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Volume 31, Issue 4
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Background and Objective

Alzheimer’s disease (AD) is an enervating and chronic progressive neurodegenerative disorder. Celecoxib (CXB) possesses efficacious antioxidants and has neuroprotective, anti-inflammatory, and immunomodulatory properties. However, the poor bioavailability of CXB limits its therapeutic utility. Thus, this study aimed to evaluate the microencapsulated celecoxib MCXB for neuroprotection.

Methodology

CXB was screened by molecular docking study using AutoDock (version 5.2), and the following proteins, such as 4EY7, 2HM1, 2Z5X, and 1PBQ were selected for predicting its neuroprotective effect. Scopolamine 20 mg/kg/day for approximately 7 days was administered to albino rats. Pure CXB 100 mg/kg/day and 200 mg/kg/day, and MCXB 100 mg/kg/day and 200 mg/kg/day were administered, respectively. Further, to assess the oxidative stress, the nitric oxide (NO), superoxide dismutase (SOD), catalase, and lipid peroxidation (LPO) were evaluated using chemical methods. The neurochemical biomarkers like AChE, glutamate, and dopamine were evaluated using the ELISA method. Further, the histopathology of brain cells was carried out to assess the neuro-regeneration and neurodegeneration of the neurons.

Results

There was a significant binding interaction of CXB (score -6.3, -6.5, -5.1, -9.1) and donepezil (score-5.5, -7.6, -7.0, and -8.6) with AchE (4EY7), β-secretase (2HM1, monoamine oxidase (2Z5X), and glutamate (1PBQ), respectively. MCXB-treated rats (100 mg/kg/day, 200 mg/kg/day) showed increased SOD levels ( 0.001), whereas NO, catalase, and LPO levels were significantly ( 0.001) decreased as compared to scopolamine-treated rats. Further, MCXB-treated rats showed a modulatory effect in the level of dopamine and AchE. However, the glutamate level was significantly ( 0.001) decreased.

Conclusion

In addition to that, histopathological examination of the hippocampus part showed remarkable improvement in brain cells. So, the findings of the results revealed that MCXB, in a dose-dependent manner, showed a neuroprotective effect against scopolamine-induced AD. This effect may be attributed to the activation of cholinergic pathways.

