Therapeutic Potential of Ocimum basilicum L. Extract in Alleviating Autistic‐Like Behaviors Induced by Maternal Separation Stress in Mice: Role of Neuroinflammation and Oxidative Stress

ABSTRACT A confluence of genetic, environmental, and epigenetic factors shapes autism spectrum disorder (ASD). Early‐life stressors like MS play a contributing role in this multifaceted neurodevelopmental disorder. This research was to explore the efficacy of Ocimum basilicum L. (O.B.) extract in mitigating behaviors reminiscent of autism prompted by maternal separation (MS) stress in male mice, focusing on its impact on neuroinflammation and oxidative stress. MS mice were treated with O.B. extract at varying dosages (20, 40, and 60 mg/kg) from postnatal days (PND) 51–53 to PND 58–60. Behavioral experiments, including the Morris water maze, three‐chamber test, shuttle box, and resident‐intruder test, were conducted post‐treatment. The method of maternal separation involved separating the pups from their mothers for 3 h daily, from PND 2 to PND 14. Molecular analysis of hippocampal tissue was performed to assess gene expression of Toll‐like receptor 4 (TLR4), tumor necrosis factor‐α (TNF‐α), and interleukin‐1β (IL‐1β). Hippocampal and serum malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were measured. O.B. extract administration resulted in the amelioration of autistic‐like behaviors in MS mice, as evidenced by improved spatial and passive avoidance memories and social interactions, as well as reduced aggression in behavioral tests. O.B. extract attenuated oxidative stress and neuroinflammation, as indicated by decreased MDA and increased TAC levels, as well as downregulation of TLR4, TNF‐α, and IL‐1β expression in the hippocampus. O.B. extract may offer a novel therapeutic avenue for ASD, potentially mediated through its anti‐inflammatory and antioxidant properties.