The Effects of Novel Thymoquinone-Loaded Nanovesicles as a Promising Avenue to Modulate Autism Associated Dysregulation by Restoring Oxidative Stress in Autism in Mice

Introduction: Representing a prominent public health challenge with a surge in cases and no currently available treatment, autism spectrum disorder (ASD) remains a puzzle to researchers. Although the exact pathogenesis of this heterogeneous disorder is yet to be established, it has been reported that neural oxidative stress and neuroinflammation are eminently implicated. With numerous research establishing thymoquinone (TQ) as a potent antioxidant, this study assessed its effectiveness in the context of cognitive and social impairments and neural oxidative stress in the idiopathic autistic model in BTBR mice. Moreover, a novel TQ-loaded nanovesicle drug delivery system was optimized and utilized to enhance the bioavailability of TQ in the central nervous system. Methods: Through a battery of standard behavioral tests, primary parameters such as social behavior, locomotor activity, and anxiety levels were assessed following systemic administration with TQ (10mg/kg, i.p). Biochemical analysis of neural oxidative stress markers in the cerebellum and hippocampus tissue samples obtained from the different treatment groups was also performed. Results: The results indicated significant enhancements in sociability and social novelty preference of assessed BTBR mice treated with TQ-loaded nanovesicles (both p<0.01) as well as free TQ (p<0.05 and p<0.01, respectively). Moreover, BTBR mice treated with TQ-loaded nanovesicles also displayed restored levels of anxiety (p<0.05) and modulated hyperactivity parameters (p<0.05). In addition, and following biochemical assessments, our observations revealed marked alleviation of neural oxidative stress in BTBR mice treated with TQ-loaded nanovesicles, with restored levels of antioxidant proteins, reduced glutathione (p<0.01), and catalase (p<0.01), and diminished levels of the oxidative stress byproduct, malondialdehyde (p<0.01). Discussion: These preclinical observations unraveled compelling findings that reinforced TQ’s antioxidant capacity, shedding new light on its potential as an effective therapeutic option for ASD. Thus, and with further experimentation, this study holds the potential to transition into a clinical study.