Molecular docking studies of various bioactive molecules from Withania somnifera against bronchial asthma

Nafaa H.  Ali; Khursheed A. Sheikh; Maaz Naqvi; Sana Rehman; Kavita Gulati; Arunabha  Ray

doi:10.12923/

Authors

Nafaa H. Ali Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Hamdard University, New Delhi, India Author https://orcid.org/0000-0003-0524-9107
Khursheed A. Sheikh Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India Author https://orcid.org/0009-0009-7896-6992
Maaz Naqvi Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Hamdard University, New Delhi, India Author https://orcid.org/0000-0002-2349-3771
Sana Rehman Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Hamdard University, New Delhi, India Author https://orcid.org/0000-0001-8183-1778
Kavita Gulati Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India Author https://orcid.org/0000-0002-8815-1879
Arunabha Ray Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Hamdard University, New Delhi, India Author https://orcid.org/0000-0003-0886-7875

DOI:

https://doi.org/10.12923/

Keywords:

Withania somnifera, asthma, molecular docking, glucocorticoids

Abstract

Asthma is a complex respiratory disorder characterized by chronic inflammation and hyperresponsiveness of the bronchial airways. Despite the availability of effective treatments and diagnostic methods, some patients remain symptomatic and exhibit a poor response to conventional asthma therapies. Herbal drugs are considered safe and effective alternative approaches that may target multiple pathogenic pathways involved in asthma. Withania somnifera (WS) is a well-known medicinal plant containing several bioactive compounds and has been extensively studied for its anti-inflammatory and immunomodulatory properties.
The present study aimed to explore the potential mechanisms of WS bioactive molecules in the treatment of asthma using an in silico screening approach.
Six active phytoconstituents (ligands) of WS were docked against two target receptor proteins, namely the glucocorticoid receptor and the β₂-adrenergic receptor, to predict binding energies and binding patterns. The obtained results were compared with those of known ligands of the glucocorticoid and β₂-adrenergic receptors (fluticasone and salbutamol, respectively).
Among all docked ligands, withaferin A, withanolide D, and withanolide B exhibited the highest binding affinities (lowest estimated free binding energy of -8.4 kcal/mol) toward the glucocorticoid receptor (GR). In contrast, the WS alkaloids tropine and anaferine showed lower affinities, as evidenced by higher binding energy values. Furthermore, withanolide D and withanolide B demonstrated the highest affinity for the β₂-adrenergic receptor among the screened compounds, whereas salbutamol and the plant alkaloids tropine and anaferine exhibited lower affinity toward the β₂-adrenergic receptor compared with the plant withanolides.
WS bioactive compounds, particularly withanolides, are predicted to possess multitarget anti-inflammatory and bronchodilator potential. Further experimental validation is warranted.

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Molecular docking studies of various bioactive molecules from Withania somnifera against bronchial asthma

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