Protective effects of thymoquinone on D-galactose and aluminum chloride induced neurotoxicity in rats: biochemical, histological and behavioral changes.

Objectives: Thymoquinone (TQ), the main active ingredient in Nigella sativa oil, exhibits various bioactivities. This study aimed to investigate the effect of TQ on neurobehavioral and neuropathological alterations induced by aluminum trichloride (AlCl) and D-galactose (D-gal)-in male rats and to explore the related mechanisms.

Methods: D-gal (60 mg/kg day) and AlCl (10 mg/kg day) were given intraperitoneally (i.p.) once daily for 42 days and after 4 weeks TQ was concomitantly administered intragastrically (i.g.) (20 mg/kg/day) once daily for 14 days. Then, memory function was evaluated by Morris water maze test (MWM). Superoxide dismutase (SOD), Total antioxidant capacity (TAC), Acetylcholinesterase (AChE) activities, and malondialdehyde (MDA), nitric oxide (NO), brain-derived neurotrophic factor (BDNF), and B-cell lymphoma-2 (Bcl-2) levels in whole brain were assessed with the biochemical technique. Tumor necrosis factor-alpha (TNF-α) and Acetylcholine (ACh) were also assessed using an immunohistochemical technique.

Results: Administration of TQ significantly improved cognition. In addition, TQ significantly increased SOD and TAC and decreased AChE activities. It also decreased MDA and NO levels as well as TNF-α immunoreactivity and increased BDNF and Bcl-2 levels as well as ACh immunoreactivity.

Discussion: Our results indicate that TQ prevents D-gal/AlCl-induced cognitive decline by enhancing cholinergic function and synaptic plasticity as well as attenuation of oxidative damage, neuronal apoptosis, and neuroinflammation. These results indicate that TQ holds potential for neuroprotection and may be a promising approach for the treatment of neurodegenerative disorders.