Skip to main content
SpringerLink
Log in

Therapeutic Effects of Geranium Oil in MPTP-Induced Parkinsonian Mouse Model

  • Research
  • Published:
Plant Foods for Human Nutrition Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) is an incurable neurodegenerative disease characterized by motor and non-motor disabilities resulting from neuronal cell death in the substantia nigra and striatum. Microglial activation and oxidative stress are two of the primary mechanisms driving that neuronal death. Here, we evaluated the effects of geranium oil on 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) mouse model for PD, on microglial activation, and oxidative stress. We demonstrate that oral treatment with geranium oil improved motor performance in this model. The therapeutic effects of geranium oil were observed as a significant increase in rotarod latency and distance among the mice treated with geranium oil, as compared to vehicle-treated MPTP mice. Geranium oil also prevented dopaminergic neuron death in the substantia nigra of the treated mice. These therapeutic effects can be partially attributed to the antioxidant and anti-inflammatory properties of geranium oil, which were observed as attenuated accumulation of reactive oxygen species and inhibition of the secretion of proinflammatory cytokines from geranium oil-treated activated microglial cells. A repeated-dose oral toxicity study showed that geranium oil is not toxic to mice. In light of that finding and since geranium oil is defined by the FDA as generally recognized as safe (GRAS), we do not foresee any toxicity problems in the future and suggest that geranium oil may be a safe and effective oral treatment for PD. Since the MPTP model is only one of the preclinical models for PD, further studies are needed to confirm that geranium oil can be used to prevent or treat PD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

Data will be made available upon request.

Abbreviations

ABAP:

2,2’-azobis(amidinopropane)

DAT:

Dopamine transporter

DCF-DA:

2’7’-dichlorofluorescein diacetate

IL-1β:

Interleukin 1β

IL-6:

Interleukin 6

GC-MS:

Gas chromatography-mass spectrometry

GRAS:

Generally recognized as safe

LPS:

Lipopolysaccharide

MCT:

Medium-chain triglyceride

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

MW:

Molecular weight

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SNc:

Substantia nigra zona compacta

References

  1. Simon DK, Tanner CM, Brundin P (2020) Parkinson disease epidemiology, pathology, genetics, and pathophysiology. Clin Geriatr Med 36:1–12. https://doi.org/10.1016/j.cger.2019.08.002

    Article  PubMed  Google Scholar 

  2. Vijiaratnam N, Simuni T, Bandmann O, Morris HR, Foltynie T (2021) Progress towards therapies for disease modification in Parkinson’s disease. Lancet Neurol 20:559–572. https://doi.org/10.1016/S1474-4422(21)00061-2

    Article  CAS  PubMed  Google Scholar 

  3. Karpenko MN, Vasilishina AA, Gromova EA, Muruzheva ZM, Miliukhina IV, Bernadotte A (2018) Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-6, interleukin-10, and tumor necrosis factor-alpha levels in CSF and serum in relation to the clinical diversity of Parkinson’s disease. Cell Immunol 327:77–82. https://doi.org/10.1016/j.cellimm.2018.02.011

    Article  CAS  PubMed  Google Scholar 

  4. Leal MC, Casabona JC, Puntel M, Pitossi FJ (2013) Interleukin-1beta and tumor necrosis factor-alpha: reliable targets for protective therapies in Parkinson’s disease? Front Cell Neurosci 7:53. https://doi.org/10.3389/fncel.2013.00053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. More SV, Kumar H, Kim IS, Song SY, Choi DK (2013) Cellular and molecular mediators of neuroinflammation in the pathogenesis of Parkinson’s disease. Mediators Inflamm 2013:952375. https://doi.org/10.1155/2013/952375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pajares M, A IR, Manda G, Bosca L, Cuadrado A (2020) Inflammation in Parkinson’s disease mechanisms and therapeutic implications. Cells 9. https://doi.org/10.3390/cells9071687

  7. Sanchez-Guajardo V, Tentillier N, Romero-Ramos M (2015) The relation between alpha-synuclein and microglia in Parkinson’s disease: recent developments. Neuroscience 302:47–58. https://doi.org/10.1016/j.neuroscience.2015.02.008

