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

Abstract

BackgroundDiabetes 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 methodsIn 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.ResultsAt 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).ConclusionOverall, 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.

WITHDRAWN: Quercetin-conjugated superparamagnetic iron oxide nanoparticles enhances Nrf2 expression through miR-27a intervention to prevent memory dysfunction in diabetic rats

“…In a previous study, we use quercetin as a phyto-derived bioactive compound and QCSPION as a nano-based delivery system to prevent cognitive dysfunction in diabetic rats. We revealed that QCSPIONs even at lower concentrations than pure QC improved learning and memory of diabetic animals, but the underlying mechanisms remained unknown [22]. In a separate study, we revealed that SPIONs enhanced the bioavailability of QC in the brain of healthy rats and could be considered as a novel therapeutic for the treatment of neurodegenerative disorders [29].…”

“…In addition, two certain peaks of oxygen and iron in the EDX spectroscopy confirmed the SPIONs identity. All of pictures presented in our previous studied (22,26).…”

“…Synthesis of QCSPIONs referred to our previous studies [22,29,47]. Briefly, anhydrous FeCl2, FeCl3 and dextran were liquefied in deionized water.…”

“…Animal maintenance, diabetes induction, and treatment schedule were elaborated in the previous study [22]. Briefly, male Wistar rats were bought from Isfahan Royan Institute, Iran and maintained for two months in animal house with standard condition.…”

“…Despite these favorable 4 properties, its bioavailability to the brain is low due to poor solubility, stability and distribution so various conjugates of QC have been developed to overcome these limitations [15,21]. In a previous report, we revealed that oral delivery of QCSPIONs in the range of 30-50 nm had significantly better efficacy on the improvement of memory performance in diabetic rats compared to pure QC and proposed an effective combined therapy in the maintenance of learning and memory [22].…”