AD evolution. Objectives: This study aimed at studying the neuroprotective effects of some phytochemicals as morin (MOR), thymol (TML), and thymoquinone (TMQ) on physical and mental activities (PhM) in Al chloride (AlCl3)-induced AD rat model. Another objective was to determine the specificity of phytochemicals to AD signaling pathways using molecular docking. Methods: Eighty male Dawley rats were divided into eight groups. Each group received: saline (control group), AlCl3, (ALAD), PhM, either alone or with a combination of MOR, TML, and/or TMQ for five weeks. Animals were then subjected to behavioral evaluation. Brain tissues were used for histopathological and biochemical analyses to determine the extent of neurodegeneration. The effect of phytochemicals on AlCl3-induced oxidative stress and the main signaling pathways involved in AD progression were also investigated. Results: AlCl3 caused a decline in spatial learning and memory, as well as histopathological changes in the brains of rats. Phytochemicals combined with PhM restored antioxidant activities, increased HO-1 and Nrf2 levels, blocked inflammasome activation, apoptosis, TLR4 expression, amyloide-β generation, and tau hyperphophorylation. They also brought ApoE4 and LRP1 levels back to normal and regulated Wnt3/β-catenin/GSK3β signaling pathway. Conclusions: The use of phytochemicals with PhM is a promising strategy for reducing AD by modulating Nrf2/HO-1, TLR4/NLRP3, APOE4/LRP1, and Wnt3/β-catenin/GSK-3β signaling pathways.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/ph15081008

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • ApoE4 activates LRP1 and subsequent intracellular signaling pathways, namely Wnt3/β-catenin/GSK3β pathway, that ultimately potentiates GSK3β-mediated tau hyperphosphorylation.

    “ApoE4 activates LRP1 and subsequent intracellular signaling pathways, namely Wnt3/β-cathenin/GSK3β pathway, that ultimately potentiates GSK3β-mediated tau hyperphosphorylation [53,54]”

    From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [53]

    The Introduction links GSK3β overactivation to tau phosphorylation, supporting that part of the claim. But the Discussion says ApoE4 binding inhibits LRP1-mediated tau uptake and Aβ clearance, not that ApoE4 activates LRP1; it also says Wnt3/β-catenin activation inhibits tau hyperphosphorylation. Neither section establishes the claimed ApoE4-to-LRP1-to-Wnt signaling cascade. Page numbers are unavailable in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 84

  1. [1]Ju Y. Tam K. Pathological mechanisms and therapeutic strategies for Alzheimer’s disease Neural Regen. Res. 2022 17 543 549 34380884 PMC8504384
  2. [2]Heilman K.M. Nadeau S.E. Emotional and Neuropsychiatric Disorders Associated with Alzheimer’s Disease Neurotherapeutics 2022 19 99 116 10.1007/s13311-021-01172-w 35013934 PMC9130428 · DOI
  3. [4]Srivastava S. Ahmad R. Khare S.K. Alzheimer’s disease and its treatment by different approaches: A review Eur. J. Med. Chem. 2021 216 113320 10.1016/j.ejmech.2021.113320 33652356 · DOI
  4. [5]Graff-Radford J. Yong K.X.X. Apostolova L.G. Bouwman F.H. Carrillo M. Dickerson B.C. Rabinovici G.D. Schott J.M. Jones D.T. Murray M.E. New insights into atypical Alzheimer’s disease in the era of biomarkers Lancet. Neurol. 2021 20 222 234 10.1016/S1474-4422(20)30440-3 33609479 PMC8056394 · DOI · Paper page
