In Silico Investigation of Dendrobium nobile Compounds as Potential β₂AR Activators for Asthma

Abstract

Asthma is a chronic respiratory disease characterized by airway inflammation and bronchoconstriction. Beta-2 Adrenergic Receptor (β2AR) is a primary target for bronchodilator therapy. This study aimed to investigate the potential of bioactive compounds from Dendrobium nobile as β2AR activators through in silico molecular interaction analysis. The methods included preparation of 24 ligands, drug-likeness screening using Lipinski’s and Veber’s rules, molecular docking with the active conformation of β2AR (PDB ID: 3P0G), molecular interaction analysis, and ADMET prediction. The results showed that 19 compounds met the drug-likeness criteria. Molecular docking revealed that several compounds had stronger binding affinities than conventional agonists formoterol (-7.2 kcal/mol) and salmeterol (-6.4 kcal/mol), with kaempferol (-9.6 kcal/mol), apigenin (-9.3 kcal/mol), quercetin (-9.2 kcal/mol) and luteolin (-9.0 kcal/mol) as the top candidates. These ligands formed hydrogen bonds and hydrophobic interactions with key catalytic residues for receptor activation, such as Asp113, Ser203, Ser204 and Ser207. Furthermore, ADMET prediction indicated that promising ligands like luteolin and coniferin have low blood-brain barrier permeability, no hERG inhibition, and, in the case of coniferin, minimal cytochrome P450 interactions, suggesting a favorable safety and pharmacokinetic profile. In conclusion, this in silico study suggests that bioactive compounds from D. nobile, particularly luteolin and coniferin, show strong potential as β2AR activators and are promising candidates for further development as plant-based bronchodilators.

Keywords: Asthma, Beta-2 adrenergic receptor, Dendrobium nobile, molecular docking, natural compound