Skip to content
2000
Volume 18, Issue 3
  • ISSN: 1874-6098
  • E-ISSN: 1874-6128

Abstract

Background

Epilepsy is a prevalent neurological disorder that can be characterized by seizures and can be caused by abnormal electrical impulses in the brain. Various genetic, environmental, age-related, and lifestyle factors are associated with its pathogenesis, which causes neuronal cells to degenerate over time.

Methodology

Epilepsy often results from an imbalance between excitatory neurotransmitters, such as glutamate, and inhibitory neurotransmitters, such as GABA. Abnormalities in glutamate receptors like N-methyl-D-aspartate (NMDA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) can lead to excessive neuronal excitation, while dysfunctions in GABA receptors can result in insufficient inhibition, both of which can provoke seizures. Additionally, a variety of receptors and pathways like NF-κB, DAPK, Trκb, COX-2, . are associated with the expression of epilepsy. This disorder often faces various limitations in treatment with current anti-epileptic drugs (AEDs), such as drug resistance, adverse effects, and high costs. In context, flavonoids exhibit significant neuroprotective properties in epilepsy through various mechanisms such as antioxidant activity, anti-inflammatory effects, neurotransmitter systems, and receptor modulation.

Results

Flavonoids communicate with different signaling pathways and adjust their activities, prompting valuable neuroprotective impacts. Essential flavonoids such as quercetin, rutin, apigenin, luteolin, genistein, fisetin, chrysin, vitexin, naringin, baicalin, catechin, morin, hesperetin, kaempferol, gallic acid, silibinin, wogonin, . have shown promising results in channel regulation, reduced oxidative stress and neuroinflammation, and neuronal excitability in experimental models of epilepsy. Given their inherent neuroprotective properties and ability to modulate multiple pathways involved in epilepsy, flavonoids hold considerable promise as multitargeted, accessible, and low-cost alternatives to conventional AEDs. Although there are challenges with target specificity and bioavailability, innovative approaches such as nanotechnology and chemical modifications are being developed to enhance these aspects.

Conclusion

Focusing on the mechanisms of action and neuroprotective benefits the paper highlights the promising role of flavonoids and flavonoid-based nanotherapeutics as a beneficial addition to epilepsy treatment strategies.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cas/10.2174/0118746098369369250119112935
2025-01-27
2026-02-22

  • From This Site

    /content/journals/cas/10.2174/0118746098369369250119112935
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. DarehbaghR.R. SeyedoshohadaeiS.A. RamezaniR. RezaeiN. Stem cell therapies for neurological disorders: Current progress, challenges, and future perspectives.Eur. J. Med. Res.202429138610.1186/s40001‑024‑01987‑1 39054501
     [Google Scholar]
  2. PotnisV.V. AlbharK.G. NanawareP.A. PoteV.S. A review on epilepsy and its management.J. Drug Deliv. Ther.202010327327910.22270/jddt.v10i3.4090
     [Google Scholar]
  3. VezzaniA. FujinamiR.S. WhiteH.S. Infections, inflammation and epilepsy.Acta Neuropathol.2016131221123410.1007/s00401‑015‑1481‑5 26423537
     [Google Scholar]
  4. DevinskyO. SpruillT. ThurmanD. FriedmanD. Recognizing and preventing epilepsy-related mortality.Neurology201686877978610.1212/WNL.0000000000002253 26674330
     [Google Scholar]
  5. KwonJ.Y. JeonM.T. JungU.J. KimD.W. MoonG.J. KimS.R. Perspective: Therapeutic potential of flavonoids as alternative medicines in epilepsy.Adv. Nutr.201910577879010.1093/advances/nmz047 31111873
     [Google Scholar]
  6. WarisA. UllahA. AsimM. Phytotherapeutic options for the treatment of epilepsy: Pharmacology, targets, and mechanism of action.Front. Pharmacol.202415140323210.3389/fphar.2024.1403232 38855752
     [Google Scholar]
  7. GilioliI. VignoliA. VisaniE. Focal epilepsies in adult patients attending two epilepsy centers: Classification of drug‐resistance, assessment of risk factors, and usefulness of “new” antiepileptic drugs.Epilepsia201253473374010.1111/j.1528‑1167.2012.03416.x 22360822
     [Google Scholar]
  8. AmiriB. TabriziY.M. NaziriM. Neuroprotective effects of flavonoids: Endoplasmic reticulum as the target.Front. Neurosci.202418134815110.3389/fnins.2024.1348151 38957188
     [Google Scholar]
  9. LiuZ. LindemeyerA.K. LiangJ. Flavonoids isolated from Tibetan medicines, binding to GABAA receptor and the anticonvulsant activity.Phytomedicine2018501710.1016/j.phymed.2018.09.198 30466968
     [Google Scholar]
  10. DongH. GaoX. LiH. GaoJ. ZhangL. Protective effects of flavonoids against intracerebral and subarachnoid hemorrhage (Review).Exp. Ther. Med.202428335010.3892/etm.2024.12639 39071910
     [Google Scholar]
  11. PancheA.N. DiwanA.D. ChandraS.R. Flavonoids: An overview.J. Nutr. Sci.20165e4710.1017/jns.2016.41 28620474
     [Google Scholar]
  12. DajasF. Rivera-MegretF. BlasinaF. Neuroprotection by flavonoids.Braz. J. Med. Biol. Res.200336121613162010.1590/S0100‑879X2003001200002 14666245
     [Google Scholar]
  13. VauzourD. VafeiadouK. Rodriguez-MateosA. RendeiroC. SpencerJ.P.E. The neuroprotective potential of flavonoids: A multiplicity of effects.Genes Nutr.200833-411512610.1007/s12263‑008‑0091‑4 18937002
     [Google Scholar]
  14. KhareN. TareH. Plants with potential neuropharmacological activity: Plant-based medicine for the brain.Inter J Pharm Qua Assu202415152353010.25258/ijpqa.15.1.79
     [Google Scholar]
  15. DinizT.C. SilvaJ.C. Lima-SaraivaS.R.G. The role of flavonoids on oxidative stress in epilepsy.Oxid. Med. Cell. Longev.201520151910.1155/2015/171756 25653736
     [Google Scholar]
  16. MovahedpourA. TaghvaeefarR. Asadi-PooyaA.A. Nano‐delivery systems as a promising therapeutic potential for epilepsy: Current status and future perspectives.CNS Neurosci. Ther.202329113150315910.1111/cns.14355 37452477
     [Google Scholar]
  17. MukhopadhyayH. KandarC. DasS. Epilepsy and its Management: A Review.J. Pharm. Sci. Technol.201212026
     [Google Scholar]
  18. AkyuzE. PolatA.K. ErogluE. KulluI. AngelopoulouE. PaudelY.N. Revisiting the role of neurotransmitters in epilepsy: An updated review.Life Sci.202126511882610.1016/j.lfs.2020.118826 33259863
     [Google Scholar]
  19. SearsS.M.S. HewettS.J. Influence of glutamate and GABA transport on brain excitatory/inhibitory balance.Exp. Biol. Med.202124691069108310.1177/1535370221989263 33554649
     [Google Scholar]
  20. AbaniO. AbbasA. AbbasF. Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial.Lancet20223991032566567610.1016/S0140‑6736(22)00163‑5 35151397
     [Google Scholar]
  21. AnwarH. KhanQ.U. NadeemN. PervaizI. AliM. CheemaF.F. Epileptic seizures.Discoveries202082e11010.15190/d.2020.7 32577498
     [Google Scholar]
  22. HusseinAF ArunkumarN GomesC Focal and Non-Focal Epilepsy Localization: A Review.IEEE Access20186493062410.1109/ACCESS.2018.2867078
     [Google Scholar]
  23. GhulaxeY. JoshiA. ChavadaJ. HuseS. KalbandeB. SardaP.P. Understanding focal seizures in adults: A comprehensive review.Cureus20231511e4817310.7759/cureus.48173 38046728
     [Google Scholar]
  24. MukherjeeS. AliS. HashmiS. History, Origin and Types of Neurological Disorders.Applications of Stem Cells and derived Exosomes in Neurodegenerative Disorders Springer Nature Singapore. JahanS. SiddiquiA.J. SingaporeSpringer Nature Singapore202313210.1007/978‑981‑99‑3848‑3_1
