Evaluation of Nigella sativa Seed Constituents for Their in vivo Toxicity in Mice

This study was designed to investigate the effects of main constituents of Nigella sativa (NS) seed on the survival and CNS responses in experimental animals. The toxicological investigations were conducted for the determination of median lethal doses $(LD_{50})$ of NS seed constituents [i.e. aqueous extract (AE), fixed oil (FO), volatile oil (VO)] and main components of its VO [i.e. thymoquinone (TQ), ${\alpha}-pinene$ (AP) and p-cymene (PC)]. A part of this study includes evaluation NS constituents in the induction of minimal neurological deficit (MND) as a parameter for neurotoxicity using chimney test. In this study, the i.p. $LD_{50}$ values of AE, FO, VO, TQ (suspended In 0.5%CMC), TQ (dissolved in corn oil), AP and PC, were 3020, 3371, 1853, 616.6, 90.3, 1726 and 1523 mg/kg, respectively. All the NS constituents can be considered moderately toxic ($LD_{50}$ ranged from 616.6 to 3371 mg/kg), except the oily solution of TQ, which was very toxic ($LD_{50}$ was 90.3 mg/kg). It appeared that the toxicity of the whole VO is mainly due to its content of TQ and to some extent PC. All the NS constituents induced different degrees of MND at certain dose levels. The median neurotoxic (or sedating) doses $(TD_{50})$ of AE, FO, VO, TQ (suspended in CMC) and AP and PC, were 950, 1403, 306, 88.1, >173 and 368 mg/kg, respectively. TQ was the most potent component in inducing MND, whereas the FO and AE were the least. Neurotoxicity induced by the VO in the chimney test may refer basically to its contents of TQ and to some extent PC and AP.