Abstract:
Alzheimer’s disease is a progressive neurodegenerative disease leading to cognitive
impairment and memory loss. The presence of amyloid ß deposition and neurofibrillary tangles
remain the neuropathologic criteria for AD diagnosis. The BBB which is necessary for proper
neuronal activity prevents solutes from the bloodstream getting into the brain. Unfortunately,
there is no effective therapy for the treatment of AD due to low drug potency and various drug
delivery issues, such as limited bioavailability and the blood-brain barrier's obstructions.
Recently nanotechnology has demonstrated encouraging advancements in the treatment of AD.
Many different types of nano-carriers have been modified to provide effective new therapeutic
approaches. This study investigated therapeutic effect of Rutin and compared them with those
of Rutin-bound nanoparticles, NCDs-Rutin and CDs-Rutin in AD rat model. AD was induced
in Wistar Han rats using AlCl3 and D-galactose. The rats were then treated with Rutin and
Rutin-bound nanoparticles and the effects were assessed using different parameters. Behavior
assessment showed that NCDs-Rutin gave significant results in MWM, Y-maze and NOR test,
while CDs-Rutin exhibited better result in open field test. Histological analysis using H & E
staining revealed that NCDs-Rutin group prevented brain tissue better than CDs-Rutin and
Rutin group, however, Rutin group had more effective amyloid plaque reduction in ThT
staining. Moreover, molecular analysis of treatment groups showed an upregulation of SOD2
expression, among them NCDs-Rutin and Rutin group showed significant results suggesting
enhanced antioxidant defense. While, CDs-Rutin group showed significant reduction in TLR4
expression, suggesting a reduced neuroinflammation. Proteomic analysis through SDS-PAGE
indicated differences protein expression across the groups. The Rutin-bound nanoparticles
significantly outperformed Rutin in terms of efficacy, most likely as a result of their focused
administration and increased bioavailability.
