Investigation of the Antiepileptic Effect of (R)-(-) and (S)-(+) Carvone in Penicillin-Induced Epileptiform Activity Model

Year 2024, Volume: 6 Issue: 1, 76 - 82, 31.01.2024

Özge Beyazçiçek , Sumeyye Altun , Ersin Beyazçiçek , Şerif Demir

https://doi.org/10.37990/medr.1404966

Abstract

Aim: Epilepsy affects approximately 70 million people worldwide. While many drugs can prevent seizures, they have a limited impact on preventing or curing the disease. In this perspective, natural compounds, especially monoterpenes derived from medicinal plants, have been investigated in epilepsy models, such as carvone (CAR). The principal constituent of peppermint oil, (R)-(-)-carvone (R-CAR), and the primary component in cumin and dill seed oils, (S)-(+)-carvone (S-CAR), find diverse applications in cosmetics, food, and pharmaceutical formulations. This study aims to investigate the antiepileptic effects of the natural compounds S-CAR and R-CAR in penicillin (PEN)-induced experimental epilepsy model in rats.
Material and Method: In the research, 91 male Wistar rats were used. The rats were grouped into 3 main groups as common groups, pre-penicillin groups and post-penicillin groups. The main groups were divided into a total of 13 subgroups. Electrocardiogram recording was taken from rats. At the end of the experiment, the latency of the first epileptiform activity (EA), spike-wave frequency (SWF), and spike-wave amplitude (SWA) of the EA were analyzed.
Results: S-CAR and R-CAR administered before penicillin prolonged the latency to the onset of the first EA. S-CAR and R-CAR administered before penicillin decreased SWF. 100 mg/kg doses of S-CAR and R-CAR injected 30 minutes after penicillin administration decreased SWF. While 200 mg/kg dose of R-CAR administered before penicillin decreased SWA in a time-dependent manner, 100 mg/kg dose of S-CAR administered after penicillin decreased SWA.
Conclusion: These findings indicate that carvone could exhibit both protective and therapeutic effects in the management of epilepsy.