    Article  CAS  PubMed  Google Scholar 

  8. Vesely B, Dufek M, Thon V, Brozman M, Kiralova S, Halaszova T, Koritakova E, Rektor I (2018) Interleukin 6 and complement serum level study in Parkinson’s disease. J Neural Transm (Vienna) 125:885–881. https://doi.org/10.1007/s00702-018-1857-5

    Article  CAS  Google Scholar 

  9. Zhang QS, Heng Y, Yuan YH, Chen NH (2017) Pathological alpha-synuclein exacerbates the progression of Parkinson’s disease through microglial activation. Toxicol Lett 265:30–37. https://doi.org/10.1016/j.toxlet.2016.11.002

    Article  CAS  PubMed  Google Scholar 

  10. Weng M, Xie X, Liu C, Lim KL, Zhang CW, Li L (2018) The sources of reactive oxygen species and its possible role in the pathogenesis of Parkinson’s Disease. Parkinsons Dis 2018:9163040. https://doi.org/10.1155/2018/9163040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Puspita L, Chung SY, Shim JW (2017) Oxidative stress and cellular pathologies in Parkinson’s disease. Mol Brain 10:53. https://doi.org/10.1186/s13041-017-0340-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Prakash J, Chouhan S, Yadav SK, Westfall S, Rai SN, Singh SP (2014) Withania somnifera alleviates parkinsonian phenotypes by inhibiting apoptotic pathways in dopaminergic neurons. Neurochem Res 39:2527–2536. https://doi.org/10.1007/s11064-014-1443-7

    Article  CAS  PubMed  Google Scholar 

  13. Yadav SK, Rai SN, Singh SP (2017) Mucuna pruriens reduces inducible nitric oxide synthase expression in parkinsonian mice model. J Chem Neuroanat 80:1–10. https://doi.org/10.1016/j.jchemneu.2016.11.00

    Article  CAS  PubMed  Google Scholar 

  14. Rai SN, Yadav SK, Singh D, Singh SP (2016) Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced parkinsonian mouse model. J Chem Neuroanat 71:41–49. https://doi.org/10.1016/j.jchemneu.2015.12.002

    Article  CAS  PubMed  Google Scholar 

  15. Ramsey JT, Shropshire BC, Nagy TR, Chambers KD, Li Y, Korach KS (2020) Essential oils and health. Yale J Biol Med 93:291–305

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Javed H, Nagoor Meeran MF, Azimullah S, Adem A, Sadek B, Ojha SK (2018) Plant extracts and phytochemicals targeting alpha-synuclein aggregation in Parkinson’s Disease Models. Front Pharmacol 9:1555. https://doi.org/10.3389/fphar.2018.01555

    Article  CAS  PubMed  Google Scholar 

  17. Shahpiri Z, Bahramsoltani R, Hosein Farzaei M, Farzaei F, Rahimi R (2016) Phytochemicals as future drugs for Parkinson’s disease: a comprehensive review. Rev Neurosci 27:651–668. https://doi.org/10.1515/revneuro-2016-0004

    Article  CAS  PubMed  Google Scholar 

  18. Williamson EM (2001) Synergy and other interactions in phytomedicines. Phytomedicine 8:401–409

    Article  CAS  PubMed  Google Scholar 

  19. Fekri N, El Amir D, Owis A, AbouZid S (2021) Studies on essential oil from rose-scented geranium, Pelargonium graveolens L’Herit. (Geraniaceae). Nat Prod Res 35:2593–2597. https://doi.org/10.1080/14786419.2019.1682581

    Article  CAS  PubMed  Google Scholar 

  20. Elmann A, Mordechay S, Rindner M, Ravid U (2010) Anti-neuroinflammatory effects of geranium oil in microglial cells. J Funct Foods 2:17–22. https://doi.org/10.1016/j.jff.2009.12.001

    Article  CAS  Google Scholar 

  21. Lis-Balchin M (2002) Geranium and pelargonium. Taylor & Francis Inc, London and Ney York

    Book  Google Scholar 

  22. Abe S, Maruyama N, Hayama K, Inouye S, Oshima H, Yamaguchi H (2004) Suppression of neutrophil recruitment in mice by geranium essential oil. Mediators Inflamm 2004 13:21–24. https://doi.org/10.1080/09629350410001664798

