Promising Therapeutic Efficacy of Kolaviron against Prenatal Valproate-Induced Autism Spectrum Disorder

Background Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition marked by impairments in social communication, language and behavior. Both genetic and environmental factors, including prenatal exposure to valproic acid (VPA), contribute to its pathogenesis. VPA exposure during critical periods of neurodevelopment induces oxidative stress, inflammation, and serotonergic dysregulation. Kolaviron (KV), a polyphenolic extract from Garcinia kola , exhibits potent antioxidant and anti-inflammatory properties, potentially offering Neuroprotection in ASD models . The aim of our study was to evaluate whether Kolaviron could improve the VPA-induced autism model in the areas of Mitochondrial dysregulation oxidative stress, inflammation, and behavior, and to compare its effects with oxytocin on the serotonergic system. Methods Pregnant Wistar rats received a single intraperitoneal dose of VPA (600 mg/kg) on gestational day 12.5 to induce autism-like features in offspring. Male pups were weaned on postnatal day (PND) 21 and randomly assigned to receive KV (50 or 100 mg/kg, oral), oxytocin (12 µg/kg, intranasal), or saline until PND 49. Behavioral tests were conducted on PNDs 42–49. Brain tissues were collected for ELISA analysis of hippocampal 5-HTT, 5-HTR7, TNF Alfa and IL-6 levels, Immunohistochemical staining for parvalbumin was performed to assess interneuron integrity. Results KV-treated VPA-exposed rats showed significant improvements in social interaction, reduced repetitive behavior, and attenuated. Biochemically, KV decreased IL-6 levels and modulated serotonergic markers (5-HTT, 5-HTR7). Histologically, KV preserved hippocampal architecture and parvalbumin-positive interneurons, suggesting Neuroprotection. Conclusions These effects were dose-dependent, indicating KV's potential as a complementary therapeutic agent in ASD. Further studies are warranted to clarify its mechanisms and clinical relevance.