Nano-hesperetin attenuates ketamine-induced schizophrenia-like symptoms in mice: participation of antioxidant parameters.

RATIONALE: Antioxidant natural herb hesperetin (Hst) offers 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 field 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 findings 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 findings 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 effective in treating behavioral impairments and oxidative damage brought on by KET.

Preventive effect of quercetin-Loaded nanophytosome against autistic-like damage in maternal separation model: The possible role of Caspase-3, Bax/Bcl-2 and Nrf2.

The autism is an abnormality in the neuronal advance which starts before age 3 recognized by defective behaviors. This study aimed to make quercetin-loaded nanophytosomes (QNP) on behavioral deficits, cerebellar oxidative stress and apoptosis in an autistic-like model caused by maternal separation (MS). The newborn rats are randomly categorized into seven groups, including control, positive control, disease, and diseases treated with quercetin (10 and 40 mg/kg) and QNP (10 and 40 mg/kg). Pups exposed to MS for 3 h per day from postnatal days (PND) 1-9 showed behavioral impairment in adult rats compared to control group. The oral administration of quercetin and QNP was constantly started after the lactation period (21 postnatal days) for three weeks. Autistic-like behaviors, antioxidant parameters, and Nrf2, Bax/Bcl-2, and Caspase-3 expressions were surveyed in the cerebellum. Quercetin (40 mg/kg) treated improved some behavioral disorders. Also, the improvement of oxidative stress parameters, Nrf2 and apoptotic factors gene expression was observed in the cerebellum of quercetin (40 mg/kg) treated (p < 0.01). QNP treatment (10 and 40 mg/kg) significantly ameliorated anxiety-like behaviors, line crossing, and grooming index (p < 0.001), lipid peroxidation (p < 0.001), and increased catalase (CAT) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione peroxidase (GPx) (p < 0.001) activity, and glutathione (GSH) levels (p < 0.05). Moreover, QNP significantly reduced Caspase-3 and Bax expression (p < 0.001), but increased Bcl-2, and Nrf2 expressions (p < 0.001). These findings indicated that QNP due to its high bioavailability was more effective than quercetin can be reduced autistic-like behavior, oxidative and apoptotic damages in the model of MS rats.

Hesperetin nanoparticles attenuate anxiogenic-like behavior and cerebral oxidative stress through the upregulation of antioxidant enzyme expression in experimental dementia of Alzheimer's type.

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.