Skip to content
2000
image of Natural Products Targeting Alzheimer’s Disease via NF-κB Pathway: A Review

Abstract

Alzheimer’s Disease (AD) is a severe neurological condition marked by cognitive decline and memory loss, affecting millions worldwide. Current therapeutic approaches for AD are primarily palliative, have slight effectiveness in arresting disease progression, and are frequently associated with significant adverse effects. In light of these limitations, there is a growing interest in exploring alternative medicinal strategies centred on phytogenic natural compounds. The nuclear factor kappa B (NF-κB) pathway is a critical biological target, essential for regulating the inflammatory response associated with the advancement of AD. Targeting the NF-κB signalling system is a promising approach for alleviating neuroinflammation and oxidative stress, although it operates in coordination with other pathways such as Nrf2 and MAPK, which also play significant roles in the complex pathophysiology of AD. This review provides a comprehensive analysis of the current studies about natural compounds and their potential therapeutic effects in AD, emphasising compounds obtained from various plant sources. We examine the mechanisms regulating the NF-κB pathway through the analysis of preclinical studies, evaluating its efficacy in reducing neurodegeneration and improving cognitive function in AD patients. Furthermore, future directions and conclusions have been incorporated, which jointly emphasise the significance of phytochemicals in modifying NF-κB and the associated signalling processes.

Loading

Article metrics loading...

/content/journals/cnsnddt/10.2174/0118715273397045250922054643
2025-10-10
2025-11-25
Loading full text...

Full text loading...

References

  1. Hippius H. Neundörfer G. The discovery of Alzheimer’s disease. Dialogues Clin. Neurosci. 2003 5 1 101 108 10.31887/DCNS.2003.5.1/hhippius 22034141
    [Google Scholar]
  2. Parums D.V. A review of the current status of disease-modifying therapies and prevention of alzheimer’s disease. Med. Sci. Monit. 2024 30 e945091 e945091 10.12659/MSM.945091 38736218
    [Google Scholar]
  3. Kawas C. Corrada M. Alzheimer’s and dementia in the oldest-old: a century of challenges. Curr. Alzheimer Res. 2006 3 5 411 419 10.2174/156720506779025233 17168640
    [Google Scholar]
  4. Farrer L.A. Cupples L.A. Haines J.L. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. JAMA 1997 278 16 1349 1356 10.1001/jama.1997.03550160069041 9343467
    [Google Scholar]
  5. Hebert L.E. Weuve J. Scherr P.A. Evans D.A. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology 2013 80 19 1778 1783 10.1212/WNL.0b013e31828726f5 23390181
    [Google Scholar]
  6. 2020 Alzheimer’s disease facts and figures. Alzheimers Dement. 2020 16 3 391 460 10.1002/alz.12068 32157811
    [Google Scholar]
  7. Maione F. Piccolo M. De Vita S. Down regulation of pro-inflammatory pathways by tanshinone IIA and cryptotanshinone in a non-genetic mouse model of Alzheimer’s disease. Pharmacol. Res. 2018 129 482 490 10.1016/j.phrs.2017.11.018 29158049
    [Google Scholar]
  8. Gordon B.A. Friedrichsen K. Brier M. The relationship between cerebrospinal fluid markers of Alzheimer pathology and positron emission tomography tau imaging. Brain 2016 139 8 2249 2260 10.1093/brain/aww139 27286736
    [Google Scholar]
  9. Kim DH Jeong M Kim JH Lactobacillus salivarius HHuMin-U activates innate immune defense against norovirus infection through TBK1-IRF3 and NF-κB signaling pathways Research 2022 2022 0007 10.34133/research.0007 39290965
    [Google Scholar]
  10. Huang Q Jiang C Xia X Pathological BBB crossing melanin-like nanoparticles as metal-ion chelators and neuroinflammation regulators against alzheimer’s disease. Research 2023 6 0180 10.34133/research.0180 37363131
    [Google Scholar]
  11. Silva M.V.F. Loures C.M.G. Alves L.C.V. de Souza L.C. Borges K.B.G. Carvalho M.G. Alzheimer’s disease: Risk factors and potentially protective measures. J. Biomed. Sci. 2019 26 1 33 10.1186/s12929‑019‑0524‑y 31072403
