Neuroprotective Effect of Levetiracetam in Combination with Berberine on Scopolamine Induced-Cognitive Impairment in Mice: A Behavioral and Biochemical Approach

Abstract

Background: Presently, only four drugs have been approved by FDA for Alzheimer’s disease (AD). A drug repurposing approach can be fruitful in searching for promising candidates for AD. Objective: The objective of the work was to evaluate the neuroprotective effect of levetiracetam (LEV) in combination with berberine (BER) in scopolamine-induced cognitive impairment in mice by applying a drug repositioning approach owing to their antioxidant potential. Methods: Cognitive impairment was induced in mice by scopolamine. Morris water maze, elevated plus maze, and Y-maze were used to evaluate behavioral parameters. Assays for acetylcholinesterase (AChE), reduced glutathione (GSH), malondialdehyde (MDA), catalase, nitrite, TNF-α, and brain histopathology were performed. Results: The transfer latency time and percentage of spontaneous alternation were significantly reduced and significant alterations in AChE and MDA levels, GSH concentration, and improvement in nitrite and catalase levels were also evidenced after the treatment of mice with a combination of LEV and BER in comparison to independent drugs, standard and disease control groups. The antioxidant defense was also improved and TNF-α levels were significantly reduced by a combination of LEV and BER. Improvement in neuronal damage by restoration of the cytoarchitecture of the brain was also seen in the histopathological study of the brain of treatment groups. Conclusion: The present study has demonstrated that the combination of LEV and BER has significantly improved cognition in mice by lipid peroxidation inhibition, augmentation of endogenous antioxidant enzymes, the decline in TNF- α levels, and AChE activity in the brain when compared to individual drugs, standard and disease control owing to their strong antioxidant and anti-inflammatory potentials.