Effect of hydro-alcoholic extract of Cinnamomum zeylanicum on nitric oxide metabolites in brain tissues following seizures induced by pentylenetetrazole in mice

Document Type : Original Research Article

Authors

1 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran. Department of Physiology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

3 Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.

4 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

5 Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

6 Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran. Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

Abstract

Objective: The effects of Cinnamomum zeylanicum on oxidative stress imposed by pentylenetetrazole (PTZ) was examined in mice brain tissues.
Materials and Methods: Animals were divided into five groups as follows: 1- control group which received saline; 2- PTZ group (100 mg/kg, ip); and groups 3 to 5 which received (100, 200, and 400 mg/kg) of C. zeylanicum for seven days prior to PTZ injection. The latencies of the first minimal clonic seizure (MCS) and the first generalized tonic-clonic seizure (GTCS) and levels of oxidant and antioxidant biomarkers were measured.
Results: Treatment with the two higher doses of the extract significantly increased the MCS and GTCS latencies (p<0.05 to p<0.001). Malondialdehyde (MDA) and nitric oxide (NO) levels were increased, but superoxide dismutase (SOD), catalase (CAT), and thiol were decreased in both cortical and hippocampal tissues of the PTZ group compared to the controls (p<0.001). Pretreatment with the two higher doses of C. zeylanicum significantly led to a significant correction in NO, MDA, SOD and CAT levels in the hippocampus and cortex compared to the PTZ group (p<0.05 to p<0.001).
Conclusion: Antioxidant and anticonvulsant effects of C. zeylanicum in PTZ-injected animals may suggest its potential therapeutic effect on nervous diseases such as seizures.