    [Google Scholar]
  12. Shal B. Ding W. Ali H. Kim Y.S. Khan S. Anti-neuroinflammatory potential of natural products in attenuation of Alzheimer’s disease. Front. Pharmacol. 2018 9 548 10.3389/fphar.2018.00548 29896105
    [Google Scholar]
  13. Sun E. Motolani A. Campos L. Lu T. The pivotal role of NF-kB in the pathogenesis and therapeutics of Alzheimer’s disease. Int. J. Mol. Sci. 2022 23 16 8972 10.3390/ijms23168972 36012242
    [Google Scholar]
  14. Ju Hwang C. Choi D.Y. Park M.H. Hong J.T. NF-κB as a key mediator of brain inflammation in Alzheimer’s disease. CNS Neurol. Disord. Drug Targets 2019 18 1 3 10 10.2174/1871527316666170807130011 28782486
    [Google Scholar]
  15. Srinivasan M. Lahiri D.K. Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer’s disease and multiple sclerosis. Expert Opin. Ther. Targets 2015 19 4 471 487 10.1517/14728222.2014.989834 25652642
    [Google Scholar]
  16. Bremner P. Heinrich M. Natural products as targeted modulators of the nuclear factor- κ B pathway. J. Pharm. Pharmacol. 2002 54 4 453 472 10.1211/0022357021778637 11999122
    [Google Scholar]
  17. Cooper E.L. Ma M.J. Alzheimer Disease: Clues from traditional and complementary medicine. J. Tradit. Complement. Med. 2017 7 4 380 385 10.1016/j.jtcme.2016.12.003 29034183
    [Google Scholar]
  18. Olajide O.A. Bhatia H.S. de Oliveira A.C.P. Wright C.W. Fiebich B.L. Inhibition of neuroinflammation in LPS-activated microglia by cryptolepine. Evid. Based Complement. Alternat. Med. 2013 2013 1 10 10.1155/2013/459723 23737832
    [Google Scholar]
  19. He F.Q. Qiu B.Y. Li T.K. Tetrandrine suppresses amyloid-β-induced inflammatory cytokines by inhibiting NF-κB pathway in murine BV2 microglial cells. Int. Immunopharmacol. 2011 11 9 1220 1225 10.1016/j.intimp.2011.03.023 21496499
    [Google Scholar]
  20. Park S.E. Sapkota K. Kim S. Kim H. Kim S.J. Kaempferol acts through mitogen‐activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells. Br. J. Pharmacol. 2011 164 3 1008 1025 10.1111/j.1476‑5381.2011.01389.x 21449918
    [Google Scholar]
  21. Velagapudi R. Ajileye O.O. Okorji U. Jain P. Aderogba M.A. Olajide O.A. Agathisflavone isolated from Anacardium occidentale suppresses SIRT1 ‐mediated neuroinflammation in BV2 microglia and neurotoxicity in APPS we‐transfected SH‐SY5Y cells. Phytother. Res. 2018 32 10 1957 1966 10.1002/ptr.6122 29786910
    [Google Scholar]
  22. Rezai-Zadeh K. Ehrhart J. Bai Y. Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. J. Neuroinflammation 2008 5 1 41 10.1186/1742‑2094‑5‑41 18817573
    [Google Scholar]
  23. Kang C.H. Choi Y.H. Moon S.K. Kim W.J. Kim G.Y. Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-dependent HO-1 pathway. Int. Immunopharmacol. 2013 17 3 808 813 10.1016/j.intimp.2013.09.009 24076371
    [Google Scholar]
  24. Olajide O.A. Kumar A. Velagapudi R. Okorji U.P. Fiebich B.L. Punicalagin inhibits neuroinflammation in LPS‐activated rat primary microglia. Mol. Nutr. Food Res. 2014 58 9 1843 1851 10.1002/mnfr.201400163 25066095
    [Google Scholar]
  25. Velagapudi R. Lepiarz I. El-Bakoush A. Induction of autophagy and activation of SIRT‐1 deacetylation mechanisms mediate neuroprotection by the pomegranate metabolite urolithin A in BV2 microglia and differentiated 3D human neural progenitor cells. Mol. Nutr. Food Res. 2019 63 10 1801237 10.1002/mnfr.201801237 30811877
    [Google Scholar]
  26. Infante-Garcia C. Ramos-Rodriguez J.J. Delgado-Olmos I. Long-term mangiferin extract treatment improves central pathology and cognitive deficits in APP/PS1 mice. Mol. Neurobiol. 2017 54 6 4696 4704 10.1007/s12035‑016‑0015‑z 27443159
    [Google Scholar]
  27. Sun X.Y. Dong Q.X. Zhu J. Resveratrol rescues tau-induced cognitive deficits and neuropathology in a mouse model of tauopathy. Curr. Alzheimer Res. 2019 16 8 710 722 10.2174/1567205016666190801153751 31368873
    [Google Scholar]