     [Google Scholar]
  25. BalestriniS. ArzimanoglouA. BlümckeI. The aetiologies of epilepsy.Epileptic Disord.202123111610.1684/epd.2021.1255 33720020
     [Google Scholar]
  26. CoursonJ. QuoyM. TimofeevaY. ManosT. An exploratory computational analysis in mice brain networks of widespread epileptic seizure onset locations along with potential strategies for effective intervention and propagation control.Front. Comput. Neurosci.202418136000910.3389/fncom.2024.1360009 38468870
     [Google Scholar]
  27. BroughtonR.J. The parasomnias and sleep related movement disorders—a look back at six decades of scientific studies.Clin Trans Neurosci202261310.3390/ctn6010003
     [Google Scholar]
  28. YacubianE.M.T. Kakooza-MwesigeA. SinghG. Common infectious and parasitic diseases as a cause of seizures: Geographic distribution and contribution to the burden of epilepsy.Epileptic Disord.2022246994101910.1684/epd.2022.1491 36219093
     [Google Scholar]
  29. VorderwülbeckeB.J. WandschneiderB. WeberY. HoltkampM. Genetic generalized epilepsies in adults - Challenging assumptions and dogmas.Nat. Rev. Neurol.2022182718310.1038/s41582‑021‑00583‑9 34837042
     [Google Scholar]
  30. BergA.T. SchefferI.E. New concepts in classification of the epilepsies: Entering the 21st century.Epilepsia20115261058106210.1111/j.1528‑1167.2011.03101.x 21635233
     [Google Scholar]
  31. RivaA. GoldaA. BalaguraG. New trends and most promising therapeutic strategies for epilepsy treatment.Front. Neurol.20211275375310.3389/fneur.2021.753753 34950099
     [Google Scholar]
  32. FallsN. ArangoJ.I. AdelsonP.D. Responsive neurostimulation in pediatric patients with drug-resistant epilepsy.Neurosurg. Focus2022534E910.3171/2022.7.FOCUS22339 36183178
     [Google Scholar]
  33. LasońW. ChlebickaM. RejdakK. Research advances in basic mechanisms of seizures and antiepileptic drug action.Pharmacol. Rep.201365478780110.1016/S1734‑1140(13)71060‑0 24145073
     [Google Scholar]
  34. BonanscoC. FuenzalidaM. Plasticity of hippocampal excitatory-inhibitory balance: Missing the synaptic control in the epileptic brain.Neural Plast.2016201611310.1155/2016/8607038 27006834
     [Google Scholar]
  35. WalkerC.M. Surges R. Mechanisms of Antiepileptic Drug Action.The Treatment of Epilepsy.1st Ed. ShorvonS. PeruccaE. EngelJ. New YorkWiley2015191
     [Google Scholar]
  36. DeebT.Z. MaguireJ. MossS.J. Possible alterations in GABA A receptor signaling that underlie benzodiazepine‐resistant seizures.Epilepsia201253Suppl. 9798810.1111/epi.12037 23216581
     [Google Scholar]
  37. LinY. WangY. Neurostimulation as a promising epilepsy therapy.Epilepsia Open20172437138710.1002/epi4.12070 29588969
     [Google Scholar]
  38. EdwardsC.A. KouzaniA. LeeK.H. RossE.K. Neurostimulation devices for the treatment of neurologic disorders.Mayo Clin. Proc.20179291427144410.1016/j.mayocp.2017.05.005 28870357
     [Google Scholar]
  39. ConwayC.R. ColijnM.A. SchachterS.C. Vagus Nerve Stimulation for Epilepsy and Depression.Brain Stimulation.1st Ed RetiI.M. New YorkWiley201530533510.1002/9781118568323.ch17
     [Google Scholar]
  40. JarosiewiczB. MorrellM. The RNS System: Brain-responsive neurostimulation for the treatment of epilepsy.Expert Rev. Med. Devices202118212913810.1080/17434440.2019.1683445 32936673
     [Google Scholar]
  41. KraussJ.K. LipsmanN. AzizT. Technology of deep brain stimulation: Current status and future directions.Nat. Rev. Neurol.2021172758710.1038/s41582‑020‑00426‑z 33244188
     [Google Scholar]
  42. Ułamek-KoziołM. CzuczwarS.J. JanuszewskiS. PlutaR. Ketogenic Diet and Epilepsy.Nutrients20191110251010.3390/nu11102510 31635247
     [Google Scholar]
  43. BrounsF. Overweight and diabetes prevention: Is a low-carbohydrate–high-fat diet recommendable?Eur. J. Nutr.20185741301131210.1007/s00394‑018‑1636‑y 29541907
     [Google Scholar]
  44. PoffA.M. RhoJ.M. D’AgostinoD.P. Ketone administration for seizure disorders: History and rationale for ketone esters and metabolic alternatives.Front. Neurosci.201913104110.3389/fnins.2019.01041 31680801
     [Google Scholar]
  45. Katsu-JiménezY. AlvesR.M.P. Giménez-CassinaA. Food for thought: Impact of metabolism on neuronal excitability.Exp. Cell Res.20173601414610.1016/j.yexcr.2017.03.002 28263755
     [Google Scholar]
  46. RoehlK. Falco-WalterJ. OuyangB. BalabanovA. Modified ketogenic diets in adults with refractory epilepsy: Efficacious improvements in seizure frequency, seizure severity, and quality of life.Epilepsy Behav.20199311311810.1016/j.yebeh.2018.12.010 30867113
     [Google Scholar]
  47. AnyanwuC. MotamediG. Diagnosis and surgical treatment of drug-resistant epilepsy.Brain Sci.2018844910.3390/brainsci8040049 29561756
     [Google Scholar]
  48. EnglotD.J. ChangE.F. Rates and predictors of seizure freedom in resective epilepsy surgery: An update.Neurosurg. Rev.201437338940510.1007/s10143‑014‑0527‑9 24497269
     [Google Scholar]
  49. ConsalesA. CasciatoS. AsioliS. The surgical treatment of epilepsy.Neurol. Sci.20214262249226010.1007/s10072‑021‑05198‑y 33797619
     [Google Scholar]
  50. MoshéS.L. PeruccaE. RyvlinP. TomsonT. Epilepsy: New advances.Lancet2015385997188489810.1016/S0140‑6736(14)60456‑6 25260236
     [Google Scholar]
  51. NiriayoY.L. GebregziabherT. DemozG.T. TesfayN. GideyK. Drug therapy problems and contributing factors among patients with epilepsy.PLoS One2024193e029996810.1371/journal.pone.0299968 38451979
     [Google Scholar]
  52. BayatA. BayatM. RubboliG. MøllerR.S. Epilepsy syndromes in the first year of life and usefulness of genetic testing for precision therapy.Genes2021127105110.3390/genes12071051 34356067
     [Google Scholar]
  53. DalicL. CookM. Managing drug-resistant epilepsy: Challenges and solutions.Neuropsychiatr. Dis. Treat.2016122605261610.2147/NDT.S84852 27789949
     [Google Scholar]
  54. BenbadisS.R. GellerE. RyvlinP. Putting it all together: Options for intractable epilepsy.Epilepsy Behav.201888333810.1016/j.yebeh.2018.05.030 30241957
     [Google Scholar]
  55. SisodiyaS.M. Precision medicine and therapies of the future.Epilepsia202162S2)(Suppl. 2S90S10510.1111/epi.16539 32776321
     [Google Scholar]
  56. LavinB. DormondC. ScantleburyM.H. FrouinP.Y. BrodieM.J. Bridging the healthcare gap: Building the case for epilepsy virtual clinics in the current healthcare environment.Epilepsy Behav.202011110726210.1016/j.yebeh.2020.107262 32645620
     [Google Scholar]
  57. LealG.B. Barros-BarbosaA. FerreirinhaF. Mesial temporal lobe epilepsy (MTLE) drug-refractoriness is associated with p2x7 receptors overexpression in the human hippocampus and temporal neocortex and may be predicted by low circulating levels of mir-22.Front. Cell. Neurosci.20221691066210.3389/fncel.2022.910662 35875355
     [Google Scholar]
  58. UsluG.S. YukselB. TekinB. SariahmetogluH. AtakliD. Cognitive impairment and drug responsiveness in mesial temporal lobe epilepsy.Epilepsy Behav.20199016216710.1016/j.yebeh.2018.10.034 30576963
     [Google Scholar]
  59. FrenchJ.A. KannerA.M. BautistaJ. Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refractory epilepsy: Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.Neurology20046281261127310.1212/01.WNL.0000123695.22623.32 15111660
     [Google Scholar]
  60. ShengJ. LiuS. QinH. LiB. ZhangX. Drug-resistant epilepsy and surgery.Curr. Neuropharmacol.20181611728 28474565
     [Google Scholar]
