Skip to main content
Log in

Antiepileptogenic effects of borneol in pentylenetetrazole-induced kindling in mice

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Borneol, a bicyclic monoterpene, can easily cross the blood brain barrier and was found to possess gamma amino butyric acid (GABA) modulatory effect. The present study was aimed at investigating the antiepileptogenic effect of borneol in the pentylenetetrazole (PTZ)-induced kindling besides its ability to suppress oxidative stress and neuroinflammatory marker, glial fibrillary acidic protein (GFAP). Repeated administration of a subconvulsive dose of PTZ (35 mg/kg, i.p.) on every alternate day for 4 weeks produced kindling in mice. Borneol (5, 10, and 25 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were given as a pretreatment prior to each PTZ injection during the progression of kindling. Oxidative stress parameters such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and lipid peroxidation (LPO) were assessed at the end of the study. Neuronal damage was assessed by hematoxylin and eosin staining technique. GFAP was also evaluated in the hippocampus region of the brain by using immunohistochemistry. Borneol significantly suppressed the process of epileptogenesis in PTZ-kindled mice. The biochemical alterations induced by PTZ kindling were ameliorated in borneol-treated animals which was indicated by decreased LPO and increased SOD, GSH, CAT levels. The distinct neuronal damage observed in the kindled group was counteracted by borneol. Furthermore, it decreased the levels of GFAP which was manifested by reduced immunostaining. The above results are suggestive of the antiepileptogenic potential of borneol in the PTZ-induced kindling model of epilepsy, and thus, it could be a prospective molecule in the treatment of epilepsy.

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

Access this article

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
Fig. 6

Similar content being viewed by others

Abbreviations

PTZ:

Pentylenetetrazole

GFAP:

Glial fibrillary acidic protein

GABA:

Gamma aminobutyric acid

MES:

Maximal electroshock

SOD:

Superoxide dismutase

CAT:

Catalase

GSH:

Reduced glutathione

LPO:

Lipid peroxidation

MDA:

Malondialdehyde

References

  • Aebi H (1974) Catalase. In: Bergmeyer HU (ed) Methods in enzymatic analysis, vol 3. Academic Press Inc, New York, pp. 673–686

    Chapter  Google Scholar 

  • Almeida JR, Souza GR, Silva JC, Saraiva SR, Oliveira Júnior RG, Quintans JS, Barreto RS, Bonjardim LR, Cavalcanti SC, Quintans Júnior LJ (2013) Borneol, a bicyclic monoterpene alcohol, reduces nociceptive behavior and inflammatory response in mice. Scientific World Journal. Hindawi Publishing Corporation 1-5

  • Cavazos JE, Sutula TP (1990) Progressive neuronal loss induced by kindling: a possible mechanism for mossy fiber synaptic reorganization and hippocampal sclerosis. Brain Res 527(1):1–6

    Article  CAS  PubMed  Google Scholar 

  • Costa LG (1994) Cell signaling and neurotoxic events. In: Chang LW, editor. Principles of neurotoxicology. New York: Marcel Dekker, 475–493.

  • Dringen R, Gutterer JM, Hirrlinger J (2000) Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem 267(16):4912–4916

    Article  CAS  PubMed  Google Scholar 

  • Franke H, Kittner H (2001) Morphological alterations of neurons and astrocytes and changes in emotional behavior in pentylenetetrazol-kindled rats. Pharmacol Biochem Behav. 70(2–3):291–303

    Article  CAS  PubMed  Google Scholar 

  • Frantseva MV, Perez Velazquez JL, Tsoraklidis G, Mendonca AJ, Adamchik Y, Mills LR, Carlen PL, Burnham MW (2000) Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience 97(3):431–435

    Article  CAS  PubMed  Google Scholar 

  • Granger RE, Campbell EL, Johnston GA (2005) (+)- and (−)-Borneol: efficacious positive modulators of GABA action at human recombinant α1β2γ2L GABAA receptors. Biochem Pharmacol 69(7):1101–1111

    Article  CAS  PubMed  Google Scholar 

  • Gupta YK, Veerendra Kumar MH, Srivastava AK (2003) Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats. Pharmacol Biochem Behav. 74(3):579–585

    Article  CAS  PubMed  Google Scholar 

  • Horváthová E, Slamenová D, Marsálková L, Sramková M, Wsólová L (2009) Effects of borneol on the level of DNA damage induced in primary rat hepatocytes and testicular cells by hydrogen peroxide. Food Chem Toxicol 47(6):1318–1323

    Article  PubMed  Google Scholar 

  • Ilhan A, Ahmet G, Ferah A, Suat K, Mustafa I (2005) Antiepileptogenic and antioxidant effects of Nigella sativa oil against pentylenetetrazole induced kindling in mice. Neuropharmacology 49(4):456–464

    Article  CAS  PubMed  Google Scholar 

  • Ishige K, Schubert D, Sagara Y (2001) Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. Free Radic Biol Med 30(4):433–446

    Article  CAS  PubMed  Google Scholar 

  • Jain S, Bharal N, Khurana S, Mediratta PK, Sharma KK (2011) Anticonvulsant and antioxidant actions of trimetazidine in pentylenetetrazole-induced kindling model in mice. Naunyn-Schmied Arch Pharmacol 383:385–392

