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 anxietylike 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.