  61. ZaitsevA.V. AmakhinD.V. DyominaA.V. Synaptic dysfunction in epilepsy.J. Evol. Biochem. Physiol.202157354256310.1134/S002209302103008X
     [Google Scholar]
  62. GhitA. AssalD. ShamiA.A.S. HusseinD.E.E. GABAA receptors: Structure, function, pharmacology, and related disorders.J. Genet. Eng. Biotechnol.202119112310.1186/s43141‑021‑00224‑0 34417930
     [Google Scholar]
  63. KaurS. SinghS. AroraA. Pharmacology of GABA and Its Receptors.Frontiers in Pharmacology of Neurotransmitters Springer Singapore. KumarP. DebP.K. SingaporeSpringer Nature Singapore202024129210.1007/978‑981‑15‑3556‑7_8
     [Google Scholar]
  64. PeruccaE. BialerM. WhiteH.S. New GABA-targeting therapies for the treatment of seizures and epilepsy: I. Role of GABA as a modulator of seizure activity and recently approved medications acting on the GABA system.CNS Drugs202337975577910.1007/s40263‑023‑01027‑2 37603262
     [Google Scholar]
  65. CherubiniE. CristoD.G. AvoliM. Dysregulation of gabaergic signaling in neurodevelomental disorders: Targeting cation-chloride co-transporters to re-establish a proper E/I balance.Front. Cell. Neurosci.20221581344110.3389/fncel.2021.813441 35069119
     [Google Scholar]
  66. GreenfieldL.J.Jr Molecular mechanisms of antiseizure drug activity at GABAA receptors.Seizure201322858960010.1016/j.seizure.2013.04.015 23683707
     [Google Scholar]
  67. ChenT.S. HuangT.H. LaiM.C. HuangC.W. The role of glutamate receptors in epilepsy.Biomedicines202311378310.3390/biomedicines11030783 36979762
     [Google Scholar]
  68. TakagoH. Oshima-TakagoT. Pre- and postsynaptic ionotropic glutamate receptors in the auditory system of mammals.Hear. Res.201836211310.1016/j.heares.2018.02.007 29510886
     [Google Scholar]
  69. ChiechioS. Modulation of chronic pain by metabotropic glutamate receptors.Adv. Pharma.201675638910.1016/bs.apha.2015.11.001
     [Google Scholar]
  70. SumadewiK.T. HarkitasariS. TjandraD.C. Biomolecular mechanisms of epileptic seizures and epilepsy: A review.Acta Epileptologica2023512810.1186/s42494‑023‑00137‑0
     [Google Scholar]
  71. CelliR. FornaiF. Targeting ionotropic glutamate receptors in the treatment of epilepsy.Curr. Neuropharmacol.202119674776510.2174/18756190MTA5DNTcey 32867642
     [Google Scholar]
  72. LauA. TymianskiM. Glutamate receptors, neurotoxicity and neurodegeneration.Pflugers Arch.2010460252554210.1007/s00424‑010‑0809‑1 20229265
     [Google Scholar]
  73. HeL.Y. HuM.B. LiR.L. Natural medicines for the treatment of epilepsy: Bioactive components, pharmacology and mechanism.Front. Pharmacol.20211260404010.3389/fphar.2021.604040 33746751
     [Google Scholar]
  74. DuflocqA. BrasL.B. BullierE. CouraudF. DavenneM. Nav1.1 is predominantly expressed in nodes of Ranvier and axon initial segments.Mol. Cell. Neurosci.200839218019210.1016/j.mcn.2008.06.008 18621130
     [Google Scholar]
  75. ContetC. GouldingS.P. KuljisD.A. BK channels in the central nervous system.Intern. Rev. Neurob.201612828134210.1016/bs.irn.2016.04.001
     [Google Scholar]
  76. Fernandez-AbascalJ. GrazianoB. EncaladaN. Glial Chloride Channels in the Function of the Nervous System Across Species.In: Ion Channels in Biophysics and Physiology.SingaporeSpringer Nature Singapore202119522310.1007/978‑981‑16‑4254‑8_10
     [Google Scholar]
  77. MartinA.D. StirlingW.J. ThorneR.S. WattG. Uncertainties on α S in global PDF analyses and implications for predicted hadronic cross sections.Eur. Phys. J. C200964465368010.1140/epjc/s10052‑009‑1164‑2
     [Google Scholar]
  78. WeiF. YanL.M. SuT. Ion channel genes and epilepsy: Functional alteration, pathogenic potential, and mechanism of epilepsy.Neurosci. Bull.201733445547710.1007/s12264‑017‑0134‑1 28488083
     [Google Scholar]
  79. SkaperS.D. DebettoP. GiustiP. The P2X 7 purinergic receptor: From physiology to neurological disorders.FASEB J.201024233734510.1096/fj.09‑138883 19812374
     [Google Scholar]
  80. NorthRA P2X receptors.Philos Trans R Soc B Biol Sci170037170020150427
     [Google Scholar]
  81. BurnstockG. KnightG.E. The potential of P2X7 receptors as a therapeutic target, including inflammation and tumour progression.Purinergic Signal.201814111810.1007/s11302‑017‑9593‑0 29164451
     [Google Scholar]
  82. CalzaferriF Ruiz-RuizC DiegodAMG The purinergic P2X7 receptor as a potential drug target to combat neuroinflammation in neurodegenerative diseases.Med. Res. Rev.20204062427246510.1002/med.21710 32677086
     [Google Scholar]
  83. GilB. SmithJ. TangY. IllesP. EngelT. Beyond seizure control: Treating comorbidities in epilepsy via targeting of the p2x7 receptor.Int. J. Mol. Sci.2022234238010.3390/ijms23042380 35216493
     [Google Scholar]
  84. KuleszaA. PaczekL. BurdzinskaA. The role of COX-2 and PGE2 in the regulation of immunomodulation and other functions of mesenchymal stromal cells.Biomedicines202311244510.3390/biomedicines11020445 36830980
     [Google Scholar]
  85. ChenY. NagibM.M. YasmenN. Neuroinflammatory mediators in acquired epilepsy: An update.Inflamm. Res.202372468370110.1007/s00011‑023‑01700‑8 36745211
     [Google Scholar]
  86. YamagataK. AndreassonK.I. KaufmannW.E. BarnesC.A. WorleyP.F. Expression of a mitogen-inducible cyclooxygenase in brain neurons: Regulation by synaptic activity and glucocorticoids.Neuro199311371386
     [Google Scholar]
  87. FerrerM.D. Busquets-CortésC. CapóX. Cyclooxygenase-2 inhibitors as a therapeutic target in inflammatory diseases.Curr. Med. Chem.201926183225324110.2174/0929867325666180514112124 29756563
     [Google Scholar]
  88. ElbadawyM. UsuiT. YamawakiH. SasakiK. Novel functions of death-associated protein kinases through mitogen-activated protein kinase-related signals.Int. J. Mol. Sci.20181910303110.3390/ijms19103031 30287790
     [Google Scholar]
  89. GanC.L. ZouY. ChenD. Blocking ERK-DAPK1 axis attenuates glutamate excitotoxicity in epilepsy.Int. J. Mol. Sci.20222312637010.3390/ijms23126370 35742817
     [Google Scholar]
  90. SaadiAMSM The expression pattern of death associated protein kinase1 in normal dorsal root ganglion neurons and following peripheral nerve injury Theses2015251
     [Google Scholar]
  91. NooriT. ShirooieS. SuredaA. Regulation of DAPK1 by natural products: An important target in treatment of stroke.Neurochem. Res.20224782142215710.1007/s11064‑022‑03628‑7 35674928
     [Google Scholar]
  92. KimN. ChenD. ZhouX.Z. LeeT.H. Death-associated protein kinase 1 phosphorylation in neuronal cell death and neurodegenerative disease.Int. J. Mol. Sci.20192013313110.3390/ijms20133131 31248062
     [Google Scholar]
  93. ZhangF. KangZ. LiW. XiaoZ. ZhouX. Roles of brain-derived neurotrophic factor/tropomyosin-related kinase B (BDNF/TrkB) signalling in Alzheimer’s disease.J. Clin. Neurosci.201219794694910.1016/j.jocn.2011.12.022 22613489
     [Google Scholar]
  94. SinghS. SinghT.G. RehniA.K. An insight into molecular mechanisms and novel therapeutic approaches in epileptogenesis.CNS Neurol. Disord. Drug Targets2021191075077910.2174/1871527319666200910153827 32914725
     [Google Scholar]
  95. BatoolZ. AzfalA. LiaquatL. Receptor tyrosine kinases (RTKS). in: Receptor tyrosine kinases in neurodegenerative and psychiatric disorders Elsevier.In: Receptor Tyrosine Kinases in Neurodegenerative and Psychiatric Disorders.New YorkAcademic Press2023117185
     [Google Scholar]