  5. [6]Abbas F. Eladl M.A. El-Sherbiny M. Abozied N. Nabil A. Mahmoud S.M. Mokhtar H.I. Zaitone S.A. Ibrahim D. Celastrol and thymoquinone alleviate aluminum chloride-induced neurotoxicity: Behavioral psychomotor performance, neurotransmitter level, oxidative-inflammatory markers, and BDNF expression in rat brain Biomed. Pharmacother. 2022 151 113072 10.1016/j.biopha.2022.113072 35576663 · DOI
  6. [7]Mehrbeheshti N. Esmaili Z. Ahmadi M. Moosavi M. A dose response effect of oral aluminum nanoparticle on novel object recognition memory, hippocampal caspase-3 and MAPKs signaling in mice Behav. Brain Res. 2022 417 113615 10.1016/j.bbr.2021.113615 34606775 · DOI
  7. [8]Chen S.X. Xiang J.Y. Han J.X. Yang-Feng Li H.Z. Chen H. Xu M. Essential Oils from Spices Inhibit Cholinesterase Activity and Improve Behavioral Disorder in AlCl 3 Induced Dementia Chem. Biodivers. 2022 1 e202100443 10.1002/cbdv.202100443 34855291 · DOI
  8. [9]Aalikhani M. Safdari Y. Jahanshahi M. Alikhani M. Khalili M. Comparison Between Hesperidin, Coumarin, and Deferoxamine Iron Chelation and Antioxidant Activity Against Excessive Iron in the Iron Overloaded Mice Front. Neurosci. 2022 15 811080 10.3389/fnins.2021.811080 35177961 PMC8846322 · DOI
  9. [10]Elbini-Dhouib I. Doghri R. Ellefi A. Degrach I. Srairi-Abid N. Gati A. Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer’s Disease Molecules 2021 26 3011 10.3390/molecules26103011 34070220 PMC8158738 · DOI
  10. [11]Mesole S.B. Alfred O.O. Yusuf U.A. Lukubi L. Ndhlovu D. Apoptotic Inducement of Neuronal Cells by Aluminium Chloride and the Neuroprotective Effect of Eugenol in Wistar Rats Oxid. Med. Cell. Longev. 2020 8425643 10.1155/2020/8425643 32089784 PMC7008282 · DOI
  11. [12]Skalny A.V. Aschner M. Jiang Y. Gluhcheva Y.G. Tizabi Y. Lobinski R. Tinkov A.A. Molecular mechanisms of aluminum neurotoxicity: Update on adverse effects and therapeutic strategies Adv. Neurotoxicology 2021 5 1 34 PMC8276946 34263089
  12. [13]Hampel H. Vassar R. De Strooper B. Hardy J. Willem M. Singh N. Zhou J. Yan R. Vanmechelen E. De Vos A. The β-Secretase BACE1 in Alzheimer’s Disease Biol. Psychiatry 2021 89 745 756 10.1016/j.biopsych.2020.02.001 32223911 PMC7533042 · DOI · Paper page
  13. [14]Morroni F. Sita G. Graziosi A. Turrini E. Fimognari C. Tarozzi A. Hrelia P. Neuroprotective effect of caffeic acid phenethyl ester in a mouse model of alzheimer’s disease involves Nrf2/HO-1 pathway Aging Dis. 2018 9 605 622 10.14336/AD.2017.0903 30090650 PMC6065293 · DOI
  14. [15]Zhou Y. Chen Y. Xu C. Zhang H. Lin C. TLR4 Targeting as a Promising Therapeutic Strategy for Alzheimer Disease Treatment Front. Neurosci. 2020 14 602508 10.3389/fnins.2020.602508 33390886 PMC7775514 · DOI
  15. [16]Kabel A.M. Arab H.H. Atef A. Estfanous R.S. Omarigliptin/galangin combination mitigates lipopolysaccharide-induced neuroinflammation in rats: Involvement of glucagon-like peptide-1, toll-like receptor-4, apoptosis and Akt/GSK-3β signaling Life Sci. 2022 295 120396 10.1016/j.lfs.2022.120396 35157909 · DOI
  16. [17]Liu Y. Dai Y. Li Q. Chen C. Chen H. Song Y. Hua F. Zhang Z. Beta-amyloid activates NLRP3 inflammasome via TLR4 in mouse microglia Neurosci. Lett. 2020 736 135279 10.1016/j.neulet.2020.135279 32726591 · DOI · Paper page
