Skip to content
2000
Volume 23, Issue 3
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

Background

Alzheimer's disease (AD) is a neurodegenerative condition that affects the elder population and is linked to behavioral instability and cognitive decline. Only a few drugs are approved for clinical management of AD. Volatile oils and their components exhibit diverse pharmacological potentials, including neuroprotective properties. The current study aimed to evaluate isoeugenol's neuroprotective potentials against cognitive impairments caused by scopolamine.

Methods

Standard protocols were followed in the antioxidant, cholinesterase inhibitory and molecular docking assays. Isoeugenol was initially evaluated for antioxidant potential using DPPH and ABTS free radicals scavenging assays. Subsequently, AChE/BChE inhibition studies were performed following Ellman’s assay. To assess the compound's binding effectiveness at the enzymes' target site, it was docked against the binding sites of cholinesterase. The effect of isoeugenol supplementation on scopolamine-induced amnesia was assessed using Shallow Water Maze (SWM), Y-Maze and Elevated Plus Maze (EPM) tests.

Results

In DPPH and ABTS assays, isoeugenol exhibited considerable efficacy against free radicals with IC of 38.97 and 43.76 μg/mL, respectively. Isoeugenol revealed 78.39 ± 0.40% and 67.73 ± 0.03% inhibitions against AChE and BChE, respectively, at 1 mg/ml concentration. In docking studies, isoeugenol exhibited a docking score of -12.2390, forming two hydrogen bonds at the active site residues of AChE. Further, with a docking score of -10.1632, isoeugenol binds adequately to the BChE enzyme two arene-hydrogen interactions and one hydrogen bond.

Conclusion

Isoeugenol offered considerable protection against scopolamine-induced memory deficits and improved the special memory of the rodents.

Loading

Article metrics loading...

/content/journals/cn/10.2174/1570159X22666240329125626
2024-04-24
2025-01-18
Loading full text...

Full text loading...