  96. Munguia-GalavizF.J. Miranda-DiazA.G. Cardenas-SosaM.A. EchavarriaR. Sigma-1 receptor signaling: In search of new therapeutic alternatives for cardiovascular and renal diseases.Int. J. Mol. Sci.2023243199710.3390/ijms24031997 36768323
     [Google Scholar]
  97. GliwińskaA. Czubilińska-ŁadaJ. WięckiewiczG. The role of brain-derived neurotrophic factor (BDNF) in diagnosis and treatment of epilepsy, depression, schizophrenia, anorexia nervosa and alzheimer’s disease as highly drug-resistant diseases: A narrative review.Brain Sci.202313216310.3390/brainsci13020163 36831706
     [Google Scholar]
  98. AmanteaD. RussoR. CertoM. Caspase-1-independent maturation of IL-1β in ischemic brain injury: Is there a role for gelatinases?Mini Rev. Med. Chem.201616972973710.2174/1389557516666160321112512 26996625
     [Google Scholar]
  99. RijkersK. MajoieH.J. HooglandG. KenisG. BaetsD.M. VlesJ.S. The role of interleukin-1 in seizures and epilepsy: A critical review.Exp. Neurol.2009216225827110.1016/j.expneurol.2008.12.014 19162013
     [Google Scholar]
  100. RutterJ. Mechanisms of interleukin-1 signalling in the regulation of seizures - proquest.2024Available from: https://www.proquest.com/openview/353662674d31fba139ad7c9d58644a93/1?pq-origsite=gscholar&cbl=2026366&diss=y
    [Google Scholar]
  101. YamanakaG. IshidaY. KanouK. Towards a treatment for neuroinflammation in epilepsy: Interleukin-1 receptor antagonist, anakinra, as a potential treatment in intractable epilepsy.Int. J. Mol. Sci.20212212628210.3390/ijms22126282 34208064
     [Google Scholar]
  102. WangP. QianH. XiaoM. LvJ. Role of signal transduction pathways in IL‐1β‐induced apoptosis: Pathological and therapeutic aspects.Immun. Inflamm. Dis.2023111e76210.1002/iid3.762 36705417
     [Google Scholar]
  103. GibbonsJ.J. AbrahamR.T. YuK. Mammalian target of rapamycin: Discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth.Semin. Oncol.200936Suppl. 3S3S1710.1053/j.seminoncol.2009.10.011 19963098
     [Google Scholar]
  104. LaSargeC.L. DanzerS.C. Mechanisms regulating neuronal excitability and seizure development following mTOR pathway hyperactivation.Front. Mol. Neurosci.201471810.3389/fnmol.2014.00018 24672426
     [Google Scholar]
  105. BockaertJ. MarinP. mTOR in brain physiology and pathologies.Physiol. Rev.20159541157118710.1152/physrev.00038.2014 26269525
     [Google Scholar]
  106. CitraroR. LeoA. ConstantiA. RussoE. SarroD.G. mTOR pathway inhibition as a new therapeutic strategy in epilepsy and epileptogenesis.Pharmacol. Res.201610733334310.1016/j.phrs.2016.03.039 27049136
     [Google Scholar]
  107. KangT.C. Nuclear factor-erythroid 2-related factor 2 (NRF2) and mitochondrial dynamics/mitophagy in neurological diseases.Antioxidants20209761710.3390/antiox9070617 32679689
     [Google Scholar]
  108. MaQ. Role of nrf2 in oxidative stress and toxicity.Annu. Rev. Pharmacol. Toxicol.201353140142610.1146/annurev‑pharmtox‑011112‑140320 23294312
     [Google Scholar]
  109. OtsukiA. YamamotoM. Cis-element architecture of NRF2–sMaf heterodimer binding sites and its relation to diseases.Arch. Pharm. Res.202043327528510.1007/s12272‑019‑01193‑2 31792803
     [Google Scholar]
  110. Lastres-BeckerI. García-YagüeA.J. ScannevinR.H. Repurposing the NRF2 Activator Dimethyl Fumarate as Therapy Against Synucleinopathy in Parkinson’s Disease.Antioxid. Redox Signal.2016252617710.1089/ars.2015.6549 27009601
     [Google Scholar]
  111. LuM.C. JiJ.A. JiangZ.Y. YouQ.D. The Keap1–NRF2–ARE pathway as a potential preventive and therapeutic target: An update.Med. Res. Rev.201636592496310.1002/med.21396 27192495
     [Google Scholar]
  112. YangN. GuanQ.W. ChenF.H. Antioxidants targeting mitochondrial oxidative stress: Promising neuroprotectants for epilepsy.Oxid. Med. Cell. Longev.2020202011410.1155/2020/6687185 33299529
     [Google Scholar]
  113. MadireddyS. MadireddyS. Therapeutic strategies to ameliorate neuronal damage in epilepsy by regulating oxidative stress, mitochondrial dysfunction, and neuroinflammation.Brain Sci.202313578410.3390/brainsci13050784 37239256
     [Google Scholar]
  114. HolE.M. PeknyM. Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system.Curr. Opin. Cell Biol.20153212113010.1016/j.ceb.2015.02.004 25726916
     [Google Scholar]
  115. DoddS. MalhiG.S. TillerJ. A consensus statement for safety monitoring guidelines of treatments for major depressive disorder.Aust. N. Z. J. Psychiatry201145971272510.3109/00048674.2011.595686 21888608
     [Google Scholar]
  116. HuY. QiH. YangJ. Wogonin mitigates microglia-mediated synaptic over-pruning and cognitive impairment following epilepsy.Phytomedicine202413515622210.1016/j.phymed.2024.156222 39547095
     [Google Scholar]
  117. ZhangX. TangN. HaddenT.J. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta BBA - Mol.Cell Res.201118131119781986
     [Google Scholar]
  118. HuangX. HuQ. ShiH. ZhengY. HuR. GuoQ. Everolimus inhibits PI3K/Akt/mTOR and NF-kB/IL-6 signaling and protects seizure-induced brain injury in rats.J. Chem. Neuroanat.202111410196010.1016/j.jchemneu.2021.101960 33915267
     [Google Scholar]
  119. WuJ.B. ShihJ.C. Valproic acid induces monoamine oxidase A via Akt/forkhead box O1 activation.Mol. Pharmacol.201180471472310.1124/mol.111.072744 21775495
     [Google Scholar]
  120. SongJ. LiM. KangN. Baicalein ameliorates cognitive impairment of vascular dementia rats via suppressing neuroinflammation and regulating intestinal microbiota.Brain Res. Bull.202420811088810.1016/j.brainresbull.2024.110888 38295883
     [Google Scholar]
  121. ZhangY. HuX. ZouL.Q. Flavonoids as therapeutic agents for epilepsy: Unveiling anti-inflammatory and antioxidant pathways for novel treatments.Front. Pharmacol.202415145728410.3389/fphar.2024.1457284 39329119
     [Google Scholar]
  122. ErdemS.A. SubakH. AslanP. Surfactant-based electrodes for the quantification of flavonoids.In: Surfactant Based Electrochemical Sensors and Biosensors.LondonElsevier202444346910.1016/B978‑0‑443‑15493‑5.00014‑2
     [Google Scholar]
  123. GhoshS. BishalA. GhoshS.K. Herbal medicines: A potent approach to human diseases, their chief compounds, formulations, present status, and future aspects.Inter J Memb Sci Tech202310144246410.15379/ijmst.v10i1.2608
     [Google Scholar]
  124. UllahA. MunirS. BadshahS.L. Important flavonoids and their role as a therapeutic agent.Molecules20202522524310.3390/molecules25225243 33187049
     [Google Scholar]
  125. Nassiri-AslM. HajialiF. TaghilooM. AbbasiE. MohseniF. YousefiF. Comparison between the effects of quercetin on seizure threshold in acute and chronic seizure models.Toxicol. Ind. Health201632593694410.1177/0748233713518603 24442347
     [Google Scholar]
  126. SefilF. KahramanI. DokuyucuR. Ameliorating effect of quercetin on acute pentylenetetrazole induced seizures in rats.Int. J. Clin. Exp. Med.20147924712477 25356099
     [Google Scholar]
  127. TomouE.M. PapakyriakopoulouP. SaitaniE.M. ValsamiG. PippaN. SkaltsaH. Recent advances in nanoformulations for quercetin delivery.Pharmaceutics2023156165610.3390/pharmaceutics15061656 37376104
     [Google Scholar]
  128. WuD. ZhengZ. FanS. Ameliorating effect of quercetin on epilepsy by inhibition of inflammation in glial cells.Exp. Ther. Med.202020285485910.3892/etm.2020.8742 32742328
     [Google Scholar]
  129. PrakashC. TyagiJ. RabidasS.S. KumarV. SharmaD. Therapeutic potential of quercetin and its derivatives in epilepsy: Evidence from preclinical studies.Neuromolecular Med.202325216317810.1007/s12017‑022‑08724‑z 35951285
     [Google Scholar]
