Phenolic Compounds from Passiflora edulis and Their Effect on Social Behavior and the AMPA Receptor in a Preclinical Model of Autism

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication and interaction, and by restricted or repetitive behaviors. The study aimed to evaluate the neuroprotective potential of a phenolic extract of Passiflora edulis (EPE) on social behavior and neurochemical markers in a murine model of ASD induced by valproic acid (VPA). Pregnant female BALB/c mice (Mus musculus) were exposed to VPA (600 mg/kg on day 12.5 of gestation), and the offspring of both sexes were subsequently treated with EPE at doses of 50, 100, or 300 mg/kg for forty two days. The EPE was characterized by UHPLC-MS/MS, identifying vicenin-2, isoschaftoside, isoorientin, vitexin-2″-O-rhamnoside, and isovitexin. Behavioral assessments included locomotion, stereotypy, anxiety, social interaction, and memory. Biochemical analyses covered antioxidant enzymes (CAT, SOD, GPx) and mRNA expression of GluA1- and GluA2 AMPA receptor subunits. The results demonstrated a significant improvement in social behavior with a normalization of GluA1 subunit expression at 300 mg/kg. In conclusion, these findings suggest that phenolic compounds from Passiflora edulis ameliorate social deficits in the ASD model through modulation of glutamatergic signaling-specifically via GluA1 subunit RNA expression-mediated CAT and SOD antioxidant activity.