  17. [18]Abu-Elfotuh K. Al-Najjar A.H. Mohammed A.A. Aboutaleb A.S. Badawi G.A. Fluoxetine ameliorates Alzheimer’s disease progression and prevents the exacerbation of cardiovascular dysfunction of socially isolated depressed rats through activation of Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathway Int. Immunopharmacol. 2022 104 108488 10.1016/j.intimp.2021.108488 35042170 · DOI
  18. [19]He W. Long T. Pan Q. Zhang S. Zhang Y. Zhang D. Qin G. Chen L. Zhou J. Microglial NLRP3 inflammasome activation mediates IL-1β release and contributes to central sensitization in a recurrent nitroglycerin-induced migraine model J. Neuroinflammation 2019 16 78 10.1186/s12974-019-1459-7 30971286 PMC6456991 · DOI
  19. [20]Ju T. Sun L. Fan Y. Wang T. Liu Y. Liu D. Liu T. Zhao C. Wang W. Chi L. Decreased Netrin-1 in Mild Cognitive Impairment and Alzheimer’s Disease Patients Front. Aging Neurosci. 2022 13 762649 10.3389/fnagi.2021.762649 35250531 PMC8888826 · DOI
  20. [21]Fan M. Li Z. Hu M. Zhao H. Wang T. Jia Y. Yang R. Wang S. Song J. Liu Y. Formononetin attenuates Aβ 25-35-induced adhesion molecules in HBMECs via Nrf2 activation Brain Res. Bull. 2022 183 162 171 10.1016/j.brainresbull.2022.03.009 35304289 · DOI
  21. [22]Van Gool B. Storck S.E. Reekmans S.M. Lechat B. Gordts P.L.S.M. Pradier L. Pietrzik C.U. Roebroek A.J.M. LRP1 Has a Predominant Role in Production over Clearance of Aβ in a Mouse Model of Alzheimer’s Disease Mol. Neurobiol. 2019 56 7234 7245 10.1007/s12035-019-1594-2 31004319 PMC6728278 · DOI · Paper page
  22. [24]Jha N.K. Chen W.C. Kumar S. Dubey R. Tsai L.W. Kar R. Jha S.K. Gupta P.K. Sharma A. Gundamaraju R. Molecular mechanisms of developmental pathways in neurological disorders: A pharmacological and therapeutic review Open Biol. 2022 12 210289 10.1098/rsob.210289 35291879 PMC8924757 · DOI
  23. [25]Knotek T. Janeckova L. Kriska J. Korinek V. Anderova M. Glia and Neural Stem and Progenitor Cells of the Healthy and Ischemic Brain: The Workplace for the Wnt Signaling Pathway Genes 2020 11 804 10.3390/genes11070804 PMC7397164 32708801 · DOI
  24. [26]Yi S. Chen S. Xiang J. Tan J. Huang K. Zhang H. Wang Y. Wu H. Genistein exerts a cell-protective effect via nrf2/ho-1/ /pi3k signaling in ab25-35-induced alzheimer’s disease models in vitro Folia Histochem. Cytobiol. 2021 59 49 56 10.5603/FHC.a2021.0006 33605427 · DOI
  25. [27]Tayab M.A. Islam M.N. Chowdhury K.A.A. Tasnim F.M. Targeting neuroinflammation by polyphenols: A promising therapeutic approach against inflammation-associated depression Biomed. Pharmacother. 2022 147 112668 10.1016/j.biopha.2022.112668 35104696 · DOI
  26. [28]Naoi M. Maruyama W. Shamoto-Nagai M. Disease-modifying treatment of Parkinson’s disease by phytochemicals: Targeting multiple pathogenic factors J. Neural Transm. 2021 129 737 753 10.1007/s00702-021-02427-8 34654977 · DOI
  27. [30]Davies D.A. Adlimoghaddam A. Albensi B.C. Role of Nrf2 in Synaptic Plasticity and Memory in Alzheimer’s Disease Cells 2021 10 1884 10.3390/cells10081884 34440653 PMC8391447 · DOI
  28. [31]Li H. Qin T. Li M. Ma S. Thymol improves high-fat diet-induced cognitive deficits in mice via ameliorating brain insulin resistance and upregulating NRF2/HO-1 pathway Metab. Brain Dis. 2017 32 385 393 27761760
  29. [32]Javed H. Azimullah S. Meeran M.N. Ansari S.A. Ojha S. Neuroprotective effects of thymol, a dietary monoterpene against dopaminergic neurodegeneration in rotenone-induced rat model of parkinson’s disease Int. J. Mol. Sci. 2019 20 1538 10.3390/ijms20071538 PMC6480243 30934738 · DOI
