Skip to main content
SpringerLink
Log in

Targeting oxidative stress, acetylcholinesterase, proinflammatory cytokine, dopamine and GABA by eucalyptus oil (Eucalyptus globulus) to alleviate ketamine-induced psychosis in rats

  • Original Article
  • Published:
Inflammopharmacology Aims and scope Submit manuscript

Abstract

Essential oil of eucalyptus species is among the most common traded essential oils in the world. There is an increasing interest in the application of eucalyptus oil as a natural additive in food and pharmaceutical industry. The present study was undertaken to identify the phytoconstituents present in the essential oil of Eucalyptus globulus leaves (EO) and ascertain their protective effect against ketamine-induced psychosis in rats. GC–MS technique was used for analysis of phytoconstituents present in EO. Ketamine (50 mg/kg, i.p.) was used to induce psychosis in rats. Photoactometer, forced swim test and pole climb avoidance test were used to evaluate the protective effects of the EO (500, 1000 and 2000 mg/kg, p.o.) on acute and chronic administration. Bar test was used to test the side effect of EO. Biochemical and neurochemical estimations were carried out to explore the possible mechanism of action. GC–MS analysis of EO showed the presence of a number of biologically active compounds. EO at the dose of 500, 1000 and 2000 mg/kg, p.o. on acute and chronic administration, decreased locomotor activity, immobility duration and latency to climb the pole. EO was effective to facilitate the release of GABA, increase GSH levels, inhibit dopamine neurotransmission and decrease TNF-α levels as well as diminish AChE activity in different regions of the brain. EO at the dose of 500, 1000 mg/kg did not produce cataleptic behavior in rats. EO at the dose of 500, 1000 mg/kg produced protective effects against ketamine-induced psychosis and can be further explored clinically against neuropsychiatric disorders.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

GC–MS:

Gas chromatography–mass spectroscopy

GABA:

Gamma-aminobutyric acid

GSH:

Glutathione

TNF-α:

Tumor necrosis factor-alpha

AChE:

Acetylcholinesterase

NMDA:

N-Methyl-d-aspartate

References

  • Aazza S, Lyoussi B, Miguel MG (2011) Antioxidant and antiacetylcholinesterase activities of some commercial essential oils and their major compounds. Molecules 16:7672–7690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Abdel-Salam OM, Youness ER, Mohammed NA, Omara EA, Sleem AA (2015) Effect of ketamine on oxidative stress following lipopolysaccharide administration. Comp Clin Path 24:53–63

    Article  CAS  Google Scholar 

  • Al-Asmari AK, Athar MT, Al-Faraidy AA, Almuhaiza MS (2017) Chemical composition of essential oil of Thymus vulgaris collected from Saudi Arabian market. Asian Pac J Trop Biomed 7:147–150

    Article  Google Scholar 

  • Andrade MA, das Graças Cardoso M, de Andrade J (2013) Chemical composition and antioxidant activity of essential oils from Cinnamodendron dinisii Schwacke and Siparuna guianensis Aublet. Antioxidants 2:384–397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Angioni A, Barra A, Coroneo V, Dessi S, Cabras P (2006) Chemical composition, seasonal variability, and antifungal activity of Lavandula stoechas L. ssp. stoichas essential oils from stem/leaves and flowers. J Agric Food Chem 54:4364–4370

    Article  CAS  PubMed  Google Scholar 

  • Aydin E, Turkez H, Tasdemir S (2013) Anticancer and antioxidant properties of terpinolene in rat brain cells. Arh Hig Rada Toksikol 64:415–424

    Article  CAS  PubMed  Google Scholar 

  • Benturquia N, Courtin C, Noble F, Marie-Claire C (2008) Involvement of D1 dopamine receptor in MDMA-induced locomotor activity and striatal gene expression in mice. Brain Res 1211:1–5

    Article  CAS  PubMed  Google Scholar 

  • Chatterjee M, Ganguly S, Srivastava M, Palit G (2011) Effect of ‘chronic’ versus ‘acute’ ketamine administration and its ‘withdrawal’ effect on behavioral alterations in mice: implications for experimental psychosis. Behav Brain Res 216:247–254

    Article  CAS  PubMed  Google Scholar 

  • Chatterjee M, Singh S, Kumari R, Verma AK, Palit G (2012) Evaluation of the antipsychotic potential of Panax quinquefolium in ketamine induced experimental psychosis model in mice. Neurochem Res 37:759–770

