Nano-hesperetin ameliorates 6-hydroxydopamine-induced behavioral deficits and oxidative damage by up-regulating gene expression of antioxidant enzymes.

Objective: Hesperetin (Hst) has shown several pharmacological effects. The efficacy of Hst is highly restricted Materials and Methods: Forty-two Wistar male rats were equally assigned to 6 groups: control, 6-OHDA, Hst5, Hst10, nano-Hst5, and nano-Hst10. Treatment with Hst and nano-Hst was initiated 1 day after the intrastriatal injection of 6-OHDA and continued for 28 days. Behavioral deficits were evaluated using apomorphine-induced rotation test (AIRT), narrow beam test (NBT) and novel object recognition test (NORT), and the hippocampus and striatum were used to evaluate oxidative stress-related parameters. Results: The rats injected only with 6-OHDA showed learning and memory deficits but Hst and nano-Hst treatments improved it (p<0.001). Compared to the control group, a marked promotion in Malondialdehyde (MDA) levels along with a marked reduction in activities and gene expression of antioxidant enzymes and reduced glutathione (GSH) levels in the hippocampus and striatum were observed in the 6-OHDA group (p<0.01). However, administration of Hst and nano-Hst remarkably diminished MDA levels (p<0.01), and significantly increased the activities (p<0.01) and gene expression of antioxidant enzymes (p<0.05) and GSH levels (p<0.01) compared to the 6-OHDA group. In most parameters, nano-Hst has shown better therapeutic effects than Hst. Conclusion: Our findings reveal that Hst can be considered as a potential candidate for the treatment of neurodegenerative diseases and that nano-Hst may have better bioavailability.