  30. [33]Asadbegi M. Yaghmaei P. Salehi I. Komaki A. Ebrahim-Habibi A. Investigation of thymol effect on learning and memory impairment induced by intrahippocampal injection of amyloid beta peptide in high fat diet- fed rats Metab. Brain Dis. 2017 32 827 839 10.1007/s11011-017-9960-0 28255862 · DOI
  31. [34]Poorgholam P. Yaghmaei P. Hajebrahimi Z. Thymoquinone recovers learning function in a rat model of Alzheimer’s disease Avicenna J. Phytomed. 2018 8 188 197 29881705 PMC5987434
  32. [35]Caselli A. Cirri P. Santi A. Paoli P. Morin: A Promising Natural Drug Curr. Med. Chem. 2016 23 774 791 10.2174/0929867323666160106150821 26018232 · DOI
  33. [36]Issac P.K. Guru A. Velayutham M. Pachaiappan R. Arasu M.V. Al-Dhabi N.A. Choi K.C. Harikrishnan R. Arockiaraj J. Oxidative stress induced antioxidant and neurotoxicity demonstrated in vivo zebrafish embryo or larval model and their normalization due to morin showing therapeutic implications Life Sci. 2021 283 119864 10.1016/j.lfs.2021.119864 34358548 · DOI
  34. [37]Kuzu M. Kandemir F.M. Yildirim S. Kucukler S. Caglayan C. Turk E. Morin attenuates doxorubicin-induced heart and brain damage by reducing oxidative stress, inflammation and apoptosis Biomed. Pharmacother. 2018 106 443 453 10.1016/j.biopha.2018.06.161 29990832 · DOI
  35. [38]Mohamed E.A. Ahmed H.I. Zaky H.S. Badr A.M. Sesame oil mitigates memory impairment, oxidative stress, and neurodegeneration in a rat model of Alzheimer’s disease. A pivotal role of NF-κB/p38MAPK/BDNF/PPAR-γ pathways J. Ethnopharmacol. 2021 267 113468 10.1016/j.jep.2020.113468 33049345 · DOI
  36. [39]Hindam M.O. Sayed R.H. Skalicka-Woźniak K. Budzyńska B. EL Sayed N.S. Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin-induced rat model of sporadic Alzheimer’s disease: The role of JAK2/STAT3 and Nrf2/HO-1 signalling pathway modulation Phyther. Res. 2020 34 2351 2365 10.1002/ptr.6686 32250498 · DOI
  37. [40]Saba K. Rajnala N. Veeraiah P. Tiwari V. Rana R.K. Lakhotia S.C. Patel A.B. Energetics of Excitatory and Inhibitory Neurotransmission in Aluminum Chloride Model of Alzheimer’s Disease: Reversal of Behavioral and Metabolic Deficits by Rasa Sindoor Front. Mol. Neurosci. 2017 10 323 10.3389/fnmol.2017.00323 29089867 PMC5651029 · DOI
  38. [41]Vaiserman A. Koliada A. Lushchak O. Neuroinflammation in pathogenesis of Alzheimer’s disease: Phytochemicals as potential therapeutics Mech. Ageing Dev. 2020 189 111259 10.1016/j.mad.2020.111259 32450086 · DOI
  39. [42]Jukic M. Politeo O. Maksimovic M. Milos M. Milos M. In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone Phytother. Res. 2007 21 259 261 10.1002/ptr.2063 17186491 · DOI
  40. [43]Bianchini A.E. Garlet Q.I. Da Cunha J.A. Bandeira Junior G. Brusque I.C.M. Salbego J. Heinzmann B.M. Baldisserotto B. Monoterpenoids (Thymol, carvacrol and S-(+)-linalool) with anesthetic activity in silver catfish (Rhamdia quelen): Evaluation of acetylcholinesterase and GABaergic activity Braz. J. Med. Biol. Res. 2017 50 e6346 10.1590/1414-431x20176346 29069225 PMC5649867 · DOI
