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2000
Volume 22, Issue 5
  • ISSN: 1567-2050
  • E-ISSN: 1875-5828

Abstract

Background

Alzheimer’s disease is associated with dysfunction of the cholinergic system, making the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) a promising therapeutic approach.

Objective

This study aimed to evaluate the neuroprotective effects and toxicity of essential oil (EO) and carlina oxide from in mice, assessing their potential for Alzheimer’s disease treatment.

Methods

The chemical composition of the essential oil extracted from the roots of was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The main component, carlina oxide, was isolated column chromatography. The inhibitory activities of AChE and BChE were evaluated for both the essential oil and carlina oxide. Additionally, toxicity was assessed in laboratory mice.

Results

Chemical analysis identified carlina oxide (81.6%) as the major constituent, along with minor compounds such as 13-methoxycarlin oxide and hexadecanoic acid. Both the essential oil and its main component, carlina oxide, exhibited significant inhibitory activity against AChE and BChE, enzymes associated with Alzheimer’s disease. The essential oil demonstrated promising IC values, with stronger anti-BChE activity compared to the reference drug, galantamine. Toxicity tests in mice revealed no adverse effects at lower doses (0.2-0.5 g/kg). However, higher doses (1.0-2.0 g/kg) resulted in mild to significant toxicity, including weight loss and mortality.

Discussion

The essential oil and carlina oxide demonstrated potent BChE inhibition, particularly relevant in advanced Alzheimer's disease. While effective at low doses, signs of toxicity were observed at higher concentrations, highlighting the importance of dose optimization. These findings suggest that may serve as a natural source of cholinesterase inhibitors, pending further studies and clinical validation.

Conclusion

essential oil and carlina oxide show promising inhibitory effects on AChE and BChE, suggesting their potential as neuroprotective agents. However, their toxicity at higher doses highlights the need for cautious use and further investigation.

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2025-11-07
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References