Keywords


Aguiar CC, Almeida AB, Araújo PV, de Abreu
RN, Chaves EM, do Vale OC, Macêdo DS,
Woods DJ, Fonteles MM, Vasconcelos SM.
2012. Oxidative stress and epilepsy:
literature review. Oxid Med Cell Longev,
2012: 1-12.
Alizadeh Behbahani B, Falah F, Lavi Arab F,
Vasiee M, Tabatabaee Yazdi F. 2020.
Chemical composition and antioxidant,
antimicrobial, and antiproliferative
activities of Cinnamomum zeylanicum bark
essential oil. Evid Based Complement
Alternat Med, 2020: 1-10.
Anaeigoudari A, Hosseini M, Karami R,
Vafaee F, Mohammadpour T, Ghorbani A,
Sadeghnia HR. 2016. The effects of
different fractions of Coriandrum sativum
on pentylenetetrazole-induced seizures and
brain tissues oxidative damage in rats.
Avicenna J Phytomed, 6: 223-235.
Chang SJ, Yu BC. 2010. Mitochondrial
matters of the brain: mitochondrial
dysfunction and oxidative status in
epilepsy. J Bioenerg Biomembr, 42: 457-
459.
Choopankareh S, Vafaee F, Shafei MN,
Sadeghnia HR, Salarinia R, Zarepoor L,
Hosseini M. 2015. Effects of melatonin and
theanine administration on
pentylenetetrazole-induced seizures and
brain tissues oxidative damage in
ovariectomized rats. Turk J Med Sci, 45:
842-849.
Devi PU, Manocha A, Vohora D. 2008.
Seizures, antiepileptics, antioxidants and
oxidative stress: an insight for researchers.
Expert Opin Pharmacother, 9: 3169-3177.
Edalatmanesh MA, Khodabandeh H, Yazdani
N, Rafiei S. 2018. Effect of Cinnamomum
Zeylanicum extract on memory and
hippocampal cell density in animal model
of diabetes. J Arak Univ Med Sci, 21: 56-
66.
Eftekhar N, Moghimi A, Boskabady MH,
Kaveh M, Shakeri F. 2019. Ocimum
basilicum affects tracheal responsiveness,
lung inflammatory cells and oxidant–
antioxidant biomarkers in sensitized rats.
Drug Chem Toxicol, 42: 286-294.
Fisher RS, Acevedo C, Arzimanoglou A,
Bogacz A, Cross JH, Elger CE, Engel J,
Forsgren L, French JA, Glynn M. 2014.
ILAE official report: a practical clinical
definition of epilepsy. Epilepsia, 55: 475-
482.
Garthwaite J, Charles SL, Chess-Williams R.
1988. Endothelium-derived relaxing factor
release on activation of NMDA receptors
suggests role as intercellular messenger in
the brain. Nature, 336: 385-388.
Garthwaite J. 1991. Glutamate, nitric oxide
and cell-cell signalling in the nervous
system. Trends Neurosci, 14: 60-67.
Ghosh T, Basu A, Adhikari D, Roy D, Pal AK.
2015. Antioxidant activity and structural
features of Cinnamomum zeylanicum.
Biotech, 5: 939-947.
Goldenberg MM. 2010. Overview of drugs
used for epilepsy and seizures: etiology,
diagnosis, and treatment. Pharm Ther, 35:
392-415.
Guna V, Saha L, Bhatia A, Banerjee D,
Chakrabarti A. 2018. Anti-oxidant and antiapoptotic effects of berberine in
pentylenetetrazole-induced kindling model
in rat. J Epilepsy Res, 8: 66-73.
Gunawardena D, Karunaweera N, Lee S, van
Der Kooy F, Harman DG, Raju R, Bennett
L, Gyengesi E, Sucher NJ, Münch G. 2015.
Anti-inflammatory activity of cinnamon
extracts–identification of Ecinnamaldehyde and o-methoxy
cinnamaldehyde as the most potent
bioactive compounds. Food func, 6: 910-
919.
Hitiris N, Mohanraj R, Norrie J, Sills GJ,
Brodie MJ. 2007. Predictors of
pharmacoresistant epilepsy. Epilepsy Res,
75: 192-196.
Homayoun M, Seghatoleslam M, Pourzaki M,
Shafieian R, Hosseini M, Bideskan AE.
2015. Anticonvulsant and neuroprotective
effects of Rosa damascena hydro-alcoholic
extract on rat hippocampus. Avicenna J
Phytomed, 5: 260-270.
Hosseinzadeh H, Sadeghnia H. 2007.
Protective effect of safranal on
pentylenetetrazol-induced seizures in the
rat: involvement of GABAergic and opioids
systems. Phytomed, 14: 256-262.
Cinnamomum zeylanicum and oxidative damage in seizures
AJP, Vol. 12, No. 3, May-Jun 2022 279
Itoh K, Watanabe M. 2009. Paradoxical
facilitation of pentylenetetrazole-induced
convulsion susceptibility in mice lacking
neuronal nitric oxide synthase.
Neuroscience, 159: 735-743.
Jain S, Sangma T, Shukla SK, Mediratta PK.
2015. Effect of Cinnamomum zeylanicum
extract on scopolamine-induced cognitive
impairment and oxidative stress in rats.
Nutr Neurosci, 18: 210-216.
Jalili C, Salahshoor M, Pourmotabbed A,
Moradi S, Roshankhah S, Darehdori AS,
Motaghi M. 2014. The effects of aqueous
extract of Boswellia Serrata on
hippocampal region CA1 and learning
deficit in kindled rats. Res Pharm Sci, 9:
351-358.
Kaneko K, Itoh K, Berliner LJ, Miyasaka K,
Fujii H. 2002. Consequences of nitric oxide
generation in epileptic‐seizure rodent
models as studied by in vivo EPR. Magn
Reson Med Sci, 48: 1051-1056.
Kaputlu İ, Uzbay T. 1997. L-NAME inhibits
pentylenetetrazole and strychnine-induced
seizures in mice. Brain Res, 753: 98-101.
Karami R, Hosseini M, Mohammadpour T,
Ghorbani A, Sadeghnia HR, Rakhshandeh
