In silico network pharmacology analysis and molecular docking validation of Swasa Kudori tablet for screening druggable phytoconstituents of asthma.

ABSTRACT

Traditional medicines are impactful in treating a cluster of respiratory-related illnesses. This paper demonstrates screening active, druggable phytoconstituents from a classical Siddha-based poly-herbal formulation called Swasa Kudori Tablet to treat asthma. The phytoconstituents of Swasa Kudori are identified as Calotropis gigantea, Piper nigrum, and (Co-drug) Abies webbiana. Active chemical compounds are extracted with the Chemical Entities of Biological Interest (ChEBI) database. The gene targets of each compound are identified based on the pharmacological activity using the DIGEP-Pred database. Thirty-two genes showing Pa> 0.7 is screened, and the target markers are selected after performing gene overlap evaluation with the asthma genes reported in GeneCards and DisGeNET database. Ten markers are identified, such as ADIPOQ, CASP8, CAT, CCL2, CD86, FKBP5, HMOX1, NFE2L2, TIMP1, VDR, in common, listed as molecular targets. Pharmacokinetic assessment (ADME) revealed five natural drug compounds 2-5-7-trihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one, (+)-catechin-3'-methyl ether, futoenone, 5-hydroxy-4',7-dimethoxyflavanone, and pinocembrin showing better druggability. Further screening delineates the target (HMOX1) and drug (pinocembrin) for molecular docking evaluation. When docked with HO-1, Pinocembrin showed a binding affinity of -8.0 kcal/mol. MD simulation studies substantiate the docking studies as HO-1 in complex with pinocembrin remains stable in the simulated trajectory. The current findings exhibit the significance of traditional medicines as potential drug candidates against asthma.