  1. AhmadF.B. CisewskiJ.A. XuJ. AndersonR.N. Provisional Mortality Data — United States, 2022.MMWR Morb. Mortal. Wkly. Rep.2023721848849210.15585/mmwr.mm7218a337141156
    [Google Scholar]
  2. SelkoeD.J. HardyJ. The amyloid hypothesis of Alzheimer’s disease at 25 years.EMBO Mol. Med.20168659560810.15252/emmm.20160621027025652
    [Google Scholar]
  3. BirksJ.S. HarveyR.J. Donepezil for dementia due to Alzheimer’s disease.Cochrane Libr.201820186CD00119010.1002/14651858.CD001190.pub329923184
    [Google Scholar]
  4. YiannopoulouK.G. PapageorgiouS.G. Current and future treatments in Alzheimer disease: An update.J. Cent. Nerv. Syst. Dis.202012117957352090739710.1177/117957352090739732165850
    [Google Scholar]
  5. HowesM.J. HoughtonP.J. Ethnobotanical treatment strategies against Alzheimer’s disease.Curr. Alzheimer Res.201291678510.2174/15672051279901504622329652
    [Google Scholar]
  6. HancianuM. CioancaO. MihasanM. HritcuL. Neuroprotective effects of inhaled lavender oil on scopolamine-induced dementia via anti-oxidative activities in rats.Phytomedicine201320544645210.1016/j.phymed.2012.12.00523351960
    [Google Scholar]
  7. LoprestiA.L. Salvia (Sage): A review of its potential cognitive-enhancing and protective effects.Drugs R D.2017171536410.1007/s40268‑016‑0157‑527888449
    [Google Scholar]
  8. ChaiyanaW. OkonogiS. Inhibition of cholinesterase by essential oil from food plant.Phytomedicine2012198-983683910.1016/j.phymed.2012.03.010
    [Google Scholar]
  9. PanelI. A.; Owokotomo, O.; Ekundayo, T.G.; Abayomi, A.V.: Chukwuka. In vitro anti-cholinesterase activity of essential oil from four tropical medicinal plants.Toxicol. Rep.2015285085710.1016/j.toxrep.2015.05.00328962420
    [Google Scholar]
  10. RahmanM.A. SultanaA. KhanM.F. BoonhokR. AfrozS. Tea tree oil, a vibrant source of neuroprotection via neuroinflammation inhibition: a critical insight into repurposing Melaleuca alternifolia by unfolding its characteristics.J. Zhejiang Univ. Sci. B202324755457310.1631/jzus.B230016837455134
    [Google Scholar]
  11. LaiS.M.S. LiewS.Y. ChearN.J.Y. GohB.H. TanW.N. KhawK.Y. Plant terpenoids as the promising source of cholinesterase inhibitors for anti-AD therapy.Biology202211230710.3390/biology1102030735205173
    [Google Scholar]
  12. BenmansourN. SaidR.M. El HanbaliF. CherifH. AkssiraM. Study of the anti-inflammatory and healing properties of the rhizomes of Carthamus Caeruleus L. (asteraceae) harvested in the region of tipaza.Med. Technol. J.20204152552610.26415/2572‑004X‑vol4iss1p525‑526
    [Google Scholar]
  13. MamiI.R. BelabbesR. DibM.A. TabtiB. Costa, J.; Muselli, A. Biological activities of carlina oxide isolated from the roots of Carthamus caeruleus. Nat. Prod. J.202010214515210.2174/2210315509666190117152740
    [Google Scholar]
  14. ĐorđevićS. PetrovićS. DobrićS. MilenkovićM. VučićevićD. ŽižićS. KukićJ. Antimicrobial, anti-inflammatory, anti-ulcer and antioxidant activities of Carlina acanthifolia root essential oil.J. Ethnopharmacol.2007109345846310.1016/j.jep.2006.08.02117011148
    [Google Scholar]
  15. HammoudiA. Tabet ZatlaA. MamiI.R. BenaribaN. Brixi-GormatR. FekhikherZ. BenramdaneH. DibM.A. α-amylase inhibition activity of carlina oxide and aplotaxene isolated from the roots of and Rhaponticum acaule.Curr. Chem. Biol.20241829410310.2174/0122127968317328240918041222
    [Google Scholar]
  16. AdamsR. Identification of essential oils by Capillary Gas Chromatography/Mass Spectroscopy, Allured Publ. Corp.ILCarol Stream2001
    [Google Scholar]
  17. KçnigW. JoulainD. HochmuthD. Terpenoids and Related Constituents of Essential Oils, Library of Mass Finder 2.1.HamburgInstitute of Organic Chemistry, University of Hamburg2001
    [Google Scholar]
  18. McLaffertyF.W. StaufferD.B. Registry of Mass Spectral Data, 6th electronic ed WileyNew York1994
    [Google Scholar]
  19. McLaffertyF.W. StaufferD.B. PC Version 1.7 of The NIST/EPA/NIH Mass Spectral Library.PerkinElmer Corporation1999
    [Google Scholar]
