Assessment of possible interactions between Citrus aurantifolia leaf alkaloid-rich compounds and relevant protein targets in scopolamine-induced amnesic rats

Aim: This study assessed the neuroprotective effect of lime (Citrus aurantifolia) leaf via the interaction of its inherent alkaloid compounds with specific neuronal protein targets [acetylcholinesterase (AChE), adenosine deaminase (ADA), and monoamine oxidase (MAO)] in scopolamine-induced amnesic rats. Methods: Lime leaf alkaloid-rich extract (LLARE) compounds were characterised using gas chromatography-mass spectrometry, and the in silico absorption, distribution, metabolism, and excretion (ADME) screening was accomplished on the SwissADME server. Ligand-protein molecular docking was performed using AutoDock Vina version 1.2.3. Experimental animals were treated with LA extract (100 mg/kg and 200 mg/kg) and donepezil (5 mg/kg) for fourteen days before inducing cognitive dysfunction with a single dose of scopolamine (3 mg/kg). Neurobehavioral evaluations that utilised the Morris water maze, Y-maze, and open field maze tests were carried out, and the AChE, ADA, and MAO activities were determined in the cortex and hippocampus. Results: Key findings supporting the neuroprotective functions of the alkaloid compounds in LA were obtained. Predictions from the in silico ADME study show that the molecular weight (MW) of the majority of LA appears to fall below 500 Da. Pyrazine trimethyl demonstrated the highest binding affinities of –5.443, –5.360, and –5.971 kcal/mol to AChE, ADA, and MAO proteins, respectively. LA-treated rats exhibited improved neurobehavioural functions: escape latency (82 to 19 s) and memory index (22% to 86%) with significantly (p < 0.01) attenuated AChE (14.38 to 2.91 μmol/min/mg protein), ADA (0.84 to 0.21 mmol/mg protein), and MAO (0.17 to 0.03 mmol/mg protein) activities relative to scopolamine-induced rats. Conclusions: The observed cognition-enhancing effects of LA extract may be attributed to its positive modulation of key neuronal enzymes, making it a promising nutraceutical agent for alleviating cognitive impairment.