Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats.
BACKGROUND
Recently we investigated some neuropharmacological aspects of thymoquinone, such as anticonvulsant, muscle relaxant, and hypnotic effects, as well as its effect on motor coordination and locomotor activity. In this study, we evaluated the effect and mechanism(s) of the action of thymoquinone more precisely via intracerebroventricular (i.c.v.) injection.


METHODS
The anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, were investigated using the pentylenetetrazole (PTZ)-induced seizure model. The animals were placed individually in plastic boxes and observed immediately after PTZ injection for a period of 30 min. The latency to and the duration of tonic-clonic seizures were recorded, as well as the percentages of protection against the incidence of seizure and mortality.


RESULTS
In PTZ-induced epileptic seizures, the i.c.v. injection of thymoquinone at doses of 200 and 400 microM prolonged the time until onset and reduced the duration of tonic-clonic seizures. The protective effect of thymoquinone against lethality was 45% and 50% in the respective doses. In this study, flumazenil (1 nM, i.c.v.) reversed the anticonvulsant activity of thymoquinone. Also, pretreatment with naloxone (10 microM, i.c.v.) antagonized the prolongation of tonic-clonic seizure latency as well as the reduction in seizure duration induced by thymoquinone (200 microM, i.c.v.).


CONCLUSIONS
These results indicate that thymoquinone may have anticonvulsant activity, probably through an opioid receptor-mediated increase in GABAergic tone.
Hosseinzadeh
Hossein
H
Department of Pharmacodynamics & Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. hosseinzadehh@yahoo.com
Parvardeh
Siavash
S
Nassiri-Asl
Marjan
M
Mansouri
Mohammad-Tagi
MT
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D016227:Benzoquinones / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D003292:Convulsants; D003975:Diazepam / Q000627:therapeutic use; D004827:Epilepsy / Q000517:prevention & control*; D005442:Flumazenil / Q000627:therapeutic use; D007276:Injections, Intraventricular; D008297:Male; D031844:Nigella; D010433:Pentylenetetrazole; D008517:Phytotherapy; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D000927:Anticonvulsants; D016227:Benzoquinones; D003292:Convulsants; D005442:Flumazenil; C003466:thymoquinone; D003975:Diazepam; D010433:Pentylenetetrazole