Neuromodulatory Effect of Thymoquinone in Attenuating Glutamate-Mediated Neurotoxicity Targeting the Amyloidogenic and Apoptotic Pathways

Abstract

Overexposure of the glutamatergic N-methyl-d-aspartate (NMDA) receptor to the excitatory neurotransmitter l-glutamic acid leads to neuronal cell death by excitotoxicity as a result of increased intracellular Ca2+, mitochondrial dysfunction, and apoptosis. Moreover, it was previously reported that prolonged activation of the NMDA receptor increased beta-amyloid (Aβ) levels in the brain. Thymoquinone (TQ), the active constituent of Nigella sativa seeds, has been shown to have potent antioxidant and antiapoptotic effects. The aim of the present study was to explore the neuromodulatory effects of different doses of TQ (2.5 and 10 mg/kg) against apoptotic cell death and Aβ formation resulting from glutamate administration in rats using vitamin E as a positive control. Behavioral changes were assessed using Y-maze and Morris water maze tests for evaluating spatial memory and cognitive functions. Caspase-3, Lactate dehydrogenase, Aβ-42, and cytochrome c gene expression were determined. TQ-treated groups showed significant decreases in the levels of all tested biochemical and behavioral parameters compared with the glutamate-treated group. These findings demonstrated that TQ has a promising neuroprotective activity against glutamate-induced neurotoxicity and this effect is mediated through its anti-amyloidogenic, antioxidant, and antiapoptotic activities.

Effects of Thymoquinone on Small-Molecule Metabolites in a Rat Model of Cerebral Ischemia Reperfusion Injury Assessed using MALDI-MSI

“…There are few reports on the regulation of the four excitatory amino acids by thymoquinone. Thymoquinone was shown to modulate glutamate-mediated neurotoxicity and inhibit cell apoptosis and Aβ formation through neuromodulation [18]. This study was the first to use mass spectrometry imaging to explore the function of thymoquinone on excitatory amino acids after cerebral ischemia-reperfusion injury.…”

The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases

“…Thymoquinone has antioxidant and antiapoptotic properties through reduction in glutamate‐mediated neurotoxicity making it and N sativa seed oil attractive as neuromodulatory agents (Figure 4). 29 Hence, TQ and N sativa may have a therapeutic role in the neurodegenerative diseases and epilepsies. Nigella sativa has been reported to improve executive function, mood, and anxiety in elderly human subjects 63 …”

Antioxidant and Anti-Inflammatory Potential of Thymoquinone and Lycopene Mitigate the Chlorpyrifos-Induced Toxic Neuropathy

“…TQ antioxidant activity is ascribed to its potent capability to scavenge various ROS promoting the oxidant scavenging system by maintaining endogenous antioxidant enzyme property [ 12 ] and inhibiting lipid peroxidation [ 13 ]. Furthermore, TQ can reinstate the abnormal matrix metalloproteinase, lowering ROS levels [ 14 ]. TQ has also been proven to suppress proinflammatory mediators in various models based on inflammation, such as encephalitis, colitis, peritonitis, and arthritis [ 13 ].…”