Neurochemical Research

, Volume 38, Issue 9, pp 1861–1870 | Cite as

Antioxidant Effects of Nerolidol in Mice Hippocampus After Open Field Test

  • José Damasceno Nogueira Neto
  • Antonia Amanda Cardoso de Almeida
  • Johanssy da Silva Oliveira
  • Pauline Sousa dos Santos
  • Damião Pergentino de Sousa
  • Rivelilson Mendes de FreitasEmail author
Original Paper


The aim of this study was to evaluate the neuroprotective effects of nerolidol in mice hippocampus against oxidative stress in neuronal cells compared to ascorbic acid (positive control) as well as evaluated the nerolidol sedative effects by open field test compared to diazepam (positive control). Thirty minutes prior to behavioral observation on open field test, mice were intraperitoneally treated with vehicle, nerolidol (25, 50 and 75 mg/kg), diazepam (1 mg/kg) or ascorbic acid (250 mg/kg). To clarify the action mechanism of of nerolidol on oxidative stress in animals subjected to the open field test, Western blot analysis of Mn-superoxide dismutase and catalase in mice hippocampus were performed. In nerolidol group, there was a significant decrease in lipid peroxidation and nitrite levels when compared to negative control (vehicle). However, a significant increase was observed in superoxide dismutase and catalase activities in this group when compared to the other groups. Vehicle, diazepam, ascorbic acid and nerolidol groups did not affected Mn-superoxide dismutase, catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus. Nerolidol showed sedative effects in animals subjected to the open field test. Oxidative process plays a crucial role on neuronal pathological consequence, and implies that antioxidant effects could be achieved using this sesquiterpene.


Hippocampus Essential oils Nerolidol Oxidative stress Open field test 



This work was supported in part by Grants from the Brazilian National Research Council (CNPq), Brazil. R.M.F and P.S.S. are fellows from CNPq.


