Proteomic Analysis of Alzheimer’s Disease Models Administered with Rutin and Rutin-Bound Nanoparticles.

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.