Artemisinin, N-acetylcysteine, Resveratrol, and Hesperidin Combination Ameliorates Hippocampal Damage in Rat AD Model

Alzheimer's disease (AD) is a devastating neurodegenerative disorder marked by progressive cognitive decline, driven by amyloid-β (Aβ) plaques and tau hyperphosphorylation. Current therapeutic strategies offer only symptomatic relief and fail to halt disease progression, leaving a significant gap in disease-modifying treatments. This highlights the urgent need for novel multi-target approaches that can address the complex pathology of AD, including neuroinflammation, oxidative stress, and neuronal apoptosis, which are critical contributors to neuronal damage and cognitive impairment.

Researchers investigated a combination of artemisinin, N-acetylcysteine, resveratrol, and hesperidin in a streptozotocin (STZ)-induced intracerebroventricular (ICV) rat model of AD. Twenty 8-week-old rats were divided into four groups: control, SHAM, STZ-ICV, and STZ-ICV receiving oral administration of the compound combination for 30 days. Cognitive performance was assessed using the Morris water maze and passive avoidance tests. Neurodegenerative and molecular changes were evaluated via Western blot for phosphorylated tau, amyloid-β markers, and apoptosis/inflammation proteins, alongside Nissl staining and immunofluorescence for amyloid deposition and caspase-3 expression.

STZ-ICV administration successfully induced significant cognitive impairment, neuronal loss, and elevated amyloid-β and phosphorylated tau levels in the rat hippocampus. Treatment with the combined compounds partially improved behavioral performance across cognitive tests. Molecular analyses revealed that the combination therapy was associated with reductions in amyloid-β deposition and tau phosphorylation.

The combined treatment also significantly reduced caspase-3 expression, a key marker of apoptosis, and improved neuronal preservation in the hippocampus. These findings suggest the multi-target approach effectively modulated oxidative stress, neuroinflammation, and apoptotic pathways, contributing to the observed neuroprotective effects and cognitive improvements in the experimental AD model.