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2025-01-28

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References

  1. Sepúlveda-LoyolaW. Rodríguez-SánchezI. Pérez-RodríguezP. GanzF. TorralbaR. OliveiraD.V. Rodríguez-MañasL. Impact of social isolation due to COVID-19 on health in older people: Mental and physical effects and recommendations.J. Nutr. Health Aging202024993894710.1007/s12603‑020‑1500‑733155618
     [Google Scholar]
  2. SouderE. BeckC. Overview of Alzheimer’s disease.Nurs. Clin. North Am.200439354555910.1016/j.cnur.2004.02.01015331301
     [Google Scholar]
  3. HuangL.K. ChaoS.P. HuC.J. Clinical trials of new drugs for Alzheimer disease.J. Biomed. Sci.20202711810.1186/s12929‑019‑0609‑731906949
     [Google Scholar]
  4. NicholsE. SzoekeC.E.I. VollsetS.E. AbbasiN. Abd-AllahF. AbdelaJ. AichourM.T.E. AkinyemiR.O. AlahdabF. AsgedomS.W. AwasthiA. Barker-ColloS.L. BauneB.T. BéjotY. BelachewA.B. BennettD.A. BiadgoB. BijaniA. Bin SayeedM.S. BrayneC. CarpenterD.O. CarvalhoF. Catalá-LópezF. CerinE. ChoiJ-Y.J. DangA.K. DegefaM.G. DjalaliniaS. DubeyM. DukenE.E. EdvardssonD. EndresM. EskandariehS. FaroA. FarzadfarF. FereshtehnejadS-M. FernandesE. FilipI. FischerF. GebreA.K. GeremewD. Ghasemi-KasmanM. GnedovskayaE.V. GuptaR. HachinskiV. HagosT.B. HamidiS. HankeyG.J. HaroJ.M. HayS.I. IrvaniS.S.N. JhaR.P. JonasJ.B. KalaniR. KarchA. KasaeianA. KhaderY.S. KhalilI.A. KhanE.A. KhannaT. KhojaT.A.M. KhubchandaniJ. KisaA. Kissimova-SkarbekK. KivimäkiM. KoyanagiA. KrohnK.J. LogroscinoG. LorkowskiS. MajdanM. MalekzadehR. MärzW. MassanoJ. MengistuG. MeretojaA. MohammadiM. Mohammadi-KhanaposhtaniM. MokdadA.H. MondelloS. MoradiG. NagelG. NaghaviM. NaikG. NguyenL.H. NguyenT.H. NirayoY.L. NixonM.R. Ofori-AsensoR. OgboF.A. OlagunjuA.T. OwolabiM.O. Panda-JonasS. PassosV.M.A. PereiraD.M. Pinilla-MonsalveG.D. PiradovM.A. PondC.D. PoustchiH. QorbaniM. RadfarA. ReinerR.C.Jr RobinsonS.R. RoshandelG. RostamiA. RussT.C. SachdevP.S. SafariH. SafiriS. SahathevanR. SalimiY. SatpathyM. SawhneyM. SaylanM. SepanlouS.G. ShafieesabetA. ShaikhM.A. SahraianM.A. ShigematsuM. ShiriR. ShiueI. SilvaJ.P. SmithM. SobhaniS. SteinD.J. Tabarés-SeisdedosR. Tovani-PaloneM.R. TranB.X. TranT.T. TsegayA.T. UllahI. VenketasubramanianN. VlassovV. WangY-P. WeissJ. WestermanR. WijeratneT. WyperG.M.A. YanoY. YimerE.M. YonemotoN. YousefifardM. ZaidiZ. ZareZ. VosT. FeiginV.L. MurrayC.J.L. GBD 2016 Dementia Collaborators Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol.20191818810610.1016/S1474‑4422(18)30403‑430497964
     [Google Scholar]
  5. BreijyehZ. KaramanR. Comprehensive review on Alzheimer’s disease: Causes and treatment.Molecules20202524578910.3390/molecules2524578933302541
     [Google Scholar]
  6. PasseriE. ElkhouryK. MorsinkM. BroersenK. LinderM. TamayolA. MalaplateC. YenF.T. Arab-TehranyE. Alzheimer’s disease: Treatment strategies and their limitations.Int. J. Mol. Sci.202223221395410.3390/ijms23221395436430432
     [Google Scholar]
  7. HolickaM. MuselíkJ. KubovaK. DeakovaV. PavlokovaS. PavelkovaM. MasekJ. VetchyD VyslouzilJ Influence of emulsification mode, stirring speed and volume on ibuprofen-loaded plga microparticles.Ceska a Slovenska Farmacie20217013240
     [Google Scholar]
  8. GopaiahK.V. ReddyP.S. NamballaM. Formulation and characterization of mucoadhesive microspheres of aceclofenac.Res. J. Pharm. Technol.2022153981988
     [Google Scholar]
  9. AlhnanM.A. BasitA.W. In-process crystallization of acidic drugs in acrylic microparticle systems: Influence of physical factors and drug-polymer interactions.J. Pharm. Sci.201110083284329310.1002/jps.2257221500197
     [Google Scholar]
