Cnicin Attenuates Aluminium Chloride-Induced Neurodegeneration Through Antioxidant and Anti-Inflammatory Mechanisms.

Abstract

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited disease-modifying therapies. Aluminium chloride (AlCl₃)-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 AlCl₃-induced rat model of Alzheimer-like neurodegeneration.

Methods: Rats were divided into five groups: normal control, AlCl₃ control (75 mg/kg/day, p.o.), AlCl₃ with cnicin (20 and 40 mg/kg/day, p.o.), and AlCl₃ 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-α, IL-1β) were analyzed, along with histopathology.

Results: AlCl₃ 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 AlCl₃-induced neurodegeneration by modulating cholinergic activity, oxidative stress, and inflammation, suggesting its potential as a therapeutic agent for AD.