Gallic acid enhances memory, learning and reduces neuroinflammation in a rat model of scopolamine-induced cholinergic dysfunction

Gallic acid (GA), a potent polyphenol antioxidant, has demonstrated beneficial effects on the nervous system. This study aimed to investigate the neuroprotective potential of GA on learning and memory in a rat model of scopolamine-induced cholinergic dysfunction. Additionally, the roles of oxidative stress and neuroinflammation were examined. Rats were divided into six groups: Control, scopolamine (2 mg/kg/day), scopolamine plus 25, 50, or 100 mg/kg of GA, and scopolamine plus 2 mg/kg of donepezil (DN, administered once daily). Behavioral performance was evaluated using the Morris Water Maze (MWM) and Passive Avoidance Test. Biochemical parameters were assessed to determine oxidative stress, and gene expression analyses were conducted to explore neuroinflammation in the hippocampus. The behavioral tests revealed that both GA and DN treatments improved the rats' performance in the MWM, as evidenced by their ability to locate the platform and spend more time in the target area. Additionally, GA administration increased the latency of entering the dark compartment and extended the time spent in the light compartment while reducing the frequency of dark compartment entries in the Passive Avoidance Test. Furthermore, GA exhibited antioxidant, anti-acetylcholinesterase, and anti-inflammatory effects, as indicated by the modulation of malondialdehyde levels, thiol content, superoxide dismutase activity, acetylcholinesterase activity, and the expression of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6. In conclusion, this study provides evidence for the potential therapeutic benefits of GA in Alzheimer's disease, highlighting its ability to enhance memory function and mitigate oxidative stress, acetylcholinesterase activity, and inflammation.