  10. Tomaro-DuchesneauC. SahaS. MalhotraM. KahouliI. PrakashS. Microencapsulation for the therapeutic delivery of drugs, live mammalian and bacterial cells, and other biopharmaceutics: Current status and future directions.J. Pharm.2013201311910.1155/2013/10352726555963
     [Google Scholar]
  11. JeeJ.P. YangD.A. KimS.T. KangD. KimD.Y. Improved dissolution and oral bioavailability of celecoxib by a dry elixir system.J. Nanosci. Nanotechnol.20181814821486
     [Google Scholar]
  12. PonnammalP. KanaujiaP. YaniY. NgW. TanR. Orally disintegrating tablets containing melt extruded amorphous solid dispersion of tacrolimus for dissolution enhancement.Pharmaceutics20181013510.3390/pharmaceutics1001003529547585
     [Google Scholar]
  13. MurphyM.P. LeVineH.III Alzheimer’s disease and the amyloid-β peptide.J. Alzheimers Dis.201019131132310.3233/JAD‑2010‑122120061647
     [Google Scholar]
  14. KumarS. ChowdhuryS. KumarS. In silico repurposing of antipsychotic drugs for Alzheimer’s disease.BMC Neurosci.20171817610.1186/s12868‑017‑0394‑829078760
     [Google Scholar]
  15. SonS.Y. MaJ. KondouY. YoshimuraM. YamashitaE. TsukiharaT. Structure of human monoamine oxidase A at 2.2-Å resolution: The control of opening the entry for substrates/inhibitors.Proc. Natl. Acad. Sci.2008105155739574410.1073/pnas.071062610518391214
     [Google Scholar]
  16. ButterfieldD.A. PocernichC.B. The glutamatergic system and Alzheimer’s disease: Therapeutic implications.CNS Drugs200317964165210.2165/00023210‑200317090‑0000412828500
     [Google Scholar]
  17. VishnumurthyR.M. Microencapsulation of celecoxib A promising tool enhance solubility against neurodegenerative diseases.Int. J. Health Sci.20226S666476662
     [Google Scholar]
  18. CheungJ. RudolphM.J. BurshteynF. CassidyM.S. GaryE.N. LoveJ. FranklinM.C. HeightJ.J. Structures of human acetylcholinesterase in complex with pharmacologically important ligands.J. Med. Chem.20125522102821028610.1021/jm300871x23035744
     [Google Scholar]
  19. ZhangY. LiP. FengJ. WuM. Dysfunction of NMDA receptors in Alzheimer’s disease.Neurol. Sci.20163771039104710.1007/s10072‑016‑2546‑526971324
     [Google Scholar]
  20. ShelleyJ.C. CholletiA. FryeL.L. GreenwoodJ.R. TimlinM.R. UchimayaM. Epik: A software program for pK a prediction and protonation state generation for drug-like molecules.J. Comput. Aided Mol. Des.2007211268169110.1007/s10822‑007‑9133‑z17899391
     [Google Scholar]
  21. BaraiP. RavalN. AcharyaS. AcharyaN. Bergenia ciliata ameliorates streptozotocin-induced spatial memory deficits through dual cholinesterase inhibition and attenuation of oxidative stress in rats.Biomed. Pharmacother.201810296698010.1016/j.biopha.2018.03.11529710552
     [Google Scholar]
  22. Abdel-AalR. HusseinO. ElsaadyR. AbdelzaherL. Celecoxib effect on rivastigmine anti-Alzheimer activity against aluminum chloride-induced neurobehavioral deficits as a rat model of Alzheimer’s disease; Novel perspectives for an old drug.J Med Life Sci202134448210.21608/jmals.2021.210630
     [Google Scholar]
  23. SimsN.R. BowenD.M. AllenS.J. SmithC.C.T. NearyD. ThomasD.J. DavisonA.N. Presynaptic cholinergic dysfunction in patients with dementia.J. Neurochem.198340250350910.1111/j.1471‑4159.1983.tb11311.x6822833
     [Google Scholar]
  24. PiubelliL. Murtas1G. RabattoniV. The role of D-amino acids in Alzheimer’s disease.J. Alzheimers Dis.202180475492
     [Google Scholar]
  25. MaitiP. SinghS.B. IlavazhaganG. Nitric oxide system is involved in hypobaric hypoxia-induced oxidative stress in rat brain.Acta Histochem.2010112322223210.1016/j.acthis.2008.10.00519428054
     [Google Scholar]
  26. ĎurfinováM. BrechtlováM. LíškaB. BaroškováŽ. Comparison of spectrophotometric and HPLC methods for determination of lipid peroxidation products in rat brain tissues.Chem. Pap.200761432132510.2478/s11696‑007‑0040‑5
