Autism spectrum disorders cover a range of neurodevelopmental disorders characterized by impairments in social interaction and cognitive deficits. Phenolic compound applications have been restricted due to their poor solubility, bioavailability, and low stability. This paper aimed to explore the neuroprotective effects of sumac and gallic acid-loaded nanophytosomes (GNP) on oxidative stress-induced cognitive impairment and Nrf2/Keap1 gene expression in the autism model. Valproic acid (VPA) was administered intraperitoneally at doses of 500 mg/kg to female rats during gestational 12.5 days (E12.5). The prenatal VPA-exposed rats were divided into five groups, including VPA, VPA treated with sumac, gallic acid (GA), sumac-loaded nanophytosome (SNP), and GNP at doses of 20 mg/kg for 4 weeks (n = 6). A novel object test was conducted and antioxidant parameters and Nrf2/Keap1gene expression were evaluated in the hippocampus. According to the obtained results, the rat model of autism exhibited recognition memory impairment. We observed an increase in glutathione peroxidase (GPx), glutathione reductase (GRx), superoxide dismutase (SOD), catalase (CAT) enzyme activity, total antioxidant capacity (TAC), and glutathione (GSH) levels. Furthermore, sumac and GNP improved recognition memory deficits and increased GPx, GRx, SOD, and CAT activities, GSH and TAC levels, and Nrf2/Keap1gene expression in the hippocampal area. Our results also suggested that SNP and GNP ameliorate VPA-induced learning and memory deficits more efficiently than sumac extract and pure GA by reducing oxidative stress, enhancing antioxidant enzyme activity, and Keap1/Nrf2 gene expression. The present study demonstrated that the utilization of SNP and GNP significantly improved recognition memory deficits.
