Skip to main content
SpringerLink
Log in

Interaction of carvacrol with the Ascaris suum nicotinic acetylcholine receptors and gamma-aminobutyric acid receptors, potential mechanism of antinematodal action

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Essential plant oils (or their active principles) are safe to use and a potentially attractive alternative to current antiparasitic drugs. In the present study, we tested the effects of carvacrol on the isolated tissues of Ascaris suum and investigated potential interactions with other antiparasitic drugs. We used somatic muscle flaps for contraction assays, as well as for electrophysiological investigations. Carvacrol 300 μM highly significantly inhibited contractions caused by 1, 3, 10, 30, and 100 μM of ACh (p = 0.0023, p = 0.0002, p = 0.0002, p < 0.0001, and p < 0.0001). The control EC50 for acetylcholine was 8.87 μM (log EC50 = 0.95 ± 0.26), while R max was 2.53 ± 0.24 g. The EC50 of acetylcholine in the presence of 300 μM of carvacrol was 27.71 μM (log EC50 = 1.44 ± 0.28) and the R max decreased to 1.63 ± 0.32 g. Furthermore, carvacrol highly significant potentiates inhibitory effect of GABA and piperazine on the contractions induced by ACh. However, carvacrol (100 and 300 μM), did not produce any changes in the membrane potential or conductance of the A. suum muscle cell. While, 300 μM of carvacrol showed a significant inhibitory effect on ACh-induced depolarization response. The mean control depolarization was 13.58 ± 0.66 mV and decreased in presence of carvacrol to 4.50 ± 1.02 mV (p < 0.0001). Mean control Δg was 0.168 ± 0.017 μS, while in the presence of 300 μM of carvacrol, Δg significantly decreased to 0.060 ± 0.018 ΔS (p = 0.0017). The inhibitory effect on contractions may be the explanation of the antinematodal potential of carvacrol. Moreover, inhibition of depolarizations caused by ACh and reduction of conductance changes directly points to an interaction with the nAChR in A. suum.

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
Fig. 6

Similar content being viewed by others

References

  • Abdel-Rahman FH, Alaniz NM, Saleh MA (2013) Nematocidal activity of terpenoids. J Environ Sci Health B 48(1):16–22

    Article  CAS  PubMed  Google Scholar 

  • Anthony RM, Rutitzky LI, Urban JF, Stadecker MJ, Gause WC (2007) Protective immune mechanisms in helminth infection. Nat Rev Immunol 7:975–987

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Barros LA, Yamanaka AR, Silva LE, Vanzeler MLA, Braum DT, Bonaldo J (2009) In vitro larvicidal activity of geraniol and citronellal against Contracaecum sp (Nematoda: Anisakidae). Braz J Med Biol Res 42:918–920

    Article  CAS  PubMed  Google Scholar 

  • Brooker S (2010) Estimating the global distribution and disease burden of intestinal nematode infections: adding up the numbers? A review. Int J Parasitol 40:1145–1154

    Article  Google Scholar 

  • Camurça-Vasconcelos ALF, Bevilaqua CML, Morais SM, Maciel MV, Costa CTC, Macedo ITF, Oliveira LMB, Braga RR, Silva RA, Vieira LS (2007) Anthelmintic activity of Croton zehntneri and Lippia sisidoides essential oils. Vet Parasitol 148:288–294

    Article  PubMed  Google Scholar 

  • Ellis MD, Baxendale FP (1997) Toxicity of seven monoterpenoids to tracheal mites (Acari: Tarsonemidae) and their honeybee (Hymenoptera: Apidae) hosts when applied as fumigants. J Econ Entomol 90:1087–1091

    Article  CAS  Google Scholar 

  • Enan EE (2005) Molecular response of Drosophila melanogaster tyramine receptor cascade to plant essential oils. Insect Biochem Mol Biol 35:309–321

    Article  CAS  PubMed  Google Scholar 

  • Hierro I, Valero A, Pérez P, González P, Cabo MM, Montilla MP, Navarro MC (2004) Action of different monoterpenic compounds against Anisakis simplex s.l. L3 larvae. Phytomedicine 11(1):77–82

    Article  CAS  PubMed  Google Scholar 

  • Holden-Dye L, Krogsgaard-Larsen P, Nielsen L, Walker RJ (1989) GABA receptors on the somatic muscle cells of the parasitic nematode, Ascaris suum: stereoselectivity indicates similarity to a GABAA-type agonist recognition site. Br J Pharmacol 98(3):841–850