  41. [44]Cascella M. Bimonte S. Barbieri A. Del Vecchio V. Muzio M.R. Vitale A. Benincasa G. Ferriello A.B. Azzariti A. Arra C. Dissecting the potential roles of Nigella sativa and its constituent thymoquinone on the prevention and on the progression of Alzheimer’s disease Front. Aging Neurosci. 2018 10 16 10.3389/fnagi.2018.00016 29479315 PMC5811465 · DOI
  42. [45]Hosseinzadeh H. Parvardeh S. Asl M.N. Sadeghnia H.R. Ziaee T. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus Phytomedicine 2007 14 621 627 10.1016/j.phymed.2006.12.005 17291733 · DOI
  43. [46]Cobourne-Duval M.K. Taka E. Mendonca P. Soliman K.F.A. Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ -activated BV-2 microglia cells J. Neuroimmunol. 2018 320 87 97 10.1016/j.jneuroim.2018.04.018 29759145 PMC5967628 · DOI
  44. [47]Farkhondeh T. Samarghandian S. Shahri A.M.P. Samini F. The Neuroprotective Effects of Thymoquinone: A Review Dose. Response. 2018 16 10.1177/1559325818761455 29662431 PMC5898665 · DOI
  45. [48]Sharma D. Singh M. Kumar P. Vikram V. Mishra N. Development and characterization of morin hydrate loaded microemulsion for the management of Alzheimer’s disease Artif. Cells Nanomed. Biotechnol. 2017 45 1620 1630 10.1080/21691401.2016.1276919 28102083 · DOI
  46. [49]Singh M. Thakur V. Deshmukh R. Sharma A. Rathore M.S. Kumar A. Mishra N. Development and characterization of morin hydrate-loaded micellar nanocarriers for the effective management of Alzheimer’s disease J. Microencapsul. 2018 35 137 148 10.1080/02652048.2018.1441916 29448848 · DOI
  47. [50]Zheng C. Zhou X.W. Wang J.Z. The dual roles of cytokines in Alzheimer’s disease: Update on interleukins, TNF-α, TGF-β and IFN-γ Transl. Neurodegener. 2016 5 7 10.1186/s40035-016-0054-4 27054030 PMC4822284 · DOI · Paper page
  48. [51]Ahmad M.H. Fatima M. Mondal A.C. Influence of microglia and astrocyte activation in the neuroinflammatory pathogenesis of Alzheimer’s disease: Rational insights for the therapeutic approaches J. Clin. Neurosci. 2019 59 6 11 10.1016/j.jocn.2018.10.034 30385170 · DOI
  49. [52]Wang J. Xin Y. Chu T. Liu C. Xu A. Dexmedetomidine attenuates perioperative neurocognitive disorders by suppressing hippocampal neuroinflammation and HMGB1/RAGE/NF-κB signaling pathway Biomed. Pharmacother. 2022 150 113006 10.1016/j.biopha.2022.113006 35486975 · DOI
  50. [53]Didonna A. Tau at the interface between neurodegeneration and neuroinflammation Genes Immun. 2020 21 288 300 10.1038/s41435-020-00113-5 33011744 · DOI · Paper page
  51. [55]Wree A. Eguchi A. Mcgeough M.D. Pena C.A. Johnson C.D. Canbay A. Hoffman H.M. Feldstein A.E. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice Hepatology 2014 59 898 910 10.1002/hep.26592 23813842 PMC4008151 · DOI · Paper page
  52. [56]Yang Y. Wang H. Kouadir M. Song H. Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors Cell Death Dis. 2019 10 1 11 10.1038/s41419-019-1413-8 30755589 PMC6372664 · DOI
  53. [57]Stancu I.C. Cremers N. Vanrusselt H. Couturier J. Vanoosthuyse A. Kessels S. Lodder C. Brône B. Huaux F. Octave J.N. Aggregated Tau activates NLRP3-ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo Acta Neuropathol. 2019 137 599 617 10.1007/s00401-018-01957-y 30721409 PMC6426830 · DOI · Paper page
  54. [58]Stancu I.C. Lodder C. Botella Lucena P. Vanherle S. Gutiérrez de Ravé M. Terwel D. Bottelbergs A. Dewachter I. The NLRP3 inflammasome modulates tau pathology and neurodegeneration in a tauopathy model Glia 2022 70 1117 1132 10.1002/glia.24160 35174546 PMC9307007 · DOI · Paper page
