Insilico analysis of Ashwagandha (Withania somnifera (L.) Dunal) for its Balya activity with special reference to Cachexia

Abstract

Cachexia is a serious but under recognised consequence of many chronic diseases. The positive role of Ashwagandha in debility has been evaluated in several studies. But the underlying molecular mechanism is unclear. In the present study, network pharmacology is used to understand the molecular basis of its action. Methods: The phytoconstituents of Ashwagandha were screened from IMPPAT database and literature. The effective compounds were screened by drug likeness score and pharmacokinetic characteristics (ADMET). The target genes of effective compounds were predicted from BindingDB. The cachexia genes were found in gene-cards database, and cachexia related target genes were screened by comparison. Then the related pathways and correlation analysis were explored by the Genomes (KEGG) database. Finally, the networks of compound-target, target-pathway, and pathway-disease of Ashwagandha were constructed by Cytoscape software v3.7.2. Docking studies were carried out with PyRx software and analyzed in Biovia discovery studio visualizer. Results: The effective ingredients of Ashwagandha in cachexia were Withanolide S, Withanolide E, Withanolide D, Withasomniferol A and Beta sitosterol. The network analysis showed the highly modulating proteins were PTGS2, AR, PRKCB, JUN, TERT, NFE2L2, MDM2 and TNF which are related to cachexia and act on the pathways like MAPK signalling, MicroRNAs in cancer, cAMP signalling etc. The ligands and targets were retrieved from the PubChem, Protein Data Bank and docked using PyRx software. Conclusion: The present study is enabling to understand scientific evidence at the molecular level of balya action which has been proved clinically earlier.