  130. AriedeM.B. JuniorG.W.A. CândidoT.M. Would rutin be a feasible strategy for environmental-friendly photoprotective samples? A review from stability to skin permeability and efficacy in sunscreen systems.Cosmetics202411414110.3390/cosmetics11040141
     [Google Scholar]
  131. CalabreseE.J. PressmanP. HayesA.W. RUTIN, a widely consumed flavonoid, that commonly induces hormetic effects.Food Chem. Toxicol.202418711462610.1016/j.fct.2024.114626 38556157
     [Google Scholar]
  132. GoyalJ. VermaP.K. An overview of biosynthetic pathway and therapeutic potential of rutin.Mini Rev. Med. Chem.202323141451146010.2174/1389557523666230125104101 36698235
     [Google Scholar]
  133. SatariA. GhasemiS. HabtemariamS. AsgharianS. LorigooiniZ. Rutin: A flavonoid as an effective sensitizer for anticancer therapy; insights into multifaceted mechanisms and applicability for combination therapy.Evid. Based Complement. Alternat. Med.202111010.1155/2021/9913179 34484407
     [Google Scholar]
  134. ChangA. ChangY. WangS.J. Rutin prevents seizures in kainic acid-treated rats: Evidence of glutamate levels, inflammation and neuronal loss modulation.Food Funct.20221320104011041410.1039/D2FO01490D 36148811
     [Google Scholar]
  135. MohamedKM AbdelfattahMS khadragyEM Rutin-loaded selenium nanoparticles modulated the redox status, inflammatory, and apoptotic pathways associated with pentylenetetrazole-induced epilepsy in mice.Green Processing and Synthesis20231212023001010.1515/gps‑2023‑0010
     [Google Scholar]
  136. RadS.S. AslM.N. ZamansoltaniF. Anticonvulsive effects of rutin in a rat model of absence seizure: A novel compound to treat seizure.Anna. Gen. Psychiatry20087Suppl 1S21910.1186/1744‑859X‑7‑S1‑S219
     [Google Scholar]
  137. NieoczymD. SocałaK. RaszewskiG. WlaźP. Effect of quercetin and rutin in some acute seizure models in mice.Prog. Neuropsychopharmacol. Biol. Psychiatry201454505810.1016/j.pnpbp.2014.05.007 24857758
     [Google Scholar]
  138. AseervathamG.S.B. SuryakalaU. Doulethunisha SundaramS. BoseP.C. SivasudhaT. Expression pattern of NMDA receptors reveals antiepileptic potential of apigenin 8-C-glucoside and chlorogenic acid in pilocarpine induced epileptic mice.Biomed. Pharmacother.201682546410.1016/j.biopha.2016.04.066 27470339
     [Google Scholar]
  139. HashemiP. BabaeiF.J. VazifekhahS. NikbakhtF. Evaluation of the neuroprotective, anticonvulsant, and cognition-improvement effects of apigenin in temporal lobe epilepsy: Involvement of the mitochondrial apoptotic pathway.Iran. J. Basic Med. Sci.2019227752758 32373296
     [Google Scholar]
  140. KramerD.J. JohnsonA.A. Apigenin: A natural molecule at the intersection of sleep and aging.Front. Nutr.202411135917610.3389/fnut.2024.1359176 38476603
     [Google Scholar]
  141. BhrateeA. AnandP. SinghS. Apigenin: Exploring its neuroprotective potential in neurodegenerative disorders: Mechanisms and promising therapeutic applications.Pharmaspire202315425726310.56933/Pharmaspire.2023.15138
     [Google Scholar]
  142. YaoL. FanZ. HanS. SunN. CheH. Apigenin acts as a partial agonist action at estrogen receptors in vivo.Eur. J. Pharmacol.202190617417510.1016/j.ejphar.2021.174175 34048736
     [Google Scholar]
  143. ChengY. ZhangY. HuangP. ChengQ. DingH. Luteolin ameliorates pentetrazole-induced seizures through the inhibition of the TLR4/NF-κB signaling pathway.Epilepsy Res.202420110732110.1016/j.eplepsyres.2024.107321 38382229
     [Google Scholar]
  144. TambeR. PatilA. JainP. SanchetiJ. SomaniG. SathayeS. Assessment of luteolin isolated from Eclipta alba leaves in animal models of epilepsy.Pharm. Biol.201755126426810.1080/13880209.2016.1260597 27927066
     [Google Scholar]
  145. BirmanH. DarA.K. KapucuA. AcarS. UzümG. EffectsofLuteolinonLiver, KidneyandBraininPentylentetrazol-Induced Seizures: Involvement of Metalloproteinases and NOS Activities.Balkan Med. J.201229218819610.5152/balkanmedj.2011.030 25206993
     [Google Scholar]
  146. ShenM.L. WangC.H. ChenR.Y.T. ZhouN. KaoS.T. WuD.C. Luteolin inhibits GABAA receptors in HEK cells and brain slices.Sci. Rep.2016612769510.1038/srep27695 27292079
     [Google Scholar]
  147. AlgazoM. RahimiN. GheshlaghiA.S. Involvement of NMDA receptor and nitric oxide pathway in the anticonvulsant effect of genistein in ovariectomized mice.J Iran Med Counc Iran Medical Council2019233541
     [Google Scholar]
  148. GheshlaghiA.S. JafariM.R. AlgazoM. RahimiN. AlshaibH. DehpourA.R. Genistein modulation of seizure: Involvement of estrogen and serotonin receptors.J. Nat. Med.201771353754410.1007/s11418‑017‑1088‑3 28439683
     [Google Scholar]
  149. ElsayedA.A. MenzeE.T. TadrosM.G. IbrahimB.M.M. SabriN.A. KhalifaA.E. Retracted article: Effects of genistein on pentylenetetrazole-induced behavioral and neurochemical deficits in ovariectomized rats.Naunyn Schmiedebergs Arch. Pharmacol.20183911273610.1007/s00210‑017‑1435‑7 29067514
     [Google Scholar]
  150. BahadirA. DemirS. OrallarH. Gender specificity of genistein treatment in penicillin-induced epileptiform activity in rats.Neurophysiology201648642142810.1007/s11062‑017‑9619‑9
     [Google Scholar]
  151. GuoJ. MinD. FengH.J. Genistein, a natural isoflavone, alleviates seizure-induced respiratory arrest in dba/1 mice.Front. Neurol.20211276191210.3389/fneur.2021.761912 34803895
     [Google Scholar]
  152. KhatoonS. AgarwalN.B. SamimM. AlamO. Neuroprotective effect of fisetin through suppression of il-1r/tlr axis and apoptosis in pentylenetetrazole-induced kindling in mice.Front. Neurol.20211268906910.3389/fneur.2021.689069 34354662
     [Google Scholar]
  153. MahawarS. RakshitD. PatelI. Fisetin-loaded chitosan nanoparticles ameliorate pilocarpine-induced temporal lobe epilepsy and associated neurobehavioral alterations in mice: Role of ROS/TNF-α-NLRP3 inflammasomes pathway.Nanomedicine20245910275210.1016/j.nano.2024.102752 38740358
     [Google Scholar]
  154. MehtaD.K. DasR. YadavS. SharmaV. GuptaS. GoyalA. SARS CoV-2 Omicron (B. 1.1. 529) recent updates and challenges worldwide.Infect. Disord. Drug Targets2023235e24032321495010.2174/1871526523666230324113146 36967463
     [Google Scholar]
  155. RaygudeK.S. KandhareA.D. GhoshP. BodhankarS.L. Anticonvulsant effect of fisetin by modulation of endogenous biomarkers.Biomedicine & Preventive Nutrition20122321522210.1016/j.bionut.2012.04.005
     [Google Scholar]
  156. ZhaiK. HuL. ChenJ. FuC. ChenQ. Chrysin induces hyperalgesia via the GABAA receptor in mice.Planta Med.200874101229123410.1055/s‑2008‑1081288 18612941
     [Google Scholar]
  157. ZhangY. ZhaoJ. AfzalO. Neuroprotective role of chrysin‐loaded poly(lactic‐co‐glycolic acid) nanoparticle against kindling‐induced epilepsy through Nrf2/ARE/HO‐1 pathway.J. Biochem. Mol. Toxicol.2021352e2263410.1002/jbt.22634 32991785
     [Google Scholar]
  158. AbbasiE. Nassiri-AslM. ShafeeiM. SheikhiM. Neuroprotective effects of vitexin, a flavonoid, on pentylenetetrazole-induced seizure in rats.Chem. Biol. Drug Des.201280227427810.1111/j.1747‑0285.2012.01400.x 22554436
     [Google Scholar]
  159. Oliveira dDD, Silva dCP, Iglesias BB, Beleboni RO. Vitexin possesses anticonvulsant and anxiolytic-like effects in murine animal models.Front. Pharmacol.202011118110.3389/fphar.2020.01181 32848784
     [Google Scholar]
  160. LuoW. MinJ. HuangW.X. Vitexin reduces epilepsy after hypoxic ischemia in the neonatal brain via inhibition of NKCC1.J. Neuroinflammation201815118610.1186/s12974‑018‑1221‑6 29925377
