Skip to main content

Evidence for the involvement of the GABAergic, but not serotonergic transmission in the anxiolytic-like effect of bisabolol in the mouse elevated plus maze

Abstract

Bisabolol (α-(−)-bisabolol) is a sesquiterpene which is a part of the essential oil of a variety of plants, but its common source is German chamomile. Several bioactivities including anti-inflammatory, anti-nociceptive, and anti-tumor effects were attributed to bisabolol. However, the neuropharmacological properties of bisabolol have not yet been reported. The present study evaluated behavioral effects of bisabolol using elevated plus maze (EPM), open field test (OFT), and rotarod test. Moreover, this study also examined whether the 5-HT1A and GABAA–benzodiazepine receptor systems are involved in the anxiolytic-like effects of bisabolol. After acute intraperitoneal treatment with bisabolol at the doses of 0.5, 1, 2, 5, and 10 mg/kg, OFT, EPM, and rotarod were utilized for investigating behavioral effects. Flumazenil, a benzodiazepine receptor antagonist, and WAY-100635, a 5-HT1A receptor antagonist, were used to determine the action mechanism in the EPM. Bisabolol especially at the dose of 1 mg/kg was effective in increasing the total number of entries and time spent in the open arms of EPM while number of rearing and grooming in OFT was decreased in comparison to the control. In the rotarod, permanence time was decreased in the mice treated with the high doses of bisabolol. Pretreatment with flumazenil, but not WAY-100635, was able to reverse the effect of bisabolol 1 mg/kg in the EPM, indicating that the anxiolytic-like activity of bisabolol occurs via the GABAergic but not serotonergic transmission. The present study supports the idea that bisabolol may mediate its anxiolytic-like and sedative mechanisms involving GABAA receptors.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  • Amsterdam JD, Li Y, Soeller I, Rockwell K, Mao JJ, Shults J (2009) A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy of generalized anxiety disorder. J Clin Psychopharmacol 29(4):378–382

    Article  PubMed  PubMed Central  Google Scholar 

  • Amsterdam JD, Shults J, Soeller I, Mao JJ, Rockwell K, Newberg AB (2012) Chamomile (Matricaria recutita) may have antidepressant activity in anxious depressed humans-an exploratory study. Altern Ther Health Med 18(5):44

    PubMed  PubMed Central  Google Scholar 

  • Aron de Miranda HA, Gonçalves JCR, Cruz JS, Araújo DAM (2010) Evaluation of the sesquiterpene (−)-α-bisabolol as a novel peripheral nervous blocker. Neurosci Lett 472:11–15

    Article  Google Scholar 

  • Benke D, Barberis A, Kopp S, Altmann KH, Schubiger M, Vogt KE, Rudolph U, Möhler H (2009) GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts. Neuropharmacology 56:174–181

    CAS  Article  PubMed  Google Scholar 

  • Can ÖD, Özkay ÜD, Kıyan HT, Demirci B (2012) Psychopharmacological profile of chamomile (Matricaria recutita L.) essential oil in mice. Phytomedicine 19:306–310

    CAS  Article  PubMed  Google Scholar 

  • Costa JP, de Oliveira GAL, de Almeida AAC, Islam MT, de Sousa DP, de Freitas RM (2014) Anxiolytic-like effects of phytol: possible involvement of GABAergic transmission. Brain Res 1547:34–42

    CAS  Article  PubMed  Google Scholar 

  • de Almeida AAC, Costa JP, de Carvalho RBF, de Sousa DP, de Freitas RM (2012) Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action. Brain Res 1448:56–62

    Article  PubMed  Google Scholar 

  • do Vale TG, Furtado EC, Santos JG, GSB V (2002) Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) NE Brown. Phytomedicine 9:709–714

    Article  PubMed  Google Scholar 

  • File SE (2001) Factors controlling measures of anxiety and responses to novelty in the mouse. Behav Brain Res 125:151–157

    CAS  Article  PubMed  Google Scholar 

  • Gomes PB, Feitosa ML, Silva MIG, Noronha EC, Moura BA, Venâncio ET, Rios ERV, de Sousa DP, de Vasconcelos SMM, de França Fonteles MM, de Sousa FCF (2010) Anxiolytic-like effect of the monoterpene 1, 4-cineole in mice. Pharmacol Biochem Behav 96:287–293