  55. [59]Tao L. Zhang L. Gao R. Jiang F. Cao J. Liu H. Andrographolide Alleviates Acute Brain Injury in a Rat Model of Traumatic Brain Injury: Possible Involvement of Inflammatory Signaling Front. Neurosci. 2018 12 657 10.3389/fnins.2018.00657 30294256 PMC6158349 · DOI
  56. [60]Qin Z.Y. Gu X. Chen Y.L. Liu J.B. Hou C.X. Lin S.Y. Hao N.N. Liang Y. Chen W. Meng H.Y. Toll-like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi-1 expression Int. J. Mol. Med. 2021 47 137 150 10.3892/ijmm.2020.4787 33236134 PMC7723510 · DOI
  57. [61]Abu-Elfotuh K. Hussein F.H. Abbas A.N. Al-Rekabi M.D. Barghash S.S. Zaghlool S.S. El-Emam S.Z. Melatonin and zinc supplements with physical and mental activities subside neurodegeneration and hepatorenal injury induced by aluminum chloride in rats: Inclusion of GSK-3β-Wnt/β-catenin signaling pathway Neurotoxicology 2022 91 69 83 10.1016/j.neuro.2022.05.002 35526705 · DOI
  58. [62]Cui W. Sun C. Ma Y. Wang S. Wang X. Zhang Y. Inhibition of TLR4 Induces M2 Microglial Polarization and Provides Neuroprotection via the NLRP3 Inflammasome in Alzheimer’s Disease Front. Neurosci. 2020 14 444 10.3389/fnins.2020.00444 32508567 PMC7251077 · DOI
  59. [63]Hung W.L. Ho C.T. Pan M.H. Targeting the NLRP3 Inflammasome in Neuroinflammation: Health Promoting Effects of Dietary Phytochemicals in Neurological Disorders Mol. Nutr. Food Res. 2020 64 1900550 10.1002/mnfr.201900550 31675164 · DOI
  60. [64]Jin X. Liu M.Y. Zhang D.F. Zhong X. Du K. Qian P. Yao W.F. Gao H. Wei M.J. Baicalin mitigates cognitive impairment and protects neurons from microglia-mediated neuroinflammation via suppressing NLRP3 inflammasomes and TLR4/NF-κB signaling pathway CNS Neurosci. Ther. 2019 25 575 10.1111/cns.13086 30676698 PMC6488900 · DOI
  61. [65]Gao Y.Y. Zhuang Z. Lu Y. Tao T. Zhou Y. Liu G.J. Wang H. Zhang D.D. Wu L.Y. Dai H.B. Curcumin Mitigates Neuro-Inflammation by Modulating Microglia Polarization Through Inhibiting TLR4 Axis Signaling Pathway Following Experimental Subarachnoid Hemorrhage Front. Neurosci. 2019 13 1223 10.3389/fnins.2019.01223 31803007 PMC6872970 · DOI
  62. [68]Li Y. Zhang J. Wan J. Liu A. Sun J. Melatonin regulates Aβ production/clearance balance and Aβ neurotoxicity: A potential therapeutic molecule for Alzheimer’s disease Biomed. Pharmacother. 2020 132 110887 10.1016/j.biopha.2020.110887 33254429 · DOI
  63. [69]Cooper J.M. Lathuiliere A. Migliorini M. Arai A.L. Wani M.M. Dujardin S. Muratoglu S.C. Hyman B.T. Strickland D.K. Regulation of tau internalization, degradation, and seeding by LRP1 reveals multiple pathways for tau catabolism J. Biol. Chem. 2021 296 10.1016/j.jbc.2021.100715 PMC8164048 33930462 · DOI · Paper page
  64. [71]Safieh M. Korczyn A.D. Michaelson D.M. ApoE4: An emerging therapeutic target for Alzheimer’s disease BMC Med. 2019 17 64 10.1186/s12916-019-1299-4 30890171 PMC6425600 · DOI · Paper page
  65. [72]Cheng Y. Tian D.Y. Wang Y.J. Peripheral clearance of brain-derived Aβ in Alzheimer’s disease: Pathophysiology and therapeutic perspectives Transl. Neurodegener. 2020 9 113 139 10.1186/s40035-020-00195-1 32381118 PMC7204069 · DOI
  66. [73]Zhang T. Wang S. Niu Q. Effect of Aluminum-Maltolate on the Content of Aβ Protein and the Expression of ApoER2, VLDLRs, and LRP1 in PC12-ApoE4 Cells Neurotox. Res. 2019 35 931 944 10.1007/s12640-019-9995-6 30649678 · DOI