     [Google Scholar]
  161. EkenH. TurkmenB.N. SenelB. ArslanR. Examination of the effects of vitexin and vitexin-loaded solid lipid nanoparticles on neuropathic pain and possible mechanisms of action.Neuropharmacology202425310996110.1016/j.neuropharm.2024.109961 38657947
     [Google Scholar]
  162. GolechhaM. ChaudhryU. BhatiaJ. SalujaD. AryaD.S. Naringin protects against kainic acid-induced status epilepticus in rats: Evidence for an antioxidant, anti-inflammatory and neuroprotective intervention.Biol. Pharm. Bull.201134336036510.1248/bpb.34.360 21372385
     [Google Scholar]
  163. JeongK.H. JungU.J. KimS.R. Naringin attenuates autophagic stress and neuroinflammation in kainic acid-treated hippocampus in vivo.Evid. Based Complement. Alternat. Med.201520151910.1155/2015/354326 26124853
     [Google Scholar]
  164. ParkJ. JeongK.H. ShinW.H. BaeY.S. JungU.J. KimS.R. Naringenin ameliorates kainic acid-induced morphological alterations in the dentate gyrus in a mouse model of temporal lobe epilepsy.Neuroreport201627151182118910.1097/WNR.0000000000000678 27584687
     [Google Scholar]
  165. BhartiS. RaniN. KrishnamurthyB. AryaD. Preclinical evidence for the pharmacological actions of naringin: A review.Planta Med.201480643745110.1055/s‑0034‑1368351 24710903
     [Google Scholar]
  166. FuP. YuanQ. SunY. Baicalein ameliorates epilepsy symptoms in a pilocarpine-induced rat model by regulation of igf1r.Neurochem. Res.202045123021303310.1007/s11064‑020‑03150‑8 33095440
     [Google Scholar]
  167. LiP. WangX. ZhangJ. Baicalein administration protects against pentylenetetrazole-induced chronic epilepsy in rats.Trop. J. Pharm. Res.201817229310.4314/tjpr.v17i2.14
     [Google Scholar]
  168. QianX. WangZ.R. ZhengJ.J. Baicalein improves cognitive deficits and hippocampus impairments in temporal lobe epilepsy rats.Brain Res.2019171411111810.1016/j.brainres.2019.02.028 30817901
     [Google Scholar]
  169. AnjaliP.B. JawaharN. KumarP.M.R. JubieS. SelvamuthukumarS. Nanocarriers in the treatment of epilepsy: Challenges and opportunities.J. Drug Deliv. Sci. Technol.20249710578810.1016/j.jddst.2024.105788
     [Google Scholar]
  170. HeidariehN. NikzadH. Jamshidi-AraniT. Effect of green tea catechins on PTZ-induced seizure in male mice.2013Available from: https://openurl.ebsco.com/contentitem/gcd:90292145?sid=ebsco:plink:crawler&id=ebsco:gcd:90292145
    [Google Scholar]
  171. KoshalP. JamwalS. AkulaK.K. Animal Models of Epilepsy. Animal Models of Neurological Disorders Springer Singapore. BansalP.K. DeshmukhR. Springer Nature Singapore2017597810.1007/978‑981‑10‑5981‑0_5
     [Google Scholar]
  172. GhayurM.N. KhanH. GilaniA.H. Antispasmodic, bronchodilator and vasodilator activities of (+)-catechin, a naturally occurring flavonoid.Arch. Pharm. Res.200730897097510.1007/BF02993965 17879750
     [Google Scholar]
  173. AltunA. Evaluation of hexarelin effects on epileptic seizures, hippocampal neuronal damage and memory impairment after pentylenetetrazole-induced acute model in rat.Am J Biomed Sci Res20195432933310.34297/AJBSR.2019.05.000938
     [Google Scholar]
  174. KumarS. IvanovS. LaguninA. GoelR.K. Bioinformatics guided rotenone adjuvant kindling in mice as a new animal model of drug-resistant epilepsy.Comput. Biol. Med.202214710575410.1016/j.compbiomed.2022.105754 35753090
     [Google Scholar]
  175. AycikF.B. AyyildizM. AgarE. Role of cannabinoid CB1 receptors in the proconvulsant effect of Apelin-13 on penicillin-induced epileptiform activity.Indian J Exp Biol IJEB20246204238244
     [Google Scholar]
  176. BaradaranS. Ghasemi-KasmanM. EbrahimpourA. Anticonvulsant effects of hesperetin in animal model of pentylenetetrazole-induced-seizures.J Babol Univ Med Sci Journal of Babol University of Medical Sciences201820111926
     [Google Scholar]
  177. KwonJ.Y. JungU.J. KimD.W. Beneficial effects of hesperetin in a mouse model of temporal lobe epilepsy.J. Med. Food201821121306130910.1089/jmf.2018.4183 30136878
     [Google Scholar]
  178. SharmaP. KumariS. SharmaJ. PurohitR. SinghD. Hesperidin interacts with CREB-BDNF signaling pathway to suppress pentylenetetrazole-induced convulsions in zebrafish.Front. Pharmacol.20211160779710.3389/fphar.2020.607797 33505312
     [Google Scholar]
  179. KumarA. LalithaS. MishraJ. Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations.Indian J. Pharmacol.201446330931510.4103/0253‑7613.132180 24987179
     [Google Scholar]
  180. LiuZ. TuK. ZouP. Hesperetin ameliorates spinal cord injury by inhibiting NLRP3 inflammasome activation and pyroptosis through enhancing Nrf2 signaling.Int. Immunopharmacol.202311811010310.1016/j.intimp.2023.110103 37001385
     [Google Scholar]
  181. SinghD. Cellular and molecular interactions of dietary flavonoids toward seizures suppression in epilepsy.In: Treatments, Nutraceuticals, Supplements, and Herbal Medicine in Neurological Disorders.New YorkElsevier202330532510.1016/B978‑0‑323‑90052‑2.00030‑5
     [Google Scholar]
  182. QuZ. JiaL. XieT. (–)-Epigallocatechin-3-gallate protects against lithium-pilocarpine-induced epilepsy by inhibiting the toll-like receptor 4 (TLR4)/Nuclear factor-κb (nf-κb) signaling pathway.Med. Sci. Monit.2019251749175810.12659/MSM.915025 30843525
     [Google Scholar]
  183. SunZ.Q. MengF.H. TuL.X. SunL. Myricetin attenuates the severity of seizures and neuroapoptosis in pentylenetetrazole kindled mice by regulating the of BDNF TrkB signaling pathway and modulating matrix metalloproteinase 9 and GABAA.Exp. Ther. Med.20191743083309110.3892/etm.2019.7282 30906480
     [Google Scholar]
  184. ZhangX.H. MaZ.G. RowlandsD.K. Flavonoid myricetin modulates G A B A A receptor activity through activation of Ca2+ channels and camk-ii pathway.Evid. Based Complement. Alternat. Med.20122012110
     [Google Scholar]
  185. SethiyaN.K. GhiloriaN. SrivastavA. Therapeutic potential of myricetin in the treatment of neurological, neuropsychiatric, and neurodegenerative disorders.CNS Neurol. Disord. Drug Targets202423786588210.2174/1871527322666230718105358 37461364
     [Google Scholar]
  186. GuoX. CaoY. HaoF. YanZ. WangM. LiuX. Tangeretin alters neuronal apoptosis and ameliorates the severity of seizures in experimental epilepsy-induced rats by modulating apoptotic protein expressions, regulating matrix metalloproteinases, and activating the PI3K/Akt cell survival pathway.Adv. Med. Sci.201762224625310.1016/j.advms.2016.11.011 28501723
     [Google Scholar]
  187. JadhavA.D. JadhavR.R. PadwalS.L. JadhavS.S. KaleA.S. GadeP.R. Evaluation of anticonvulsant activity of angiotensin receptor antagonists in an animal model.Int. J. Basic Clin. Pharmacol.20201012910.18203/2319‑2003.ijbcp20205534
     [Google Scholar]
  188. Jamali-RaeufyN. BaluchnejadmojaradT. RoghaniM. keimasiS. goudarziM. Isorhamnetin exerts neuroprotective effects in STZ-induced diabetic rats via attenuation of oxidative stress, inflammation and apoptosis.J. Chem. Neuroanat.201910210170910.1016/j.jchemneu.2019.101709 31698018
     [Google Scholar]
  189. AlqudahA. QnaisE.Y. WedyanM.A. Isorhamnetin reduces glucose level, inflammation, and oxidative stress in high-fat diet/streptozotocin diabetic mice model.Molecules202328250210.3390/molecules28020502 36677559
     [Google Scholar]
  190. LiY. ChiG. ShenB. TianY. FengH. Isorhamnetin ameliorates LPS-induced inflammatory response through downregulation of NF-κB signaling.Inflammation20163941291130110.1007/s10753‑016‑0361‑z 27138362
