The Potential Neuroprotective Effect of Thymoquinone on Scopolamine-Induced In Vivo Alzheimer’s Disease-like Condition: Mechanistic Insights

Abstract

Background: Alzheimer’s disease (AD) is a common neurodegenerative disorder without effective treatment. Thymoquinone (TQ) has demonstrated potential in exhibiting anti-inflammatory, anti-cancer, and antioxidant characteristics. Despite TQ’s neuroprotection effect, there is a scarcity of information regarding its application in AD research, and its molecular trajectories remain ambiguous. Thus, the objective of the current investigation was to examine the potential beneficial effects and underlying mechanisms of TQ in scopolamine (SCOP)-induced neuronal injury to mimic AD in vivo model. Methods: Thirty mice were divided into normal, SCOP, and TQ groups. The Y-maze and pole climbing tests were performed to measure memory and motor performance. Afterwards, histopathological and immunohistochemical examinations were carried out. Furthermore, peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway-related proteins and genes were detected with an emphasis on the role of miR-9. Results: TQ has the potential to ameliorate cognitive deficits observed in SCOP-induced AD-like model, as evidenced by the improvement in behavioral outcomes, histopathological changes, modulation of the expression pattern of PPAR-γ downstream targets with a significant decrease in the deposition of amyloid beta (Aβ). Conclusions: TQ provided meaningful multilevel neuroprotection through its anti-inflammatory and its PPAR-γ agonist activity. Consequently, TQ may possess a potential beneficial role against AD development.

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“…However, these effects were mitigated when mice were pretreated with DON and CTN. Previous studies have found comparable findings concerning the impacts of scopolamine [50,51] and DON [50,52].…”

“…In 0.1 M phosphate buffer (pH 7.4), a 10% (w/v) tissue homogenate was created. The homogenates (10% w/v) were then centrifuged at 10,000× g for 15 min to generate the supernatant, and the resultant cloudy supernatant liquid was used to estimate brain biochemical parameters [51].…”