References

  1. AlamW. HussainY. AhmadS. AliA. KhanH. Neuroprotective effect of essential oils. In: Phytonutrients and Neurological Disorders Therapeutic and Toxicological Aspects.Academic Press2023305333
    [Google Scholar]
  2. AlharthyK. BalahaM. DeviS. AltharawiA. YusufogluH. AldossariR. AlamA. GiacomoD.V. Ameliorative effects of isoeugenol and eugenol against impaired nerve function and inflammatory and oxidative mediators in diabetic neuropathic rats.Biomedicines2023114120310.3390/biomedicines11041203 37189822
    [Google Scholar]
  3. Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures.Alzheimers Dement.201612445950910.1016/j.jalz.2016.03.001 27570871
    [Google Scholar]
  4. AyazM. JunaidM. UllahF. SubhanF. SadiqA. AliG. OvaisM. ShahidM. AhmadA. WadoodA. El-ShazlyM. AhmadN. AhmadS. Anti-Alzheimer’s studies on β-sitosterol isolated from Polygonum hydropiper L.Front. Pharmacol.20178869710.3389/fphar.2017.00697 29056913
    [Google Scholar]
  5. AyazM. NawazA. NazF. UllahF. SadiqA. Ul IslamZ. Phytochemicals-based therapeutics against Alzheimer’s disease: An update.Curr. Top. Med. Chem.202222221811182010.2174/1568026622666220815104305 36029077
    [Google Scholar]
  6. BaiX. YanC. YangG. LuP. MaD. SunL. ZhouR. ScheresS.H.W. ShiY. An atomic structure of human γ-secretase.Nature2015525756821221710.1038/nature14892 26280335
    [Google Scholar]
  7. ButterfieldD.A. GriffinS. MunchG. PasinettiG.M. Amyloid β-peptide and amyloid pathology are central to the oxidative stress and inflammatory cascades under which Alzheimer’s disease brain exists.J. Alzheimers Dis.20024319320110.3233/JAD‑2002‑4309 12226538
    [Google Scholar]
  8. ChangC.C. ChangC-Y. HuangJ-P. HungL-M. Effect of resveratrol on oxidative and inflammatory stress in liver and spleen of streptozotocin-induced type 1 diabetic rats.Chin. J. Physiol.201255319220110.4077/CJP.2012.BAA012 22784284
    [Google Scholar]
  9. ChenW.N. YeongK.Y. Scopolamine, a toxin-induced experimental model, used for research in Alzheimer’s disease.CNS Neurol. Disord. Drug Targets2020192859310.2174/1871527319666200214104331 32056532
    [Google Scholar]
  10. ColombresM. SagalJ. InestrosaN. An overview of the current and novel drugs for Alzheimer’s disease with particular reference to anti-cholinesterase compounds.Curr. Pharm. Des.200410253121313010.2174/1381612043383359 15544502
    [Google Scholar]
  11. da CostaI.M. PedrosaE.C.G.A. de BezerraC.A.P. FernandesL.C.B. de CavalcantiP.J.R.L. FreireM.A.M. de AraújoD.P. do RegoA.C.M. FilhoA.I. PinheiroF.I. Extracts and essential oils from medicinal plants and their neuroprotective effect. In: Neuroprotection- New Approaches and Prospects; IntechOpen, 2020
    [Google Scholar]
  12. DeaconR.M. Shallow water (paddling) variants of water maze tests in mice.J. Vis. Exp.201376e2608 23770614
    [Google Scholar]
  13. EllmanG.L. CourtneyK.D. AndresV.Jr FeatherstoneR.M. A new and rapid colorimetric determination of acetylcholinesterase activity.Biochem. Pharmacol.196172889510.1016/0006‑2952(61)90145‑9 13726518
    [Google Scholar]
  14. GhufranM. UllahM. KhanH.A. GhufranS. AyazM. SiddiqM. AbbasS.Q. HassanS.S. BungauS. In-silico lead druggable compounds identification against SARS COVID-19 main protease target from in-house, chembridge and zinc databases by structure-based virtual screening, molecular docking and molecular dynamics simulations.Bioengineering 202310110010.3390/bioengineering10010100 36671672
    [Google Scholar]
  15. GolechhaM. BhatiaJ. AryaD.S. Studies on effects of Emblica officinalis (Amla) on oxidative stress and cholinergic function in scopolamine induced amnesia in mice.J. Environ. Biol.201233195100 23033650
    [Google Scholar]
  16. HalliwellB. Free radicals, antioxidants, and human disease: Curiosity, cause, or consequence?Lancet1994344892472172410.1016/S0140‑6736(94)92211‑X 7915779
    [Google Scholar]
  17. BagciE. AydinE. MihasanM. ManiuC. HritcuL. Anxiolytic and antidepressant-like effects of Ferulago angulata essential oil in the scopolamine rat model of Alzheimer’s disease.Flavour Fragrance J.2016311708010.1002/ffj.3289
    [Google Scholar]