    CAS  Article  PubMed  Google Scholar 

  • Grundmann O, Nakajima JI, Kamata K, Seo S, Butterweck V (2009) Kaempferol from the leaves of Apocynum venetum possesses anxiolytic activities in the elevated plus maze test in mice. Phytomedicine 16:295–302

    CAS  Article  PubMed  Google Scholar 

  • Hendriks H, Bos R, Woerdenbag HJ, Koster AS (1985) Central nervous depressant activity of valerenic acid in the mouse. Planta Med 51:28–31

    CAS  Article  PubMed  Google Scholar 

  • Kamatou GP, Viljoen AM (2010) A review of the application and pharmacological properties of α-bisabolol and α-bisabolol-rich oils. J Am Oil Chem Soc 87(1):1–7

    CAS  Article  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

    CAS  Article  PubMed  Google Scholar 

  • Liu J, Zhai WM, Yang YX, Shi JL, Liu QT, Liu GL, Guo JY (2015) GABA and 5-HT systems are implicated in the anxiolytic-like effect of spinosin in mice. Pharmacol Biochem Behav 128:41–49

    CAS  Article  PubMed  Google Scholar 

  • Manayi A, Nabavi SM, Daglia M, Jafari S (2016) Natural terpenoids as a promising source for modulation of GABAergic system and treatment of neurological diseases. Pharmacol Rep 68:671–679

    CAS  Article  PubMed  Google Scholar 

  • Mansouri MT, Soltani M, Naghizadeh B, Farbood Y, Mashak A, Sarkaki A (2014) A possible mechanism for the anxiolytic-like effect of gallic acid in the rat elevated plus maze. Pharmacol Biochem Behav 117:40–46

    CAS  Article  PubMed  Google Scholar 

  • Melo FHC, Venâncio ET, De Sousa DP, De França Fonteles MM, De Vasconcelos SMM, Viana GSB, De Sousa FCF (2010) Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission. Fundam Clin Pharmacol 24:437–443

    CAS  Article  PubMed  Google Scholar 

  • Moreira MRC, Salvadori MGDSS, de Almeida AAC, de Sousa DP, Jordán J, Satyal P, de Freitas RM, de Almeida RN (2014) Anxiolytic-like effects and mechanism of (−)-myrtenol: a monoterpene alcohol. Neurosci Lett 579:119–124

    CAS  Article  PubMed  Google Scholar 

  • Neto JDN, de Almeida AAC, da Silva OJ, dos Santos PS, de Sousa DP, de Freitas RM (2013) Antioxidant effects of nerolidol in mice hippocampus after open field test. Neurochem Res 38:1861–1870

    Article  Google Scholar 

  • Rocha NFM, de Oliveira GV, de Araújo FYR, Rios ERV, Carvalho AMR, Vasconcelos LF, Macêdo DS, Soares PMG, De Sousa DP, de Sousa FCF (2011) (−)-α-Bisabolol-induced gastroprotection is associated with reduction in lipid peroxidation, superoxide dismutase activity and neutrophil migration. Eur J Pharm Sci 44:455–461

    CAS  Article  PubMed  Google Scholar 

  • Seki T, Kokuryo T, Yokoyama Y, Suzuki H, Itatsu K, Nakagawa A, Mizutani T, Miyake T, Uno M, Yamauchi K, Nagino M (2011) Antitumor effects of a-bisabolol against pancreatic cancer. Cancer Sci 102(12):2199–2205

    CAS  Article  PubMed  Google Scholar 

  • Yamada K, Miura T, Mimaki Y, Sashida Y (1996) Effect of inhalation of chamomile oil vapour on plasma ACTH level in ovariectomized-rat under restriction stress. Biol Pharm Bull 19(9):1244–1246

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was financially supported by the Amol University of Special Modern Technologies, Amol, Iran.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mohaddeseh Abouhosseini Tabari.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tabari, M.A., Tehrani, M.A.B. Evidence for the involvement of the GABAergic, but not serotonergic transmission in the anxiolytic-like effect of bisabolol in the mouse elevated plus maze. Naunyn-Schmiedeberg's Arch Pharmacol 390, 1041–1046 (2017). https://doi.org/10.1007/s00210-017-1405-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-017-1405-0

Keywords

  • Bisabolol
  • Sesquiterpene
  • Locomotor activity
  • Anxiolytic-like
  • Sedative
  • GABAergic modulators