Linalool (LIN) is a monoterpene, responsible for the aroma of essential oils in some species. It presents a sedative and anxiolytic potential, enhancing GABAergic currents and behaving as a benzodiazepine-type of drug. The objectives of the present work were to study the neuroprotective effects of LIN on a model of Parkinson’s disease. For that, male Wistar rats were divided into the following groups: sham-operated (SO), 6-OHDA-lesioned, and 6-OHDA-lesioned and treated with LIN (25, 50, and 100 mg/kg, p.o.) for 2 weeks. Afterwards, the animals were subjected to behavioral tests (apomorphine-induced rotations, open field, and forced swimming tests). Then, the animals were euthanized, and the striatum, hippocampus, and prefrontal cortex were processed for neurochemistry (nitrite and lipoperoxidation measurements) and immunohistochemistry (TH and DAT) assays. The results were analyzed by ANOVA and Tukey’s test for multiple comparisons and considered significant at p < 0.05. LIN significantly improved the behavioral alterations of the 6-OHDA-lesioned group, as evaluated by the apomorphine-induced rotations, open field, and forced swimming tests. In addition, LIN partially reversed the decreased DA, DOPAC, and HVA contents observed in the 6-OHDA-lesioned striatum. The untreated 6-OHDA group presented increased nitrite contents and lipoperoxidation in all the brain areas studied, and these changes were completely reversed after LIN treatments. Finally, LIN significantly prevented the reduction in TH and DAT expressions demonstrated in the right 6-OHDA-lesioned striatum. All these data strongly suggest that LIN presents a neuroprotective action in hemiparkinsonian rats, probably related to the drug anti-inflammatory and antioxidant activities.
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Ayaz M, Sadiq A, Junaid M, Ullah F, Subhan F, Ahmed J (2017) Neuroprotective and anti-aging potentials of essential oils from aromatic and medicinal plants. Front Aging Neurosci 9:168. https://doi.org/10.3389/fngi,2017.00168
Batista PA, Werner MF, Oliveira EC, Burgos L, Pereira P, Brum LF, Story GM, Santos AR (2010) The antinociceptive effect of (-)-linalool in models of chronic inflammatory and neuropathic hipersensitivity in mice. J Pain 11:1229–1239.
Blesa J, Trigo-Damas I, Quiroga-Varela A, Jackson-Lewis VR (2015) Oxidative stress and Parkinson's disease. Front Neuroanat 9:91. https://doi.org/10.3389/fnana.2015.00091
Brooks DJ (2010) Imaging dopamine transporters in Parkinson's disease. Biomark Med 4:651–660
Brum LFS, Emanuelli T, Souza DO, Elisabetsky E (2001) Effects of linalool on glutamate release and uptake in mouse cortical synaptosomes. Neurochem Res 26:191–194
Caputo L, Reguilon MD, Minarro J, De Feo V, Rodriguez-Arias M (2018) Lavandula angustifólia essential oil and linalool counteract social aversion induced by social defeat. Molecules. 2018:23,2694. https://doi.org/10.3390/molecules23102694
CONCEA (2010) Diretriz Brasileira para o Cuidado e Utilização de Animais para Fins Científicos e Didáticos. Resolução Normativa n.30. Ministériom da Ciência, Tecnologia e Inovação. http://www.mct.gov.br/upd_blob/0238/238685.pdf
Dali LM, Ulrich H, Real CC, Feng ZP, Sun HS, Britto LR (2017) Carvacrol promotes neuroprotection in the mouse hemiparkinsonian model. Neurosci. 356:176–181
Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Meth Enzymol 186:421–431
Elisabetsky E, Marschner J, Souza DO (1995) Effects of linalool on glutamatergic system in the rat cerebral cortex. Neurochem Res 20:461–465
Elisabetsky E, Brum LF, Souza DO (1999) Anticonvulsant properties of linalool in glutamate-related seizure models. Phytomed. 6:107–113
Galvan A, Wichmann T (2008) Pathophysiology of parkinsonism. Clin Neurophysiol 119:1459–1474
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138
Haavik J, Toska K (1998) Tyrosine hydroxylase and Parkinson's disease. Mol Neurobiol 16:285–309
Harada H, Kashiwadani H, Kanmura Y, Kuwaki T (2018) Linalool odor-induced anxiolytic effects in mice. Front Behav Neurosci 12:241. https://doi.org/10.3389/fnbeh.2018.00241 eCollection 2018
Hefti F, Melamed E, Sahakian BJ, Wurtman RJ (1980) Circling behavior in rats with partial, unilateral nigro-striatal lesions: effect of amphetamine, apomorphine, and DOPA. Pharmacol Biochem Behav 12:185–188
Hudson JL, van Horne CG, Strömberg I, Brock S, Clayton J, Masserano J, Hoffer BJ, Gerhardt GA (1993) Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats. Brain Res 626:167–174