     [Google Scholar]
  191. EdwardsS.E. RochaCdI. WilliamsonEM. Phytopharmacy: An evidence-based guide to herbal medicinal products.New YorkJohn Wiley & Sons201510.1002/9781118543436
     [Google Scholar]
  192. AonumaK. XuD. MurakoshiN. Impact of isorhamnetin for suppression of action potential aberrations associated with atrial fibrillation.Europ. Heart J.202344Supplement_2ehad655317510.1093/eurheartj/ehad655.3175
     [Google Scholar]
  193. ZhaoJ.J. SongJ.Q. PanS.Y. WangK. Treatment with isorhamnetin protects the brain against ischemic injury in mice.Neurochem. Res.20164181939194810.1007/s11064‑016‑1904‑2 27161367
     [Google Scholar]
  194. QiH. LiuL. Rhoifolin attenuates damage to hippocampal neuronal culture model of acquired epilepsy in vitro by regulating NF-κB/iNOS/COX-2 axis.Qual. Assur. Saf. Crops Foods202214311612310.15586/qas.v14i3.1093
     [Google Scholar]
  195. RatnoglikS.L. AokiC. SudarmonoP. Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus.Microbiol. Immunol.201458318819410.1111/1348‑0421.12133 24438164
     [Google Scholar]
  196. DedeurwaerdereS. Neuromodulation in Experimetal Animal Models of Epilepsy2005
     [Google Scholar]
  197. ZhuangJ. PengY. GuC. Wogonin accelerates hematoma clearance and improves neurological outcome via the ppar-γ pathway after intracerebral hemorrhage.Transl. Stroke Res.202112466067510.1007/s12975‑020‑00842‑9 32918259
     [Google Scholar]
  198. AspatwarA. NathR. BhowmikR. Nanoparticles of herbal extracts in treatment of neurodegenerative disorders.ChemRxiv20248238
     [Google Scholar]
  199. FernandesF. Dias-TeixeiraM. Delerue-MatosC. GrossoC. Critical review of lipid-based nanoparticles as carriers of neuroprotective drugs and extracts.Nanomaterials202111356310.3390/nano11030563 33668341
     [Google Scholar]
  200. AhmadN. AhmadR. AlrasheedR. Quantification and evaluations of catechin hydrate polymeric nanoparticles used in brain targeting for the treatment of epilepsy.Pharmaceutics202012320310.3390/pharmaceutics12030203 32120778
     [Google Scholar]
  201. GeorgeM.Y. DeranyE.M.O. AhmedY. Design and evaluation of chrysin-loaded nanoemulsion against lithium/pilocarpine-induced status epilepticus in rats; emphasis on formulation, neuronal excitotoxicity, oxidative stress, microglia polarization, and AMPK/SIRT-1/PGC-1α pathway.Expert Opin. Drug Deliv.202320115917410.1080/17425247.2023.2153831 36446395
     [Google Scholar]
  202. RehmanM.U. TariqL. ArafahA. Nanogel-based transdermal drug delivery system: A therapeutic strategy with under discussed potential.Curr. Top. Med. Chem.2023231446110.2174/1568026622666220818112728 35984019
     [Google Scholar]
  203. BhattacharyaT. SoaresG.A.B. ChopraH. Applications of phyto-nanotechnology for the treatment of neurodegenerative disorders.Materials202215380410.3390/ma15030804 35160749
     [Google Scholar]
  204. JanaK. GhoshS. DebnathB. Recent advancements of hyaluronic acid nanoscaffolds in arthritis management.ChemistrySelect2024932e20240203510.1002/slct.202402035
     [Google Scholar]
  205. ElkomyM.H. ZakiR.M. AlsaidanO.A. Intranasal nanotransferosomal gel for quercetin brain targeting: I. optimization, characterization, brain localization, and cytotoxic studies.Pharmaceutics2023157180510.3390/pharmaceutics15071805 37513991
     [Google Scholar]
  206. CanoA. EttchetoM. EspinaM. Epigallocatechin-3-gallate loaded PEGylated-PLGA nanoparticles: A new anti-seizure strategy for temporal lobe epilepsy.Nanomedicine20181441073108510.1016/j.nano.2018.01.019 29454994
     [Google Scholar]
  207. MissiryE.M.A. OthmanA.I. AmerM.A. SedkiM. AliS.M. SherbinyE.I.M. Nanoformulated ellagic acid ameliorates pentylenetetrazol-induced experimental epileptic seizures by modulating oxidative stress, inflammatory cytokines and apoptosis in the brains of male mice.Metab. Brain Dis.202035238539910.1007/s11011‑019‑00502‑4 31728888
     [Google Scholar]
  208. GuptaI. AdinS.N. AqilM. MujeebM. Nose to brain delivery of naringin loaded transniosomes for epilepsy: Formulation, characterisation, blood-brain distribution and in vivo pharmacodynamic evaluation.J. Liposome Res.2024341607610.1080/08982104.2023.2214619 37212622
     [Google Scholar]
  209. GhoshA. KhanamN. NathD. Solid lipid nanoparticle: A potent vehicle of the kaempferol for brain delivery through the blood-brain barrier in the focal cerebral ischemic rat.Chem. Biol. Interact.202439711108410.1016/j.cbi.2024.111084 38823537
     [Google Scholar]
  210. AlrashdiB.M. FehaidA. KassabR.B. RizkS. HabottaO.A. MoneimA.A.E. Biosynthesized selenium nanoparticles using epigallocatechin gallate protect against pentylenetetrazole-induced acute epileptic seizures in mice via antioxidative, anti-inflammatory, and anti-apoptotic activities.Biomedicines2023117195510.3390/biomedicines11071955 37509594
     [Google Scholar]
  211. CanbolatF. DemirN. YayıntasO.T. Chitosan nanoparticles loaded with quercetin and valproic acid: A novel approach for enhancing antioxidant activity against oxidative stress in the sh-sy5y human neuroblastoma cell line.Biomedicines202412228710.3390/biomedicines12020287 38397889
     [Google Scholar]
  212. PuriV. KanojiaN. SharmaA. HuanbuttaK. DheerD. SangnimT. Natural product-based pharmacological studies for neurological disorders.Front. Pharmacol.202213101174010.3389/fphar.2022.1011740 36419628
     [Google Scholar]
  213. Sharifi-RadJ. QuispeC. Herrera-BravoJ. A pharmacological perspective on plant-derived bioactive molecules for epilepsy.Neurochem. Res.20214692205222510.1007/s11064‑021‑03376‑0 34120291
     [Google Scholar]
  214. ChopraB. DhingraA.K. KapoorR.P. PrasadD.N. Piperine and its various physicochemical and biological aspects: A review.Open Chem. J.201631759610.2174/1874842201603010075
     [Google Scholar]
  215. AsgarshiraziM. ShariatM. SheikhM. Comparison of efficacy of folic acid and silymarin in the management of antiepileptic drug induced liver injury: A randomized clinical trial.Hepatobiliary Pancreat. Dis. Int.201716329630210.1016/S1499‑3872(16)60142‑X 28603098
     [Google Scholar]
  216. LevinJ. MaaßS. SchuberthM. Safety and efficacy of epigallocatechin gallate in multiple system atrophy (PROMESA): A randomised, double-blind, placebo-controlled trial.Lancet Neurol.201918872473510.1016/S1474‑4422(19)30141‑3 31278067
     [Google Scholar]
  217. ElkommosS. MulaM. Current and future pharmacotherapy options for drug-resistant epilepsy.Expert Opin. Pharmacother.202223182023203410.1080/14656566.2022.2128670 36154780
     [Google Scholar]
  218. DavidB. WolfenderJ.L. DiasD.A. The pharmaceutical industry and natural products: Historical status and new trends.Phytochem. Rev.201514229931510.1007/s11101‑014‑9367‑z
     [Google Scholar]
  219. MahimaK. KumarS.K.N. RakheshK.V. RajeswaranP.S. SharmaA. SathishkumarR. Advancements and future prospective of DNA barcodes in the herbal drug industry.Front. Pharmacol.20221394751210.3389/fphar.2022.947512 36339543
     [Google Scholar]
  220. NabaviSF BraidyN GortziO Luteolin as an anti-inflammatory and neuroprotective agent: A brief review.Brain Res Bull2015119Pt A11110.1016/j.brainresbull.2015.09.00226361743
     [Google Scholar]
  221. DereD.M. KhanA.A. Potentials of encapsulated flavonoids in biologics: A review.Am J Biomed Life Sci2020849710.11648/j.ajbls.20200804.16
     [Google Scholar]