  20. BensaadM.S. DassamiourS. HambabaL. BensouiciC. HabaH. In vitro assessment of antioxidant, anti-inflammatory, neuroprotective and antimicrobial activities of Centaurea tougourensis Boiss. & Reut.J. Pharm. Pharmacogn. Res.20219679080210.56499/jppres21.1103_9.6.790
    [Google Scholar]
  21. BenhamidatL. Amine DibM.E. BensaidO. ZatlaA.T. KenicheA. OuarI.E. NassimD. MuselliA. Chemical composition and antioxidant, anti-inflammatory and anticholinesterase properties of the aerial and root parts of Centaurea acaulis essential oils: Study of the combinatorial activities of aplotaxene with reference standards.J. Essent. Oil-Bear. Plants202225112614610.1080/0972060X.2022.2046177
    [Google Scholar]
  22. SemaouiM. DibM.E.A. DjabouN. CostaJ. MuselliA. Chemical composition, biological activities and toxicity study of carduncellus pinnatus essential oil from West Algeria.Curr. Bioact. Compd.2022183e02082119518610.2174/1573407217666210802113423
    [Google Scholar]
  23. MejdoubK. MamiI.R. BelabbesR. DibM.E.A. DJabouN. TabtiB. BenyellesN.G. CostaJ. MuselliA. Chemical variability of Atractylis gummifera essential oils at three developmental stages and investigation of their antioxidant, antifungal and insecticidal activities.Curr. Bioact. Compd.202016448949710.2174/1573407215666190126152112
    [Google Scholar]
  24. SchmidtB. AudörschS. Stereoselective total syntheses of polyacetylene plant metabolites via ester-tethered ring closing metathesis.J. Org. Chem.20178231743176010.1021/acs.joc.6b0298728085285
    [Google Scholar]
  25. SemmlerF.W. Zusammensetzung des ätherischen Oels der Eberwurzel (Carlina acaulis L.).Ber. Dtsch. Chem. Ges.190639172673110.1002/cber.190603901108
    [Google Scholar]
  26. DosokyN.S. SetzerW.N. Biological activities of Cistus spp. essential oils.Int. J. Mol. Sci.2018197196610.3390/ijms1907196629976894
    [Google Scholar]
  27. LoizzoM.R. MenichiniF. TundisR. BonesiM. ConfortiF. NadjafiF. StattiG.A. FregaN.G. MenichiniF. In vitro biological activity of Salvia leriifolia benth essential oil relevant to the treatment of Alzheimer’s disease.J. Oleo Sci.200958844344610.5650/jos.58.44319584571
    [Google Scholar]
  28. GarcionE. Wion-BarbotN. Montero-MeneiC.N. BergerF. WionD. New clues about vitamin D functions in the nervous system.Trends Endocrinol. Metab.200213310010510.1016/S1043‑2760(01)00547‑111893522
    [Google Scholar]
  29. GrimmM. MettJ. HartmannT. The impact of vitamin E and other fat-soluble vitamins on Alzheimer´s disease.Int. J. Mol. Sci.20161711178510.3390/ijms1711178527792188
    [Google Scholar]
  30. CiroA. ParkJ. BurkhardG. YanN. GeulaC. Biochemical differentiation of cholinesterases from normal and Alzheimer’s disease cortex.Curr. Alzheimer Res.20129113814310.2174/15672051279901512721244353
    [Google Scholar]
  31. Darreh-ShoriT. BrimijoinS. KadirA. AlmkvistO. NordbergA. Differential CSF butyrylcholinesterase levels in Alzheimer’s disease patients with the ApoE ε4 allele, in relation to cognitive function and cerebral glucose metabolism.Neurobiol. Dis.200624232633310.1016/j.nbd.2006.07.01316973370
    [Google Scholar]
  32. HerrmannF. HamoudR. SporerF. TahraniA. WinkM. Carlina oxide--a natural polyacetylene from Carlina acaulis (Asteraceae) with potent antitrypanosomal and antimicrobial properties.Planta Med.201177171905191110.1055/s‑0031‑127998421678234
    [Google Scholar]
  33. Stojanović-RadićZ. ČomićL. RadulovićN. BlagojevićP. Mihajilov-KrstevT. RajkovićJ. Commercial Carlinae radix herbal drug: Botanical identity, chemical composition and antimicrobial properties.Pharm. Biol.201250893394010.3109/13880209.2011.64921422480199
    [Google Scholar]
  34. DjordjevicS. PetrovicS. RisticM. DjokovicD. Composition of Carlina acanthifolia root essential oil.Chem. Nat. Compd.200541441041210.1007/s10600‑005‑0163‑2
    [Google Scholar]
  35. MamiI.R. AminaT.Z. PérardJ. ArrarZ. DibM.E.A. Hemisyntheses and in-silico study of new analogues of carlina oxide from Carthamus Caeruleus roots.Comb. Chem. High Throughput Screen.20212491503151310.2174/138620732399920110321414133155891
    [Google Scholar]
