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2000
Volume 24, Issue 7
  • ISSN: 1871-5273
  • E-ISSN: 1996-3181

Abstract

Introduction

Memory loss and cognitive decline are prominent symptoms of various neurodegenerative diseases, impacting daily activities and posing a significant burden on healthcare systems. The study aimed to explore the effect of barbigerone against LPS-induced memory impairment in rats and may offer novel therapeutics for neurodegenerative diseases.

Methods

A total of 30 male Wistar rats were utilized and subsequently divided into five distinct experimental groups: group I received saline as a control, group II- received LPS, group III -received LPS, and barbigerone (10 mg/kg/p.o.), group IV- received LPS and a higher dose of barbigerone (20 mg/kg/p.o.), and group V -barbigerone alone (20 mg/kg/p.o.). Behavioural test was performed through the Morris water maze (MWM) and Y-maze test. Biochemical markers such as oxidative, proinflammatory, apoptotic, and further molecular docking and simulations elucidate the mechanisms of barbigerone effects.

Results

Barbigerone significantly improved the learning capacity of rats in both the MWM and Y-maze tests, indicating enhanced memory and reduced latency times. Furthermore, barbigerone exhibited beneficial effects on oxidative stress and inflammation markers, suggesting its potential to protect against neuronal damage and promote cognitive function. Based on molecular docking, barbigerone showed a greater binding affinity with different intermolecular interactions; among them, NF-KB (ISVC) had the most potent interaction. Molecular dynamics simulations were performed to assess the stability and convergence of complexes formed by Barbigerone with 1NME_ Barbigerone, 1SVC_Barbigerone, and 4AQ3 4AQ3_Barbigerone.

Conclusion

These findings demonstrate that barbigerone possesses neuronal protective effects against LPS-induced memory deficits in rats by restoring endogenous antioxidant and pro-inflammatory cytokines.