Keywords

Carvone, Epilepsy, Penicillin, Rat

Ethical Statement

AIBU Animal Research Local Ethics Committee with code number 2013/08

Supporting Institution

Duzce University

Project Number

2013.04.01.167

References

• Christensen J, Dreier JW, Sun Y, et al. Estimates of epilepsy prevalence, psychiatric co-morbidity and cost. Seizure. 2023;107:162-71.
• Wang J, Huang P, Yu Q, et al. Epilepsy and long-term risk of arrhythmias. Eur Heart J. 2023;44:3374-82.
• Gesche J, Antonson S, Dreier JW, et al. Social outcome and psychiatric comorbidity of generalized epilepsies – a case-control study. Epilepsia. 2021;62:1158-69.
• Thijs RD, Ryvlin P, Surges R. Autonomic manifestations of epilepsy: emerging pathways to sudden death?. Nat Rev Neurol. 2021;17:774-88.
• Thijs RD, Surges R, O'Brien TJ, Sander JW. Epilepsy in adults. Lancet. 2019;393:689-701.
• Bahr TA, Rodriguez D, Beaumont C, Allred K. The effects of various essential oils on epilepsy and acute seizure: a systematic review. Evid Based Complement Alternat Med. 2019;2019:6216745.
• Sabir SM, Singh D, Rocha JBT. In vitro antioxidant activity of S-carvone isolated from zanthoxylum alatum. Pharm Chem J+. 2015;49:187-91.
• Pina LTS, Serafini MR, Oliveira MA, et al. Carvone and its pharmacological activities: a systematic review. Phytochemistry. 2022;196:113080.
• Zhao M, Du J. Anti-inflammatory and protective effects of D-carvone on lipopolysaccharide (LPS)-induced acute lung injury in mice. Journal of King Saud University - Science. 2020;32:1592-6.
• Asle-Rousta M, Amini R, Aghazadeh S. Carvone suppresses oxidative stress and inflammation in the liver of immobilised rats. Arch Physiol Biochem. 2023;129:597-602.
• Brosnan RJ, Cenani A, Costa LR, et al. Analgesic effect of the mint terpenoid L-carvone in sheep. Vet Anaesth Analg. 2023;50:459-65.
• Silva CMS, Wanderley CWS, Lima-Junior FJB, et al. Carvone (R)-(-) and (S)-(+) enantiomers inhibits upper gastrointestinal motility in mice. Flavour and Fragrance Journal. 2015;30:439-44.
• Abdullah, Alam W, Hussain Y, et al. Neuroprotective effect of essential oils. In: Khan H, Aschner M, Mirzaei H, eds. Phytonutrients and Neurological Disorders. Academic Press; 2023:305-33.
• Nesterkina M, Barbalat D, Zheltvay I, et al. (2S,5R)-2-Isopropyl-5-methylcyclohexanone hydrazones. Molbank. 2019;2019:M1062.
• Kopečná M, Macháček M, Nováčková A, et al. Esters of terpene alcohols as highly potent, reversible, and low toxic skin penetration enhancers. Sci Rep. 2019;9:14617.
• Kessler A, Sahin-Nadeem H, Lummis SCR, et al. GABA(A) receptor modulation by terpenoids from Sideritis extracts. Mol Nutr Food Res. 2014;58:851-62.
• López V, Nielsen B, Solas M, et al. Exploring pharmacological mechanisms of lavender (lavandula angustifolia) essential oil on central nervous system targets. Front Pharmacol. 2017;8:280.
• Ullah I, Badshah H, Naseer MI, et al. Thymoquinone and Vitamin C attenuates pentylenetetrazole-induced seizures via activation of GABAB1 receptor in adult rats cortex and hippocampus. NeuroMolecular Med. 2015;17:35-46.
• Huang C-W, Chow JC, Tsai J-J, Wu S-N. Characterizing the effects of Eugenol on neuronal ionic currents and hyperexcitability. Psychopharmacology. 2012;221:575-87.
• Ankaralı S, Beyazçiçek E, Ankaralı H, Demir Ş. The effect of rapamycin on penicillin-induced epileptiform activity in rats: an electrophysiological study. Anatolian Clin. 2016;21:197-206.
• Beyazcicek E. Investigation of the effect of propolis on penicillin induced epileptiform activity in rats. Med Records. 2023;5:97-103.
• Beyazcicek E, Ankarali S, Beyazcicek O, et al. Effects of thymoquinone, the major constituent of Nigella sativa seeds, on penicillin-induced epileptiform activity in rats. Neurosciences (Riyadh). 2016;21:131-7.
• De Sousa DP, De Farias Nóbrega FF, De Almeida RN. Influence of the chirality of (R)-(-)- and (S)-(+)-carvone in the central nervous system: a comparative study. Chirality. 2007;19:264-8.
• Costa DA, de Oliveira GAL, Lima TC, et al. Anticonvulsant and antioxidant effects of cyano-carvone and its action on acetylcholinesterase activity in mice hippocampus. Cell Mol Neurobiol. 2012;32:633-40.
• Marques THC, Marques MLBGCB, Medeiros J-VR, et al. Anticonvulsant effects of acute treatment with cyane-carvone at repeated oral doses in epilepsy models. Pharmacol Biochem Behav. 2014;124:421-4.
• Alvi AM, Al Kury LT, Alattar A, et al. Carveol attenuates seizure severity and neuroinflammation in pentylenetetrazole-kindled epileptic rats by regulating the Nrf2 signaling pathway. Oxid Med Cell Longev. 2021;2021:9966663.
• Dichter MA, Ayala G. Cellular mechanisms of epilepsy: a status report. Science. 1987;237:157-64.
• Erfanparast A, Tamaddonfard E. Effects of intracortical microinjection of vitamin B12 on penicillin-induced epileptiform activity in rats. Acta Neurobiol Exp (Wars). 2015;75:200-7.
• Arık AE, Bağırıcı F, Sefil F, Marangoz C. Effect of levetiracetam on penicillin induced epileptic activity in rats. Acta Neurobiol Exp (Wars). 2014;74:266-75.
• Hussein AM, Ghalwash M, Magdy K, Abulseoud OA. Beta lactams antibiotic ceftriaxone modulates seizures, oxidative stress and connexin 43 expression in hippocampus of pentylenetetrazole kindled rats. J Epilepsy Res. 2016;6:8-15.