Effect of quercetin-conjugated superparamagnetic iron oxide nanoparticles on diabetes-induced learning and memory impairment in rats.

Background: Diabetes mellitus plays a causative role in cognitive decline. Newly, neuroprotective effects of flavonoids have been widely investigated in neurodegenerative diseases. Quercetin (QC) is a phyto-derived bioactive flavone with numerous beneficial activities. However, its limited permeability to cross the blood-brain barrier, low oral bioavailability, poor aqueous solubility, and rapid gastrointestinal digestion lead to the administration of high dose of QC in clinical application.

Materials and methods: In order to overcome these limitations, we conjugated QC with superparamagnetic iron oxide nanoparticles (QCSPIONs) and supplemented streptozotocin-induced diabetic rats with it to improve diabetes-related memory impairment. In this regard, 40 rats were distributed into five groups with eight animals: control, diabetes, and diabetes treated with SPIONs, QC, and QCSPIONs. All treatments (at the dose of 25 mg/kg) were dissolved in deionized water and gavaged for 35 consecutive days.

Results: At the end of the study, QCSPIONs possessed significantly better efficacy than free QC on the improvement of memory performance. In the Morris water maze test, QCSPIONs compared to free QC reduced much better the escape latency over training trials ( P <0.01) and increased the time spent in the target quadrant in probe trial ( P <0.001). In the passive avoidance test, it increased step-through latency ( P <0.05) and reduced the time spent in the dark compartment ( P <0.01). In addition, both free QC and QCSPIONs were able to prevent the changes in body weight and decrease blood glucose levels in diabetic rats ( P <0.05).

Conclusion: Overall, according to these results, we conclude that QC in the conjugated state with lower dose offers significantly higher potency in ameliorating diabetes-related memory impairment. Thus, this study offers an effective combined therapy for improving learning and memory.