Network ethnopharmacological evaluation of the immunomodulatory activity of Withania somnifera.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: This study aimed the evaluation of the immunomodulatory effect of WS using network ethnopharmacology technique to elucidate the in silico molecular mechanism. MATERIALS AND 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. CONCLUSION: 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.

Immune modulation enables a specialist insect to benefit from antibacterial withanolides in its host plant.

The development of novel plant chemical defenses and counter adaptations by herbivorous insect could continually drive speciation, producing more insect specialists than generalists. One approach to test this hypothesis is to compare closely related generalist and specialist species to reveal the associated costs and benefits of these different adaptive strategies. We use the specialized moth Heliothis subflexa, which feeds exclusively on plants in the genus Physalis, and its close generalist relative H. virescens. Specialization on Physalis plants necessitates the ability to tolerate withanolides, the secondary metabolites of Physalis species that are known to have feeding deterrent and immune inhibiting properties for other insects. Here we find that only H. subflexa benefits from the antibacterial properties of withanolides, and thereby gains a higher tolerance of the pathogen Bacillus thuringiensis. We argue that the specialization in H. subflexa has been guided to a large extent by a unique role of plant chemistry on ecological immunology.