Exploration of Mechanism of Withania somnifera (L.) Dunal in the Treatment of Huntington Disease: A Network Pharmacology Approaches Integrated with Molecular Docking and Dynamics

Background: Withania somnifera (L.) Dunal (Ashwagandha) is a traditional medicine that has several health-promoting and therapeutic benefits, including neuroprotective, sedative, and adaptogenic effects. Aim: The objective of current study is to investigate the mechanism of action of W. somnifera in the management of Huntington's disease by combining network pharmacology techniques with molecular docking and dynamics. Methodology: The literature was searched to identify the main phytoconstituents of W. somnifera. The Swiss Target perdition database and SEA database were used to identify the targets of various phytoconstituents of W. somnifera, whereas targets associated with Huntington's disease were identified using GeneCards and DisGeNet database. A Venn diagram was used to identify overlapping targets and interaction among targets was checked using the STRING database. Cytoscape 3.10.1 was used to construct and analyse the network. The enrichment studies of the Kyoto Encyclopaedia of Genes and Genomes (KEGG) and gene ontology pathways were also performed. The molecular docking and molecular dynamic studies were performed using Schrodinger software. Results: A total of 948 targets were identified which can be hit by W. somnifera and 513 targets were identified in Huntington’s disease. A total of 111 targets were identified. Network Pharmacology results have shown that the phytoconstituents of W. somnifera can be useful in Huntington disease through the modulation of inflammatory and apoptotic signalling pathways. The selected phytoconstituents of W. somnifera have also shown favoured interactions in the active site of targets involved in inflammation and apoptosis as indicated by molecular docking and dynamics results. Conclusion: Overall, it can be concluded that W. somnifera plays an important role in Huntington disease through the modulation of inflammatory and apoptogenic signalling pathways.