Yu_2026_Dose.Response_24_15593258261471150

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited disease-modifying therapies. Aluminium chloride (AlCl(3))-induced neurotoxicity mimics key pathological features of AD, including oxidative stress, neuroinflammation, and cholinergic dysfunction. OBJECTIVE: This study aimed to evaluate the neuroprotective effect of cnicin in an AlCl(3)-induced rat model of Alzheimer-like neurodegeneration. METHODS: Rats were divided into five groups: normal control, AlCl(3) control (75 mg/kg/day, p.o.), AlCl(3) with cnicin (20 and 40 mg/kg/day, p.o.), and AlCl(3) with donepezil (5 mg/kg/day, p.o.) for 30 days. Behavioral performance was assessed using hanging wire and beam walking tests. Biochemical parameters, including acetylcholinesterase (AChE), antioxidant enzymes (SOD, CAT, GSH), malondialdehyde (MDA), and inflammatory cytokines (TNF-alpha, IL-1beta) were analyzed, along with histopathology. RESULTS: AlCl(3) administration induced significant behavioral deficits, increased AChE activity, oxidative stress, neuroinflammation, and neuronal damage. Cnicin treatment dose-dependently improved motor function, reduced AChE activity, restored antioxidant levels, decreased lipid peroxidation, and suppressed inflammatory markers. Histological analysis confirmed preservation of neuronal architecture, comparable to that of donepezil. CONCLUSION: Cnicin exhibits significant neuroprotective effects against AlCl(3)-induced neurodegeneration by modulating cholinergic activity, oxidative stress, and inflammation, suggesting its potential as a therapeutic agent for AD.