  1. 1.
    Freitas RM, Souza FCF, Vasconcelos SMM, Viana GSB, Fonteles MMF (2005) Oxidative stress in the hippocampus after status epilepticus in rats. FEBS J 272:1307–1312PubMedCrossRefGoogle Scholar
  2. 2.
    Surmeier DJ, Guzman JN, Sanchez-Padilla J, Schumacker PT (2011) The role of calcium and mitochondrial oxidant stress in the loss of substantia nigra pars compacta dopaminergic neurons in Parkinson’s disease. Neuroscience 198:221–231PubMedCrossRefGoogle Scholar
  3. 3.
    Avery SV (2011) Molecular targets of oxidative stress. Biochem J 434:201–210PubMedCrossRefGoogle Scholar
  4. 4.
    Militão GCG, Ferreira PMP, Freitas RM (2010) Effects of lipoic acid on oxidative stress in rat striatum after pilocarpine-induced seizures. Neurochem Int 56:16–20PubMedCrossRefGoogle Scholar
  5. 5.
    Ferreira PMP, Santos AG, Tininis AG, Costa PM, Cavalheiro AJ, Bolzani VS, Moraes MO, Costa-Lotufo LV, Montenegro RC, Pessoa C (2010) Casearin X exhibits cytotoxic effects in leukemia cells triggered by apoptosis. Chem Biol Interact 188:497–504PubMedCrossRefGoogle Scholar
  6. 6.
    Ferreira PMP, Costa-Lotufo LV, Moraes MO, Barros FW, Martins AM, Cavalheiro AJ, Bolzani VS, Santos AG, Pessoa C (2011) Folk uses and pharmacological properties of Casearia sylvestris: a medicinal review. An Acad Bras Cienc 83:1373–1384PubMedCrossRefGoogle Scholar
  7. 7.
    Barros DO, Xavier SM, Barbosa CO, Silva RF, Maia DF, Oliveira AA, Freitas RM (2007) Efeitos da vitamina E da catalase de hipocampo após estado epiléptico induzido pela pilocarpina em ratos Wistar. Neurosci Lett 416:227–230PubMedCrossRefGoogle Scholar
  8. 8.
    Ferreira PMP, Carvalho AFFU, Sousa DF, Magalhães JF, Martins AR, Martins MAC, Queiroz MGR (2007) Water extract of Moringa oleifera seeds: a toxicological approach. Rev Eletr Pesq Med 1:45–57Google Scholar
  9. 9.
    Freitas RM, Silva FO, Silva MGV, Feng D (2011) Antioxidant mechanisms of iso-6-cassine in suppressing seizures induced by pilocarpine. Rev Bras Farmacogn 21:437–443CrossRefGoogle Scholar
  10. 10.
    Costa JP, Ferreira PB, De Sousa DP, Jordan J, Freitas RM (2012) Anticonvulsant effect of phytol in a pilocarpine model in mice. Neurosci Lett 523:115–118PubMedCrossRefGoogle Scholar
  11. 11.
    De Sousa DP (2011) Analgesic-like activity of essential oils constituents. Molecules 16:2233–2252PubMedCrossRefGoogle Scholar
  12. 12.
    Almeida AAC, Costa JP, Carvalho RBF, De Sousa DP, Freitas RM (2012) Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action. Brain Res 1448:56–62PubMedCrossRefGoogle Scholar
  13. 13.
    Campelo LML, Gonçalves FCM, Feitosa CM, Freitas RM (2011) Antioxidant activity of Citrus limon essential oil in mouse hippocampus. Pharm Biol 49:709–715PubMedCrossRefGoogle Scholar
  14. 14.
    Bagamboula CF, Uyttendaele M, Debevere J (2004) Inhibitory effect of thyme and basil essential oils, carvacrol, thymol, estragol, linalool and p-cymene towards Shigella sonnei and Shigellaflexneri. Food Microbiol 21:33–42CrossRefGoogle Scholar
  15. 15.
    Botelho MA, Nogueira NA, Bastos GM, Fonseca SG, Lemos TL, Matos FJ, Montenegro D, Heukelbach J, Rao VS, Brito GA (2007) Antimicrobial activity of the essential oil from Lippia sidoides, carvacrol and thymol against oral pathogens. Braz J Med Biol Res 40:349–356PubMedCrossRefGoogle Scholar
  16. 16.
    Klopell FC, Lemos M, Sousa JP, Comunello E, Maistro EL, Bastos JK, Andrade SF (2007) Nerolidol, an antiulcer constituent from the essential oil of Baccharis dracunculifolia DC (Asteraceae). Z Naturforsch 62:537–542Google Scholar
  17. 17.
    Pacifico S, D’Abrosca B, Golino A, Mastellone C, Piccolella S, Fiorentino A, Monaco P (2008) Antioxidant evaluation of polyhydroxylated nerolidols from redroot pigweed (Amaranthus retroflexus) leaves. LWT Food Sci Technol 41:1665–1671CrossRefGoogle Scholar
  18. 18.
    Koudou J, Abena AA, Ngaissona P, Bessiére JM (2005) Chemical composition and pharmacological activity of essential oil of Canarium schweinfurthii. Fitoterapia 76:700–703PubMedCrossRefGoogle Scholar
  19. 19.
    IFRA (International Fragrance Association) (2004) Use level surveyGoogle Scholar
  20. 20.
    IFRA (International Fragrance Association) (2007) Volume of use surveyGoogle Scholar
  21. 21.
    Motai T, Kitanaka S (2006) Sesquiterpenoids from Ferula fukanensis and their inhibitory effects on nitric oxide production. J Nat Med 60:54–57CrossRefGoogle Scholar
  22. 22.
    Nogueira Neto JD, Almeida AAC, Silva OA, Carvalho RBF, De Sousa DP, Freitas RM (2012) Avaliação da toxicidade aguda e das propriedades ansiolíticas do nerolidol em camundongos. Biofar Revista de Biologia e Farmácia 8:42–55Google Scholar
