Abstract

EVALUATION OF NEUROPROTECTIVE EFFECT OF SITAGLIPTIN IN STREPTOZOTOCIN INDUCED ALZHEIMER’S DISEASE IN WISTAR RATS

Pooja T.*, Samiya Eram, Sindhu L., C. M. Chandana, Abhishek C. Pasarad

Abstract

Background: This study explores the neuroprotective potential of sitagliptin, an anti-diabetic drug, in managing Alzheimer's disease (AD) symptoms in a streptozotocin (STZ)-induced rat model. Objective: This research aimed to assess whether sitagliptin could improve cognitive function and reduce anxiety by modulating acetylcholinesterase (AChE) activity. Methods: Rats were divided into five groups: a control, a negative control with only STZ, a standard treatment group with STZ and Rivastigmine, and low- and high-dose sitagliptin groups (5 mg/kg and 10 mg/kg, respectively). Cognitive performance was evaluated using the elevated plus-maze test, which measures spatial memory and anxiety-like behaviors. Results: It was showed that both low and high doses of sitagliptin led to significant behavioral improvements, with the high dose producing effects comparable to Rivastigmine, the standard AD treatment. Notably, sitagliptin administration reduced AChE activity, correlating with observed cognitive and anxiety-related improvements, suggesting its action may involve modulation of cholinergic pathways. These findings support sitagliptin's potential as an adjunct or alternative treatment for AD, especially considering its dosedependent effects. Conclusion: The study underscores the need for further research into sitagliptin’s broader neuroprotective mechanisms, particularly its impact on AD biomarkers such as amyloid-beta and tau proteins. This research provides promising insights into the potential repositioning of sitagliptin for neurodegenerative disease management, highlighting its prospective benefits in AD treatment.

Keywords: Sitagliptin, Alzheimer’s Disease (AD), Streptozotocin, Neuroprotective, Acetylcholinesterase.