The anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, were investigated using pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizure models. We also studied the effect of thymoquinone on pentobarbital-induced hypnosis, locomotor activity, and motor coordination. In PTZ-induced seizure, the intraperitoneally injection of thymoquinone with doses of 40 and 80 mg/kg, prolonged the onset of seizures and reduced the duration of myoclonic seizures.
The protective effect of thymoquinone against mortality was 71.4% and 100% in the mentioned doses, respectively. In MES model, thymoquinone failed to reduce the duration of seizure, whereas exhibited a complete protection against mortality.
The composition and properties of N. sativa seeds have been fairly investigated, and the results of the researches have been reviewed (Riaz et al. 1996; Siddiqui and Sharma, 1996; Worthen et al. 1998). N. sativa seeds contain 36%-38% fixed oils, proteins, alkaloids, saponin and 0.4%-2.5% essential oil. The fixed oil is composed mainly of unsaturated fatty acids. The essential oil was analysed using GC-MS. Many components were characterized, but the major ones were thymoquinone (27.8%-57.0%), [rho]-cymene (7.1%-15.5%), carvacrol (5.8%-11.6%), t-anethole (0.25%-2.3%), 4-terpineol (2.0%-6.6%) and longifoline (1.0%-8.0%). Thymoquinone readily dimerizes to form dithymoquinone. Four alkaloids have been reported as constituents of N. sativa seeds. Two, nigellicine and nigellidine have an indazole nucleus, whereas nigellimine and its N-oxide are isoquinolines (Ali and Blunden, 2003). Most properties of whole seeds or their extracts are mainly attributed to quinone constituents, of which thymoquinone is a more abundant compound (Mahfouz et al. 1960; DAntuono et al. 2002). More recently, a great deal of attention has been given to this pharmacologically active quinone. It has been shown that thymoquinone possesses several properties including analgesic and anti-inflammatory actions (Abdel-Fattah et al. 2000; Houghton et al. 1995), protection against chemicals induced carcinogenesis (Hassan and El-Dakhakhny, 1992; Worthen et al. 1998), the inhibition of eicosanoids generation and membrane lipid peroxidation (Houghton et al. 1995).
To our knowledge, no data are available concerned with the pharmacological effects of N. sativa seed extracts or its oil and thymoquinone in the central nervous system (CNS), apart from Khanna et al. (1993) who reported analgesic and CNS depressant activities of N. sativa oil, and Abdel-Fattah et al. (2000) who determined the antinociceptive effect of thymoquinone with a central mechanism through opioid receptors.
In the present study, to clarify the neuropharmacological profiles of thymoquinone, as the major constituent of N. sativa seeds, we investigated the anticonvulsant activity of thymoquinone using pentylenetetrazole (PTZ) and maximum electroshock induced seizures as petit mal and grand mal epilepsy models in mice, respectively. We further studied the effect of thymoquinone in pentobarbital-induced hypnosis and its effects on motor coordination with the rotarod test. We also elucidated the possible mechanism(s) underlying the actions of thymoquinone on the CNS and assessed the probable involvement of benzodiazepine receptors and opioid system.
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