    Article  CAS  Google Scholar 

  • Khurgel M, Ivy GO (1996) Astrocytes in kindling: relevance to epileptogenesis. Epilepsy Res 26(1):163–175

    Article  CAS  PubMed  Google Scholar 

  • Li X (2012) Improved pyrogallol autoxidation method: a reliable and cheap superoxide scavenging assay suitable for all antioxidants. J Agric Food Chem 60(25):6418–6424

    Article  CAS  PubMed  Google Scholar 

  • Liu R, Zhang L, Lan X, Li L, Zhang TT, Sun JH, Du GH (2011) Protection by borneol on cortical neurons against oxygen-glucose deprivation/reperfusion: involvement of anti-oxidation and anti-inflammation through nuclear transcription factor κappaB signaling pathway. Neuroscience 176:408–419

    Article  CAS  PubMed  Google Scholar 

  • Löscher W, Schmidt D (2011) Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia 52(4):657–678

    Article  PubMed  Google Scholar 

  • Lucindo J, Guimarães A, Araújo B, Oliveira G, Santana M, Moreira F, Santos M, Cavalcanti S, Lucca W, Botelho M, Ribeiro L, Nóbrega F, Almeida R (2010) Carvacrol, (−)-borneol and citral reduce convulsant activity in rodents. Afr J Biotechnol 9(39):6566–6572

    Google Scholar 

  • Matsuda S, Umeda M, Uchida H, Kato H, Araki T (2009) Alterations of oxidative stress markers and apoptosis markers in the striatum after transient focal cerebral ischemia in rats. J Neural Transm 116(4):395–404

    Article  CAS  PubMed  Google Scholar 

  • Nandi A, Chatterjee B (1988) Assay of superoxide dismutase activity in animal tissues. J Biosci 13(3):305–315

    Article  CAS  Google Scholar 

  • Okhawa H, Nobuko O, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358

    Article  Google Scholar 

  • Pohle W, Becker A, Grecksch G, Juhre A, Willenberg A (1997) Piracetam prevents pentylenetetrazol kindling-induced neuronal loss and learning deficits. Seizure 6(6):467–474

    Article  CAS  PubMed  Google Scholar 

  • Rauca C, Zerbe R, Jantze H (1999) Formation of free hydroxyl radicals after pentylenetetrazole-induced seizure and kindling. Brain Res 847(2):347–351

    Article  CAS  PubMed  Google Scholar 

  • Reilly CA, Aust SD (1999) Measurement of lipid peroxidation. Curr Protoc Toxicol 2(4):1–13

    Google Scholar 

  • Saha L, Bhandari S, Bhatia A, Banerjee D, Chakrabarti A (2014) Anti-kindling effect of bezafibrate, a peroxisome proliferator-activated receptors alpha agonist, in pentylenetetrazole induced kindling seizure model. J Epilepsy Res 4(2):45–54

    Article  PubMed  PubMed Central  Google Scholar 

  • Sakuma M, Hayakawa N, Kato H, Araki T (2008) Time dependent changes of striatal interneurons after focal cerebral ischemia. J Neural Transm 115(3):413–422

    Article  CAS  PubMed  Google Scholar 

  • Schmidt D (2002) The clinical impact of new antiepileptic drugs after a decade of use in epilepsy. Epilepsy Res 50(1–2):21–32

    Article  CAS  PubMed  Google Scholar 

  • Sedlak J, Lindsay RH (1968) Estimation of total and non-protein sulfhydryl groups in tissues with Ellman’s reagent. Anal Biochem 25(1):192–205

    Article  CAS  PubMed  Google Scholar 

  • Sherafat MA, Ronaghi A, Molaei L, Nejadhoseynian M, Ghasemi R, Hosseini A, Naderi N, Motamedi F (2013) Kindling-induced learning deficiency and possible cellular and molecular involved mechanisms. Neurol Sci 34(6):883–890

    Article  PubMed  Google Scholar 

  • Silveira e Sá R, LN A, de Sousa D P (2013) A review on anti-inflammatory activity of monoterpenes. Molecules 18(1):1227–1254

    Article  Google Scholar 

  • Sinha AK (1972) Calorimetric assay of catalase. Anal Biochem 47(2):389–394

    Article  CAS  PubMed  Google Scholar 

  • Sleven H, Gibbs J, Heales S, Thom M, Cock HR (2006) Depletion of reduced glutathione precedes inactivation of mitochondrial enzymes following limbic status epilepticus in the rat hippocampus. Neurochem Int 48(2):75–82

    Article  CAS  PubMed  Google Scholar 

  • Smith IK, Vierheller TL, Thorne CA (1988) Assay of glutathione reductase in crude tissue homogenates using 5,5′-dithiobis(2-nitrobenzoic acid). Anal Biochem 175(2):408–413

    Article  CAS  PubMed  Google Scholar 

  • Weydert CJ, Cullen JJ (2010) Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc 5(1):51–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by University grants commission (UGC), New Delhi, India.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sadhana Sathaye.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tambe, R., Jain, P., Patil, S. et al. Antiepileptogenic effects of borneol in pentylenetetrazole-induced kindling in mice. Naunyn-Schmiedeberg's Arch Pharmacol 389, 467–475 (2016). https://doi.org/10.1007/s00210-016-1220-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-016-1220-z

Keywords

Navigation