Clin Psychopharmacol Neurosci.  2020 Feb;18(1):81-92. 10.9758/cpn.2020.18.1.81.

Protective Effects of Citicoline and Benfotiamine Each Alone and in Combination on Streptozotocin-induced Memory Impairment in Mice

  • 1Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, IR Iran


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.
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 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.
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.


Citicoline; Benfotiamine; Memory; Dementia; Cognitive; Streptozotocin
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