  222. PaczkowskaM. McDonaghA.F. BialekK. TajberL. Cielecka-PiontekJ. Mechanochemical activation with cyclodextrins followed by compaction as an effective approach to improving dissolution of rutin.Int. J. Pharm.202058111929410.1016/j.ijpharm.2020.119294 32247814
     [Google Scholar]
  223. ShelyginY. KrivokapicZ. FrolovS.A. Clinical acceptability study of micronized purified flavonoid fraction 1000 mg tablets versus 500 mg tablets in patients suffering acute hemorrhoidal disease.Curr. Med. Res. Opin.201632111821182610.1080/03007995.2016.1211520 27404053
     [Google Scholar]
  224. PetersenB EgertS Bosy-WestphalA Bioavailability of quercetin in humans and the influence of food matrix comparing quercetin capsules and different apple sources.Food Res Int201688Pt A1596510.1016/j.foodres.2016.02.013 28847395
     [Google Scholar]
  225. TaliouA. ZintzarasE. LykourasL. FrancisK. An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders.Clin. Ther.201335559260210.1016/j.clinthera.2013.04.006 23688534
     [Google Scholar]
  226. GokhaleJ.P. MahajanH.S. SuranaS.J. Quercetin loaded nanoemulsion-based gel for rheumatoid arthritis: In vivo and in vitro studies.Biomed. Pharmacother.201911210862210.1016/j.biopha.2019.108622 30797146
     [Google Scholar]
  227. SguizzatoM. ValacchiG. PecorelliA. Gallic acid loaded poloxamer gel as new adjuvant strategy for melanoma: A preliminary study.Colloids Surf. B Biointerfaces202018511061310.1016/j.colsurfb.2019.110613 31715454
     [Google Scholar]
  228. RabidasS.S. PrakashC. TyagiJ. A comprehensive review on anti-inflammatory response of flavonoids in experimentally-induced epileptic seizures.Brain Sci.202313110210.3390/brainsci13010102 36672083
     [Google Scholar]
  229. ChenP. ChenF. GuoZ. LeiJ. ZhouB. Recent advancement in bioeffect, metabolism, stability, and delivery systems of apigenin, a natural flavonoid compound: Challenges and perspectives.Front. Nutr.202310122122710.3389/fnut.2023.1221227 37565039
     [Google Scholar]
  230. ShivaniS.G. SinghG. NarwalS. Balram ChopraB. DhingraA.K. Nano-formulations for the management of epilepsy: Synthetic and herbal drug perspectives.Curr. Nanomed.2024151510.2174/0124681873302617241018085244
     [Google Scholar]
  231. FerreiraM.D. DuarteJ. VeigaF. Paiva-SantosA.C. PiresP.C. Nanosystems for brain targeting of antipsychotic drugs: An update on the most promising nanocarriers for increased bioavailability and therapeutic efficacy.Pharmaceutics202315267810.3390/pharmaceutics15020678 36840000
     [Google Scholar]
  232. MokhtariT. SheikhbahaeiF. SaadatM. Nose-to-Brain Delivery of Nanoformulations for Treatment of Depression: Focus on Antioxidant and Anti-Inflammatory Pathways. New York: Advances in Medical Diagnosis, Treatment, and Care IGI Global ErisenD.E. UludagK. AhmadN. 2024245274
     [Google Scholar]
  233. SmoligaJ.M. VangO. BaurJ.A. Challenges of translating basic research into therapeutics: Resveratrol as an example.J. Gerontol. A Biol. Sci. Med. Sci.201267A215816710.1093/gerona/glr062 21746739
     [Google Scholar]
  234. MelroseJ. The potential of flavonoids and flavonoid metabolites in the treatment of neurodegenerative pathology in disorders of cognitive decline.Antioxidants202312366310.3390/antiox12030663 36978911
     [Google Scholar]
  235. BishnoiS. Herbs as Functional Foods.In: Functional Foods. BaraBocaSources and Health Benefits Scientific Publishers2016141172
     [Google Scholar]
  236. HuM. WuB. LiuZ. Bioavailability of polyphenols and flavonoids in the era of precision medicine.Mol. Pharm.20171492861286310.1021/acs.molpharmaceut.7b00545 28870081
     [Google Scholar]
  237. WuC.T. ChenM.C. LiuS.H. Bioactive flavonoids icaritin and icariin protect against cerebral ischemia–reperfusion-associated apoptosis and extracellular matrix accumulation in an ischemic stroke mouse model.Biomedicines2021911171910.3390/biomedicines9111719 34829948
     [Google Scholar]
  238. SpeiskyH. ShahidiF. Costa de CamargoA. FuentesJ. Revisiting the oxidation of flavonoids: Loss, conservation or enhancement of their antioxidant properties.Antioxidants202211113310.3390/antiox11010133 35052636
     [Google Scholar]
  239. BeheraP.C. SenapatiM.R. Oxidative stress and its management through phytoconstituents.In: Recent frontiers of phytochemicals.New YorkElsevier202348349910.1016/B978‑0‑443‑19143‑5.00014‑1
     [Google Scholar]
  240. ZhangX. WuC. In silico, in vitro, and in vivo evaluation of the developmental toxicity, estrogenic activity, and mutagenicity of four natural phenolic flavonoids at low exposure levels.ACS Omega2022764757476810.1021/acsomega.1c04239 35187296
     [Google Scholar]
  241. HasanS. KhatriN. RahmanZ.N. Neuroprotective potential of flavonoids in brain disorders.Brain Sci.2023139125810.3390/brainsci13091258 37759859
     [Google Scholar]
  242. BjørklundG. AntonyakH. PolishchukA. Effect of methylmercury on fetal neurobehavioral development: An overview of the possible mechanisms of toxicity and the neuroprotective effect of phytochemicals.Arch. Toxicol.202296123175319910.1007/s00204‑022‑03366‑3 36063174
     [Google Scholar]
  243. WhiteD.L. KanwalF. JiaoL. Epidemiology of Hepatocellular Carcinoma.Hepatocellular Carcinoma Springer International Publishing. CarrB.I. ChamSpringer201632410.1007/978‑3‑319‑34214‑6_1
     [Google Scholar]
  244. AsgharianP. QuispeC. Herrera-BravoJ. Pharmacological effects and therapeutic potential of natural compounds in neuropsychiatric disorders: An update.Front. Pharmacol.20221392660710.3389/fphar.2022.926607 36188551
     [Google Scholar]
  245. LöscherW. KleinP. New approaches for developing multi-targeted drug combinations for disease modification of complex brain disorders. Does epilepsy prevention become a realistic goal?Pharmacol. Ther.202222910793410.1016/j.pharmthera.2021.107934 34216705
     [Google Scholar]
  246. DajasF. AndresJ.A-C. FlorenciaA. Neuroprotective actions of flavones and flavonols: Mechanisms and relationship to flavonoid structural features.Cent. Nerv. Syst. Agents Med. Chem.20131313035
     [Google Scholar]
  247. StreetJ.S. QiuY. LignaniG. Are genetic therapies for epilepsy ready for the clinic?Epilepsy Curr.202323424525010.1177/15357597231176234 37662470
     [Google Scholar]
  248. MaanG. SikdarB. KumarA. ShuklaR. MishraA. Role of flavonoids in neurodegenerative diseases: Limitations and future perspectives.Curr. Top. Med. Chem.202020131169119410.2174/1568026620666200416085330 32297582
     [Google Scholar]
  249. Barker-HaliskiM. DePaula-SilvaA.B. PitschJ. Brain on Fire: How brain infection and neuroinflammation drive worldwide epilepsy burden.Epilepsy Curr.20241535759724124223810.1177/15357597241242238 39554268
     [Google Scholar]
  250. CostaB. ValeN. Virus-induced epilepsy vs. epilepsy patients acquiring viral infection: Unravelling the complex relationship for precision treatment.Int. J. Mol. Sci.2024257373010.3390/ijms25073730 38612542
     [Google Scholar]
/content/journals/cas/10.2174/0118746098369369250119112935
Loading
Recent Advances in Bioactive Flavonoids-based Nanotherapeutics as Promising Neuroprotectants in Epilepsy
Curr Aging Sci 18, 211 (2025); https://doi.org/10.2174/0118746098369369250119112935
/content/journals/cas/10.2174/0118746098369369250119112935
/content/journals/cas/10.2174/0118746098369369250119112935
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): clinical status; epilepsy; flavonoids; nanoformulations; Neuroprotective; seizure

Most Cited Most Cited RSS feed

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