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2025-02-10
2025-09-06

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References

  1. ZakariaR. Wan YaacobW.M.H. OthmanZ. LongI. AhmadA.H. Al-RahbiB. Lipopolysaccharide-induced memory impairment in rats: A model of Alzheimer’s disease.Physiol. Res.201766455356510.33549/physiolres.933480 28406691
     [Google Scholar]
  2. ThingoreC. KshirsagarV. JuvekarA. Amelioration of oxidative stress and neuroinflammation in lipopolysaccharide-induced memory impairment using Rosmarinic acid in mice.Metab. Brain Dis.202136229931310.1007/s11011‑020‑00629‑9 33068223
     [Google Scholar]
  3. RodríguezJ.J. ButtA.M. GardenalE. ParpuraV. VerkhratskyA. Complex and differential glial responses in Alzheimer’s disease and ageing.Curr. Alzheimer Res.201613434335810.2174/1567205013666160229112911 26923267
     [Google Scholar]
  4. ChoiJ.Y. HwangC.J. LeeH.P. KimH.S. HanS.B. HongJ.T. Inhibitory effect of ethanol extract of Nannochloropsis oceanica on lipopolysaccharide-induced neuroinflammation, oxidative stress, amyloidogenesis and memory impairment.Oncotarget2017828455174553010.18632/oncotarget.17268 28489589
     [Google Scholar]
  5. ZhaoY. LiQ. NiuJ. Neutrophil membrane‐camouflaged polyprodrug nanomedicine for inflammation suppression in ischemic stroke therapy.Adv. Mater.20243621231180310.1002/adma.202311803 38519052
     [Google Scholar]
  6. DiSabatoD.J. QuanN. GodboutJ.P. Neuroinflammation: The devil is in the details.J. Neurochem.2016139S2Suppl. 213615310.1111/jnc.13607 26990767
     [Google Scholar]
  7. HwangC.J. ParkM.H. HwangJ.Y. CCR5 deficiency accelerates lipopolysaccharide-induced astrogliosis, amyloid-beta deposit and impaired memory function.Oncotarget2016711119841199910.18632/oncotarget.7453 26910914
     [Google Scholar]
  8. SayyedN. HafeezA. Al-AbbasiF.A. Erucic acid ameliorates the lipopolysaccharide‐induced memory deficit in rats through inhibited inflammation cytokines expression/caspase 3/NF‐κB pathways.Eur. J. Lipid Sci. Technol.20231259220020510.1002/ejlt.202200205
     [Google Scholar]
  9. AlshehriS. ImamS.S. Rosinidin attenuates lipopolysaccharide-induced memory impairment in rats: Possible mechanisms of action include antioxidant and anti-inflammatory effects.Biomolecules20211112174710.3390/biom11121747 34944391
     [Google Scholar]
  10. ZhouJ. YuW. ZhangM. TianX. LiY. LüY. Imbalance of microglial TLR4/TREM2 in LPS-treated APP/PS1 transgenic mice: A potential link between Alzheimer’s disease and systemic inflammation.Neurochem. Res.20194451138115110.1007/s11064‑019‑02748‑x 30756214
     [Google Scholar]
  11. ZhaoJ. BiW. XiaoS. Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice.Sci. Rep.201991579010.1038/s41598‑019‑42286‑8 30962497
     [Google Scholar]
  12. GaltsC.P.C. BettioL.E.B. JewettD.C. Depression in neurodegenerative diseases: Common mechanisms and current treatment options.Neurosci. Biobehav. Rev.2019102568410.1016/j.neubiorev.2019.04.002 30995512
     [Google Scholar]
  13. LampteyR.N.L. ChaulagainB. TrivediR. GothwalA. LayekB. SinghJ. A review of the common neurodegenerative disorders: Current therapeutic approaches and the potential role of nanotherapeutics.Int. J. Mol. Sci.2022233185110.3390/ijms23031851 35163773
     [Google Scholar]
  14. WangJ. SongY. ChenZ. LengS.X. Connection between systemic inflammation and neuroinflammation underlies neuroprotective mechanism of several phytochemicals in neurodegenerative diseases.Oxid. Med. Cell. Longev.201820181197271410.1155/2018/1972714 30402203
     [Google Scholar]
  15. LiuY. SiZ-Z. ZouC-J. Targeting neuroinflammation in Alzheimer’s disease: From mechanisms to clinical applications.Neural Regen. Res.202318470871510.4103/1673‑5374.353484 36204826
     [Google Scholar]
  16. El-Saber BatihaG. AlkazmiL.M. WasefL.G. BeshbishyA.M. NadwaE.H. RashwanE.K. Syzygium aromaticum L.(Myrtaceae): Traditional uses, bioactive chemical constituents, pharmacological and toxicological activities.Biomolecules202010220210.3390/biom10020202 32019140
     [Google Scholar]
  17. AkhtarM. SwamyM. SinniahU. Saboon, Chaudhari SK, Arshad S, Amjad MS, Akhtar MS. Natural compounds extracted from medicinal plants and their applications.Natural Bio-active Compounds.SingaporeSpringer201910.1007/978‑981‑13‑7154‑7_7
