Background: In this study, we investigate the neuroprotective effects of Hesperetin (Hst) and Nano-Hst on anxiogenic-like behavior and cerebral antioxidant defenses at transcriptional and enzymatic levels in a streptozotocin (STZ)-induced Alzheimer rat model. Methods: Wistar rats were administrated with Hst and Nano-Hst (10 and 20 mg/kg/d) for three weeks. The elevated plus-maze test assessed anxiogenic-like behavior. After behavioral test, activity and gene expression of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GRx) enzymes, as well as malondialdehyde (MDA) and glutathione (GSH) levels, were measured in the cerebral cortex. Results: Based on our results, a rat model of Alzheimer’s disease (AD) exhibited anxiogenic-like behavior, activity and gene expression of cerebral antioxidant enzymes and GSH level was decreased while the MDA level was increased. Hst and Nano-Hst treatment reversed anxiogenic-like behavior, and the activities of antioxidant enzymes were elevated. Hst and Nano-Hst effects on the gene expression of CAT, SOD and GRx were confirmed by quantitative real-time PCR (qRT-PCR) in which the expression levels of these genes in the cerebral brain were significantly increased compared to STZ group. Conclusions: These findings indicated that the administration of Hst and Nano-Hst may be used to treat anxiety -related to AD via an up-regulation of cerebral antioxidant enzyme gene.
