Neuroprotective Effects of Tephrosin on Aluminium Chloride-induced Oxidative Stress Mediated Neuroinflammation in Rat Model of Alzheimer's Disease

Aim/Background: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder with limited therapeutic options. Tephrosin (TP), a natural rotenoid, exhibits antioxidant and anti-inflammatory properties. This study investigated the neuroprotective effects of TP in an Aluminum Chloride (AlCl₃)-induced rat model of Alzheimer-like pathology. Materials and Methods: Twenty-four adult rats were divided into four groups (n=6): Control, AlCl₃, AlCl₃ + TP, and AlCl₃ + Donepezil. AD-like symptoms were induced by oral AlCl₃ (100 mg/kg) for six weeks. TP (10 mg/kg) or Donepezil (1 mg/kg) was administered orally during the last three weeks. Behavioral performance was evaluated using the wire hang and beam walking tests. Acetylcholinesterase (AChE) activity, oxidative stress markers [Malondialdehyde (MDA), Glutathione (GSH), Catalase (CAT), Superoxide Dismutase (SOD)], and pro-inflammatory cytokines [Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α)] were measured. Hippocampal histology was assessed using hematoxylin and eosin staining. Results: AlCl₃ exposure impaired motor function, increased MDA and AChE activity, elevated IL-1β and TNF-α levels, and caused hippocampal neuronal degeneration, while reducing GSH, CAT, and SOD activities. TP treatment significantly improved behavioral outcomes, restored antioxidant enzyme levels, reduced oxidative stress and inflammatory markers, and preserved hippocampal neuronal integrity. Conclusion: Tephrosin exerts neuroprotective effects against AlCl₃-induced Alzheimer-like pathology, likely via its antioxidant, anti-inflammatory, and anti-cholinesterase activities. These findings support TP as a promising candidate for AD therapy.