  28. Zhang J. Zheng Y. Luo Y. Du Y. Zhang X. Fu J. Curcumin inhibits LPS-induced neuroinflammation by promoting microglial M2 polarization via TREM2/TLR4/NF-κB pathways in BV2 cells. Mol. Immunol. 2019 116 29 37 10.1016/j.molimm.2019.09.020 31590042
    [Google Scholar]
  29. Yu Y. Shen Q. Lai Y. Anti-inflammatory effects of curcumin in microglial cells. Front. Pharmacol. 2018 9 386 10.3389/fphar.2018.00386 29731715
    [Google Scholar]
  30. Wang J. Tong M. Zhao B. Zhu G. Xi D. Yang J. Parthenolide ameliorates intracerebral hemorrhage‐induced brain injury in rats. Phytother. Res. 2020 34 1 153 160 10.1002/ptr.6510 31497910
    [Google Scholar]
  31. Qiang W. Cai W. Yang Q. Artemisinin B improves learning and memory impairment in AD dementia mice by suppressing neuroinflammation. Neuroscience 2018 395 1 12 10.1016/j.neuroscience.2018.10.041 30399421
    [Google Scholar]
  32. Abulfadl Y.S. El-Maraghy N.N. Ahmed A.A.E. Nofal S. Abdel-Mottaleb Y. Badary O.A. Thymoquinone alleviates the experimentally induced Alzheimer’s disease inflammation by modulation of TLRs signaling. Hum. Exp. Toxicol. 2018 37 10 1092 1104 10.1177/0960327118755256 29405769
    [Google Scholar]
  33. Shi C. Liu J. Wu F. Yew D. Ginkgo biloba extract in Alzheimer’s disease: From action mechanisms to medical practice. Int. J. Mol. Sci. 2010 11 1 107 123 10.3390/ijms11010107 20162004
    [Google Scholar]
  34. Goedert M. Spillantini M.G. Propagation of Tau aggregates. Mol. Brain 2017 10 1 18 10.1186/s13041‑017‑0298‑7 28558799
    [Google Scholar]
  35. Savelieff M.G. Nam G. Kang J. Lee H.J. Lee M. Lim M.H. Development of multifunctional molecules as potential therapeutic candidates for Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis in the last decade. Chem. Rev. 2019 119 2 1221 1322 10.1021/acs.chemrev.8b00138 30095897
    [Google Scholar]
  36. Hampel H. Mesulam M.M. Cuello A.C. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain 2018 141 7 1917 1933 10.1093/brain/awy132 29850777
    [Google Scholar]
  37. Cole S.L. Vassar R. The Alzheimer’s disease β-secretase enzyme, BACE1. Mol. Neurodegener. 2007 2 1 22 10.1186/1750‑1326‑2‑22 18005427
    [Google Scholar]
  38. Chiarini A. Armato U. Hu P. Dal Prà I. Danger‐sensing/patten recognition receptors and neuroinflammation in alzheimer’s disease. Int. J. Mol. Sci. 2020 21 23 9036 10.3390/ijms21239036 33261147
    [Google Scholar]
  39. Thawkar B.S. Kaur G. Inhibitors of NF-κB and P2X7/NLRP3/] Caspase 1 pathway in microglia: Novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer’s disease. J. Neuroimmunol. 2019 326 62 74 10.1016/j.jneuroim.2018.11.010 30502599
    [Google Scholar]
  40. Ries M. Sastre M. Mechanisms of Aβ clearance and degradation by glial cells. Front. Aging Neurosci. 2016 8 160 10.3389/fnagi.2016.00160 27458370
    [Google Scholar]
  41. Spires-Jones T.L. Hyman B.T. The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron 2014 82 4 756 771 10.1016/j.neuron.2014.05.004 24853936
    [Google Scholar]
  42. Calsolaro V. Edison P. Neuroinflammation in Alzheimer’s disease: Current evidence and future directions. Alzheimers Dement. 2016 12 6 719 732 10.1016/j.jalz.2016.02.010 27179961
    [Google Scholar]
  43. Jha N.K. Jha S.K. Kar R. Nand P. Swati K. Goswami V.K. Nuclear factor‐kappa β as a therapeutic target for Alzheimer’s disease. J. Neurochem. 2019 150 2 113 137 10.1111/jnc.14687 30802950
    [Google Scholar]
  44. Shih R.H. Wang C.Y. Yang C.M. NF-kappaB signaling pathways in neurological inflammation: A mini review. Front. Mol. Neurosci. 2015 8 77 10.3389/fnmol.2015.00077 26733801
    [Google Scholar]
  45. Calhoun A. King C. Khoury R. Grossberg G.T. An evaluation of memantine ER + donepezil for the treatment of Alzheimer’s disease. Expert Opin. Pharmacother. 2018 19 15 1711 1717 10.1080/14656566.2018.1519022 30244611
    [Google Scholar]
  46. Birks J.S. Harvey R.J. Donepezil for dementia due to Alzheimer’s disease. Cochrane Libr. 2018 2018 6 CD001190 10.1002/14651858.CD001190.pub3 29923184
