The antiepileptic activity of Safranal in kindling model of epilepsy in male rats

Fatemeh  Saberi; Mehdi Saberi; Mohammad Sayyah; Mahdi Mashhadi Akbar Boojar

doi:10.1590/s2175-97902022e20066

Authors

Fatemeh Saberi Department of pharmacology, Iran University of Medical Sciences, Tehran, Iran
Mehdi Saberi Department of Pharmacology and Toxicology, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran; Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
Mohammad Sayyah Department of Physiology and Pharmacology, Pasture Institute, Tehran, Iran
Mahdi Mashhadi Akbar Boojar Department of Pharmacology and Toxicology, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran; Nano Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0002-2002-9332

DOI:

https://doi.org/10.1590/s2175-97902022e20066

Keywords:

Safranal, Epilepsy, Electrical Kindling, Amygdala, Seizure, Male Rat

Abstract

Recent studies suggested that safranal exerts anticonvulsant properties. The present study aimed to investigate the effect of safranal on epileptic activities in the amygdala electrical kindling model in male rats. Animals were implanted with a recording electrode on the skull and a tripolar in the amygdala. After 10 days of recovery, the afterdischarge (AD) threshold of each animal was determined and stimulated once daily the AD threshold for full kindling development. Then, parameters including afterdischarge duration (ADD), stage 4 latency (S4L), stage 5 duration (S5D), and stimulation threshold were determined before and after injection of safranal (0.05, 0.1, 0.2 ml/ kg; i.p). While the dose of 0.05 ml/kg had no significant effect, the dose of 0.1 ml/kg increased the AD threshold as well as S4L and decreased the S5D (P<0.05). Injection of 0.2 ml/kg of the safranal significantly decreased the ADD and S5D (P<0.05) and 83.3% of animals had no stage 4 and stage 5 of kindling (P<0.001). Based on the obtained data safranal has anticonvulsant effects dosedependently. It seems that a dose of 0.2 ml/kg is the minimum effective dose. Further investigation is warranted to conduct the clinical implications for the treatment of epileptic disorders.

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References

Amin B, Hosseinzadeh H. Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction injury model of neuropathic pain in rats. Fitoterapia. 2012;83(5):888-95.

Armijo JA, Shushtarian M, Valdizan EM, Cuadrado A, Adin J. Ion channels and epilepsy. Curr Pharm Des. 2005;11(15):1975-2003.

Bhosle V. Anticonvulsant and antioxidant activity of aqueous leaves extract of Desmodium triflorum in mice against pentylenetetrazole and maximal electroshock induced convulsion. Rev Bras Farmacogn. 2013;23(4):692-98.

Bie X, Chen Y, Zheng X, Dai H. The role of crocetin in protection following cerebral contusion and in the enhancement of angiogenesis in rats. Fitoterapia. 2011;82(7):997-1002.

Brodie MJ, Sills GJ. Combining antiepileptic drugs- Rational polytherapy? Seizure. 2011;20(5):369-75. doi: https://doi.org/10.1016/j.seizure.2011.01.004

» https://doi.org/10.1016/j.seizure.2011.01.004

Escayg A, Goldin AL. Sodium channel SCN1A and epilepsy: mutations and mechanisms. Epilepsia. 2010;51(9):1650-8. doi: 10.1111/j.1528-1167.2010.02640.x.

» https://doi.org/10.1111/j.1528-1167.2010.02640.x

French JA, Pedley TA. Initial Management of Epilepsy. N Engl J Med. 2008;359(2):166-76. doi: 10.1056/NEJMcp0801738.

» https://doi.org/10.1056/NEJMcp0801738

Hosseinzadeh H, Sadeghnia HR. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: Involvement of GABAergic and opioids systems. Phytomedicine. 2007;14(4):256-62. doi: https://doi.org/10.1016/j.phymed.2006.03.007

» https://doi.org/10.1016/j.phymed.2006.03.007

Hosseinzadeh H, Talebzadeh F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia. 2005;76(7-8):722-4. doi: https://doi.org/10.1016/j.fitote.2005.07.008

» https://doi.org/10.1016/j.fitote.2005.07.008

Hosseinzadeh H, Younesi HM. Antinociceptive and antiinflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol. 2002;2:7.

IJff DM, Kinderen R, Vader C, Majoie MH, Aldenkamp AP. Subjectively perceived side-effects of anti-epileptic drugs in chronic refractory epilepsy. Adv Pharmacoepidemiol Drug Saf. 2015;4(4):186.

Jacob S, Nair AB. An updated overview on therapeutic drug monitoring of recent antiepileptic drugs. Drugs R D. 2016;16(4):303-16.

Jones-Bolin S. Guidelines for the care and use of laboratory animals in biomedical research. Curr Protoc Pharmacol. 2012;59(1):A-4B.

