Protective Effects of Thymoquinone Against Convulsant Activity Induced by Lithium-Pilocarpine in a Model of Status Epilepticus

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2016 Oct 19

PMID 27752802

Citations 13

Authors

Yiye Shao

Yonghao Feng

Yangmei Xie

Qiong Luo

Long Chen

Bing Li

Yinghui Chen

Affiliations

Soon will be listed here.

Abstract

Inflammation plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black seed (Nigella sativa) oil, which has anti-inflammatory properties in the context of various diseases. This study explored the protective effects of TQ in SE and used a lithium-pilocarpine model of SE to investigate the underlying mechanism, which was related to inflammation mediated by the NF-κB signaling pathway. In the present study, latency to SE increased in the TQ-pretreated group compared with the SE group, and the incidence of SE was significantly reduced. The seizure severity score measured on the Racine scale was significantly decreased in the TQ group compared with the SE group. Moreover, the results of the behavioral tests suggested that TQ may also have a protective effect on learning and memory functions. Finally, we further investigated the protective mechanism of TQ. The results showed that TQ-pretreatment significantly downregulated the protein levels of COX-2 and TNF-α in the brain, in a manner mediated by the NF-κB signaling pathway. These findings demonstrate that TQ attenuates convulsant activity via an anti- inflammation signaling pathway in a model of SE.

Citing Articles

Cognitive comorbidities in the rat pilocarpine model of epilepsy.

Guarino A, Pignata P, Lovisari F, Asth L, Simonato M, Soukupova M Front Neurol. 2024; 15:1392977.

PMID: 38872822 PMC: 11171745. DOI: 10.3389/fneur.2024.1392977.

Effects of thymoquinone and memantine alone and in combination on memory and hippocampal morphology in rats with streptozotocin-induced Alzheimer's disease.

Ozsoy S, Cakir Z, Akcay E, Gevrek F Turk J Med Sci. 2023; 53(4):894-901.

PMID: 38031940 PMC: 10760553. DOI: 10.55730/1300-0144.5653.

Therapeutic potential of thymoquinone and its nanoformulations in neuropsychological disorders: a comprehensive review on molecular mechanisms in preclinical studies.

Saadat M, Dahmardeh N, Sheikhbahaei F, Mokhtari T Naunyn Schmiedebergs Arch Pharmacol. 2023; 397(6):3541-3564.

PMID: 38010395 DOI: 10.1007/s00210-023-02832-8.

Treating Epilepsy with Natural Products: Nonsense or Possibility?.

Malanik M, culenova M, Sychrova A, Skiba A, Skalicka-Wozniak K, Smejkal K Pharmaceuticals (Basel). 2023; 16(8).

PMID: 37630977 PMC: 10459181. DOI: 10.3390/ph16081061.

Molecular mechanisms and signaling pathways of black cumin (Nigella sativa) and its active constituent, thymoquinone: a review.

Sadeghi E, Imenshahidi M, Hosseinzadeh H Mol Biol Rep. 2023; 50(6):5439-5454.

PMID: 37155017 DOI: 10.1007/s11033-023-08363-y.

References

Ullah I, Badshah H, Naseer M, Lee H, Kim M . Thymoquinone and vitamin C attenuates pentylenetetrazole-induced seizures via activation of GABAB1 receptor in adult rats cortex and hippocampus. Neuromolecular Med. 2014; 17(1):35-46. DOI: 10.1007/s12017-014-8337-3. View

Shih R, Wang C, Yang C . NF-kappaB Signaling Pathways in Neurological Inflammation: A Mini Review. Front Mol Neurosci. 2016; 8:77. PMC: 4683208. DOI: 10.3389/fnmol.2015.00077. View

Meng X, Tan L, Tan M, Jiang T, Tan C, Li M . Inhibition of the NLRP3 inflammasome provides neuroprotection in rats following amygdala kindling-induced status epilepticus. J Neuroinflammation. 2014; 11:212. PMC: 4275944. DOI: 10.1186/s12974-014-0212-5. View

Vezzani A, French J, Bartfai T, Baram T . The role of inflammation in epilepsy. Nat Rev Neurol. 2010; 7(1):31-40. PMC: 3378051. DOI: 10.1038/nrneurol.2010.178. View