    [Google Scholar]
  47. Davis B.M. Mohs R.C. Greenwald B.S. Clinical studies of the cholinergic deficit in Alzheimer’s disease. I. Neurochemical and neuroendocrine studies. J. Am. Geriatr. Soc. 1985 33 11 741 748 10.1111/j.1532‑5415.1985.tb04184.x 2414354
    [Google Scholar]
  48. Doody R.S. Cummings J.L. Farlow M.R. Reviewing the role of donepezil in the treatment of Alzheimer’s disease. Curr. Alzheimer Res. 2012 9 7 773 781 10.2174/156720512802455412 22175653
    [Google Scholar]
  49. Birks J.S. Grimley Evans J. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst. Rev. 2015 10 4 CD001191 10.1002/14651858.CD001191.pub3 25858345
    [Google Scholar]
  50. Coelho Filho J.M.J.M.C. Birks J. Physostigmine for dementia due to Alzheimer’s disease. Cochrane Libr. 2001 2001 2 CD001499 10.1002/14651858.CD001499 11405996
    [Google Scholar]
  51. Danysz W. Parsons C.G. The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer’s disease: Preclinical evidence. Int. J. Geriatr. Psychiatry 2003 18 S1 S23 S32 10.1002/gps.938 12973747
    [Google Scholar]
  52. Sharman M.J. Verdile G. Kirubakaran S. Targeting inflammatory pathways in alzheimer’s disease: A focus on natural products and phytomedicines. CNS Drugs 2019 33 5 457 480 10.1007/s40263‑019‑00619‑1 30900203
    [Google Scholar]
  53. Wang C.H. Wang L.S. Zhu N. Cholinesterase inhibitors and non-steroidal anti-inflammatory drugs as Alzheimer’s disease therapies: an updated umbrella review of systematic reviews and meta-analyses. Eur. Rev. Med. Pharmacol. Sci. 2016 20 22 4801 4817 27906438
    [Google Scholar]
  54. Zhumanova K. Lee G. Baiseitova A. Inhibitory mechanism of O-methylated quercetins, highly potent β-secretase inhibitors isolated from Caragana balchaschensis (Kom.) Pojark. J. Ethnopharmacol. 2021 272 113935 10.1016/j.jep.2021.113935 33609726
    [Google Scholar]
  55. Baiseitova A. Shah A.B. Khan A.M. Antioxidant potentials of furanodihydrobenzoxanthones from Artocarpus elasticus and their protection against oxLDL induced injury in SH-SY5Y cells. Biomed. Pharmacother. 2023 165 115278 10.1016/j.biopha.2023.115278 37536031
    [Google Scholar]
  56. Baiseitova A. Shah A.B. Kim J.Y. O-alkylated quercetins with selective acetylcholinesterase and β-secretase inhibitions from Melicope glabra leaves, and their flavonols profile by LC-ESI-Q-TOF/MS. J. Funct. Foods 2021 84 104602 10.1016/j.jff.2021.104602
    [Google Scholar]
  57. Chakraborty B. Mukerjee N. Maitra S. Therapeutic potential of different natural products for the treatment of Alzheimer’s Disease. Oxid. Med. Cell. Longev. 2022 2022 1 6873874 10.1155/2022/6873874 35910833
    [Google Scholar]
  58. Essa M.M. Vijayan R.K. Castellano-Gonzalez G. Memon M.A. Braidy N. Guillemin G.J. Neuroprotective effect of natural products against Alzheimer’s disease. Neurochem. Res. 2012 37 9 1829 1842 10.1007/s11064‑012‑0799‑9 22614926
    [Google Scholar]
  59. Libro R. Giacoppo S. Soundara Rajan T. Bramanti P. Mazzon E. Natural phytochemicals in the treatment and prevention of dementia: An overview. Molecules 2016 21 4 518 10.3390/molecules21040518 27110749
    [Google Scholar]
  60. Morales I. Guzmán-Martínez L. Cerda-Troncoso C. Farías G.A. Maccioni R.B. Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front. Cell. Neurosci. 2014 8 1 112 10.3389/fncel.2014.00112 24795567
    [Google Scholar]
  61. Kim J. Lee H.J. Lee K.W. Naturally occurring phytochemicals for the prevention of Alzheimer’s disease. J. Neurochem. 2010 112 6 1415 1430 10.1111/j.1471‑4159.2009.06562.x 20050972
    [Google Scholar]
  62. Liu M. Chen F. Sha L. (-)-Epigallocatechin-3-gallate ameliorates learning and memory deficits by adjusting the balance of TrkA/p75NTR signaling in APP/PS1 transgenic mice. Mol. Neurobiol. 2014 49 3 1350 1363 10.1007/s12035‑013‑8608‑2 24356899
    [Google Scholar]
