Phytochemical profiling and mechanistic insights into the anxiolytic potential of Sphaeranthus indicus Linn.: A network pharmacology, molecular docking and simulation approach.
Anxiety problems, such as Generalized Anxiety Disorder, are a significant source of concern for people worldwide. Current medicines frequently have side effects or are ineffective. Sphaeranthus indicus Linn, often known as Mundi, is an Ayurvedic medication that has demonstrated promising results to aid with anxiety. However, the molecular mechanism underlying its function is not known. In this study we used computational tools to understand how Sphaeranthus indicus Linn might assist persons with anxiety disorders. A library of 57 phytochemicals was compiled from databases and literature sources and was tested for BBB permeability, ADMET and toxicity. Subsequently a network was built to link the compounds with their targets and anxiety related diseases. Upon investigation of the network, it was discovered that eight phytochemicals including Eugenol, β-sitosterol, Estragole, and Camphor interacted with several targets, while four targets seemed to be most important, the serotonin transporter (SLC6A4), the glucocorticoid receptor (NR3C1), acetylcholinesterase (ACHE) and the dopamine D2 receptor (DRD2). Docking of the eight phytochemicals was performed with all four targets, which revealed that β-sitosterol docked best to all targets, while several phytochemicals exhibited favourable binding. Further, 100 ns atomistic simulations were performed for β-sitosterol with all four targets, which indicated stable binding. Thus, we conclude that these phytochemicals probably work as serotonin reuptake inhibitors by blocking the serotonin transporter, probably modulate dopamine signalling as well by interacting with dopamine D2 receptor. We also predict that these phytochemicals interact with the acetylcholinesterase and the glucocorticoid receptor, suggesting their potential to modulate neurotransmission and glucocorticoid signalling that may influence neurotransmission and stress-related signalling. Taken together, the findings from this work, provide the first network pharmacology-based evidence for S. indicus' multitarget anxiolytic processes, support its traditional use in neuropsychiatric diseases, and identify various phytochemicals as promising natural lead candidates for anxiolytic medication development.