Promising therapeutic efficacy of kolaviron against prenatal valproate-induced autism spectrum disorder

Objective(s): Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition marked by impairments in social communication, language, and behavior. Prenatal exposure to valproic acid (VPA) contributes to its pathogenesis. kolaviron (KV), a polyphenolic extract from Garcinia kola, has potent antioxidant and anti-inflammatory properties, offering neuroprotective potential in ASD models. Our study aimed to evaluate whether KV could improve the VPA-induced autism model through targeting serotonergic system, mitochondrial dysregulation, oxidative stress, and inflammation.Materials and Methods: Pregnant Wistar rats received a single intraperitoneal dose of VPA (۶۰۰ mg/kg) on gestational day ۱۲.۵ to induce autism-like features in offspring. Male pups were weaned on postnatal day (PND) ۲۱ and randomly assigned to receive KV (۵۰ or ۱۰۰ mg/kg, oral), or saline until PND ۴۹. Behavioral tests were finally conducted and brain tissue was collected for analysis of hippocampal oxidative stress, mitochondrial dysfunction, serotonin transporter (۵-HTT), serotonin receptor ۷ (۵-HTR۷), tumor necrosis factor α (TNF), and interleukin ۶ (IL-۶) levels. Immunohistochemical staining for glial fibrillary acidic protein (GFAP) was also performed to assess astrocytic reaction.Results: KV-treated VPA-exposed rats showed significant improvements in social interaction and with lower repetitive behavior. Biochemically, KV decreased malondialdehyde (MDA), IL-۶ and TNFα levels, improved catalase activity and mitochondrial membrane potential (MMP), and modulated serotonergic markers (۵-HTT and ۵-HTR۷). Histologically, KV also attenuated hippocampal GFAP immunoreactivity (IRA). Conclusion: KV showed its promising potential as a complementary therapeutic agent in ASD murine model. Further studies are still warranted to clarify its further mechanisms and clinical relevance.

کلیدواژه ها:

Autism spectrum disorder ، Hippocampus ، Kolaviron ، Serotonin ، Valproic acid