  18. KernS. ZetterbergH. KernJ. ZettergrenA. WaernM. HöglundK. AndreassonU. WetterbergH. Börjesson-HansonA. BlennowK. SkoogI. Prevalence of preclinical Alzheimer disease.Neurology20189019e1682e169110.1212/WNL.0000000000005476 29653987
    [Google Scholar]
  19. KraeuterA-K. GuestP.C. SarnyaiZ. The Y-maze for assessment of spatial working and reference memory in mice. In: Preclinical models: Techniques and protocols; Humana Press: New York, NY, 2019191610511110.1007/978‑1‑4939‑8994‑2_10
    [Google Scholar]
  20. KühnauJ. The flavonoids. A class of semi-essential food components: their role in human nutrition.World Rev. Nutr. Diet.19762411719110.1159/000399407 790781
    [Google Scholar]
  21. KumarA. SinghA. Ekavali, A review on Alzheimer’s disease pathophysiology and its management: An update.Pharmacol. Rep.201567219520310.1016/j.pharep.2014.09.004 25712639
    [Google Scholar]
  22. KumpulainenJ.T. SalonenJ.T. Natural Antioxidants and Anticarcinogens in Nutrition, Health and Disease.LondonThe Royal Society of Chemistry199917818710.1533/9781845698409
    [Google Scholar]
  23. LeeJ.S. KimH.G. LeeH.W. HanJ.M. LeeS.K. KimD.W. SaravanakumarA. SonC.G. Hippocampal memory enhancing activity of pine needle extract against scopolamine-induced amnesia in a mouse model.Sci. Rep.201551965110.1038/srep09651 25974329
    [Google Scholar]
  24. LombardoS. MaskosU. Role of the nicotinic acetylcholine receptor in Alzheimer’s disease pathology and treatment.Neuropharmacology,201596Pt B25526210.1016/j.neuropharm.2014.11.01825514383
    [Google Scholar]
  25. MaggioA. RosselliS. BrunoM. Essential oils and pure volatile compounds as potential drugs in Alzheimer’s disease therapy: An updated review of the literature.Curr. Pharm. Des.201622264011402710.2174/1381612822666160607065917 27281330
    [Google Scholar]
  26. MahnashiM.H. AshrafM. AlhasaniahA.H. UllahH. ZebA. GhufranM. FahadS. AyazM. DagliaM. Polyphenol-enriched Desmodium elegans DC. ameliorate scopolamine-induced amnesia in animal model of Alzheimer’s disease: In vitro, in vivo and in silico approaches.Biomed. Pharmacother.202316511514410.1016/j.biopha.2023.115144 37437376
    [Google Scholar]
  27. MahnashiM.H. AyazM. AlqahtaniY.S. AlyamiB.A. ShahidM. AlqahtaniO. KabrahS.M. ZebA. UllahF. SadiqA. Quantitative-HPLC-DAD polyphenols analysis, anxiolytic and cognition enhancing potentials of Sorbaria tomentosa Lindl.Rehder. J. Ethnopharmacol.202331711678610.1016/j.jep.2023.116786 37328081
    [Google Scholar]
  28. MahnashiM.H. AyazM. GhufranM. AlmazniI.A. AlqahtaniO. AlyamiB.A. AlqahtaniY.S. KhanH.A. SadiqA. WaqasM. Phytochemicals-based β-amyloid cleaving enzyme-1 and MAOB inhibitors for the treatment of Alzheimer’s disease: Molecular simulations-based predictions.J. Biomol. Struct. Dyn.2023202311310.1080/07391102.2023.2265494 37815007
    [Google Scholar]
  29. MarcheseA. BarbieriR. CoppoE. OrhanI.E. DagliaM. NabaviS.F. IzadiM. AbdollahiM. NabaviS.M. AjamiM. Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint.Crit. Rev. Microbiol.201743666868910.1080/1040841X.2017.1295225 28346030
    [Google Scholar]
  30. MassoudF. GauthierS. Update on the pharmacological treatment of Alzheimer’s disease.Curr. Neuropharmacol.201081698010.2174/157015910790909520 20808547
    [Google Scholar]
  31. MastersC.L. BatemanR. BlennowK. RoweC.C. SperlingR.A. CummingsJ.L. Alzheimer’s disease.Nat. Rev. Dis. Primers2015111505610.1038/nrdp.2015.56 27188934
    [Google Scholar]
  32. Mikuła-PietrasikJ. KuczmarskaA. RubiśB. FilasV. MuriasM. ZielińskiP. PiwockaK. KsiążekK. Resveratrol delays replicative senescence of human mesothelial cells via mobilization of antioxidative and DNA repair mechanisms.Free Radic. Biol. Med.20125211-122234224510.1016/j.freeradbiomed.2012.03.014 22579575
    [Google Scholar]
  33. MollicaA. CostanteR. StefanucciA. PinnenF. LucenteG. FidanzaS. PierettiS. Antinociceptive profile of potent opioid peptide AM94, a fluorinated analogue of biphalin with non-hydrazine linker.J. Pept. Sci.201319423323910.1002/psc.2465 23136069
    [Google Scholar]
