Neuroprotective efficacy of thymoquinone against amyloid beta-induced neurotoxicity in human induced pluripotent stem cell-derived cholinergic neurons

The natural antioxidant Thymoquinone (TQ) is the most abundant ingredient in the curative plant Nigella sativa seed's oil. An extensive number of studies have revealed that TQ is the most active and most responsible component for the plant's pharmacological properties. It has been documented in several studies that TQ has a wide range of protective activities and many neuropharmacological attributes. Amyloid beta (Aβ) is the major role player peptide in the progression of Alzheimer's disease (AD). Our current study has been implemented to explore the protective possibilities of TQ on Aβ1–42 -induced neurotoxicity. To test TQ's effect we used cultured human induced pluripotent stem cell (hiPSC)-derived cholinergic neurons. The obtained results showed that Aβ1–42 caused cell death and apoptosis, which was efficiently attenuated by the co-treatment of TQ. Moreover, TQ restored the decrease in the intracellular antioxidant enzyme glutathione levels and inhibited the generation of reactive oxygen species induced by Aβ1–42. Furthermore, using the fluorescent dye FM1–43 we demonstrated that TQ was able to reduce synaptic toxicity caused by Aβ1–42. Thus, the findings of our study suggest that TQ holds a neuroprotective potential and could be a promising therapeutic agent to reduce the risk of developing AD and other disorders of the central nervous system. Keywords: Thymoquinone, Amyloid beta, Alzheimer's disease, Human induced pluripotent stem cell-derived cholinergic neurons, Oxidative stres