Betanin-encapsulated nanoparticles mitigate neurotoxicity against AlCl3-induced Alzheimer's disease via modulation of AChE/TNF-α/IL-1β expression.

Alzheimer's disease (AD), the most common health problem, is significantly characterized by oxidative stress, neuroinflammation, and cholinergic dysfunction, provoking growing interest in natural antioxidants with improved bioavailability. This study is intended to evaluate the neuroprotective impact and the probable mechanism of betanin and formulated betanin-encapsulated nanoparticles (ChBetNPs) in an AlCl3 and D-galactose-induced rat model Alzheimer's-like neurotoxicity. The rats were treated daily with AlCl3 and D-galactose for 21 days to induce neurotoxicity, followed by two weeks of treatment with low and high doses of betanin and ChBetNPs. After treatment, cognitive performance, oxidative stress markers, acetylcholinesterase (AChE) activity, and hippocampal inflammatory gene expression were assessed. Both low and high doses of ChBetNPs (40 mg/kg/day and 80 mg/kg/day respectively) significantly improved learning and memory performance in AlCl3 + D-galactose-treated rats. Treatment with ChBetNPs also markedly restored antioxidant defenses, as evidenced by increased activities of CAT (∗∗P < 0.01), elevated reduced GSH, and reduced levels of the lipid peroxidation marker MDA. The higher dose of ChBetNPs produced a pronounced protective effect on cholinergic function, reflected by a robust reduction in brain AChE activity (∗∗∗∗P < 0.0001). In addition, both free betanin and ChBetNPs at low and high doses significantly (∗∗P < 0.01) downregulated the hippocampal mRNA expression of AChE, α-synuclein, TNF-α, and IL-1β in hippocampal region of brain as compared with untreated group, indicating attenuation of neuroinflammatory and protein-aggregation-related pathways. In summary, our findings demonstrate that ChBetNPs enhanced learning, memory, and cholinergic neurotransmission, likely by mitigating oxidative stress and the associated NF-κB-mediated inflammatory responses.