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Home / Equine Research Bank / Pharmaceuticals (Basel) / Action of Carvacrol on Parascaris sp. and Antagonistic Effec...
Pharmaceuticals (Basel, Switzerland)2021; 14(6); 505; doi: 10.3390/ph14060505

Action of Carvacrol on Parascaris sp. and Antagonistic Effect on Nicotinic Acetylcholine Receptors.

Abstract: sp. is the only ascarid parasitic nematode in equids and one of the most threatening infectious organisms in horses. Only a limited number of compounds are available for treatment of horse helminthiasis, and sp. worms have developed resistance to the three major anthelmintic families. In order to overcome the appearance of resistance, there is an urgent need for new therapeutic strategies. The active ingredients of herbal essential oils are potentially effective antiparasitic drugs. Carvacrol is one of the principal chemicals of essential oil from , , , , and herbs. However, the antiparasitic mode of action of carvacrol is poorly understood. Here, the objective of the work was to characterize the activity of carvacrol on sp. nicotinic acetylcholine receptor (nAChR) function both in vivo with the use of worm neuromuscular flap preparations and in vitro with two-electrode voltage-clamp electrophysiology on nAChRs expressed in oocytes. We developed a neuromuscular contraction assay for body flaps and obtained acetylcholine concentration-dependent contraction responses. Strikingly, we observed that 300 µM carvacrol fully and irreversibly abolished sp. muscle contractions elicited by acetylcholine. Similarly, carvacrol antagonized acetylcholine-induced currents from both the nicotine-sensitive AChR and the morantel-sensitive AChR subtypes. Thus, we show for the first time that body muscle flap preparation is a tractable approach to investigating the pharmacology of sp. neuromuscular system. Our results suggest an intriguing mode of action for carvacrol, being a potent antagonist of muscle nAChRs of sp. worms, which may account for its antiparasitic potency.
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Publication Date: 2021-05-26 PubMed ID: 34073197PubMed Central: PMC8226574DOI: 10.3390/ph14060505Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the effects of carvacrol, a compound in certain essential oils, on Parascaris sp., a parasitic worm in horses and discusses how it inhibits the function of specific receptors in these worms, potentially providing an effective treatment.

Objective of the Research

  • The research aimed to understand the modality, or mode of action, of carvacrol, an active ingredient in essential oils derived from various herbs, on Parascaris sp., a type of parasitic worm prevalent in horses.

Methods of the Study

  • This study examined the effects of carvacrol on the worm’s nicotinic acetylcholine receptor (nAChR) both live (in vivo) and in a controlled lab setting (in vitro).
  • Neuromuscular flap preparations of the worm were used for in vivo studies, while the in vitro studies involved acetylcholine receptors expressed in Xenopus oocytes (immature egg cells commonly used in scientific research).
  • A neuromuscular contraction assay was also developed for Parascaris sp. body flaps, providing acetylcholine concentration-dependent contraction responses.

Findings of the Study

  • The assays revealed that a concentration of 300 µM carvacrol completely abolished the parasitic worm’s muscle contractions elicited by acetylcholine, suggesting an antagonistic effect on the nAChR.
  • The in vitro tests also revealed that carvacrol inhibited acetylcholine-induced currents from both the nicotine-sensitive AChR and the morantel-sensitive AChR subtypes.

Significance of the Study

  • The research demonstrates the potential of carvacrol as an influential antagonist of muscle nAChRs in Parascaris sp. worms, which may account for its significant antiparasitic properties.
  • This study is the first to show that body muscle flap preparation can help investigate the pharmacology of the Parascaris sp. neuromuscular system, offering a unique approach to exploring potential treatments for parasitic infections in horses.

Cite This Article

APA
Trailovic SM, Rajkovic M, Marjanovic DS, Neveu C, Charvet CL. (2021). Action of Carvacrol on Parascaris sp. and Antagonistic Effect on Nicotinic Acetylcholine Receptors. Pharmaceuticals (Basel), 14(6), 505. https://doi.org/10.3390/ph14060505

Publication

Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
NlmUniqueID: 101238453
Country: Switzerland
Language: English
Volume: 14
Issue: 6
PII: 505

Researcher Affiliations

Trailovic, Sasa M
  • Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Rajkovic, Milan
  • Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, 11000 Belgrade, Serbia.
  • Department of Biology, Faculty of Veterinary Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Marjanovic, Djordje S
  • Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Neveu, Cédric
  • INRAE, Université de Tours, ISP, 37380 Nouzilly, France.
Charvet, Claude L
  • INRAE, Université de Tours, ISP, 37380 Nouzilly, France.

Conflict of Interest Statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results.