     [Google Scholar]
  27. GaurV. AggarwalA. KumarA. Protective effect of naringin against ischemic reperfusion cerebral injury: Possible neurobehavioral, biochemical and cellular alterations in rat brain.Eur. J. Pharmacol.20096161-314715410.1016/j.ejphar.2009.06.05619577560
     [Google Scholar]
  28. RezgR. MornaguiB. El-FazaaS. GharbiN. Biochemical evaluation of hepatic damage in subchronic exposure to malathion in rats: Effect on superoxide dismutase and catalase activities using native PAGE.C. R. Biol.2008331965566210.1016/j.crvi.2008.06.00418722984
     [Google Scholar]
  29. KhalidS. ZahidM.A. AliH. Biaryl scaffold-focused virtual screening for anti-aggregatory and neuroprotective effects in Alzheimer’s disease.BMC Neurosci2018197410.1186/s12868‑018‑0472‑6
     [Google Scholar]
  30. Bossy-WetzelE. SchwarzenbacherR. LiptonS.A. Molecular pathways to neurodegeneration.Nat. Med.200410S7Suppl.S2S910.1038/nm106715272266
     [Google Scholar]
  31. García-AyllónM.S. SmallD.H. AvilaJ. Sáez-ValeroJ. Revisiting the role of acetylcholinesterase in Alzheimer’s disease: Cross-talk with P-tau and β-amyloid.Front. Mol. Neurosci.201142210.3389/fnmol.2011.0002221949503
     [Google Scholar]
  32. HafezH.S. GhareebD.A. SalehS.R. AbadyM.M. El DemellawyM.A. HussienH. Abdel-MonemN. Neuroprotective effect of ipriflavone against scopolamine-induced memory impairment in rats.Psychopharmacology2017234203037305310.1007/s00213‑017‑4690‑x28733814
     [Google Scholar]
  33. RahimzadeganM. SoodiM. Comparison of memory impairment and oxidative stress following single or repeated doses administration of scopolamine in rat hippocampus.Basic Clin. Neurosci.20189151410.29252/nirp.bcn.9.1.529942435
     [Google Scholar]
  34. HerholzK. Acetylcholine esterase activity in mild cognitive impairment and Alzheimer’s disease.Eur. J. Nucl. Med. Mol. Imaging200735Suppl 1S25S2918196237
     [Google Scholar]
  35. DanyszW. ParsonsC.G. MÖbiusH.J.Ö. StÖfflerA. QuackG.Ü. Neuroprotective and symptomatological action of memantine relevant for Alzheimer’s disease - a unified glutamatergic hypothesis on the mechanism of action.Neurotox. Res.200022-3859710.1007/BF0303378716787834
     [Google Scholar]
  36. LesterD.B. RogersT.D. BlahaC.D. Acetylcholine-dopamine interactions in the pathophysiology and treatment of CNS disorders.CNS Neurosci. Ther.201016313716210.1111/j.1755‑5949.2010.00142.x20370804
     [Google Scholar]
  37. KangralkarV.A. PatilS.D. BandivadekarR.M. Oxidative stress, and diabetes: A review.Intl J Pharm Appl.201013845
     [Google Scholar]
  38. BottiG. BianchiA. PavanB. TedeschiP. AlbaneseV. FerraroL. SpizzoF. Del BiancoL. DalpiazA. Effects of microencapsulated ferulic acid or its prodrug methyl ferulate on neuroinflammation induced by muramyl dipeptide.Int. J. Environ. Res. Public Health202219171060910.3390/ijerph19171060936078325
     [Google Scholar]
/content/journals/cpd/10.2174/0113816128298289240723103828
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In-silico Studies and Antioxidant and Neuroprotective Assessment of Microencapsulated Celecoxib against Scopolamine-induced Alzheimer’s Disease
Curr. Pharm. Des. 31, 320 (2025); https://doi.org/10.2174/0113816128298289240723103828
/content/journals/cpd/10.2174/0113816128298289240723103828
/content/journals/cpd/10.2174/0113816128298289240723103828
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  • Article Type:     Research Article
Keyword(s): Alzheimer’s disease; celecoxib; Microencapsulation; molecular docking, antioxidant, neurodegenerative disorder

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