  63. Lou H. Jing X. Wei X. Shi H. Ren D. Zhang X. Naringenin protects against 6-OHDA-induced neurotoxicity via activation of the Nrf2/ARE signaling pathway. Neuropharmacology 2014 79 380 388 10.1016/j.neuropharm.2013.11.026 24333330
    [Google Scholar]
  64. Pany S. Pal A. Sahu K. Neuroprotective effect of quercetin in neurotoxicity induced rats: role of neuroinflammation in neurodegeneration. AJPCR 2014 7 4 1 5
    [Google Scholar]
  65. Junsaeng D. Anukunwithaya T. Songvut P. Sritularak B. Likhitwitayawuid K. Khemawoot P. Comparative pharmacokinetics of oxyresveratrol alone and in combination with piperine as a bioenhancer in rats. BMC Complement. Altern. Med. 2019 19 1 235 10.1186/s12906‑019‑2653‑y 31477089
    [Google Scholar]
  66. Song J. Cheon S. Jung W. Lee W. Lee J. Resveratrol induces the expression of interleukin-10 and brain-derived neurotrophic factor in BV2 microglia under hypoxia. Int. J. Mol. Sci. 2014 15 9 15512 15529 10.3390/ijms150915512 25184950
    [Google Scholar]
  67. Ha S.K. Moon E. Ju M.S. 6-Shogaol, a ginger product, modulates neuroinflammation: A new approach to neuroprotection. Neuropharmacology 2012 63 2 211 223 10.1016/j.neuropharm.2012.03.016 22465818
    [Google Scholar]
  68. Jia L. Liu J. Song Z. Berberine suppresses amyloid-beta-induced inflammatory response in microglia by inhibiting nuclear factor-kappaB and mitogen-activated protein kinase signalling pathways. J. Pharm. Pharmacol. 2012 64 10 1510 1521 10.1111/j.2042‑7158.2012.01529.x 22943182
    [Google Scholar]
  69. Mao X.Y. Cao D.F. Li X. Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats. Int. J. Mol. Sci. 2014 15 5 7667 7683 10.3390/ijms15057667 24857910
    [Google Scholar]
  70. Xiao Q. Wang C. Li J. Ginkgolide B protects hippocampal neurons from apoptosis induced by beta-amyloid 25-35 partly via up-regulation of brain-derived neurotrophic factor. Eur. J. Pharmacol. 2010 647 1-3 48 54 10.1016/j.ejphar.2010.08.002 20709055
    [Google Scholar]
  71. Kim J.H. Yi Y.S. Kim M.Y. Cho J.Y. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J. Ginseng Res. 2017 41 4 435 443 10.1016/j.jgr.2016.08.004 29021688
    [Google Scholar]
  72. Hirai S. Uemura T. Mizoguchi N. Diosgenin attenuates inflammatory changes in the interaction between adipocytes and macrophages. Mol. Nutr. Food Res. 2010 54 6 797 804 10.1002/mnfr.200900208 19998383
    [Google Scholar]
  73. Han Y. Jung H.W. Lee D.H. Kwon S.Y. Son K.H. Park Y.K. Anti-inflammatory effects of prosapogenin III from the dried roots of Liriope platyphylla in LPS-stimulated RAW264.7 cells. J. Asian Nat. Prod. Res. 2013 15 9 1038 1049 10.1080/10286020.2013.825253 23944983
    [Google Scholar]
  74. Gu S.M. Lee H.P. Ham Y.W. Piperlongumine improves lipopolysaccharide-induced amyloidogenesis by suppressing NF-KappaB pathway. Neuromolecular Med. 2018 20 3 312 327 10.1007/s12017‑018‑8495‑9 29802525
    [Google Scholar]
  75. Kim Y.E. Hwang C.J. Lee H.P. Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB. Neuropharmacology 2017 117 21 32 10.1016/j.neuropharm.2017.01.025 28132781
    [Google Scholar]
  76. Chen S. Jia J. Tenuifolin attenuates amyloid-β42-induced neuroinflammation in microglia through the NF-κB signaling pathway. J. Alzheimers Dis. 2020 76 1 195 205 10.3233/JAD‑200077 32444542
    [Google Scholar]
  77. Shahbazi S. Zakerali T. Frycz B.A. Kaur J. The critical role of piperamide derivative D4 in the regulation of inflammatory response by the microglia and astrocytic glial cells. Biomed. Pharmacother. 2020 132 110895 10.1016/j.biopha.2020.110895 33113430
    [Google Scholar]
  78. Park W.H. Kang S. Piao Y. Ethanol extract of Bupleurum falcatum and saikosaponins inhibit neuroinflammation via inhibition of NF-κB. J. Ethnopharmacol. 2015 174 37 44 10.1016/j.jep.2015.07.039 26231448
    [Google Scholar]
  79. Leláková V. Béraud-Dufour S. Hošek J. Therapeutic potential of prenylated stilbenoid macasiamenene F through its anti-inflammatory and cytoprotective effects on LPS-challenged monocytes and microglia. J. Ethnopharmacol. 2020 263 113147 10.1016/j.jep.2020.113147 32736058
