Neuroprotective Effects of Nigella sativa Extract in a Rat model of Propionic Acid-Induced Autism Spectrum Disorder

Abstract

BackgroundAutism Spectrum Disorder (ASD) is neurodevelopmental disorder with characteristics of impairments in social interaction, communication, and repetitive behaviors. Current pharmacological interventions often focus on alleviating symptoms, but they rarely address the underlying neurobiological disruptions or have sustained therapeutic effects. AimsThe present study explores the therapeutic effect of Nigella sativa (black cumin) extract in a propionic acid (PPA)-induced wistar rat model of ASD. MethodsForty male Wistar rats (n = 10 per group) were randomly assigned to four experimental groups, including control, PPA, N. sativa Low-Dose (NSL), and N. sativa High-Dose (NSH). The control group received daily intravenous (i.v.) injections (1 mL/kg) of saline (0.9% NaCl) over five days. The PPA group received daily intraperitoneal (i.p.) injections of 250 mg/Kg PPA for five days to induce ASD-like behaviors. NSL and NSH groups received N. sativa extract (10 mg/Kg and 50 mg/Kg, respectively) orally for 28 days, starting 7 days before PPA administration. Behavioral assessments, including social interaction, stereotypic behaviors, and anxiety, were conducted on day 28. Then, biochemical analyses (i.e., oxidative stress, inflammatory markers, neurotransmitter levels, caspase-3 expression, and histopathology) were performed. ResultsThe PPA group showed significantly (p < 0.05) reduced social interaction and increased stereotypic behaviors and heightened anxiety-like responses, indicative of ASD-like symptoms. Treatment with N. sativa resulted in a significant (p < 0.05) improvement in social behaviors, a reduction in stereotypic behaviors, and a decrease in anxiety-like responses. Biochemical analysis revealed that N. sativa treatment significantly (p < 0.05) reduced oxidative stress, evidenced by lower MDA levels, higher GSH, and restored SOD activity. In both NSL and NSH groups, it was observed that (i) inflammatory cytokines (i.e., TNF- and IL-1{beta}) were significantly (p < 0.05), (ii) neurotransmitter levels (i.e., dopamine and serotonin) were normalized, (iii) caspase-3 expression was significantly reduced, leading to a reduction in neuronal apoptosis-induced cell death, and (iv) histopathological analysis revealed reduced neuronal damages and a glial activation. ConclusionsN. sativa extract appears highly effective in ameliorating ASD behavioral and biochemical pathology abnormalities associated with ASD in a PPA-rat model. These results underscore the role of N. sativa for the treatment of ASD, including as possible adjunctive therapeutic option for this challenging neurodevelopmental disorder, though further research studies are necessary, including to determine the key phytochemical(s) involved in such beneficial effects. HighlightsO_LIHigh-dose Nigella sativa (NSH) acted as a potent brain antioxidant and anti-inflammatory agent; C_LIO_LINSH restored neurotransmitter balance by normalizing dopamine and serotonin levels; C_LIO_LINSH significantly reduced propionic acid (PPA)-induced neuronal apoptosis and caspase-3 expression; C_LIO_LINSH minimized neuronal damages and preserved brain tissue structure; C_LIO_LINSH improved core ASD-like behaviors, including social deficits and stereotypy. C_LI