References

This article includes 49 references
  1. Nielsen MK. Universal challenges for parasite control: a perspective from equine parasitology.. Trends Parasitol 2015 Jul;31(7):282-4.
    doi: 10.1016/j.pt.2015.04.013pubmed: 26143301google scholar: lookup
  2. Reinemeyer CR, Nielsen MK. Parasitism and colic.. Vet Clin North Am Equine Pract 2009 Aug;25(2):233-45.
    doi: 10.1016/j.cveq.2009.04.003pubmed: 19580936google scholar: lookup
  3. Sallé G, Guillot J, Tapprest J, Foucher N, Sevin C, Laugier C. Compilation of 29 years of postmortem examinations identifies major shifts in equine parasite prevalence from 2000 onwards.. Int J Parasitol 2020 Feb;50(2):125-132.
    doi: 10.1016/j.ijpara.2019.11.004pubmed: 31981673google scholar: lookup
  4. Gokbulut C, McKellar QA. Anthelmintic drugs used in equine species.. Vet Parasitol 2018 Sep 15;261:27-52.
    doi: 10.1016/j.vetpar.2018.08.002pubmed: 30253849google scholar: lookup
  5. von Samson-Himmelstjerna G. Anthelmintic resistance in equine parasites - detection, potential clinical relevance and implications for control.. Vet Parasitol 2012 Apr 19;185(1):2-8.
    doi: 10.1016/j.vetpar.2011.10.010pubmed: 22100141google scholar: lookup
  6. Matthews JB. Anthelmintic resistance in equine nematodes.. Int J Parasitol Drugs Drug Resist 2014 Dec;4(3):310-5.
    doi: 10.1016/j.ijpddr.2014.10.003pmc: PMC4266799pubmed: 25516842google scholar: lookup
  7. Nielsen MK, Reinemeyer CR, Donecker JM, Leathwick DM, Marchiondo AA, Kaplan RM. Anthelmintic resistance in equine parasites--current evidence and knowledge gaps.. Vet Parasitol 2014 Jul 30;204(1-2):55-63.
    doi: 10.1016/j.vetpar.2013.11.030pubmed: 24433852google scholar: lookup
  8. Peregrine AS, Molento MB, Kaplan RM, Nielsen MK. Anthelmintic resistance in important parasites of horses: does it really matter?. Vet Parasitol 2014 Mar 17;201(1-2):1-8.
    doi: 10.1016/j.vetpar.2014.01.004pubmed: 24485565google scholar: lookup
  9. Martin F, Höglund J, Bergström TF, Karlsson Lindsjö O, Tydén E. Resistance to pyrantel embonate and efficacy of fenbendazole in Parascaris univalens on Swedish stud farms.. Vet Parasitol 2018 Dec 15;264:69-73.
    doi: 10.1016/j.vetpar.2018.11.003pubmed: 30503095google scholar: lookup
  10. Raza A, Qamar AG, Hayat K, Ashraf S, Williams AR. Anthelmintic resistance and novel control options in equine gastrointestinal nematodes.. Parasitology 2019 Apr;146(4):425-437.
    doi: 10.1017/S0031182018001786pubmed: 30392477google scholar: lookup
  11. Anthony JP, Fyfe L, Smith H. Plant active components - a resource for antiparasitic agents?. Trends Parasitol 2005 Oct;21(10):462-8.
    doi: 10.1016/j.pt.2005.08.004pubmed: 16099722google scholar: lookup
  12. Kaplan RM, Storey BE, Vidyashankar AN, Bissinger BW, Mitchell SM, Howell SB, Mason ME, Lee MD, Pedroso AA, Akashe A, Skrypec DJ. Antiparasitic efficacy of a novel plant-based functional food using an Ascaris suum model in pigs.. Acta Trop 2014 Nov;139:15-22.
    doi: 10.1016/j.actatropica.2014.06.008pubmed: 24979686google scholar: lookup
  13. Saha S, Lachance S. Effect of essential oils on cattle gastrointestinal nematodes assessed by egg hatch, larval migration and mortality testing.. J Helminthol 2019 Dec 17;94:e111.
    doi: 10.1017/S0022149X19001081pubmed: 31843032google scholar: lookup
  14. López V, Cascella M, Benelli G, Maggi F, Gómez-Rincón C. Green drugs in the fight against Anisakis simplex-larvicidal activity and acetylcholinesterase inhibition of Origanum compactum essential oil.. Parasitol Res 2018 Mar;117(3):861-867.
    doi: 10.1007/s00436-018-5764-3pmc: PMC5876267pubmed: 29368038google scholar: lookup