  23. 23.
    Péres VF, Moura DJ, Sperotto ARM, Damasceno FC, Caramão EB, Zini CA, Saffi J (2009) Chemical composition and cytotoxic, mutagenic and genotoxic activities of the essential oil from Piper gaudichaudianum Kunth leaves. Food Chem Toxicol 47:2389–2395PubMedCrossRefGoogle Scholar
  24. 24.
    Nogueira Neto JD, De Sousa DP, Freitas RM (2013) Evaluation of antioxidant potential in vitro of nerolidol. J Basic Appl Pharma Sci 34:125–130Google Scholar
  25. 25.
    Silva APS, Cerqueira GS, Nunes LCC, Freitas RM (2012) Effects of an aqueous extract of Orbignya phalerata Mart on locomotor activity and motor coordination in mice and as antioxidant in vitro. Pharmazie 67:260–263PubMedGoogle Scholar
  26. 26.
    Fortes AC, Almeida AAC, Mendonça-Júnior FJB, Freitas RM, Soares Sobrinho JL, Soares MFR (2013) Anxiolytic properties of new chemical entity, 5TIO1. Neurochem Res 38:726–731PubMedCrossRefGoogle Scholar
  27. 27.
    Draper HH, Hadley M (1990) Malondialdehyde determination as an index of lipid peroxidation. Meth Enzymol 186:421–431PubMedCrossRefGoogle Scholar
  28. 28.
    Freitas RLM, Santos IMS, Souza GF, Saldanha GB, Tomé AR, Freitas RM (2010) Oxidative stress in rat hippocampus caused by pilocarpine-induced seizures is reversed by buspirone. Brain Res Bull 81:505–509PubMedCrossRefGoogle Scholar
  29. 29.
    Green LC, Tannenbaum SR, Goldman P (1981) Nitrate synthesis in the germfree and conventional rat. Science 212:56–58PubMedCrossRefGoogle Scholar
  30. 30.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  31. 31.
    Flohé L, Ötting F (1984) Superoxide dismutase assays. Meth Enzymol 105:93–104PubMedCrossRefGoogle Scholar
  32. 32.
    Freitas RM (2009) Investigation of oxidative stress involvement in hippocampus in epilepsy model induced by pilocarpine. Neurosc Lett 462:225–229CrossRefGoogle Scholar
  33. 33.
    Chance B, Maehly AC (1955) Assay catalases and peroxidases. Meth Enzymol 2:764–768CrossRefGoogle Scholar
  34. 34.
    Santos IMS, Tomé AR, Saldanha GB, Ferreira PMP, Militao GCG, Freitas RM (2009) Oxidative stress in the hippocampus during experimental seizures can be ameliorated with the antioxidant ascorbic acid. Oxid Med Cell Longev 2:1–8CrossRefGoogle Scholar
  35. 35.
    Santos PS, Costa JP, Tomé AR, Saldanha GB, Souza GF, Feng D, Freitas RM (2011) Oxidative stress in rat striatum after pilocarpine-induced seizures is diminished by alpha-tocopherol. Eur J Pharmacol 668:65–71PubMedCrossRefGoogle Scholar
  36. 36.
    Lapczynski A, Bhatia SP, Letizia CS, Api AM (2008) Fragrance material review on nerolidol (isomer unspecified). Food ChemToxicol 46:S247–S250CrossRefGoogle Scholar
  37. 37.
    Bakkali F, Averbeck D, Idaomar M (2008) Biological effects of essential oils. Food Chem Toxicol 46:446–475PubMedCrossRefGoogle Scholar
  38. 38.
    Arruda DC, D’alexandri FL, Katzin AM, Uliana SRB (2005) Antileishmanial activity of the terpene nerolidol. Antimicrob Agents Chemother 49:1679–1687PubMedCrossRefGoogle Scholar
  39. 39.
    Lee SJ, Han JI, Lee GS, Park MJ, Choi IG, Na KJ, Jeung EB (2007) Antifungal effect of eugenol and nerolidol against Microsporum gypseum in a guinea pig model. Biol Pharm Bull 30:184–188PubMedCrossRefGoogle Scholar
  40. 40.
    Roussis V, Chinou IB, Tsitsimpikou C, Vagias C, Petrakis PV (2001) Antibacterial activity of volatile secondary metabolites from caribbean soft corals of the genus Gorgonia. Flavour Fragr J 16:364–366CrossRefGoogle Scholar
  41. 41.
    Canalle R, Burim RV, Lopes JLC, Takahashi CS (2001) Assessment of the cytotoxic and clastogenic activities os the sesquiterpene lactone lychnopholide in mammalian cells in vitro and in vivo. Cancer Detect Prev 25:93–101PubMedGoogle Scholar
  42. 42.
    Pículo F, Guiraldeli MC, Andrade SF, Luis ME (2011) In vivo genotoxicity assessment of nerolidol. J Appl Toxicol 7:633–639CrossRefGoogle Scholar
  43. 43.
    Hollis L, Jones RS (2009) US Environmental Protection Agency Office of Pesticide Programs. Biopesticides and Pollution Prevention Division, Farnesol Nerolidol 1:24Google Scholar
  44. 44.
    Johri A, Beal FM (2012) Antioxidants in Huntington’s disease. Biochim Biophys Acta 1822:664–674PubMedCrossRefGoogle Scholar
  45. 45.
    Greenough MA, Camakaris J, Bush AI (2013) Metal dyshomeostasis and oxidative stress in Alzheimer’s disease. Neurochem Int 62:540–555PubMedCrossRefGoogle Scholar
  46. 46.
