Geniposide and Harpagoside Functionalized Cerium Oxide Nanoparticles as a Potential Neuroprotective

Area of Science:

• Neuroscience
• Materials Science
• Pharmacology

Background:

• Alzheimer's disease (AD) is characterized by protein aggregation and oxidative stress.
• Acetylcholinesterase plays a key role in AD pathology.
• Geniposide and harpagoside (GH) are known neuroprotective agents, while cerium nanoparticles (CeO2 NPs) possess antioxidant properties.

Purpose of the Study:

• To investigate the therapeutic potential of GH/CeO2 NPs in ameliorating AD pathogenesis.
• To evaluate the effects of GH/CeO2 NPs on protein aggregation and cognitive function in an AlCl3-induced AD mouse model and in vitro assays.

Main Methods:

• Spectroscopy analysis to characterize GH/CeO2 NPs.
• In vitro assays to assess inhibition of Tau and amyloid-beta (Aβ1-42) aggregation.
• Assessment of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition.
• Evaluation of memory and cognitive function in AlCl3-induced AD mice.

Main Results:

• GH/CeO2 NPs were found to be stable, nano-sized, spherical, and amorphous with complete GH encapsulation.
• GH/CeO2 NPs, CeO2 NPs, and donepezil inhibited fibril formation, protein aggregation, and AChE/BuChE activities.
• GH/CeO2 NPs treatment in AD mice reduced Aβ1-42, improved memory, and cognitive coordination.

Conclusions:

• Combined iridoids and nanoparticles demonstrate significant chemoprotective activities.
• GH/CeO2 NPs show potential for alleviating AD pathogenesis by reducing the amyloidogenic pathway and inhibiting AChE/BuChE.
• This study provides a basis for developing new therapeutic strategies for neurodegenerative diseases.