  15. Baser KH. Biological and pharmacological activities of carvacrol and carvacrol bearing essential oils.. Curr Pharm Des 2008;14(29):3106-19.
    doi: 10.2174/138161208786404227pubmed: 19075694google scholar: lookup
  16. Friedman M. Chemistry and multibeneficial bioactivities of carvacrol (4-isopropyl-2-methylphenol), a component of essential oils produced by aromatic plants and spices.. J Agric Food Chem 2014 Aug 6;62(31):7652-70.
    doi: 10.1021/jf5023862pubmed: 25058878google scholar: lookup
  17. Sakkas H, Papadopoulou C. Antimicrobial Activity of Basil, Oregano, and Thyme Essential Oils.. J Microbiol Biotechnol 2017 Mar 28;27(3):429-438.
    doi: 10.4014/jmb.1608.08024pubmed: 27994215google scholar: lookup
  18. Lei J, Leser M, Enan E. Nematicidal activity of two monoterpenoids and SER-2 tyramine receptor of Caenorhabditis elegans.. Biochem Pharmacol 2010 Apr 1;79(7):1062-71.
    doi: 10.1016/j.bcp.2009.11.002pubmed: 19896925google scholar: lookup
  19. Andre WP, Ribeiro WL, Cavalcante GS, dos Santos JM, Macedo IT, de Paula HC, de Freitas RM, de Morais SM, de Melo JV, Bevilaqua CM. Comparative efficacy and toxic effects of carvacryl acetate and carvacrol on sheep gastrointestinal nematodes and mice.. Vet Parasitol 2016 Mar 15;218:52-8.
    doi: 10.1016/j.vetpar.2016.01.001pubmed: 26872928google scholar: lookup
  20. Katiki LM, Barbieri AME, Araujo RC, Veríssimo CJ, Louvandini H, Ferreira JFS. Synergistic interaction of ten essential oils against Haemonchus contortus in vitro.. Vet Parasitol 2017 Aug 30;243:47-51.
    doi: 10.1016/j.vetpar.2017.06.008pubmed: 28807309google scholar: lookup
  21. Hierro I, Valero A, Pérez P, González P, Cabo MM, Montilla MP, Navarro MC. Action of different monoterpenic compounds against Anisakis simplex s.l. L3 larvae.. Phytomedicine 2004 Jan;11(1):77-82.
    doi: 10.1078/0944-7113-00375pubmed: 14971725google scholar: lookup
  22. Andres MF, Gonzalez-Coloma A, Sanz J, Burillo J, Sainz P. Nematicidal activity of essential oils: A review.. Phytochem. Rev. 2012;11:371–390.
    doi: 10.1007/s11101-012-9263-3google scholar: lookup
  23. Abdel-Rahman FH, Alaniz NM, Saleh MA. Nematicidal activity of terpenoids.. J Environ Sci Health B 2013;48(1):16-22.
    doi: 10.1080/03601234.2012.716686pubmed: 23030436google scholar: lookup
  24. Marjanovic SD, Bogunovic D, Milovanovic M, Marinkovic D, Zdravkovic N, Magas V, Trailovic MS. Antihelminic Activity of Carvacrol, Thymol, Cinnamaldehyde and P-Cymen against the Free-Living Nematode Caenorhabditis Elegans and Rat Pinworm Syphacia Muris.. Acta Vet. Beogr. 2018;68:445–456.
    doi: 10.2478/acve-2018-0036google scholar: lookup
  25. Hernando G, Turani O, Bouzat C. Caenorhabditis elegans muscle Cys-loop receptors as novel targets of terpenoids with potential anthelmintic activity.. PLoS Negl Trop Dis 2019 Nov;13(11):e0007895.
    doi: 10.1371/journal.pntd.0007895pmc: PMC6901230pubmed: 31765374google scholar: lookup
  26. Trailović SM, Marjanović DS, Nedeljković Trailović J, Robertson AP, Martin RJ. Interaction of carvacrol with the Ascaris suum nicotinic acetylcholine receptors and gamma-aminobutyric acid receptors, potential mechanism of antinematodal action.. Parasitol Res 2015 Aug;114(8):3059-68.
    doi: 10.1007/s00436-015-4508-xpmc: PMC4607277pubmed: 25944741google scholar: lookup
  27. Choudhary S, Marjianović DS, Wong CR, Zhang X, Abongwa M, Coats JR, Trailović SM, Martin RJ, Robertson AP. Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors.. Int J Parasitol Drugs Drug Resist 2019 Apr;9:44-53.
    doi: 10.1016/j.ijpddr.2018.12.005pmc: PMC6352305pubmed: 30682641google scholar: lookup