    Article  CAS  PubMed  Google Scholar 

  • Ciftci O, Ozdemir I, Tanyildizi S, Yildiz S, Oguzturk H (2011) Antioxidative effects of curcumin, β-myrcene and 1, 8-cineole against 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in rats liver. Toxicol Ind Health 27:447–453

    Article  CAS  PubMed  Google Scholar 

  • da Silva FC, de Oliveira Cito MD, da Silva MI, Moura BA, de Aquino Neto MR, Feitosa ML, de Castro Chaves R, Macedo DS, de Vasconcelos SM, de França Fonteles MM, de Sousa FC (2010) Behavioral alterations and pro-oxidant effect of a single ketamine administration to mice. Brain Res Bull 83:9–15

    Article  CAS  PubMed  Google Scholar 

  • Davis J, Moylan S, Harvey BH, Maes M, Berk M (2014) Neuroprogression in schizophrenia: pathways underpinning clinical staging and therapeutic corollaries. Aust N Z J Psychiatry 48:512–529

    Article  PubMed  Google Scholar 

  • Dhingra MS, Dhingra S, Kumria R, Chadha R, Singh T, Kumar A, Karan M (2014) Effect of trimethylgallic acid esters against chronic stress-induced anxiety-like behavior and oxidative stress in mice. Pharmacol Rep 66(4):606–612

    Article  CAS  PubMed  Google Scholar 

  • Dobetsberger C, Buchbauer G (2011) Actions of essential oils on the central nervous system: an updated review. Flavour Fragr J 26:300–316

    Article  CAS  Google Scholar 

  • Ellman GL (1959) Tissue sulphydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A newand rapid colorimetric determination of acetylcholinesteraseactivity. Biochem Pharmacol 7:88–95

    Article  CAS  Google Scholar 

  • Faludi G, Dome P, Lazary J (2011) Origins and perspectives of schizophrenia research. Neuropsychopharmacol Hung 13:185–192

    PubMed  Google Scholar 

  • Fell MJ, McKinzie DL, Monn JA, Svensson KA (2012) Group II metabotropic glutamate receptor agonists and positive allosteric modulators as novel treatments for schizophrenia. Neuropharmacology 62:1473–1483

    Article  CAS  PubMed  Google Scholar 

  • Hons J, Zirko R, Ulrychova M, Cermakova E, Doubek P, Libiger J (2010) Glycine serum level in schizophrenia: relation to negativesymptoms. Psychiatry Res 176:103–108

    Article  CAS  PubMed  Google Scholar 

  • Kandi P, Hayslett RL (2011) Nicotine and 17b-estradiol produce an antidepressant- like effect in female ovariectomized rats. Brain Res Bull 84:224–228

    Article  CAS  PubMed  Google Scholar 

  • Kessler A, Sahin-Nadeem H, Lummis SC, Weigel I, Pischetsrieder M, Buettner A, Villmann C (2014) GABAA receptor modulation by terpenoids from Sideritis extracts. Mol Nutr Food Res 58:851–862

    Article  CAS  PubMed  Google Scholar 

  • Kim YD, Lantz-McPeak SM, Ali SF, Kleinman MT, Choi YS, Kim H (2014) Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells. Environ Toxicol Pharmacol 37:954–959

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Yadav M, Parle M, Dhingra S, Dhull DK (2017) Potential drug targets and treatment of schizophrenia. Inflammopharmacol 25(3):277–292

    Article  CAS  Google Scholar 

  • Lowe IP, Robins E, Eyerman GS (1958) The fluorimetric measurement of glutamic decarboxylase and its distribution in brain. J Neurochem 3(1):8–18

    Article  CAS  PubMed  Google Scholar 

  • Macedo EM, Santos WC, Sousa Neto BP, Lopes EM, Piauilino CA, Cunha FV, Sousa DP, Oliveira FA, Almeida FR (2016) Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation. Braz J Med Biol Res 49:e5103

    Article  CAS  PubMed Central  Google Scholar 

  • Masotti V, Juteau F, Bessière JM, Viano J (2003) Seasonal and phenological variations of the essential oil from the narrow endemic species Artemisia molinieri and its biological activities. J Agric Food Chem 51:7115–7121

    Article  CAS  PubMed  Google Scholar 

  • Miyazawa M, Yamafuji C (2005) Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids. J Agric Food Chem 53:1765–1768

    Article  CAS  PubMed  Google Scholar 

  • Monji A, Kato T, Kanba S (2009) Cytokines and schizophrenia: microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci 63:257–265

    Article  CAS  PubMed  Google Scholar 

  • Sanberg PR, Bunsey MD, Giordano M, Norman AB (1988) The catalepsy test: its ups and downs. Behav Neurosci 102:748–759