  67. [74]Ismail N. Ismail M. Azmi N.H. Bakar M.F.A. Yida Z. Abdullah M.A. Basri H. Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aβ40 and Aβ42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats Biomed. Pharmacother. 2017 95 780 788 10.1016/j.biopha.2017.08.074 28892789 · DOI
  68. [75]Mountaki C. Dafnis I. Panagopoulou E.A. Vasilakopoulou P.B. Karvelas M. Chiou A. Karathanos V.T. Chroni A. Mechanistic insight into the capacity of natural polar phenolic compounds to abolish Alzheimer’s disease-associated pathogenic effects of apoE4 forms Free Radic. Biol. Med. 2021 171 284 301 10.1016/j.freeradbiomed.2021.05.022 34019932 · DOI
  69. [76]Liu D. Chen L. Zhao H. Vaziri N.D. Ma S.-C. Zhao Y.-Y. Small molecules from natural products targeting the Wnt/β-catenin pathway as a therapeutic strategy Biomed. Pharmacother. 2019 117 108990 10.1016/j.biopha.2019.108990 31226638 · DOI
  70. [77]Hu S. Begum A.N. Jones M.R. Oh M.S. Beech W.K. Beech B.H. Yang F. Chen P. Ubeda O.J. Kim P.C. GSK3 inhibitors show benefits in an Alzheimer’s disease (AD) model of neurodegeneration but adverse effects in control animals Neurobiol. Dis. 2009 33 193 206 10.1016/j.nbd.2008.10.007 19038340 PMC4313761 · DOI
  71. [79]Ali A.A. Abd El-Fattah A.I. Abu-Elfotuh K. Elariny H.A. Natural antioxidants enhance the power of physical and mental activities versus risk factors inducing progression of Alzheimer’s disease in rats Int. Immunopharmacol. 2021 96 107729 10.1016/j.intimp.2021.107729 33971493 · DOI
  72. [80]Mohammadi N. Asle-Rousta M. Rahnema M. Amini R. Morin attenuates memory deficits in a rat model of Alzheimer’s disease by ameliorating oxidative stress and neuroinflammation Eur. J. Pharmacol. 2021 910 174506 10.1016/j.ejphar.2021.174506 34534533 · DOI
  73. [82]Elariny H.A. Abu Elfotuh K. Ali A.A. Khalil M.G. The Role of Mental and Physical Activities against Development of Alzheimer ’s Disease in Socialized and Isolated Rats Brain Disord. Ther. 2017 06 1 17 10.4172/2168-975X.1000240 · DOI
  74. [83]Wadenberg M.-L.G. Fjällström A.-K. Federley M. Persson P. Stenqvist P. Effects of adjunct galantamine to risperidone, or haloperidol, in animal models of antipsychotic activity and extrapyramidal side-effect liability: Involvement of the cholinergic muscarinic receptor Int. J. Neuropsychopharmacol. 2011 14 644 654 10.1017/S1461145710000921 20701827 · DOI
  75. [84]Chou S. Davis C. Li M. Maternal immune activation and repeated maternal separation alter offspring conditioned avoidance response learning and antipsychotic response in male rats Behav. Brain Res. 2021 403 113145 10.1016/j.bbr.2021.113145 33515643 PMC7902402 · DOI
  76. [85]Hritcu L. Cioanca O. Hancianu M. Effects of lavender oil inhalation on improving scopolamine-induced spatial memory impairment in laboratory rats Phytomedicine 2012 19 529 534 10.1016/j.phymed.2012.02.002 22402245 · DOI
  77. [86]Cleal M. Fontana B.D. Parker M.O. The cognitive and behavioral effects of D-amphetamine and nicotine sensitization in adult zebrafish Psychopharmacology 2021 238 2191 2200 10.1007/s00213-021-05844-5 33963883 PMC8292302 · DOI
  78. [87]Morris R. Developments of a water-maze procedure for studying spatial learning in the rat J. Neurosci. Methods 1984 11 47 60 10.1016/0165-0270(84)90007-4 6471907 · DOI · Paper page