     [Google Scholar]
  18. AyazM. SadiqA. JunaidM. Flavonoids as prospective neuroprotectants and their therapeutic propensity in aging associated neurological disorders.Front. Aging Neurosci.20191115510.3389/fnagi.2019.00155 31293414
     [Google Scholar]
  19. KimY.E. HwangC.J. LeeH.P. Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB.Neuropharmacology2017117213210.1016/j.neuropharm.2017.01.025 28132781
     [Google Scholar]
  20. YangJ.H. HuJ. WanL. ChenL.J. Barbigerone inhibits tumor angiogenesis, growth and metastasis in melanoma.Asian Pac. J. Cancer Prev.201415116717410.7314/APJCP.2014.15.1.167 24528020
     [Google Scholar]
  21. YanW. LiY. LiuY. Crystal structure of tubulin-barbigerone complex enables rational design of potent anticancer agents with isoflavone skeleton.Phytomedicine202310915455010.1016/j.phymed.2022.154550 36610121
     [Google Scholar]
  22. AlharthyK.M. AlthurwiH.N. AlbaqamiF.F. Barbigerone potentially alleviates rotenone-activated Parkinson’s disease in a rodent model by reducing oxidative stress and neuroinflammatory cytokines.ACS Omega2023854608461510.1021/acsomega.2c05837 36777578
     [Google Scholar]
  23. AlGhamdiS.A. Al-AbbasiF.A. AlghamdiA.M. Barbigerone prevents scopolamine-induced memory impairment in rats by inhibiting oxidative stress and acetylcholinesterase levels.R. Soc. Open Sci.202310423001310.1098/rsos.230013 37063992
     [Google Scholar]
  24. GalassiF. AlkhalilM. LeeR. 3D reconstruction of coronary arteries from 2D angiographic projections using non-uniform rational basis splines (NURBS) for accurate modelling of coronary stenoses.PLoS One2018131e019065010.1371/journal.pone.0190650 29298341
     [Google Scholar]
  25. OmerA.B. Al-AbbasiF.A. AlGhamdiS.A. Protective effect of barbigerone against ethanol-induced ulcers via the interleukins/ICAM-1/Bcl-2 pathway.Eur. Rev. Med. Pharmacol. Sci.202327241202912042 38164865
     [Google Scholar]
  26. LiX. WangX. YeH. PengA. ChenL. Barbigerone, an isoflavone, inhibits tumor angiogenesis and human non-small-cell lung cancer xenografts growth through VEGFR2 signaling pathways.Cancer Chemother. Pharmacol.201270342543710.1007/s00280‑012‑1923‑x 22814678
     [Google Scholar]
  27. KhaliliM. AlaviM. Esmaeil-JamaatE. BaluchnejadmojaradT. RoghaniM. Trigonelline mitigates lipopolysaccharide-induced learning and memory impairment in the rat due to its anti-oxidative and anti-inflammatory effect.Int. Immunopharmacol.20186135536210.1016/j.intimp.2018.06.019 29935483
     [Google Scholar]
  28. ChowdhuryA.A. GawaliN.B. ShindeP. MunshiR. JuvekarA.R. Imperatorin ameliorates lipopolysaccharide induced memory deficit by mitigating proinflammatory cytokines, oxidative stress and modulating brain-derived neurotropic factor.Cytokine2018110788610.1016/j.cyto.2018.04.018 29705395
     [Google Scholar]
  29. MirahmadiS.M.S. ShahmohammadiA. RoustaA.M. Soy isoflavone genistein attenuates lipopolysaccharide-induced cognitive impairments in the rat via exerting anti-oxidative and anti-inflammatory effects.Cytokine201810415115910.1016/j.cyto.2017.10.008 29102164
     [Google Scholar]
  30. BermanH.M. WestbrookJ. FengZ. The protein data bank.Nucleic Acids Res.200028123524210.1093/nar/28.1.235 10592235
     [Google Scholar]
  31. PettersenE.F. GoddardT.D. HuangC.C. UCSF Chimera—A visualization system for exploratory research and analysis.J. Comput. Chem.200425131605161210.1002/jcc.20084 15264254
     [Google Scholar]
  32. MorrisG.M. HueyR. LindstromW. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility.J. Comput. Chem.200930162785279110.1002/jcc.21256 19399780
     [Google Scholar]
  33. SchrödingerL. Schrödinger Release 2022-3: LigPrep.New York, NY, USASchrödinger, LLC2021
     [Google Scholar]
  34. TianW. ChenC. LeiX. ZhaoJ. LiangJ. CASTp 3.0: Computed atlas of surface topography of proteins.Nucleic Acids Res.201846W1W363-710.1093/nar/gky473 29860391
     [Google Scholar]
  35. EberhardtJ. Santos-MartinsD. TillackA.F. ForliS. AutoDock Vina 1.2. 0: New docking methods, expanded force field, and python bindings.J. Chem. Inf. Model.20216183891389810.1021/acs.jcim.1c00203 34278794
     [Google Scholar]
  36. TrottO. OlsonA.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.J. Comput. Chem.201031245546110.1002/jcc.21334 19499576
     [Google Scholar]
