Protective Effects of Pomiferin on Aluminum Chloride-induced Memory Impairment: Evidence from Behavioral, Biochemical, and Insilico Studies.

This investigation aims to assess the neuroprotective effect of pomiferin against aluminum chloride (AlCl₃)-induced memory dysfunction in rats. Wistar rats (180 ± 20 g; 10–12 weeks old) were randomly divided into four groups (n = 8) and treated over 47 days. Group I received normal saline (control), and Group II was administered AlCl₃ (100 mg/kg, p.o.) to induce neurotoxicity. In comparison, Groups III and IV received pomiferin (10 and 20 mg/kg, p.o., respectively) once daily for 42 consecutive days, administered orally 1 h prior to AlCl₃ during the morning session to ensure optimal absorption and assess its preventive neuroprotective potential. To assess spatial and working memory performance, behavioral evaluations were conducted using the Morris Water Maze on day 42 and the Y-maze test on day 47 of the experimental period. Subsequently, biochemical analyses were performed to measure acetylcholinesterase (AChE), choline acetyltransferase (ChAT), acetylcholine (ACh), γ-aminobutyric acid (GABA), glutamate, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), caspase-3, cAMP response element-binding protein (CREB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and p38 mitogen-activated protein kinase (p38 MAPK) levels. Additionally, histopathological analyses, molecular docking, and molecular dynamics simulations (MDS) were carried out. AlCl₃ induced substantial alterations in biochemical, neuroinflammatory, and neuronal enzymatic parameters, as well as in brain histology. However, these changes were ameliorated by pomiferin, accompanied by the regulation of apoptotic markers. Furthermore, pomiferin significantly improved working and spatial memory in behavioral paradigms. Furthermore, pomiferin demonstrated favorable binding affinities to target proteins, including TNF-α (-8.831 kcal/mol), CREB (-8.101 kcal/mol), caspase-3 (-7.624 kcal/mol), and BDNF (-7.080 kcal/mol). Additionally, MDS demonstrated significant conformational changes induced by pomiferin, resulting in a more favorable binding affinity to TNF-α and CREB. In conclusion, pomiferin exhibits promising neuroprotective potential in experimental models of neurodegeneration induced by AlCl₃.