Neuroprotective Effect of Empagliflozin/Rivastigmine in Alzheimer's Disease Rat Model: Optimization of Multifaceted Mechanism of Action
Research Abstract
This study assessed the neuroprotective potential of empagliflozin (EMPA) as antidiabetic drug on glucose metabolism,
comparing it to rivastigmine (RIVA) as standard treatment for Alzheimer's disease (AD), and their combination. Male rats were
sorted into five groups. Group I served as the control, while groups II, III, IV, and V received the scopolamine plus heavy metal
mixture for AD induction. Groups III and IV were administered RIVA and EMPA, respectively, and group V received both
treatments. Cognitive function was evaluated behaviorally. Subsequently, glucose levels, acetylcholinesterase, oxidative stress,
and inflammatory markers were assessed. Alongside the brain histopathological changes, the expression of phosphorylated tau
protein was assessed. Moreover, glycolytic enzymes and glucose transporters were assessed using PCR analysis. The findings
were attributed to a notable suppressive impact of EMPA on lipid peroxidation, acetylcholinesterase, glucose levels, phos
phorylated tau protein, pro‐inflammatory cytokines, and neuropathological changes, while enhancing antioxidant and
interleukin‐10 levels. It also improves glucose metabolism. The findings suggest that EMPA may be a viable candidate for future
therapeutic exploration in AD, which has a multifaceted mechanism of action encompassing anti‐neuroinflammation, anti
oxidant stress, and enhanced glucose metabolism, as well as decreased acetylcholinesterase activity and phosphorylated tau
protein levels. Interestingly, combined treatment showed a superior effect than EMPA alone.
Research Date
Research Department
Research Journal
Drug Development Research
Research Member
Research Publisher
Wiley
Research Rank
Q1
Research Vol
86
Research Website
https://doi.org/10.1002/ddr.70180
Research Year
2025