    Article  CAS  Google Scholar 

  23. Maruyama N, Ishibashi H, Hu W, Morofuji S, Inouye S, Yamaguchi H, Abe S (2006) Suppression of carrageenan- and collagen II-induced inflammation in mice by geranium oil. Mediators Inflamm 2006:62537. https://doi.org/10.1155/MI/2006/62537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Maruyama N, Sekimoto Y, Ishibashi H, Inouye S, Oshima H, Yamaguchi H, Abe S (2005) Suppression of neutrophil accumulation in mice by cutaneous application of geranium essential oil. J Inflamm (Lond) 2:1. https://doi.org/10.1186/1476-9255-2-1

    Article  CAS  PubMed  Google Scholar 

  25. Rai SN, Singh P (2020) Advancement in the modelling and therapeutics of Parkinson’s disease. J Chem Neuroanat 104:101752. https://doi.org/10.1016/j.jchemneu.2020.101752

    Article  CAS  PubMed  Google Scholar 

  26. Wolfe KL, Liu RH (2007) Cellular antioxidant activity (CAA) assay for assessing antioxidants, foods, and dietary supplements. J Agric Food Chem 55:8896–8907

    Article  CAS  PubMed  Google Scholar 

  27. Ferrari E, Cardinale A, Picconi B, Gardoni F (2020) From cell lines to pluripotent stem cells for modelling Parkinson’s Disease. J Neurosci Methods 340:108741. https://doi.org/10.1016/j.jneumeth.2020.108741

    Article  CAS  PubMed  Google Scholar 

  28. Nair AB, Jacob S (2016) A simple practice guide for dose conversion between animals and human. J Basic and clin Pharmacy 7:27–31

    Article  Google Scholar 

  29. Shan S, Tian L, Fang R (2019) Chlorogenic acid exerts beneficial effects in 6-hydroxydopamine-induced neurotoxicity by inhibition of endoplasmic reticulum stress. Med Sci Monit 25:453–459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Palermo G, Giannoni S, Bellini G, Siciliano G, Ceravolo R (2021) Dopamine transporter imaging, current status of a potential biomarker: a comprehensive review. Int J Mol Sci 22. https://doi.org/10.3390/ijms222011234

Download references

Funding

This work was supported by the Chief Scientist of the Ministry of Agriculture, Israel (grant No. 421-0135-09).

Author information

Authors and Affiliations

  1. Department of Food Sciences, Agricultural Research Organization, The Volcani Center, P.O. Box 15159, Rishon LeZion, 7505101, Israel

    Alona Telerman & Anat Elmann

  2. Medicinal and Aromatic Plants Unit, Newe Ya’ar Research Center, Agricultural Research Organization, Ramat Yishay, Israel

    Uzi Ravid & Nativ Dudai

Authors
  1. Alona Telerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Uzi Ravid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nativ Dudai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anat Elmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Anat Elmann: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing. Alona Telerman: Formal analysis, Investigation. Nativ Dudai: Funding acquisition, Formal analysis, Supervision. Uzi Ravid: Funding acquisition, Formal analysis, Supervision.

Corresponding author

Correspondence to Anat Elmann.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics Approval

1. Preparation of primary cultures: The research was conducted in accordance with the US National Institute of Health (NIH) guidelines for the care and use of laboratory animals and was approved by the National Permit Committee for Animal Science (IL-135/07). 2. In vivo experiments: All animal experiments were carried out in accordance with the US National Institute of Health (NIH) Guidelines for the Care and Use of Laboratory Animals and were approved by the National Permit Committee for Animal Science (IL-10-12-111 and IL-12-12-223).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Telerman, A., Ravid, U., Dudai, N. et al. Therapeutic Effects of Geranium Oil in MPTP-Induced Parkinsonian Mouse Model. Plant Foods Hum Nutr 78, 768–775 (2023). https://doi.org/10.1007/s11130-023-01112-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11130-023-01112-3

Keywords

Search

Navigation