  37. BioviaD.S. Discovery Studio Visualizer v21 10 20298.San DiegoDassault Systèmes2021
     [Google Scholar]
  38. WallaceA.C. LaskowskiR.A. ThorntonJ.M. LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions.Protein Eng. Des. Sel.19958212713410.1093/protein/8.2.127 7630882
     [Google Scholar]
  39. HritcuL. ClicinschiM. NabeshimaT. Brain serotonin depletion impairs short-term memory, but not long-term memory in rats.Physiol. Behav.200791565265710.1016/j.physbeh.2007.03.028 17481676
     [Google Scholar]
  40. ConradC.D. LupienS.J. ThanasoulisL.C. McEwenB.S. The effects of Type I and Type II corticosteroid receptor agonists on exploratory behavior and spatial memory in the Y-maze.Brain Res.19977591768310.1016/S0006‑8993(97)00236‑9 9219865
     [Google Scholar]
  41. PrieurE.A.K. JadavjiN.M. Assessing spatial working memory using the spontaneous alternation Y-maze test in aged male mice.Bio Protoc.201993e316210.21769/BioProtoc.3162 33654968
     [Google Scholar]
  42. Ferreira-VieiraT.H. GuimaraesI.M. SilvaF.R. RibeiroF.M. Alzheimer’s disease: Targeting the cholinergic system.Curr. Neuropharmacol.2016141101115 26813123
     [Google Scholar]
  43. ChenZ.R. HuangJ.B. YangS.L. HongF.F. Role of cholinergic signaling in Alzheimer’s disease.Molecules2022276181610.3390/molecules27061816 35335180
     [Google Scholar]
  44. MassaadC.A. KlannE. Reactive oxygen species in the regulation of synaptic plasticity and memory.Antioxid. Redox Signal.201114102013205410.1089/ars.2010.3208 20649473
     [Google Scholar]
  45. PrietoG.A. TongL. SmithE.D. CotmanC.W. TNFα and IL-1β but not IL-18 suppresses hippocampal long-term potentiation directly at the synapse.Neurochem. Res.2019441496010.1007/s11064‑018‑2517‑8 29619614
     [Google Scholar]
  46. CarnielB.P. da RochaN.S. Brain-derived neurotrophic factor (BDNF) and inflammatory markers: Perspectives for the management of depression.Prog. Neuropsychopharmacol. Biol. Psychiatry202110811015110.1016/j.pnpbp.2020.110151 33096156
     [Google Scholar]
  47. MirandaM. MoriciJ.F. ZanoniM.B. BekinschteinP. Brain-derived neurotrophic factor: A key molecule for memory in the healthy and the pathological brain.Front. Cell. Neurosci.20191336310.3389/fncel.2019.00363 31440144
     [Google Scholar]
  48. McIlwainD.R. BergerT. MakT.W. Caspase functions in cell death and disease.Cold Spring Harb. Perspect. Biol.201354a00865610.1101/cshperspect.a008656 23545416
     [Google Scholar]
  49. BrentnallM. Rodriguez-MenocalL. De GuevaraR.L. CeperoE. BoiseL.H. Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis.BMC Cell Biol.20131413210.1186/1471‑2121‑14‑32 23834359
     [Google Scholar]
  50. BathinaS. DasU.N. Brain-derived neurotrophic factor and its clinical implications.Arch. Med. Sci.2015661164117810.5114/aoms.2015.56342 26788077
     [Google Scholar]
  51. KunacN. FilipovićN. KostićS. VukojevićK. The expression pattern of Bcl-2 and Bax in the tumor and stromal cells in colorectal carcinoma.Medicina (Kaunas)2022588113510.3390/medicina58081135 36013602
     [Google Scholar]
  52. Al-AbbasiF.A. Potential antidiabetic activity of barbigerone on glucose and inflammatory cytokine levels in streptozotocin activated diabetic rats.J. King Saud Univ. Sci.202234710224910.1016/j.jksus.2022.102249
     [Google Scholar]
  53. KerdilesO. LayéS. CalonF. Omega-3 polyunsaturated fatty acids and brain health: Preclinical evidence for the prevention of neurodegenerative diseases.Trends Food Sci. Technol.20176920321310.1016/j.tifs.2017.09.003
     [Google Scholar]
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Barbigerone against Lipopolysaccharide-Induced Memory Deficit in Rats via Alteration of Inflammatory and Oxidative Stress Pathway: In vivo, Molecular Docking and Molecular Dynamics Simulations Study
CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 24, 554 (2025); https://doi.org/10.2174/0118715273332347250122112850
/content/journals/cnsnddt/10.2174/0118715273332347250122112850
/content/journals/cnsnddt/10.2174/0118715273332347250122112850
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  • Article Type:     Research Article
Keyword(s): Alzheimer’s disease; cognitive dysfunction; learning; lipopolysaccharides; memory; neuroinflammation; oxidative stress

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