Objective: Diabetes mellitus is associated with cognitive disorders such as Alzheimer’s disease. Studies have shown that citicoline and benfotiamine can improve memory and learning through different mechanism of actions. The aim of this study was to compare the individual effects of benfotiamine (100, 200, 300 mg/kg) and citicoline (50, 100, 250, 500 mg/kg, gavage) and their co-administration on memory impairments in diabetic mice. Methods: Diabetes was induced by a single dose of streptozotocin (STZ, 140 mg/kg, intraperitoneal) and benfotiamine and/or citicoline were administered for three weeks. Memory was evaluated using the object recognition task (ORT) and passive avoidance test (PAT). Results: Results from ORT shows that citicoline at 50, 100, 250, and 500 mg/kg and benfotiamine at 100, 200, and 300 mg/kg and their combination (benfotiamine at 100 mg/kg added to citicoline at 50, 100, and 250 mg/kg) are equally effective in reversing the memory loss induced by STZ (p ＜ 0.001). PAT results demonstrate that citicoline at 100, 250, and 500 mg/kg and benfotiamine at above doses did not improve the latency time when administered separately, but benfotiamine at a fixed dose of 100 mg/kg in the presence of citicoline at 50, 100, and 250 mg/kg increased the latency time and improved memory significantly. Conclusion In conclusion, in PAT, co-administration of benfotiamine and citicoline was more effective than either alone in improving memory. Regarding ORT, although benfotiamine added to citicoline improved memory notably, the difference between combination therapy and single-drug therapy was not considerable.

Objective: Alzheimer’s disease is a popular neurodegenerative disorder which is growing in the elderly people. Exposure to environmental pollutant like aluminum could trigger or accelerate its involved mechanisms like tau phosphorylation. The current study will evaluate the effect of alone or co-administration of Citicoline or/and magnesium on the aluminum chloride induced memory impairment. Methods: Male albino mice were randomly divided into different groups (n = 7). Memory impairment was induced via orally administration of 300 mg/kg Aluminum Chloride for 28 days. Based on respective group, animals received 100, 250, 500 mg/kg of Citicoline or 50, 100, 150 mg/kg of Magnesium sulfate (MgSO4), intraperitoneally. In co-administration, 50 mg/kg of MgSO4 injected concomitantly with 100, 250, or 500 mg/kg of Citicoline. Rivastigmine (2 mg/kg intraperitoneally) was used as a positive control. Memory was evaluated using the Object Recognition Task (ORT) and Passive Avoidance Test (PAT). Results: The studied doses of Citicoline or MgSO4 when administered individually showed significant increase in the discrimination index in ORT and latency time in the PAT compared to the Aluminium chloride (AlCl3) treated group. Concomitant injection of 50 mg/kg MgSO4 with the different doses of Citicoline strongly increased the above indices values in comparison to each alone. Conclusion The findings show, individual administration of Citicoline or MgSO4 inverted the AlCl3-induced memory impairment in a dose independent manner. The addition of MgSO4 to the Citicoline showed a synergistic effect in the PAT and likely additive effect in the ORT.