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hugot JP, Baujard P, Morand S (2001) Biodiversity in helminths and nematodes as a field of study: an overview. Nematology 3:199–208

    Article  Google Scholar 

  • Kaplan RM, Storey BE, Vidyashankar AN, Bissinger BW, Mitchell SM, Howell SB, Mason ME, Lee MD, Pedroso AA, Akashe A, Skrypec DJ (2014) Antiparasitic efficacy of a novel plant based functional food using an Ascaris suum model in pigs. Acta Trop 139:15–22

    Article  CAS  PubMed  Google Scholar 

  • Komuniecki R, Law WJ, Jex A, Geldhof P, Gray J, Bamber B, Gasser RB (2012) Monoaminergic signaling as a target for anthelmintic drug discovery: receptor conservation among the free-living and parasitic nematodes. Mol Biochem Parasitol 183(1):1–7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lacey E (1990) Mode of action of benzimidazoles. Parasitol Today 6(4):112–115

    Article  CAS  PubMed  Google Scholar 

  • Lei J, Leser M, Enan E (2010) Nematicidal activity of two monoterpenoids and SER-2 tyramine receptor of Caenorhabditis elegans. Biochem Pharmacol 79(7):1062–1071

    Article  CAS  PubMed  Google Scholar 

  • Martin RJ (1982) Electrophysiological effects of piperazine and diethylcarbamazine on Ascaris suum somatic muscle. Br J Pharmacol 77(2):255–265

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Martin RJ, Puttachary S, Buxton SK, Verma S, Robertson AP (2014) The Conqueror Worm: recent advances with cholinergic anthelmintics and techniques excite research for better therapeutic drugs. J Helminthol 29:1–11

    Google Scholar 

  • Paterson S, Barber R (2007) Experimental evolution of parasite lifehistory traits in Strongyloides ratti (Nematoda). Proc Biol Sci 274:146–174

    Article  Google Scholar 

  • Payne L, Fitchett JR (2010) Bringing neglected tropical diseases into the spotlight. Trends Parasitol 26(9):421–423

    Article  PubMed  Google Scholar 

  • Pirri JK, McPherson AD, Donnelly JL, Francis MM, Alkema MJ (2009) A tyramine-gated chloride channel coordinates distinct motor programs of a Caenorhabditis elegans escape response. Neuron 62(4):526–38

  • Richmond JE, Jorgensen EM (1999) One GABA and two acetylcholine receptors function at the C. elegans neuromuscular junction. Nat Neurosci 2(9):791–797

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tong F, Coats JR (2012) Quantitative structure-activity relationships of monoterpenoid binding activities to the housefly GABA receptor. Pest Manag Sci 68(8):1122–1129

    Article  CAS  PubMed  Google Scholar 

  • Tong F, Gross AD, Dolan MC, Coats JR (2013) The phenolic monoterpenoid carvacrol inhibits the binding of nicotine to the housefly nicotinic acetylcholine receptor. Pest Manag Sci 69(7):775–780

    Article  CAS  PubMed  Google Scholar 

  • Trailovic SM, Clark CL, Robertson AP, Martin RJ (2005) Brief application of AF2 produces long lasting potentiation of nAChR responses in Ascaris suum. Mol Biochem Parasitol 139(1):51–64

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Ministry of Education and Science Republic of Serbia, Grant No TR31087.

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia

    Saša M. Trailović & Djordje S. Marjanović

  2. Department of Nutrition and Botany, Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia

    Jelena Nedeljković Trailović

  3. Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA

    Alan P. Robertson & Richard J. Martin

Authors
  1. Saša M. Trailović
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Djordje S. Marjanović
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jelena Nedeljković Trailović
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alan P. Robertson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard J. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Saša M. Trailović.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Trailović, S.M., Marjanović, D.S., Nedeljković Trailović, J. et al. Interaction of carvacrol with the Ascaris suum nicotinic acetylcholine receptors and gamma-aminobutyric acid receptors, potential mechanism of antinematodal action. Parasitol Res 114, 3059–3068 (2015). https://doi.org/10.1007/s00436-015-4508-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-015-4508-x

Keywords

Search

Navigation