Hui L, He L, Huan L, Xiao Lan L, Al Guo Z (2010) Chemical composition of lavender essential oil and its antioxidant activity and inhibition against rhinitis-related bacterial. African J Microbiol Res 4:309–313
Huo M, Cui X, Xue J, Chi G, Gao R, Deng X, Guan S, Wei J, Soromou LW, Feng H, Wang D (2013) Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model. J Surg Res 180:e47–e54
Hwang O (2013) Role of oxidative stress in Parkinson's disease. Exp Neurobiol 22:11–17
Jarvis GE, Barbosa R, and Thompson AJ (2016a). J Pharmacol Exp Ther. 356:549–562
Jarvis GE, Barbosa R, Thompson AJ (2016b) Noncompetitive inhibition of 5-HT3 receptors by citral, linalool and eucalyptol revealed by nonlinear mixed-effects modeling. J Pharmacol Exp Ther 356:549–563
Jasinska-Myga B, Putzke JD, Wider C, Wszolek ZK, Uitti RJ (2010) Depression in Parkinson’s disease. Can J Neurol Sci 37:61–66
Jaul E, Barron J (2017) Age-related diseases and clinical and public health implications for the 85 years old and over population. Front Publ Health 11(5):335
Javed H, Azirnullah S, Khair SBA, Ojha S, Haque ME (2016) Neuroprotective effect of nerolidol against neuroinflammation and oxidative stress induced by rotenone. BMC Neurosci 17:58. https://doi.org/10.1186/s12868-016-0293-4
Javed H, Azimullah S, Meeran MFN, Ansari SA, Ojha S (2019) Neuroprotective effects of thymol, a dietary monoterpene against dopaminergic neurodegeneration in rotenone-induced rat model of Parkinson’s disease. Int J Mol Sci 20:1538. https://doi.org/10.3390/ijms20071538
Kasper S, Gastpar M, Muller WE, Volz HP, Moller HJ, Dienel A, Schlafke S (2010) Efficacy and safety of silexan, a new, orally administered lavender oil preparation, in subthreshold anxiety disorder-evidence from clinical trials. Wien Med Wochenschr 160:547–556
Leszek J, Barreto GE, Gasiorowski K, Koutsouraki E, Ávila-Rodrigues M, Aliev G (2016) Inflammatory mechanisms and oxidative stress as key factors responsible for progression of neurodegeneration: role of brain innate immune system. CNS Neurol Disord Drug Targets 15(3):2016. https://doi.org/10.2174/187152731566660202125914
Li XJ, Yang YJ, YS LI, Zhang WK, Tang HB (2016) α-Pinene, linalool, and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2. J Ethnopharmacol 179:22–26
Liu K, Chen Q, Liu Y, Zhou X, Wang X (2012) Isolation and biological activities of decanal, linalool, valencene, and octanal from sweet orange oil. J Food Sci 77:C1156–C1161
Mehri S, Meshki MA, Hosseinzadeh H (2015) Linalool as a neuroprotective agent against acrylamide-induced neurotoxicity in Wistar rats. Drug Chem Toxicol 38:162–166
Mercanti G, Bazzu G, Giusti P (2012) A 6-hydroxydopamine in vivo model of Parkinson's disease. Methods Mol Biol 846:355–364
Mosley RL, Benner EJ, Kadiu I, Thomas M, Boska MD, Hasan K, Laurie C, Gendelman HE (2006) Neuroinflammation, oxidative stress and the pathogenesis of Parkinson’s disease. Clin Neurosci Res 6:261–281
National Research Council (2011) Guide for the Care and Use of Laboratory 8th edition. The National Academies Press. Washington, D.C. www.nap.edu
Nutt JG, Burchiel KJ, Comella CL, Jankovic J, Lang AE, Laws ER Jr et al (2003) Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology. 14:69–73
Park SN, Lim YK, Freire MO, Cho E, Jin D, Kook JK (2012) Antimicrobial effect of linalool and α-terpineol against periodontopathic and cariogenic bacteria. Anaerobe 18:369–372
Park H, Seol GH, Ryu S, Choi IY (2016) Neuroprotective effects of (−)-linalool against oxygen-glucose deprivation-induced neuronal injury. Arch Pharm Res 39:555–564
Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates, 5th edn. Academic Press, San Diego
Peana AT, D’Aquila PS, Panin F, Serra G, Pippia P, Moretti MDL (2002) Anti-inflammatory activity of linalool and linalyl acetate constituents of essential oils. Phytomed 9:721–726
Perez-Pardo P, Kliest T, Dodiya HB, Broersen LM, Garssen J, Keshavarzian A, Kraneveld AD (2017) The gut-brain axis in Parkinson’s disease: possibilities for food-base therapies. Eur J Pharmacol 817:86–95
Porres-Martinez M, González-Burgos E, Carretero ME, Gómez-Serranillos MP (2016) In vitro neuroprotective potential of the monoterpenes alpha-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells. Naturforsch C 71:191–199
Sabogal-Guáqueta AM, Osorio E, Cardona-Gómez GP (2016) Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer’s mice. Neuropharmacol 102:111–120
Salvatore MF (2014) Ser 31 Tyrosine hydroxylase phosphorilation parallels differences in dopamine recovery in nigrostriatal pathway following 6-OHDA lesion. J Neurochem 129:548–558