  28. Marjanović DS, Zdravković N, Milovanović M, Trailović JN, Robertson AP, Todorović Z, Trailović SM. Carvacrol acts as a potent selective antagonist of different types of nicotinic acetylcholine receptors and enhances the effect of monepantel in the parasitic nematode Ascaris suum.. Vet Parasitol 2020 Feb;278:109031.
    doi: 10.1016/j.vetpar.2020.109031pubmed: 32032866google scholar: lookup
  29. Courtot E, Charvet CL, Beech RN, Harmache A, Wolstenholme AJ, Holden-Dye L, O'Connor V, Peineau N, Woods DJ, Neveu C. Functional Characterization of a Novel Class of Morantel-Sensitive Acetylcholine Receptors in Nematodes.. PLoS Pathog 2015 Dec;11(12):e1005267.
    doi: 10.1371/journal.ppat.1005267pmc: PMC4666645pubmed: 26625142google scholar: lookup
  30. Blanchard A, Guégnard F, Charvet CL, Crisford A, Courtot E, Sauvé C, Harmache A, Duguet T, O'Connor V, Castagnone-Sereno P, Reaves B, Wolstenholme AJ, Beech RN, Holden-Dye L, Neveu C. Deciphering the molecular determinants of cholinergic anthelmintic sensitivity in nematodes: When novel functional validation approaches highlight major differences between the model Caenorhabditis elegans and parasitic species.. PLoS Pathog 2018 May;14(5):e1006996.
    doi: 10.1371/journal.ppat.1006996pmc: PMC5931475pubmed: 29719008google scholar: lookup
  31. Beech RN, Neveu C. The evolution of pentameric ligand-gated ion-channels and the changing family of anthelmintic drug targets.. Parasitology 2015 Feb;142(2):303-17.
    doi: 10.1017/S003118201400170Xpubmed: 25354656google scholar: lookup
  32. Richmond JE, Jorgensen EM. One GABA and two acetylcholine receptors function at the C. elegans neuromuscular junction.. Nat Neurosci 1999 Sep;2(9):791-7.
    doi: 10.1038/12160pmc: PMC2585773pubmed: 10461217google scholar: lookup
  33. Raymond V, Mongan NP, Sattelle DB. Anthelmintic actions on homomer-forming nicotinic acetylcholine receptor subunits: chicken alpha7 and ACR-16 from the nematode Caenorhabditis elegans.. Neuroscience 2000;101(3):785-91.
    doi: 10.1016/S0306-4522(00)00279-7pubmed: 11113327google scholar: lookup
  34. Boulin T, Fauvin A, Charvet CL, Cortet J, Cabaret J, Bessereau JL, Neveu C. Functional reconstitution of Haemonchus contortus acetylcholine receptors in Xenopus oocytes provides mechanistic insights into levamisole resistance.. Br J Pharmacol 2011 Nov;164(5):1421-32.
    doi: 10.1111/j.1476-5381.2011.01420.xpmc: PMC3221097pubmed: 21486278google scholar: lookup
  35. Abongwa M, Buxton SK, Courtot E, Charvet CL, Neveu C, McCoy CJ, Verma S, Robertson AP, Martin RJ. Pharmacological profile of Ascaris suum ACR-16, a new homomeric nicotinic acetylcholine receptor widely distributed in Ascaris tissues.. Br J Pharmacol 2016 Aug;173(16):2463-77.
    doi: 10.1111/bph.13524pmc: PMC4959957pubmed: 27238203google scholar: lookup
  36. Charvet CL, Guégnard F, Courtot E, Cortet J, Neveu C. Nicotine-sensitive acetylcholine receptors are relevant pharmacological targets for the control of multidrug resistant parasitic nematodes.. Int J Parasitol Drugs Drug Resist 2018 Dec;8(3):540-549.
    doi: 10.1016/j.ijpddr.2018.11.003pmc: PMC6287576pubmed: 30502120google scholar: lookup
  37. Trailović SM, Zurovac Z, Gruborović S, Marjanović DS, Nedeljković-Trailović J. Presynaptic and postsynaptic regulation of muscle contractions in the ascarid nematode Ascaris suum: a target for drug action.. J Helminthol 2016 Nov;90(6):698-705.
    doi: 10.1017/S0022149X15000978pubmed: 26610818google scholar: lookup
  38. Zheng F, Robertson AP, Abongwa M, Yu EW, Martin RJ. The Ascaris suum nicotinic receptor, ACR-16, as a drug target: Four novel negative allosteric modulators from virtual screening.. Int J Parasitol Drugs Drug Resist 2016 Apr;6(1):60-73.