    [Google Scholar]
  80. Chen R. Wang Z. Zhi Z. Tian J. Zhao Y. Sun J. Targeting the TLR4/NF-κB pathway in β-amyloid-stimulated microglial cells: A possible mechanism that oxysophoridine exerts anti-oxidative and anti-inflammatory effects in an in vitro model of Alzheimer’s disease. Brain Res. Bull. 2021 175 150 157 10.1016/j.brainresbull.2021.07.019 34329731
    [Google Scholar]
  81. Zeng K.W. Zhao M.B. Ma Z.Z. Jiang Y. Tu P.F. Protosappanin A inhibits oxidative and nitrative stress via interfering the interaction of transmembrane protein CD14 with Toll-like receptor-4 in lipopolysaccharide-induced BV-2 microglia. Int. Immunopharmacol. 2012 14 4 558 569 10.1016/j.intimp.2012.09.004 23000519
    [Google Scholar]
  82. Capiralla H. Vingtdeux V. Zhao H. Resveratrol mitigates lipopolysaccharide‐ and Aβ‐mediated microglial inflammation by inhibiting the TLR4/NF‐κB/STAT signaling cascade. J. Neurochem. 2012 120 3 461 472 10.1111/j.1471‑4159.2011.07594.x 22118570
    [Google Scholar]
  83. Zhou J. Deng Y. Li F. Yin C. Shi J. Gong Q. Icariside II attenuates lipopolysaccharide-induced neuroinflammation through inhibiting TLR4/MyD88/NF-κB pathway in rats. Biomed. Pharmacother. 2019 111 315 324 10.1016/j.biopha.2018.10.201 30590319
    [Google Scholar]
  84. Zhong J. Qiu X. Yu Q. Chen H. Yan C. A novel polysaccharide from corus tatarinowii protects against LPS-induced neuroinflammation and neurotoxicity by inhibiting TLR4-mediated MyD88/NF-κB and PI3K/Akt signaling pathways. Int. J. Biol. Macromol. 2020 163 464 475 10.1016/j.ijbiomac.2020.06.266 32621930
    [Google Scholar]
  85. Tang N. Ma J. Wang K.S. Dihydromyricetin suppresses TNF-α-induced NF-κB activation and target gene expression. Mol. Cell. Biochem. 2016 422 1-2 11 20 10.1007/s11010‑016‑2799‑6 27686451
    [Google Scholar]
  86. Shi S. Liang D. Chen Y. Gx‐50 reduces β‐amyloid‐induced TNF‐α, IL‐1β, NO, and PGE 2 expression and inhibits NF‐κB signaling in a mouse model of Alzheimer’s disease. Eur. J. Immunol. 2016 46 3 665 676 10.1002/eji.201545855 26643273
    [Google Scholar]
  87. Kong F. Jiang X. Wang R. Zhai S. Zhang Y. Wang D. Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer’s disease. J. Neuroinflammation 2020 17 1 305 10.1186/s12974‑020‑01967‑2 33059746
    [Google Scholar]
  88. Lu B.L. Li J. Zhou J. Li W.W. Wu H.F. Tanshinone IIA decreases the levels of inflammation induced by Aβ1-42 in brain tissues of Alzheimer’s disease model rats. Neuroreport 2016 27 12 883 893 10.1097/WNR.0000000000000618 27348015
    [Google Scholar]
  89. Li J. Wen P. Li W. Zhou J. Upregulation effects of Tanshinone IIA on the expressions of NeuN, Nissl body, and IκB and downregulation effects on the expressions of GFAP and NF-κB in the brain tissues of rat models of Alzheimer’s disease. Neuroreport 2015 26 13 758 766 10.1097/WNR.0000000000000419 26164608
    [Google Scholar]
  90. Carpi S. Quarta S. Doccini S. Tanshinone IIA and cryptotanshinone counteract inflammation by regulating gene and miRNA expression in human SGBS adipocytes. Biomolecules 2023 13 7 1029 10.3390/biom13071029 37509065
    [Google Scholar]
  91. Ding B. Lin C. Liu Q. Tanshinone IIA attenuates neuroinflammation via inhibiting RAGE/NF-κB signaling pathway in vivo and in vitro. J. Neuroinflammation 2020 17 1 302 10.1186/s12974‑020‑01981‑4 33054814
    [Google Scholar]
  92. Kato M. Natarajan R. Epigenetics and epigenomics in diabetic kidney disease and metabolic memory. Nat. Rev. Nephrol. 2019 15 6 327 345 10.1038/s41581‑019‑0135‑6 30894700
    [Google Scholar]
  93. Amić D. Davidović-Amić D. Beslo D. Rastija V. Lucić B. Trinajstić N. SAR and QSAR of the antioxidant activity of flavonoids. Curr. Med. Chem. 2007 14 7 827 845 10.2174/092986707780090954 17346166
    [Google Scholar]
  94. Singh S. Pathak N. Fatima E. Negi A.S. Plant isoquinoline alkaloids: Advances in the chemistry and biology of berberine. Eur. J. Med. Chem. 2021 226 113839 10.1016/j.ejmech.2021.113839 34536668
    [Google Scholar]
