Thymoquinone Prevents β-Amyloid Neurotoxicity in Primary Cultured Cerebellar Granule Neurons

Thymoquinone (TQ), a bioactive constituent of Nigella sativa Linn (N. sativa) has demonstrated several neuropharmacological attributes. In the present study, the neuroprotective properties of TQ were investigated by studying its anti-apoptotic potential to diminish beta-amyloid peptide 1-40 sequence (A beta(1-40))-induced neuronal cell death in primary cultured cerebellar granule neurons (CGNs). The effects of TQ against A beta(1-40)-induced neurotoxicity, morphological damages, DNA condensation, the generation of reactive oxygen species, and caspase-3, -8, and -9 activation were investigated. Pretreatment of CGNs with TQ (0.1 and 1 mu M) and subsequent exposure to 10 mu M A beta(1-40) protected the CGNs against the neurotoxic effects of the latter. In addition, the CGNs were better preserved with intact cell bodies, extensive neurite networks, a loss of condensed chromatin and less free radical generation than those exposed to A beta(1-40) alone. TQ pretreatment inhibited A beta(1-40)-induced apoptosis of CGNs via both extrinsic and intrinsic caspase pathways. Thus, the findings of this study suggest that TQ may prevent neurotoxicity and A beta(1-40)-induced apoptosis. TQ is, therefore, worth studying further for its potential to reduce the risks of developing Alzheimer's disease.