Anticholinesterase, Antioxidative and Neuroprotective Effects of Hydroethanolic Extracts of Guiera Senegalensis J. F. Gmel. Leaves on Scopolamine Induced Alzheimer’s Disease in Wistar Rat Models

Background: Medicinal plants like Guiera senegalensis J. F. Gmel. (GS) have gained attention for their potential neuroprotective effects due to their rich composition of bioactive compounds, including flavonoids and polyphenolic acids. While previous studies have highlighted the antioxidant, anti-inflammatory, and neuroplasticity-enhancing properties of GS extract, its efficacy in mitigating dementia-related pathology remains to be fully understood. Objectives: This study aimed to investigate the neuroprotective effects of hydroethanolic GS extract against scopolamine (Sco)-induced dementia in Wistar rats, focusing on its impact on cholinergic function, oxidative stress, neuroinflammation, neurodegeneration, and memory impairment. Methods: Fresh leaves were processed for extraction using standard methods. Antioxidant activity was evaluated using FRAP and DPPH assays. Adult male Wistar rats were used for behavioral tests (Y-maze, NOR, MWM) and biochemical analyses, including ELISA for cholinergic activity, oxidative stress markers (Aβ1-42, phosphorylated Tau), pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IFN-γ), GFAP, BDNF, and IL-10. Brain tissues underwent histopathological examination. Data were analyzed using GraphPad Prism software. Results: The study assessed the antioxidant potential of GS extract and found that it significantly scavenged DPPH radicals (70.29%) and reduced Fe3+ (49.69%). Behavioral tests showed that GS extract (100 - 400 mg/kg) improved spatial memory and learning in Sco-treated rats. Y-maze results indicated increased spontaneous alternation with GS extract (P < 0.01). NOR and MWM tests showed improved memory and learning, with GS extract-treated rats spending more time in the target quadrant. Biochemical analysis revealed that GS extract increased acetylcholine (ACh), Superoxide Dismutase (SOD), Catalase (CAT), Glutathione (GSH), IL-10, and BDNF levels, while decreasing acetylcholinesterase (AChE), malondialdehyde (MDA), nitrite, Aβ1-42, phosphorylated Tau, IL-1β, TNF-α, IL-6, IFN-γ, and GFAP levels in the hippocampus. Histological analysis confirmed restored hippocampal tissue architecture in AD rats treated with GS extract. Conclusions: Our findings suggest that GS modulates cholinergic, antioxidant, anti-inflammatory, and neuroplasticity pathways, exerting beneficial effects on cognitive functions and biochemical markers associated with Alzheimer's disease (AD) pathology. These results indicate the potential of GS as a neuroprotective agent for the treatment of AD.