    doi: 10.1016/j.ijpddr.2016.02.001pmc: PMC4805779pubmed: 27054065google scholar: lookup
  39. Robertson AP, Clark CL, Burns TA, Thompson DP, Geary TG, Trailovic SM, Martin RJ. Paraherquamide and 2-deoxy-paraherquamide distinguish cholinergic receptor subtypes in Ascaris muscle.. J Pharmacol Exp Ther 2002 Sep;302(3):853-60.
    doi: 10.1124/jpet.102.034272pubmed: 12183640google scholar: lookup
  40. Sangster NC, Davis CW, Collins GH. Effects of cholinergic drugs on longitudinal contraction in levamisole-susceptible and -resistant Haemonchus contortus.. Int J Parasitol 1991 Oct;21(6):689-95.
    doi: 10.1016/0020-7519(91)90080-Qpubmed: 1757196google scholar: lookup
  41. Kopp SR, Coleman GT, McCarthy JS, Kotze AC. Phenotypic characterization of two Ancylostoma caninum isolates with different susceptibilities to the anthelmintic pyrantel.. Antimicrob Agents Chemother 2008 Nov;52(11):3980-6.
    doi: 10.1128/AAC.00523-08pmc: PMC2573120pubmed: 18710918google scholar: lookup
  42. Martin RJ, Robertson AP, Buxton SK, Beech RN, Charvet CL, Neveu C. Levamisole receptors: a second awakening.. Trends Parasitol 2012 Jul;28(7):289-96.
    doi: 10.1016/j.pt.2012.04.003pmc: PMC3378725pubmed: 22607692google scholar: lookup
  43. Robertson AP, Bjorn HE, Martin RJ. Resistance to levamisole resolved at the single-channel level.. FASEB J 1999 Apr;13(6):749-60.
    doi: 10.1096/fasebj.13.6.749pubmed: 10094935google scholar: lookup
  44. Qian H, Martin RJ, Robertson AP. Pharmacology of N-, L-, and B-subtypes of nematode nAChR resolved at the single-channel level in Ascaris suum.. FASEB J 2006 Dec;20(14):2606-8.
    doi: 10.1096/fj.06-6264fjepubmed: 17056760google scholar: lookup
  45. Qian H, Robertson AP, Powell-Coffman JA, Martin RJ. Levamisole resistance resolved at the single-channel level in Caenorhabditis elegans.. FASEB J 2008 Sep;22(9):3247-54.
    doi: 10.1096/fj.08-110502pmc: PMC2518249pubmed: 18519804google scholar: lookup
  46. Garcia-Bustos JF, Sleebs BE, Gasser RB. An appraisal of natural products active against parasitic nematodes of animals.. Parasit Vectors 2019 Jun 17;12(1):306.
    doi: 10.1186/s13071-019-3537-1pmc: PMC6580475pubmed: 31208455google scholar: lookup
  47. Miró MV, E Silva CR, Viviani P, Luque S, Lloberas M, Costa-Júnior LM, Lanusse C, Virkel G, Lifschitz A. Combination of bioactive phytochemicals and synthetic anthelmintics: In vivo and in vitro assessment of the albendazole-thymol association.. Vet Parasitol 2020 May;281:109121.
    doi: 10.1016/j.vetpar.2020.109121pubmed: 32361524google scholar: lookup
  48. Minsakorn S, Watthanadirek A, Poolsawat N, Puttarak P, Chawengkirttikul R, Anuracpreeda P. The anthelmintic potentials of medicinal plant extracts and an isolated compound (rutin, C(27)H(30)O(16)) from Terminalia catappa L. against Gastrothylax crumenifer.. Vet Parasitol 2021 Mar;291:109385.
    doi: 10.1016/j.vetpar.2021.109385pubmed: 33667989google scholar: lookup
  49. Silva CR, Lifschitz AL, Macedo SRD, Campos NRCL, Viana-Filho M, Alcântara ACS, Araújo JG, Alencar LMR, Costa-Junior LM. Combination of synthetic anthelmintics and monoterpenes: Assessment of efficacy, and ultrastructural and biophysical properties of Haemonchus contortus using atomic force microscopy.. Vet Parasitol 2021 Feb;290:109345.
    doi: 10.1016/j.vetpar.2021.109345pubmed: 33482425google scholar: lookup

Citations

This article has been cited 1 times.
  1. Cain JL, Nielsen MK. The equine ascarids: resuscitating historic model organisms for modern purposes.. Parasitol Res 2022 Oct;121(10):2775-2791.
    doi: 10.1007/s00436-022-07627-zpubmed: 35986167google scholar: lookup
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