Computational Repurposing of Asparagus racemosus and Withania somnifera for Postpartum Depression: Insights into MAO-A and Inflammatory Signaling Modulation.

Postpartum depression (PPD) is a debilitating mental health disorder which necessitates effective and accessible management strategies. This study explores the mechanistic potential of Asparagus racemosus and Withania somnifera as therapeutic options for PPD, using in silico approaches. Phytoconstituents of both herbs were identified from literature and were then assessed for pharmacokinetics, drug-likeness and toxicity. PPD-related gene targets were obtained via DisGeNet and GeneCards. Key target proteins, signaling pathways and biological processes have been determined using PPI network analysis, KEGG enrichment and Gene Ontology. Molecular Docking, Molecular Mechanics Generalized Born Surface Area (MM-GBSA) analysis and Molecular Dynamics Simulations (MDS) were performed to evaluate binding affinities and complex stability of drug-like phytoconstituents with key target proteins. Methanolic root extracts of both herbs were further profiled using LC-QToF-MS. Twelve drug-like phytoconstituents were found to interact with PPD-related targets such as GSK3β , MMP-9, PTGS2, MAO-A etc. Serotonergic synapse (hsa04726) and inflammatory pathways showed significant involvement in PPD-associated targets in enrichment analysis. In Molecular Docking and MDS, kaempferol showed the highest binding affinities with MAO-A (-9.7 kcal/mol) and PTGS2 (-9 kcal/mol). Phytochemical profiling reflected the presence of key phytoconstituents like kaempferol, nicotine, and cuscohygrine in the extracts. These study findings suggest that Asparagus racemosus and Withania somnifera have the potential to modulate important neuroendocrine and inflammatory processes linked to postpartum depression.