title: Network ethnopharmacological evaluation of the immunomodulatory activity of Withania somnifera.
abstract: BACKGROUND
  Withania somnifera (L.) Dunal (Ashwagandha, WS) is one of the extensively explored Ayurvedic botanicals. Several properties including immunomodulation, anti-cancer and neuro-protection of the botanical have been reported. Even though, in indigenous medicine, WS is well known for its immunomodulatory activity, the molecular mechanism of immunomodulation has not been elucidated.
  
  
  OBJECTIVE
  This study aimed the evaluation of the immunomodulatory effect of WS using network ethnopharmacology technique to elucidate the in silico molecular mechanism.
  
  
  METHODS
  Databases- DPED, UNPD, PubChem, Binding DB, ChEMBL, KEGG and STRING were used to gather information to develop the networks. The networks were constructed using Cytoscape 3.2.1. Data analysis was performed with the help of Excel pivot table and Cytoscape network analyzer tool.
  
  
  RESULTS
  Investigation for WS immune modulation mechanism identified five bioactives that are capable of regulating 15 immune system pathways through 16 target proteins by bioactive-target and protein-protein interactions. The study also unveils the potential of withanolide-phytosterol combination to achieve effective immunomodulation and seven novel bioactive-immune target combinations.
  
  
  CONCLUSIONS
  The study elucidated an in silico molecular mechanism of immunomodulation of WS. It unveils the potential of withanolide-phytosterol combination to achieve a better immunomodulation. Experimental validation of the network findings would aid in understanding the rationale behind WS immunomodulation as well as aid in bioactive formulation based drug discovery.
authors.affiliation: Bioprospecting Laboratory, Interdisciplinary School of Health Sciences, Savitribai Phule Pune University, Pune 411 007, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Chandran
authors.affiliation: Bioprospecting Laboratory, Interdisciplinary School of Health Sciences, Savitribai Phule Pune University, Pune 411 007, India. Electronic address: bpatwardhan@gmail.com.
authors.forename: Bhushan
authors.initials: B
authors.lastname: Patwardhan
mesh_terms: D020834:Ethnopharmacology / Q000379:methods; D007155:Immunologic Factors / Q000276:immunology*; D008515:Medicine, Ayurvedic; D010840:Phytosterols / Q000276:immunology; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000276:immunology*; D018517:Plant Roots / Q000276:immunology; D060066:Protein Interaction Maps / Q000276:immunology; D032341:Withania / Q000276:immunology*; D054358:Withanolides / Q000276:immunology*
chemical_list: D007155:Immunologic Factors; D010840:Phytosterols; D010936:Plant Extracts; D054358:Withanolides; C030693:Ashwagandha
keywords: Ashwagandha; Immunomodulatory; Network ethnopharmacology; Withania somnifera; Withanolide-phytosterol