Kandratavicius L, Balista PA, Lopes-Aguiar C, Ruggiero RN, Umeoka EH, Garcia-Cairasco N, et al. Animal models of epilepsy: use and limitations. Neuropsychiatr Dis Treat. 2014;10:1693-705. doi: 10.2147/NDT.S50371.

» https://doi.org/10.2147/NDT.S50371

Khazdair MR, Boskabady MH, Hosseini M, Rezaee R, M. Tsatsakis A. The effects of Crocus sativus (saffron) and its constituents on nervous system: A review. Avicenna J Phytomed. 2015;5(5):376-91.

Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med . 2011;365(10):919-26.

Nassiri-Asl M, Shariati-Rad S, Zamansoltani F. Anticonvulsant effects of aerial parts of Passiflora incarnata extract in mice: involvement of benzodiazepine and opioid receptors. BMC Complem Altern M. 2007;7:26. doi: 10.1186/1472-1468.

» https://doi.org/10.1186/1472-1468

National Research Council (United States). Guide for the care and use of laboratory animals. National Academies Press. 2010, 27.

O’Dell CM, Das A, Wallace Gt, Ray SK, Banik NL. Understanding the basic mechanisms underlying seizures in mesial temporal lobe epilepsy and possible therapeutic targets: a review. J Neurosci Res. 2012;90(5):913-24. doi: 10.1002/jnr.22829.

» https://doi.org/10.1002/jnr.22829

Perez DL, LaFrance WC. Nonepileptic seizures: an updated review. CNS Spectr. 2016;21(3):239-46.

Rezaee R, Hosseinzadeh H. Safranal: From an Aromatic Natural Product to a Rewarding Pharmacological Agent. Iran J Basic Med Sci. 2013;16(1):12-26.

Saberi F, Bahrami F, Saberi M, Mashhadi Akbar Boojar M. The pro-convulsant effects of diazinon low dose in male rats under amygdala kindling. Drug Chem Toxicol. 2020;4:1-8.

Saberi M, Pourgholami MH, Jorjani M. The acute effects of estradiol benzoate on amygdala-kindled seizures in male rats. Brain Res. 2001;891(1-2):1-6.

Saberi M, Rezvanizadeh A, Bakhtiarian A. The antiepileptic activity of Vitex agnus castus extract on amygdala kindled seizures in male rats. Neurosci Lett. 2008;441(2):193-6. doi: 10.1016/j.neulet.2008.06.034.

» https://doi.org/10.1016/j.neulet.2008.06.034

Sadeghnia HR, Cortez MA, Liu D, Hosseinzadeh H, Snead OC, 3rd. Antiabsence effects of safranal in acute experimental seizure models: EEG and autoradiography. J Pharm Pharm Sci. 2008;11(3):1-14.

Schmidt D, Beyenburg S. Chapter 7 Antiepileptic drugs. In: Aronson JK, editor. Side Effects of Drugs Annual: Elsevier; 2009. p. 105-48.

Srivastava R, Ahmed H, Dixit RK, Dharamveer Saraf SA. Crocus sativus L.: A comprehensive review. Pharmacogn Rev. 2010;4(8):200-8. doi: 10.4103/0973-7847.70919.

» https://doi.org/10.4103/0973-7847.70919

St Louis EK. Minimizing AED adverse effects: Improving quality of life in the interictal state in epilepsy care. Curr Neuropharmacol. 2009;7(2):106-14. doi: 10.2174/157015909788848857.

» https://doi.org/10.2174/157015909788848857

Stafstrom CE, Carmant L. Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Biol. 2015;5(6):a022426. doi: 10.1101/cshperspect.a022426.

» https://doi.org/10.1101/cshperspect.a022426

Ventola CL. Epilepsy Management: Newer Agents, Unmet Needs, and Future Treatment Strategies. P T. 2014;39(11):77692.

Wu YV, Liu J, Chen Z, Burnham WM. Benzyl alcohol suppresses seizures in two different animal models. Neurol Res. 2019;41(7):652-657.

Zagaja M, Andres-Mach M, Patrzylas P, Pyrka D, Szpringer M, Florek-Łuszczki M, et al. Influence of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of various novel antiepileptic drugs against maximal electroshockinduced seizures in mice. Fitoterapia. 2016;115:86-91. doi: 10.1016/j.fitote.2016.09.020.

» https://doi.org/10.1016/j.fitote.2016.09.020

Zeka K, Ruparelia KC, Continenza MA, Stagos D, Vegliò F, Arroo RR. Petals of Crocus sativus L. as a potential source of the antioxidants crocin and kaempferol. Fitoterapia. 2015;107:128-34. doi: 10.1016/j.fitote.2015.05.014.

» https://doi.org/10.1016/j.fitote.2015.05.014