H, Vafaee F, Esmaeilizadeh M. 2015.
Effects of hydroalcoholic extract of
Coriandrum sativum on oxidative damage
in pentylenetetrazole-induced seizures in
rats. Iran J Neurol, 14: 59-66.
Khodabakhshi T, Beheshti F, Hosseini M,
Mousavi SM, Rakhshandeh H, Sadeghnia
HR, Aghaei A. 2017. Effect of Ocimum
basilicum hydro-alcoholic extract on
oxidative damage of brain tissues following
seizures induced by pentylenetetrazole in
mice. Physiol Pharmacol, 21: 295-303.
Kim HC, Choi DY, Jhoo WK, Lee DW, Koo
CH, Kim C. 1997. Aspalatone, a new
antiplatelet agent, attenuates the
neurotoxicity induced by kainic acid in the
rat. Life Sci, 61: 373-381.
Kudin AP, Kudina TA, Seyfried J, Vielhaber
S, Beck H, Elger CE, Kunz WS. 2002.
Seizure‐dependent modulation of
mitochondrial oxidative phosphorylation in
rat hippocampus. Europ J Neurosci, 15:
1105-1114.
Liang LP, Patel M. 2004. Mitochondrial
oxidative stress and increased seizure
susceptibility in Sod2−/+ mice. Free Radic
Biol Med 36: 542-554.
Lin TK, Chen SD. 2020. Seizure-induced
oxidative stress in status epilepticus: is
antioxidant beneficial? Antioxidants, 9: 1-
10.
Lodhi M, Shaikh S, Afridi A, Baig MT,
Farooq L, Sadiq S. 2019. Comparison of
anti-seizure efficacy of combined extract of
Swertia chirata and Brassica nigra with
standard anti-epileptic drugs in PTZ model.
Health Sci, 8: 160-167.
Löscher W, Hönack D, Fassbender CP,
Nolting B. 1991. The role of technical,
biological and pharmacological factors in
the laboratory evaluation of anticonvulsant
drugs. III. Pentylenetetrazole seizure
models. Epilepsy Res, 8: 171-189.
Manzoni O, Prezeau L, Marin P, Deshager S,
Bockaert J, Fagni L. 1992. Nitric oxideinduced blockade of NMDA receptors.
Neuron, 8: 653-662.
Mehla J, Reeta K, Gupta P, Gupta YK. 2010.
Protective effect of curcumin against
seizures and cognitive impairment in a
pentylenetetrazole-kindled epileptic rat
model. Life Sci, 87: 596-603.
Moncada S, Bolaños JP. 2006. Nitric oxide,
cell bioenergetics and neurodegeneration. J
Neurochem, 97: 1676-1689.
Nidhi G, Balakrishnan S, Pandhi P. 1999. Role
of nitric oxide in electroshock and
pentylenetetrazole. Methods Find Exp Clin
Pharmacol, 21: 609-612.
Pelligrino DA, Baughman VL, Koenig HM.
1996. Nitric oxide and the brain. Inter
Anesthesiol Clin, 34: 113-132.
Picón Pagès P, Garcia-Buendia J, Muñoz FJ.
2019. Functions and dysfunctions of nitric
oxide in brain. Biochimica et biophysica
acta. Mol Basis Dis, 1865: 1949-1967.
Porter RJ, Cereghino J, Gladding GD, Hessie
B, Kupferberg HJ, Scoville B, White BG.
1984. Antiepileptic drug development
program. Cleveland Clin Quart, 51: 293-
305.
Riazi K, Roshanpour M, Rafiei‐Tabatabaei N,
Homayoun H, Ebrahimi F, Dehpour AR.
2006. The proconvulsant effect of sildenafil
in mice: role of nitric oxide–cGMP
pathway. British J pharmacol, 147: 935-
943.
Robello M, Amico C, Bucossi G, Cupello A,
Rapallino M, Thellung S. 1996. Nitric
oxide and GABAA receptor function the rat
cerebral cortex and cerebellar granule cells.
Neurosci, 74: 99-105.
Sahebari M, Shakeri F, Azadi HG, Arjmand
Assaran et al.
AJP, Vol. 12, No. 3, May-Jun 2022 280
MH, Ghayour-Mobarhan M, Parizadeh
MR, Alamdari DH. 2015. Pro-oxidantantioxidant balance (PAB) in rheumatoid
arthritis and its relationship to disease
activity. Curr Rheumatol Rev, 11: 28-33.
Seema J, Sparsh G. 2019. Effects of
Cinnamomum zeylanicum bark extract on
nociception and anxiety like behavior in
mice. Asian J Pharm Clin Res, 12: 236-241.
Sendrowski K, Sobaniec W. 2013.
Hippocampus, hippocampal sclerosis and
epilepsy. Pharmacol Rep, 65: 555-565.
Shah AH, Al-Shareef AH, Ageel AM, Qureshi
S. 1998. Toxicity studies in mice of
common spices, Cinnamomum zeylanicum
bark and Piper longum fruits. Plant Foods
Hum Nutr, 52: 231-239.
Silva Brum L, Elisabetsky E, Souza D. 2001.
Effects of linalool on [3H] MK801 and
[3H] muscimol binding in mouse cortical
membranes. Phytother Res, 15: 422-425.
Theard MA, Baughman VL, Wang Q,
Pelligrino DA, Albrecht RF. 1995. The role
of nitric oxide in modulating brain activity
and blood flow during seizure. Neuroreport,
6: 921-924.
Trinka E, Cock H, Hesdorffer D, Rossetti AO,
Scheffer IE, Shinnar S, Shorvon S,
Lowenstein DH. 2015. A definition and
classification of status epilepticus–report of
the ilae task force on classification of status
epilepticus. Epilepsia, 56: 1515-1523.
Unlu M, Ergene E, Unlu GV, Zeytinoglu HS,
Vural N. 2010. Composition, antimicrobial
activity and in vitro cytotoxicity of essential
oil from Cinnamomum zeylanicum Blume
(Lauraceae). Food Chem Toxicol, 48:
3274-3280.
Wojtal K, Gniatkowska-Nowakowska A,
Czuczwar SJ. 2003. Is nitric oxide involved
in the anticonvulsant action of antiepileptic
drugs? Pol J Pharmacol, 55: 535-542