Neuroprotective and antioxidant effects of Azadirachta indica: A comprehensive GC-MS and preclinical study

Background: Herbal and Ayurvedic remedies are increasingly explored for mental health disorders such as anxiety and depression. Azadirachta indica (Neem) has long been recognized for its medicinal value. Objectives: The current study evaluated the neuroprotective, anxiolytic, antidepressant, antioxidant, and toxicological effects of the ethanolic fruit extract of Azadirachta indica in preclinical models. Methods: Anxiolytic activity was assessed through the open field test, elevated plus maze, and hole board test, whereas forced swimming and tail suspension tests were used to evaluate antidepressant effects. Corticosterone and acetylcholinesterase levels, brain histopathology, and GC-MS analysis of bioactive constituents were also performed. Results: Azadirachta indica fruit extract exhibited strong antioxidant activity (68.6%) and a high safety margin (LD50> 5000 mg/kg). Azadirachta indica produced notable behavioral changes across multiple tests. Azadirachta indica at 400 mg/kg reduced locomotor activity, increased exploratory behavior, and improved open arm preference, while also reducing head-dipping and immobility in depression models. The histopathological evaluations showed no morphological changes. Azadirachta indica at 200-400 mg/Kg also significantly decreased corticosterone levels and improved acetylcholinesterase levels. GC-MS analysis identified 51 metabolites that may contribute to these pharmacological effects. Conclusion: Overall, these findings suggest that Azadirachta indica fruit extract possesses anxiolytic and antidepressant potential, supporting its role as a natural therapeutic candidate for neuropsychiatric disorders.