Persistent Administration of Datura stramonium L. Water-Based Extract Triggers Spatial Memory- Like Deficit in Rats by Disrupting Cholinergic and Oxidative Mechanisms: Exploring The Role of Donepezil Intervention

Background: Datura stramonium (DS) is a potent plant with psychoactive and anticholinergic properties used to treat human ailments. However, its toxicity or insult can cause cognitive impairments. The present study aimed to determine whether donepezil could mitigate this deficit and elucidate the potential mechanisms involved in male Wistar rats Methods: Rats were randomly divided into seven groups (n = 5/group). While group 1 received distilled water (10 mL/kg), groups 2–4 received graded doses of DS (50, 100, 200 mg/kg), and groups 5–7 were coadministered with donepezil and graded doses of DS. The treatments were given orally and lasted 28 days. Afterward, behavioral testing in the Y maze paradigm and biochemical assays in plasma were performed. Chromatography and Mass Spectrometry (GC-MS) were used for the phytochemical characterization of DS. Results: GC-MS analysis revealed 33 phytochemical compounds in DS, including scopolamine, atropine, and 3,6-epoxytropane tropane alkaloids. DS insult reduced spatial memory performance compared to the control group (p<0.05). But donepezil administration mitigated the effect of the DS insult. Donepezil elevated the cholinergic system affected by DS by boosting acetylcholine levels (p<0.05). Conclusion: Donepezil possibly protects rats from DS-induced spatial memory impairment, possibly through its ability to up-regulate the cholinergic system and decrease oxidative processes.