ObjectivesAluminium (Al) is also a popular neurotoxin that accelerates oxidative damage to biomolecules, which is correlated to the aetiology of Alzheimer's disease (AD). It is a common metal on the globe and can easily enter the body through food and water additives, cutlery, deodorants, and medications. It accumulates mostly in the brain's frontal cortex and hippocampus, and its elimination half-life in the human brain is estimated to be 7 years. It is known to be particularly vulnerable to AD, which is a crippling neurological ailment that primarily affects ageing adults and has a large socioeconomic impact. Niruriflavone (NF) is a natural flavonoid isolated from Phyllanthus niruri Linn. It demonstrated remarkable neuroprotective efficacy by inhibiting oxidative stress, acetylcholinesterase (AChE), and 5-lipoxygenase. The efficacy of NF was improved by the formulation of NF-loaded chitosan nanoparticle (NFLC). Consequently, the current study sought to assess the neuroprotective role of synthesized NFLC against aluminium chloride (AlCl3)-induced AD through the neurobehavioural, biochemical, and histopathological analysis.MethodsChronic administration of 100 mg/kg body weight of AlCl3 orally to Wistar rats resulted in AD. Neurobehavioural tests such the open-field test, elevated plus maze tests, and Morris water maze were used to evaluate the impact of NFLC treatment. The activity of the acetylcholinesterase enzyme and level of aluminium were also measured in AlCl3-induced AD rats. Cresyl violet staining was used to study the histopathological variations.ResultsNFLC treatment considerably increased learning and memory skills, improved the exploratory activities, and reduced the anxiety-related behaviour. NFLC-treated rats had lower Al levels and higher AChE inhibition activity. NFLC prevented the neuronal loss in the AD rat brains which was observed in histopathological studies.ConclusionNFLC helps to treat AD brought on by Al poisoning through the inhibition of AChE activity, oxidative stress, neuroinflammation, and neuronal loss. The development of these efficacious multitargeted NFLC could help people afflicted by AD.