  34. MollicaA. PellicciaS. FamigliniV. StefanucciA. MacedonioG. ChiavaroliA. OrlandoG. BrunettiL. FerranteC. PierettiS. NovellinoE. BenyheS. ZadorF. ErdeiA. SzucsE. SamavatiR. DvorácskóS. TombolyC. RagnoR. PatsilinakosA. SilvestriR. Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors.J. Enzyme Inhib. Med. Chem.201732144445110.1080/14756366.2016.1260565 28097916
    [Google Scholar]
  35. MountC. DowntonC. Alzheimer disease: Progress or profit?Nat. Med.200612778078410.1038/nm0706‑780 16829947
    [Google Scholar]
  36. NasarM.Q. ZohraT. KhalilA.T. OvaisM. UllahI. AyazM. ZahoorM. ShinwariZ.K. Extraction optimization, total phenolic-flavonoids content, HPLC-DAD finger printing, antimicrobial, antioxidant and cytotoxic potentials of Chinese folklore Ephedra intermedia Schrenk & CA Mey.Bra. J. Pharma. Sci.202358e20989
    [Google Scholar]
  37. NenadisN. WangL.F. TsimidouM. ZhangH.Y. Estimation of scavenging activity of phenolic compounds using the ABTS(*+) assay.J. Agric. Food Chem.200452154669467410.1021/jf0400056 15264898
    [Google Scholar]
  38. PákáskiM. KálmánJ. Interactions between the amyloid and cholinergic mechanisms in Alzheimer’s disease.Neurochem. Int.200853510311110.1016/j.neuint.2008.06.005 18602955
    [Google Scholar]
  39. PrasadS.N. Muralidhara, Neuroprotective efficacy of eugenol and isoeugenol in acrylamide-induced neuropathy in rats: Behavioral and biochemical evidence.Neurochem. Res.201338233034510.1007/s11064‑012‑0924‑9 23161090
    [Google Scholar]
  40. PushpalathaB. VenumadhavN. SwathiM. RajuB. Neuroprotective effect of resveratrol against scopolamine-induced cognitive impairment and oxidative stress in rats.Arch. Biol. Sci.20136541381138610.2298/ABS1304381P
    [Google Scholar]
  41. RennerU.D. OertelR. KirchW. Pharmacokinetics and pharmacodynamics in clinical use of scopolamine.Ther. Drug Monit.200527565566510.1097/01.ftd.0000168293.48226.57 16175141
    [Google Scholar]
  42. SarnyaiZ. SibilleE.L. PavlidesC. FensterR.J. McEwenB.S. TóthM. Impaired hippocampal-dependent learning and functional abnormalities in the hippocampus in mice lacking serotonin 1A receptors.Proc. Natl. Acad. Sci. 20009726147311473610.1073/pnas.97.26.14731 11121072
    [Google Scholar]
  43. SethiS. JoshiA. AroraB. BhowmikA. SharmaR.R. KumarP. Significance of FRAP, DPPH, and CUPRAC assays for antioxidant activity determination in apple fruit extracts.Eur. Food Res. Technol.2020246359159810.1007/s00217‑020‑03432‑z
    [Google Scholar]
  44. ShojiH. MiyakawaT. Effects of test experience, closed-arm wall color, and illumination level on behavior and plasma corticosterone response in an elevated plus maze in male C57BL/6J mice: A challenge against conventional interpretation of the test.Mol. Brain20211413410.1186/s13041‑020‑00721‑2 33588907
    [Google Scholar]
  45. SinghR.K. Recent trends in the management of Alzheimer’s disease: Current therapeutic options and drug repurposing approaches.Curr. Neuropharmacol.202018986888210.2174/1570159X18666200128121920 31989900
    [Google Scholar]
  46. StefanucciA. DimmitoM.P. ZenginG. LuisiG. MirzaieS. NovellinoE. MollicaA. Discovery of novel amide tripeptides as pancreatic lipase inhibitors by virtual screening.New J. Chem.20194373208321710.1039/C8NJ05884A
    [Google Scholar]
  47. SueishiY. IshikawaM. YoshiokaD. EndohN. OowadaS. ShimmeiM. FujiiH. KotakeY. Oxygen radical absorbance capacity (ORAC) of cyclodextrin-solubilized flavonoids, resveratrol and astaxanthin as measured with the ORAC-EPR method.J. Clin. Biochem. Nutr.201250212713210.3164/jcbn.11‑21 22448093
    [Google Scholar]
  48. SwongerA.K. RechR.H. Serotonergic and cholinergic involvement in habituation of activity and spontaneous alternation of rats in a maze.J. Comp. Physiol. Psychol.197281350952210.1037/h0033690 4265289
    [Google Scholar]
  49. TongX. LiX. AyazM. UllahF. SadiqA. OvaisM. ShahidM. KhayrullinM. HazratA. Neuroprotective studies on Polygonum hydropiper L. essential oils using transgenic animal models.Front. Pharmacol.20211158006910.3389/fphar.2020.580069 33584260
    [Google Scholar]
/content/journals/cn/10.2174/1570159X22666240329125626
Loading
/content/journals/cn/10.2174/1570159X22666240329125626
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