    Chirayu D, Pandya KR, Howell AP (2012) Antioxidants as potential therapeutics for neuropsychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry (in press)Google Scholar
  47. 47.
    Mecocci P, Polidori MP (2012) Antioxidant clinical trials in mild cognitive impairment and Alzheimer’s disease. Biochim Biophys Acta 1822:631–638PubMedCrossRefGoogle Scholar
  48. 48.
    Kim D, Lee C (2004) Comprehensive study on vitamin C equivalent antioxidant capacity (VCEAC) of various polyphenols in scavenging a free radical and its structural relationship. Crit Rev Food Sci Nutr 44:253–273PubMedCrossRefGoogle Scholar
  49. 49.
    Tiburcio JEV, Hoyos LAC, Asquieri ER (2010) Antocianinas, ácido ascórbico, polifenoles totales y actividad antioxidante, em la Cáscara de camu–camu (Myrciaria dubia (H.B.K) McVaugh). Ciênc Tecnol Aliment 30:151–160CrossRefGoogle Scholar
  50. 50.
    Kim DO, Lee WK, Lee HJ, Lee CY (2002) Vitamin C equivalent antioxidant capacity (VCEAC) of phenolic phytochemicals. J Agr Food Chem 50:3713–3717CrossRefGoogle Scholar
  51. 51.
    Janowska B, Kurpios-Piec D, Prorok P, Szparecki G, Komisarski M, Kowalczyk P, Janion C, Tudek B (2012) Role of damage-specific DNA polymerases in M13 phage mutagenesis induced by a major lipid peroxidation product trans-4-hydroxy-2-nonenal. Mutat Res 29:41–51Google Scholar
  52. 52.
    Raedschelders K, Ansley DM, Chen DDY (2012) The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion. Pharmacol Therap 133:230–255CrossRefGoogle Scholar
  53. 53.
    Halliwell B, Gutteridge JCM (1999) Free radicals in biology and medicine, 3rd edn. Oxford Science Publications, LondonGoogle Scholar
  54. 54.
    Vanhatalo S, Riikonen R (2001) Nitric oxide metabolites, nitrates and nitrites in the cerebrospinal fluid in children with west syndrome. Epilepsy Res 46:3–13PubMedCrossRefGoogle Scholar
  55. 55.
    Yoshida WB, Tardini DMS (2003) Brain injury due to ischemia and reperfusion in carotid edndarterectomy surgery. J Vasc Br 2:119–128Google Scholar
  56. 56.
    Michiels C, Raes M, Toussaint O, Remacle J (1994) Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic Biol Med 17:235–248PubMedCrossRefGoogle Scholar
  57. 57.
    Meister A (1995) Glutathione biosynthesis and its inhibition. Meth Enzymol 252:26–30PubMedCrossRefGoogle Scholar
  58. 58.
    Simonié A, Laginja J, Varljen J, Zupan G, Erakovié V (2000) Lithium plus pilocarpine induced status epilepticus—biochemical changes. Neurosci Res 36:157–166CrossRefGoogle Scholar
  59. 59.
    Naffah-Mazzacoratti MG, Cavalheiro EA, Ferreira EC, Abdalla DSP, Amado D, Bellissimo MI (2001) Pilocarpine-induced status epilepticus increases glutamate release in rat hippocampal synaptosomes. Epilepsy Res 46:121–128PubMedCrossRefGoogle Scholar
  60. 60.
    Pong K, Yongqi Y, Doctrow SR, Baudry M (2002) Attenuation zinc-induced intracellular dysfunction and neurotoxicity by a synthetic superoxide dismutase/catalase mimetic, in cultured cortical neurons. Brain Res 950:218–230PubMedCrossRefGoogle Scholar
  61. 61.
    Halliwell B, Gutteridge JMC (1992) Free radicals, antioxidants and human diseases: where are we now? J Lab Clin Med 119:598–620PubMedGoogle Scholar
  62. 62.
    Rauca C, Wiswedel I, Zerbe R, Keilhoff G, Krug M (2004) The role of superoxide dismutase and α-tocopherol in the development of seizures and kindling induced by pentylenetetrazol-influence of the radical scavenger a-phenyl-N-tert-butyl nitrone. Brain Res 1009:203–212PubMedCrossRefGoogle Scholar
  63. 63.
    Nasuti C, Falcioni ML, Nwankwo LE, Cantalamessa F, Gabbianelli R (2008) Effect of permethrin plus antioxidants on locomotor activity and striatum in adolescent rats. Toxicol 251:45–50CrossRefGoogle Scholar
  64. 64.
    Correa M, Sanchis-Segura C, Aragon CM (2001) Brain catalase activity is highly correlated with ethanol-induced locomotor activity in mice. Physiol Behav 73:641–647PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • José Damasceno Nogueira Neto
    • 1
  • Antonia Amanda Cardoso de Almeida
    • 2
  • Johanssy da Silva Oliveira
    • 3
  • Pauline Sousa dos Santos
    • 3
  • Damião Pergentino de Sousa
    • 4
  • Rivelilson Mendes de Freitas
    • 1
    • 2
    • 3
    Email author
  1. 1.Postgraduate Program in PharmacologyFederal University of PiauíTeresinaBrazil
  2. 2.Postgraduate Program in Pharmaceutical SciencesFederal University of PiauíIninga, TeresinaBrazil
  3. 3.Pharmacy CourseFederal University of PiauíTeresinaBrazil
  4. 4.Department of PhysiologyFederal University of ParaíbaJoão PessoaBrazil

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