Neuropharmacological insights into artesunate alone and rivastigmine Co-therapy: Synergistic modulation of cognitive impairment in Alzheimer's disease.

Abstract

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) plaque deposition, neuroinflammation, oxidative stress, and hippocampal neurodegeneration, leading to cognitive decline. Artesunate has shown neuroprotective potential in previous models. This study evaluated artesunate alone and in combination with rivastigmine in an Aβinduced AD rat model. METHODS: Six-month-old Wistar rats received intracerebroventricular injections of Aβto induce AD. The animals were treated orally with artesunate (28 mg/kg) or rivastigmine (1 mg/kg), alone or in combination, for 30 days. Cognitive function was assessed via novel object recognition, passive avoidance, and Morris water maze tests. Hippocampal tissue was analyzed for Aβ, NF-κB, TNF-α, IL-1β, malondialdehyde, glutathione, and acetylcholinesterase activity. Histological examination of the CA1 and CA3 regions was used to assess neuronal viability and dendritic morphology. RESULTS: AD-vehicle rats exhibited marked deficits in recognition, aversive, and spatial memory, alongside elevated levels of Aβ, proinflammatory mediators, and oxidative stress, with reduced glutathione and acetylcholinesterase activity. Artesunate significantly improved cognitive performance and biochemical markers, with combination therapy showing greater efficacy. Histology revealed pronounced neuronal loss and dendritic degeneration in AD-vehicle rats, which were attenuated by artesunate, particularly when artesunate was combined with rivastigmine, preserving pyramidal neuron and dendritic spine density. CONCLUSION: Artesunate exerts neuroprotective effects in experimental AD by attenuating amyloid deposition, neuroinflammation, and oxidative stress and preserving hippocampal neuronal architecture. Coadministration of rivastigmine provides synergistic cognitive and neuroprotective benefits, supporting further investigation of this combination as a potential therapeutic approach for AD.