    Article  CAS  PubMed  Google Scholar 

  • Schlumpf M, Lichtensteiger W, Langemann H, Waser PG, Hefti F (1974) A fluorometric micromethod for the simultaneous determination of serotonin, noradrenaline and dopamine in milligram amounts of brain tissue. Biochem Pharmacol 23:2437–2446

    Article  CAS  Google Scholar 

  • Shah R, Subhan F, Ali G, Ullah I, Ullah S, Shahid M, Ahmad N, Fawad K (2016) Olanzapine induced biochemical and histopathological changes after its chronic administration in rats. Saudi Pharm J 24:698–704

    Article  PubMed  Google Scholar 

  • Sharma K, Parle M, Yadav M (2016) Evaluation of antipsychotic effect of methanolic extract of Ocimum sanctum leaves on laboratory animals. J App Pharm Sci 6:171–177

    Article  CAS  Google Scholar 

  • Silva Brum LF, Elisabetsky E (2001) Effects of linalool on [3H] MK801 and [3H] muscimol binding in mouse cortical membranes. Psychiatry Res 15:422–425

    Google Scholar 

  • Slattery DA, Cryan JF (2012) Using the rat forced swim test to assess antidepressant-like activity in rodents. Nat Protoc 7:1009–1014

    Article  CAS  PubMed  Google Scholar 

  • Soni K, Parle M (2017) Trachyspermum ammi seeds supplementation helps reverse scopolamine, alprazolam and electroshock induced amnesia. ‎Neurochem Res 42:1333–1344

    Article  CAS  PubMed  Google Scholar 

  • Tandon R, Gaebel W, Barch DM, Bustillo J, Gur RE, Heckers S, Malaspina D, Owen MJ, Schultz S, Tsuang M, Van Os J (2013) Definition and description of schizophrenia in the DSM-5. Schizophr Res 150:3–10

    Article  PubMed  Google Scholar 

  • Wagner C, Sefkow M, Kopka J (2003) Construction and application of a mass spectral and retention time index database generated from plant GC/EI-TOF-MS metabolite profiles. Phytochemistry 62:887–900

    Article  CAS  PubMed  Google Scholar 

  • Yadav M, Parle M (2017) Eucalyptus oil decreases stereotypic behaviours induced by NMDA receptor antagonist ketamine. Int J Herb Med 5:27–30

    Google Scholar 

  • Yadav M, Jindal DK, Dhingra MS, Kumar A, Parle M, Dhingra S (2017a) Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations. Inflammopharmacol. https://doi.org/10.1007/s10787-017-0366-8

    Article  Google Scholar 

  • Yadav M, Parle M, Sharma N, Dhingra S, Raina N, Jindal DK (2017b) Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice. Drug Deliv 24:1429–1440

    Article  CAS  PubMed  Google Scholar 

  • Yadav M, Parle M, Jindal DK, Dhingra S (2018) Protective effects of stigmasterol against ketamine-induced psychotic symptoms: possible behavioral, biochemical and histopathological changes in mice. Pharmacol Rep. https://doi.org/10.1016/j.pharep.2018.01.001

    Article  PubMed  Google Scholar 

  • Zhao CX, Liang YZ, Fang HZ, Li XN (2005) Temperature-programmed retention indices for gas chromatography–mass spectroscopy analysis of plant essential oils. J Chromatogr A 1096:76–85

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Guru Jambheshwar University of Science and Technology, Hisar, Haryana (India) for financial assistance.

Author information

Authors and Affiliations

  1. Faculty of Medical Sciences, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, India

    Monu Yadav, Deepak Kumar Jindal & Milind Parle

  2. University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study (UGC-CAS) in Pharmaceutical Sciences, Panjab University, Chandigarh, India

    Anil Kumar

  3. Faculty of Medical Sciences, School of Pharmacy, The University of the West Indies, St. Augustine Campus, St. Augustine, Trinidad and Tobago

    Sameer Dhingra

Authors
  1. Monu Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deepak Kumar Jindal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Milind Parle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anil Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sameer Dhingra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sameer Dhingra.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yadav, M., Jindal, D.K., Parle, M. et al. Targeting oxidative stress, acetylcholinesterase, proinflammatory cytokine, dopamine and GABA by eucalyptus oil (Eucalyptus globulus) to alleviate ketamine-induced psychosis in rats. Inflammopharmacol 27, 301–311 (2019). https://doi.org/10.1007/s10787-018-0455-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-018-0455-3

Keywords

Search

Navigation