Thymoquinone (TQ) demonstrates its neuroprotective effect via an anti-inflammatory action on the Aβ(1-42)-infused rat model of Alzheimer's disease

OBJECTIVES: Alzheimer's disease (AD) is a severe neurodegenerative disease with presentation of the neuronal death, memory loss and cognitive decline. The relationship between neuroinflammation and AD has been well documented. However, the options of anti-inflammatory treatment are very limited in patients with AD. Previous studies showed that flavonoids might be an effective treatment and thymoquinone (TQ), an aromatic hydrocarbon found in Nigella sativa suggested as a candidate molecule due to having strong anti-inflammatory effects. Our study aimed to investigate the effects of TQ on neuroinflammation and neuroprotection in A beta((1-42)) infused rat model of AD. METHODS: A rat model of AD was established in 6 month-old rats (n = 23) by intra-hippocampal infusion during 14 days via a micro-osmotic pump containing aggregated A beta((1-42)). After model establishment, TQ at a dosage of 20mg/kg/day was intubated intragastrically for 15 days. The functional recovery was determined using the Morris Water Maze task by measuring memory consolidation. The content of cytokine levels of Tumour Necrosis Factor-alpha (TNF-alpha), Interleukin-1 beta (IL-1 beta), Interleukin-1 alpha (IL-1 alpha) and Interferon-gamma (IFN-gamma) in the hippocampus was assessed by Magnetic Luminex assay. In order to reveal the functional molecular changes in hippocampal tissue upon TQ administration, the protein expression profile of neuronal migration protein Doublecortin (DCX), synaptic plasticity marker Mitogen Activated Protein Kinase2 (MAP2) and apoptosis related protein Poly (ADP-ribose) Polymerase (PARP) was analyzed by Western blotting. RESULTS: A beta((1-42)) infused group had worse memory performance than sham control group on Day 4 with an amelioration in this behaviour by TQ. In our study, the levels of TNF-alpha, IL-1 alpha and IL-1 beta did not significantly alter among groups. On the other hand, A beta((1-42)) infusion slightly decreased the level of IFN-gamma compared to sham control group. TQ treatment ameliorated both impaired memory performance and IFN-gamma levels. It was found that TQ treatment increased the protein levels of DCX compared to the sham control group. Also, the levels of MAP2 and the activation of PARP protein markedly decreased in both A beta((1-42)) and A beta((1-42))+TQ groups compared to the sham control groups Pearson's correlation test showed a positive relation between IL-1 beta and DCX in the A beta((1-42)) group. DISCUSSION: Our data suggested that TQ-related functional improvement might result from the increasing level of neurogenesis and ameliorating the level of IFN-gamma in the A beta((1-42)) infused rat model of AD.