  79. [88]Ali F.E.M. Sayed A.M. El-Bahrawy A.H. Omar Z.M.M. Hassanein E.H.M. Targeting KEAP1/Nrf2, AKT, and PPAR-γ signals as a potential protective mechanism of diosmin against gentamicin-induced nephrotoxicity Life Sci. 2021 275 119349 10.1016/j.lfs.2021.119349 33744325 · DOI
  80. [89]Greenblatt H.M. Kryger G. Lewis T. Silman I. Sussman J.L. Structure of acetylcholinesterase complexed with (−)-galanthamine at 2.3 Å resolution FEBS Lett. 1999 463 321 326 10.1016/S0014-5793(99)01637-3 10606746 · DOI
  81. [90]Ahn J.S. Radhakrishnan M.L. Mapelli M. Choi S. Tidor B. Cuny G.D. Musacchio A. Yeh L.-A. Kosik K.S. Defining Cdk5 Ligand Chemical Space with Small Molecule Inhibitors of Tau Phosphorylation Chem. Biol. 2005 12 811 823 10.1016/j.chembiol.2005.05.011 16039528 · DOI
  82. [91]Fujimoto K. Yoshida S. Tadano G. Asada N. Fuchino K. Suzuki S. Matsuoka E. Yamamoto T. Yamamoto S. Ando S. Structure-Based Approaches to Improving Selectivity through Utilizing Explicit Water Molecules: Discovery of Selective β-Secretase (BACE1) Inhibitors over BACE2 J. Med. Chem. 2021 64 3075 3085 10.1021/acs.jmedchem.0c01858 33719429 · DOI
  83. [92]Wagner F.F. Bishop J.A. Gale J.P. Shi X. Walk M. Ketterman J. Patnaik D. Barker D. Walpita D. Campbell A.J. Inhibitors of Glycogen Synthase Kinase 3 with Exquisite Kinome-Wide Selectivity and Their Functional Effects ACS Chem. Biol. 2016 11 1952 1963 10.1021/acschembio.6b00306 27128528 · DOI
  84. [93]Pinto A. El Ali Z. Moniot S. Tamborini L. Steegborn C. Foresti R. de Micheli C. Effects of 3-Bromo-4,5-dihydroisoxazole Derivatives on Nrf2 Activation and Heme Oxygenase-1 Expression ChemistryOpen. 2018 7 858 864 10.1002/open.201800185 30397576 PMC6207109 · DOI

Cited by

Sorted by citations

Authors
Hamdan, A. M. E., Alharthi, F. H. J., Alanazi, A. H., El-Emam, S. Z., Zaghlool, S. S., Metwally, K., Albalawi, S. A., Abdu, Y. S., Mansour, R. E.-S., Salem, H. A., Abd Elmageed, Z. Y., & Abu-Elfotuh, K.
Affiliations
  • University of Tabuk (SA)
  • King Fahad Specialist Hospital (SA)
  • Pharmacology and Toxicology Department, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt
  • Modern University for Information and Technology (EG)
  • Zagazig University (EG)
  • Ain Shams University (EG)
  • Al-Azhar University (EG)
  • Department of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana at Monroe, Monroe, LA 71203, USA
  • Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo 11651, Egypt
Corresponding author
Hamdan, Ahmed Mohsen Elsaid
ORCID
Venue
Pharmaceuticals
Publisher
MDPI AG
Published
2022-08-17
Volume
15
Issue
8
Pages
1008
ISSN
1424-8247 (ISSN-L)
DOI
10.3390/ph15081008
PMC
PMC9416484
OpenAlex
W4292264156
Cited by
82
References
8
Citations by year
2026: 26 · 2025: 24 · 2024: 18 · 2023: 12 · 2022: 2
FWCI
8.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceuticals (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Deanship of Scientific Research, University of Tabuk, Tabuk, Saudi Arabia (00085-1442-S)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Aluminum toxicity and tolerance in plants and animals
Keywords
Alzheimer's disease, aluminum chloride-induced neurotoxicity, phytochemicals, morin, thymol, thymoquinone, Nrf2/HO-1 pathway, oxidative stress, amyloid-beta, tau hyperphosphorylation, neuroprotection, spatial learning and memory, neuroinflammation, apoptosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review