Anti-Amnesic and Neuroprotective Potential of a Polyherbal Nutritional Supplement Against Lipopolysaccharide-Induced Neuroinflammation in Rats: Behavioral, Histopathological, and Molecular Insights

Background: The nutritional supplement (NS), composed of Prunus amygdalus, Juglans regia, and Cucumis melo, contains bioactive phytoconstituents such as tocopherol, linoleic acid, and phenolic compounds that contribute to its anti-inflammatory, antioxidant, and neuroprotective potential. The current investigation was conducted to evaluate the neuroprotective potential of the nutritional supplement in a lipopolysaccharide (LPS)-induced neuroinflammatory model and resulting memory deficit in Wistar rats by analyzing oxidative stress, histological features, and molecular outcomes. Methods: Adult Wistar rats were divided into five groups (n = 8/group): control (distilled water), LPS (0.25 mg/kg, i.p.), NS (500 mg/kg), NS (500 mg/kg, p.o.) + memantine (5 mg/kg, p.o.), and memantine (5 mg/kg, p.o.). Phytoconstituents of the NS were analyzed by gas chromatography–mass spectrometry (GC–MS). Total phenolic content and antioxidant activity were assessed using the Folin–Ciocalteu method and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging assay, respectively. Cognitive function was assessed using the passive avoidance and Morris Water Maze tests. Rats were sacrificed on day 35, after 30 days of dosing. Brain tissue homogenates were evaluated for malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD); histopathological alterations were examined by hematoxylin–eosin staining; amyloid-like deposition was assessed by Congo red staining; cytokine and amyloid precursor protein (APP) gene expression were assessed by real-time polymerase chain reaction (PCR); enzyme-linked immunosorbent assay (ELISA) was used to measure protein concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Result: The phytoconstituents identified were linoleic acid (65.04%) and tocopherol (9.29%). Total phenolic compounds were present in significant amounts, and the DPPH assay showed 67.9% radical-scavenging activity. The LPS group showed reduced cognitive function and spatial memory. Moreover, LPS increased MDA levels, decreased antioxidant levels, altered neuronal cell architecture on histology, increased amyloid-like deposition, and elevated cytokine gene and protein expression compared with the control. NS mitigates LPS-mediated neuroinflammation by improving cognitive function and memory. Furthermore, NS reduces MDA levels and elevates antioxidant levels, thereby restoring neuronal architecture compared with the LPS group. Real-time PCR analysis showed a significant decrease in the targeted gene, while ELISA showed a significant reduction in TNF-α and IL-6 protein levels in brain tissue of the nutritional supplement-treated group compared with the LPS group. Conclusions: These findings suggest that NS treatment protects brain tissue from LPS-induced neuroinflammation through antioxidant and anti-inflammatory mechanisms, supporting its potential as a neuroprotective agent to restore cognitive function.