Santos SF, Oliveira HL, Yamada ES, Neves BC, Pereira A Jr (2019) The gut and Parkinson’s disease- a bidirectional pathway. Front Neurol 10:574. https://doi.org/10.3389/fneur.2019.00574 eCollection 2019
Silberman CD, Rodrigues CS, Engelhardt E, Laks J (2013) The impact of depression on survival of Parkinson’s disease patients: a five-year study. J Bras Psiquiatr 62:8–12
Silva LL, Balconi LS, Gressler LT, Garlet QI, Sutili FJ, Vargas APC, Baldisserotto B, Morel AF, Heinzmann BM (2017) S-(+)- and R-(−)-linalool: a comparison of the in vitro anti-Aeromonas hydrophila activity and anesthetic properties in fish. An Acad Bras Ciênc 89:203–212
Simola N, Morelli M, Carta AR (2007) The 6-hydroxydopamine model of Parkinson's disease. Neurotox Res 11:151–167
Snijders AH, Leunissen I, Bakker M, Overeem S, Helmich RC, Bloem BR, Toni I (2011) Gait-related cerebral alterations in patients with Parkinson's disease with freezing of gait. Brain 134(Pt 1):59–72
Souto-Maior FN, de Carvalho FL, de Morais LC, Netto SM, de Sousa DP, de Almeida RN (2011) Anxiolytic-like effects of inhaled linalool oxide in experimental mouse anxiety models. Pharmacol Biochem Behav 100:259–263
Storch A, Ludolph AC, Schwarz J (2004) Dopamine transporter: involvement in selective dopaminergic neurotoxicity and degeneration. J Neural Transm 111:1267–1286
Sugawara Y, Hara C, Tamura K, Fujii T, Nakamura K, Masujima T, Aoki T (1998) Sedative effect on humans of inhalation of essential oil of linalool: sensory evaluation and physiological measurements using optically active linalools. Anal Chim Acta 365:293–299
Sun Y, Sukumaran P, Schaar SBB (2015) TRPM7 and its role in neurodegenerative diseases. Channels. 95:253–261
Tabrez S, Jabir NR, Shaki S, Greig NH, Alam Q, Abuzenadah AM et al (2012) A synopsis on the role of tyrosine hydroxylase in Parkinson’s disease. CNS Neurol Disord Drug Targets 11:395–409
Taylor JM, Main BS, Crack PJ (2013) Neuroinflammation and oxidative stress: co-conspirators in the pathology of Parkinson’s disease. Neurochem Int 62:803–819
Tieu K (2011) A guide to neurotoxic animal models of Parkinson’s disease. Cold Spring Harb Perspect Med 1(1):a009316. https://doi.org/10.1101/cshperspect.a009316
Tysnes OB, Storstein A (2017) Epidemiology of Parkinson's disease. J Neural Transm 124:901–905
Uehleke B, Schaper S, Dienel A, Schlafke S, Stange R (2012) Phase II trial on the effects of silexan in patients with neurasthenia, post-traumatic stress disorder or somatization disorder. Phytomed 19(665–671):2012
Wang Z-J, Heinbockel T (2018) Essential oils and their constituents targeting the GABAergic system and sodium channels as treatment of neurological diseases. Molecules 23(5):E1061. https://doi.org/10.3390/molecules23051061
Xu P, Wang K, Lu C, Dong L, Gao L, Yan M, Aibai S, Yang Y, Liu X (2017a) Protective effect of linalool against beta-induced cognitive deficits and damages in mice. Life Sci 174:21–27
Xu P, Wang K, Lu C, Dong L, Gao L, Yan M, Aibai S, Yang Y, Liu X (2017b) The protective effect of lavender essential oil and its main component linalool against the cognitive deficits induced by d-galactose and aluminum trichloride in mice. Evid Based Complement Alternat Med 2017:7426538. https://doi.org/10.1155/2017/7426538
Zalachoras I, Kagiava A, Vokou D, Theophilidis G (2010) Assessing the local anesthetic effect of five essential oil constituents. Planta Med 76:1647–1653
Zhu X, Libby RT, de Vries WN, Smith RS, Wright DL, Bronson RT, Seburn KL, John SW (2012) Mutations in a P-type ATPase gene cause axonal degeneration. PLoS Genet 8:e1002853. https://doi.org/10.1371/journal.pgen.1002853
The authors are grateful to the financial supports of the Brazilian National Research Council (CNPq), Coordination for Improvement of Higher Level Personnel (CAPES), and Foundation for Scientific and Technological Development Support of the State of Ceará (FUNCAP).
Conflict of interest
The authors declare no conflict of interest.
Experiments were carried out observing the guidelines of the USA National Research Council for care and use of laboratory animals (National Research Council 2011). The experimental procedures and protocols were approved by the Local Ethics Committee of the Faculty of Medicine of the Federal University of Ceará, Fortaleza, Brazil.
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de Lucena, J.D., Gadelha-Filho, C.V.J., da Costa, R.O. et al. L-linalool exerts a neuroprotective action on hemiparkinsonian rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1077–1088 (2020). https://doi.org/10.1007/s00210-019-01793-1
- Parkinson’s disease
- Anti-inflammatory and antioxidant activities