Rationale Antioxidant natural herb hesperetin (Hst) ofers powerful medicinal properties. Despite having noticeable antioxidant properties, it has limited absorption, which is a major pharmacological obstacle. Objectives The goal of the current investigation was to determine if Hst and nano-Hst might protect mice against oxidative stress and schizophrenia (SCZ)-like behaviors brought on by ketamine (KET). Methods Seven treatment groups (n=7) were created for the animals. For 10 days, they received distilled water or KET (10 mg/kg) intraperitoneally (i.p). From the 11th to the 40th day, they received daily oral administration of Hst and nano-Hst (10, 20 mg/kg) or vehicle. With the use of the forced swimming test (FST), open feld test (OFT), and novel object recognition test (NORT), SCZ-like behaviors were evaluated. Malondialdehyde (MDA) and glutathione levels and antioxidant enzyme activities were assessed in the cerebral cortex. Results Our fndings displayed that behavioral disorders induced by KET would be improved by nano-Hst treated. MDA levels were much lower after treatment with nano-Hst, and brain antioxidant levels and activities were noticeably higher. The mice treated with nano-Hst had improved outcomes in the behavioral and biochemical tests when compared to the Hst group. Conclusions Our study’s fndings showed that nano-Hst had a stronger neuroprotective impact than Hst. In cerebral cortex tissues, nano-Hst treatment dramatically reduced KET-induced (SCZ)-like behavior and oxidative stress indicators. As a result, nano-Hst may have more therapeutic potential and may be efective in treating behavioral impairments and oxidative damage brought on by KET.