  36. BenelliG. PavoniL. ZeniV. RicciardiR. CosciF. CacopardoG. GendusaS. SpinozziE. PetrelliR. CappellacciL. MaggiF. PavelaR. BonacucinaG. LucchiA. Developing a highly stable Carlina acaulis essential oil nanoemulsion for managing Lobesia botrana.Nanomaterials2020109186710.3390/nano1009186732961890
    [Google Scholar]
  37. BelabbesR. MamiI.R. DibM.E.A. MejdoubK. TabtiB. CostaJ. MuselliA. I.R.; Dib, M.A.; Mejdoub, K.; Tabti, B.; Costa, J.; Muselli, M. Chemical composition and biological activities of essential oils of Echinops spinosus and Carlina vulgaris rich in polyacetylene compounds.Curr. Nutr. Food Sci.202016456357010.2174/1573401315666190206142929
    [Google Scholar]
  38. MejdoubK. MamiI.R. BelabbesR. DibM.E.A. DJabouN. TabtiB. BenyellesN.G. CostaJ. MuselliA. DJabou, N.; Tabti, B.; Benyelles, N.; Costa, J.; Muselli, A. Chemical variability of Atractylis gummifera essential oils at three developmental stages and investigation of their antioxidant, antifungal and insecticidal activities.Curr. Bioact. Compd.202016448949710.2174/1573407215666190126152112
    [Google Scholar]
  39. BenelliG. PavelaR. PetrelliR. NzekoueF.K. CappellacciL. LupidiG. QuassintiL. BramucciM. SutS. Dall’AcquaS. CanaleA. MaggiF. Carlina oxide from Carlina acaulis root essential oil acts as a potent mosquito larvicide.Ind. Crops Prod.201913735636610.1016/j.indcrop.2019.05.037
    [Google Scholar]
  40. AyazM. JunaidM. AhmedJ. UllahF. SadiqA. AhmadS. ImranM. Phenolic contents, antioxidant and anticholinesterase potentials of crude extract, subsequent fractions and crude saponins from Polygonum hydropiper L.BMC Complement. Altern. Med.201414114510.1186/1472‑6882‑14‑14524884823
    [Google Scholar]
  41. AhmadS. UllahF. SadiqA. AyazM. ImranM. AliI. ZebA. UllahF. ShahM.R. Chemical composition, antioxidant and anticholinesterase potentials of essential oil of Rumex hastatus D. Don collected from the North West of Pakistan.BMC Complement. Altern. Med.20161612910.1186/s12906‑016‑0998‑z26810212
    [Google Scholar]
  42. SouzaA. SilvaM.C. Cardoso-LopesE.M. CordeiroI. SobralM.E.G. YoungM.C.M. MorenoP.R.H. Differential acetyl cholinesterase inhibition by volatile oils from two specimens of Marlierea racemosa (Myrtaceae) collected from different areas of the Atlantic Rain Forest.Nat. Prod. Commun.2009481934578X090040082610.1177/1934578X090040082619769001
    [Google Scholar]
  43. OkelloE. DimakiC. HowesM. HoughtonP. PerryE. In vitro inhibition of human acetyl-and butyryl-cholinesterase by Narcissus poeticus L. (Amaryllidaceae) flower absolute.Int. J. Essent. Oil Ther20082105110
    [Google Scholar]
  44. HungN.H. QuanP.M. SatyalP. DaiD.N. HoaV.V. HuyN.G. GiangL.D. HaN.T. HuongL.T. HienV.T. SetzerW.N. Acetylcholinesterase inhibitory activities of essential oils from Vietnamese traditional medicinal plants.Molecules20222720709210.3390/molecules2720709236296686
    [Google Scholar]
  45. Staton LawsJ.III SmidS.D. Sesquiterpene-evoked phytochemical toxicity in PC12 neuronal cells reveals a variable degree of oxidative stress and alpha-tocopherol and glutathione-dependent protection.Curr. Res. Toxicol.2024610014410.1016/j.crtox.2023.10014438193034
    [Google Scholar]
  46. SalviM. FioreC. BattagliaV. PalermoM. ArmaniniD. ToninelloA. Carbenoxolone induces oxidative stress in liver mitochondria, which is responsible for transition pore opening.Endocrinology200514652306231210.1210/en.2004‑112815677764
    [Google Scholar]
  47. PreetiD. SambhakarS. MalikR. BhatiaS. Al HarrasiA. RaniC. SaharanR. KumarS. Geeta SehrawatR. Nanoemulsion: An emerging novel technology for improving the bioavailability of drugs.Scientifica (Cairo)2023202312510.1155/2023/664010337928749
    [Google Scholar]
  48. Ávila-GálvezM.Á. MarquesD. FigueiraI. CankarK. BoschD. BritoM.A. dos SantosC.N. Costunolide and parthenolide: Novel blood-brain barrier permeable sesquiterpene lactones to improve barrier tightness.Biomed. Pharmacother.202316711541310.1016/j.biopha.2023.11541337683593
    [Google Scholar]
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