Gokce E, Kahveci R, Gokce A, Cemil B, Aksoy N, Sargon M . Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis. J Neurosurg Spine. 2016; 24(6):949-59. DOI: 10.3171/2015.10.SPINE15612. View

Alyoussef A, Al-Gayyar M . Thymoquinone ameliorated elevated inflammatory cytokines in testicular tissue and sex hormones imbalance induced by oral chronic toxicity with sodium nitrite. Cytokine. 2016; 83:64-74. DOI: 10.1016/j.cyto.2016.03.018. View

Spatola M, Novy J, Du Pasquier R, Dalmau J, Rossetti A . Status epilepticus of inflammatory etiology: a cohort study. Neurology. 2015; 85(5):464-70. PMC: 4534074. DOI: 10.1212/WNL.0000000000001717. View

Banerjee S, Padhye S, Azmi A, Wang Z, Philip P, Kucuk O . Review on molecular and therapeutic potential of thymoquinone in cancer. Nutr Cancer. 2010; 62(7):938-46. PMC: 4167365. DOI: 10.1080/01635581.2010.509832. View

Taka E, Mazzio E, Goodman C, Redmon N, Flores-Rozas H, Reams R . Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells. J Neuroimmunol. 2015; 286:5-12. PMC: 4548297. DOI: 10.1016/j.jneuroim.2015.06.011. View

10.

Trinka E, Cock H, Hesdorffer D, Rossetti A, Scheffer I, Shinnar S . A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015; 56(10):1515-23. DOI: 10.1111/epi.13121. View

11.

Knake S, Rosenow F, Vescovi M, Oertel W, Mueller H, Wirbatz A . Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia. 2001; 42(6):714-8. DOI: 10.1046/j.1528-1157.2001.01101.x. View

12.

Morcos M, Schlotterer A, Sayed A, Kukudov G, Oikomonou D, Ibrahim Y . Rosiglitazone reduces angiotensin II and advanced glycation end product-dependent sustained nuclear factor-kappaB activation in cultured human proximal tubular epithelial cells. Horm Metab Res. 2008; 40(11):752-9. DOI: 10.1055/s-0028-1082039. View

13.

De Simoni M, Perego C, Ravizza T, Moneta D, Conti M, Marchesi F . Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci. 2000; 12(7):2623-33. DOI: 10.1046/j.1460-9568.2000.00140.x. View

14.

Racine R . Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 1972; 32(3):281-94. DOI: 10.1016/0013-4694(72)90177-0. View

15.

Choi J, Nordli Jr D, Alden T, DiPatri Jr A, Laux L, Kelley K . Cellular injury and neuroinflammation in children with chronic intractable epilepsy. J Neuroinflammation. 2009; 6:38. PMC: 2811703. DOI: 10.1186/1742-2094-6-38. View

16.

Ma L, Cui X, Wang Y, Li X, Yang F, Wei D . Aspirin attenuates spontaneous recurrent seizures and inhibits hippocampal neuronal loss, mossy fiber sprouting and aberrant neurogenesis following pilocarpine-induced status epilepticus in rats. Brain Res. 2012; 1469:103-13. DOI: 10.1016/j.brainres.2012.05.058. View

17.

Vezzani A, Balosso S, Ravizza T . The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun. 2008; 22(6):797-803. DOI: 10.1016/j.bbi.2008.03.009. View

18.

Hosseinzadeh H, Parvardeh S, Nassiri-Asl M, Mansouri M . Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats. Med Sci Monit. 2005; 11(4):BR106-10. View

19.

Vezzani A, Friedman A, Dingledine R . The role of inflammation in epileptogenesis. Neuropharmacology. 2012; 69:16-24. PMC: 3447120. DOI: 10.1016/j.neuropharm.2012.04.004. View

20.

Jiang J, Yang M, Quan Y, Gueorguieva P, Ganesh T, Dingledine R . Therapeutic window for cyclooxygenase-2 related anti-inflammatory therapy after status epilepticus. Neurobiol Dis. 2015; 76:126-136. PMC: 4408774. DOI: 10.1016/j.nbd.2014.12.032. View