  95. Joshi P. Verma K. Kumar Semwal D. Dwivedi J. Sharma S. Mechanism insights of curcumin and its analogues in cancer: An update. Phytother. Res. 2023 37 12 5435 5463 10.1002/ptr.7983 37649266
    [Google Scholar]
  96. Cheemanapalli S. Chinthakunta N. Shaikh N.M. Shivaranjani V. Pamuru R.R. Chitta S.K. Comparative binding studies of curcumin and tangeretin on up-stream nlms of NF-kB cascade: A combined molecular docking approach. Netw. Model. Anal. Health Inform. Bioinform. 2019 8 1 15 10.1007/s13721‑019‑0196‑2
    [Google Scholar]
  97. Nag S.A. Qin J-J. Wang W. Wang M-H. Wang H. Zhang R. Ginsenosides as anticancer agents: In vitro and in vivo activities, structure-activity relationships, and molecular mechanisms of action. Front. Pharmacol. 2012 3 25 10.3389/fphar.2012.00025 22403544
    [Google Scholar]
  98. Huang X. An R. Zhang W. Developments in the antitumor activity, mechanisms of action, structural modifications, and structure-activity relationships of steroidal saponins. Mini Rev. Med. Chem. 2022 22 17 2188 2212 10.2174/1389557522666220217113719 35176980
    [Google Scholar]
  99. Snarska J. Jakimiuk K. Strawa J.W. A comprehensive review of pedunculagin: Sources, chemistry, biological and pharmacological insights. Int. J. Mol. Sci. 2024 25 21 11511 10.3390/ijms252111511 39519063
    [Google Scholar]
  100. Zhu P. Qian J. Xu Z. Overview of piperlongumine analogues and their therapeutic potential. Eur. J. Med. Chem. 2021 220 113471 10.1016/j.ejmech.2021.113471 33930801
    [Google Scholar]
  101. Wu L. Georgiev M.I. Cao H. Therapeutic potential of phenylethanoid glycosides: A systematic review. Med. Res. Rev. 2020 40 6 2605 2649 10.1002/med.21717 32779240
    [Google Scholar]
  102. Liu C.F. Recent advances on natural Aryl-C-glycoside scaffolds: Structure, bioactivities, and synthesis: A comprehensive review. Molecules 2022 27 21 7439 10.3390/molecules27217439 36364266
    [Google Scholar]
  103. Vaz M. Silvestre S. Alzheimer’s disease: Recent treatment strategies. Eur. J. Pharmacol. 2020 887 15 173554 10.1016/j.ejphar.2020.173554 32941929
    [Google Scholar]
  104. Folch J. Petrov D. Ettcheto M. Current research therapeutic strategies for alzheimer’s disease treatment. Neural Plast. 2016 2016 1 15 10.1155/2016/8501693 26881137
    [Google Scholar]
  105. Kumar A. Singh A. A review on Alzheimer’s disease pathophysiology and its management: An update. Pharmacol. Rep. 2015 67 2 195 10.1016/j.pharep.2014.09.004
    [Google Scholar]
  106. Farlow M.R. Miller M.L. Pejovic V. Treatment options in Alzheimer’s disease: Maximizing benefit, managing expectations. Dement. Geriatr. Cogn. Disord. 2008 25 5 408 422 10.1159/000122962 18391487
    [Google Scholar]
  107. Ramirez-Bermudez J. Alzheimer’s disease: Critical notes on the history of a medical concept. Arch. Med. Res. 2012 43 8 595 599 10.1016/j.arcmed.2012.11.008 23178566
    [Google Scholar]
  108. Kurz A. Perneczky R. Novel insights for the treatment of Alzheimer’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 2011 35 2 373 379 10.1016/j.pnpbp.2010.07.018 20655969
    [Google Scholar]
  109. Auld D.S. Kornecook T.J. Bastianetto S. Quirion R. Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies. Prog. Neurobiol. 2002 68 3 209 245 10.1016/S0301‑0082(02)00079‑5 12450488
    [Google Scholar]
  110. Chen R. Chan P.T. Chu H. Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: A meta-analysis. PLoS One 2017 12 8 e0183586 10.1371/journal.pone.0183586 28827830
    [Google Scholar]
  111. McShane R. Westby M.J. Roberts E. Memantine for dementia. Cochrane Libr. 2019 3 3 CD003154 10.1002/14651858.CD003154.pub6 30891742
    [Google Scholar]
  112. Atri A. Current and future treatments in alzheimer’s disease. Semin. Neurol. 2019 39 2 227 240 10.1055/s‑0039‑1678581 30925615
    [Google Scholar]
  113. Yaghi N. El Hayeck R. Boulos C. Abifadel M. Yaghi C. Effect of Mediterranean dietary pattern on cognitive status in community-dwelling older adults. Nutrients 2023 15 18 3911 10.3390/nu15183911 37764695
