Alzheimer disease (AD) is a progressive dementia affecting a large proportion of 
the aging population. There is evidence that brain tissue in patients with AD is 
exposed to oxidative stress during the course of the disease. Hesperetin (Hst) 
is a natural flavonoid, which has been reported to exert various biological 
activities such as antioxidant and anti-inflammatory effect. The present study 
aimed to investigate the effects of hesperetin and nano-hesperetin on 
neurobehavioral activity and superoxide dismutase (SOD), glutathione peroxidase 
(GPx), glutathione reductase (GRx) and catalase (CAT) enzymes activity, 
malondialdehyde (MDA) and glutathione (GSH) levels in hippocampal area of rats 
in an experimental model of AD. The AD was induced in animals by 
intracerebroventricular injection of STZ (icv-STZ) unilaterally. Animals were 
treated with the Hst and nano-Hst (10, 20 mg/kg body weight), then after three 
successive weeks, recognition memory was examined (passive avoidance test and 
novel object recognition test) and antioxidant parameters were evaluated. In our 
study behavioral testes showed improvement on memory retrieval and recognition 
memory consolidation. Furthermore the Hst and nano-Hst increased the activity of 
antioxidant enzymes (SOD, glutathione GPx, GRx and CAT) and GSH levels and 
decreased MDA in the hippocampal area. These results suggested that Hst and 
nano-Hst may inhibit STZ-induced oxidative stress, and that it may possess 
therapeutic potential for the treatment of AD.