A Multi-Target mechanism of Withania somnifera bioactive compounds in autism spectrum disorder (ASD) Treatment: Network pharmacology, molecular docking, and molecular dynamics simulations studies

Abstract

Autism spectrum disorder (ASD) is a developmental disorder resulting from variations in brain structure and function. Individuals with ASD often experience challenges in communication and social interaction, along with engaging in repetitive or restricted patterns of behavior and interests. The lack of documented data and the wide range of pathophysiological processes associated with ASD make it challenging to work which causes a major financial burden on health care management. Withania somnifera, often referred to as ashwagandha is the tropical winter cherry in the Solanaceae family that can be used to treat several ailments such as asthma, stress, hypertension, diabetes, cancer, arthritic, and neural disorders including ASD. In this investigation, we examined the active compound-target-pathway network and discovered that Withanolide J, Withanone, and Withaferin A have a great role in the onset of ASD by influencing the IL6 gene. Later, the molecular docking method was applied for confirmation of the active compound's effective action against the prospective target. The molecular dynamics simulation exhibited that the complexes of Withanolide J and Withanone had stable intermolecular binding conformation and unveiled very stable dynamics during the simulation time. A combined network pharmacology and molecular docking approach demonstrated that W. somnifera exhibits a promising preventive impact on ASD by targeting relevant signaling pathways associated with the disorder. This establishes a foundation for comprehending the underlying mechanism of the anti-ASD activity of W. somnifera.

Keywords

• Bioactive compounds
• Autism spectrum disorder
• Withania somnifera
• Network pharmacology
• Bioinformatics, molecular modeling