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

Abstract

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.

Black Cumin (Nigella sativa L.): A Comprehensive Review on Phytochemistry, Health Benefits, Molecular Pharmacology, and Safety

“…Black cumin and TQ were shown to confer neuroprotection and improved disease outcomes in AD animal models. For example, in Aβ1–42 induced neurotoxicity, TQ protected cholinergic hiPSC neurons by restoring intracellular antioxidant levels and by inhibiting ROS generation, cell death, and apoptosis [ 51 ], and subsequently reduced quantal size of ready to release synaptic vesicle pools caused by Aβ1–42 [ 51 ]. Furthermore, in high fat/cholesterol diet (HFCD)-induced rats, TQ rich fraction nanoemulsion (TQRFNE) of black cumin decreased the brain Aβ fragment length 1–40 and 1–42 (Aβ40 and Aβ42) by modulating APP processing enzymes such as BACE1, PSEN1 and PSEN2 [ 52 ].…”

“…Activation of Nrf2 by either cellular redox status or pharmacological intervention leads to the up-regulation of over 250 genes encoding proteins that are involved in antioxidant defense systems, redox homeostasis, and xenobiotic detoxification [ 81 ]. Increased expression of antioxidant molecules and subsequent decline in oxidative markers by black cumin and TQ in various pharmacological effects indicate the involvement of Nrf2 activation [ 51 , 55 , 58 , 69 , 132 , 136 ].…”

Effects of Medicinal Plants and Flavonoids on Parkinson's Disease, a Review on Basic and Clinical Evidences

“… 47 The results of other study suggested that TQ had neuro-protective potential and could exert as a promising therapeutic agent to reduce the risk of developing of AD and other neurodegenerative disorders of the CNS such as PD. 48 …”

Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection

“…Thymoquinone is the most abundant ingredient in Nigella sativa seed oil. This molecule protects human-induced pluripotent stem cell (hiPSC)-derived cholinergic neurons treated with Aβ(1-42) from cell death, oxidative stress and synaptic toxicity [98]. Thymoquinone reduces inflammation in a model of Alzheimer's disease by likely acting on the TLR pathway and NF-κB-signaling pathway [99,100].…”