    [Google Scholar]
  114. Barnard N.D. Bush A.I. Ceccarelli A. Dietary and lifestyle guidelines for the prevention of Alzheimer’s disease. Neurobiol. Aging 2014 35 2 S74 S78 10.1016/j.neurobiolaging.2014.03.033 24913896
    [Google Scholar]
  115. Santana I. Farinha F. Freitas S. Rodrigues V. Carvalho Å. The epidemiology of dementia and alzheimer disease in portugal: Estimations of prevalence and treatment-costs. Acta Med. Port. 2015 28 2 182 188 10.20344/amp.6025 26061508
    [Google Scholar]
  116. Humpel C. Identifying and validating biomarkers for Alzheimer’s disease. Trends Biotechnol. 2011 29 1 26 32 10.1016/j.tibtech.2010.09.007 20971518
    [Google Scholar]
  117. Wallon D. Rousseau S. Rovelet-Lecrux A. The French series of autosomal dominant early onset Alzheimer’s disease cases: Mutation spectrum and cerebrospinal fluid biomarkers. J. Alzheimers Dis. 2012 30 4 847 856 10.3233/JAD‑2012‑120172 22475797
    [Google Scholar]
  118. Ayaz M. Ullah F. Sadiq A. Kim M.O. Ali T. Natural products-based drugs: potential therapeutics against Alzheimer’s disease and other neurological disorders. Front. Pharmacol. 2019 10 1417 10.3389/fphar.2019.01417 31849668
    [Google Scholar]
  119. Singh M. Arseneault M. Sanderson T. Murthy V. Ramassamy C. Challenges for research on polyphenols from foods in Alzheimer’s disease: bioavailability, metabolism, and cellular and molecular mechanisms. J. Agric. Food Chem. 2008 56 13 4855 4873 10.1021/jf0735073 18557624
    [Google Scholar]
  120. Awasthi M. Singh S. Tiwari S. Pandey V.P. Dwivedi U.N. Computational approaches for therapeutic application of natural products in Alzheimer’s disease. In: Computational Modeling of Drugs Against Alzheimer’s Disease. Springer 2018 483 511
    [Google Scholar]
  121. Sahoo A.K. Dandapat J. Dash U.C. Kanhar S. Features and outcomes of drugs for combination therapy as multi-targets strategy to combat Alzheimer’s disease. J. Ethnopharmacol. 2018 215 42 73 10.1016/j.jep.2017.12.015 29248451
    [Google Scholar]
  122. Griñán-Ferré C. Bellver-Sanchis A. Olivares-Martín M. Bañuelos-Hortigüela O. Pallàs M. Synergistic neuroprotective effects of a natural product Mixture against AD hallmarks and cognitive decline in Caenorhabditis elegans and an SAMP8 mice model. Nutrients 2021 13 7 2411 10.3390/nu13072411 34371921
    [Google Scholar]
  123. John O.O. Amarachi I.S. Chinazom A.P. Phytotherapy: A promising approach for the treatment of Alzheimer’s disease. Pharm. Res. Modern. Chin. Med. 2022 2 100030 10.1016/j.prmcm.2021.100030
    [Google Scholar]
  124. Shukla S. Hernandez C. Liposome based drug delivery as a potential treatment option for Alzheimer’s disease. Neural Regen. Res. 2022 17 6 1190 1198 10.4103/1673‑5374.327328 34782553
    [Google Scholar]
  125. Sahni J.K. Doggui S. Ali J. Baboota S. Dao L. Ramassamy C. Neurotherapeutic applications of nanoparticles in Alzheimer’s disease. J. Control. Release 2011 152 2 208 231 10.1016/j.jconrel.2010.11.033 21134407
    [Google Scholar]
  126. Hu Y.S. Xin J. Hu Y. Zhang L. Wang J. Analyzing the genes related to Alzheimer’s disease via a network and pathway-based approach. Alzheimers Res. Ther. 2017 9 1 29 10.1186/s13195‑017‑0252‑z 28446202
    [Google Scholar]
  127. Chu F Tan R Wang X Transcranial magneto-acoustic stimulation attenuates synaptic plasticity impairment through the activation of piezo1 in alzheimer’s disease mouse model. Research 2023 6 0130 10.34133/research.0130 37223482
    [Google Scholar]
  128. Rollo J.L. Banihashemi N. Vafaee F. Crawford J.W. Kuncic Z. Holsinger R.M.D. Unraveling the mechanistic complexity of Alzheimer’s disease through systems biology. Alzheimers Dement. 2016 12 6 708 718 10.1016/j.jalz.2015.10.010 26703952
    [Google Scholar]
/content/journals/cnsnddt/10.2174/0118715273397045250922054643
Loading
/content/journals/cnsnddt/10.2174/0118715273397045250922054643
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test