The Potential Pharmacological Mechanism of Medicinal Herbs for the Treatment of Cough and Cold via Network Pharmacology, Molecular Docking and Simulation

Cough and cold are among the most common upper respiratory tract disorders, primarily of viral origin, and remain significant causes of morbidity across all age groups. While symptoms are often self-limiting and seasonal, they can impair quality of life and lead to complications in vulnerable populations. Traditional medicinal systems have long used botanicals for respiratory care because of their multi-target therapeutic potential. This study investigated five medicinal herbs, Curcuma longa, Glycyrrhiza glabra, Terminalia chebula, Adhatoda vasica, and Ocimum sanctum using network pharmacology and molecular docking to elucidate their mechanisms against cough and cold. Bioactive compounds were retrieved from phytochemical databases (IMPPAT, Dr. Duke’s), screened for drug-likeness via SwissADME, and mapped to potential human protein targets using SwissTarget Prediction and BindingDB. Disease-related targets were identified from DisGeNET and GeneCards, and overlapping targets were analyzed using cytoscape-based bioactive-target and protein–protein interaction (PPI) networks. GO and KEGG enrichment analyses were performed, followed by molecular docking and simulations with key hub proteins. Ninety-three compounds met the drug-likeness criteria, yielding 56 overlapping targets including AKT1, EGFR, SRC, PTGS2, MMP9, MMP2, and KDR. Enrichment analysis indicated the involvement of PI3K-Akt, EGFR, and focal adhesion pathways, which are central to inflammation, immune regulation, and epithelial repair. Molecular docking revealed strong (−5.2 to −9.66 kcal/mol) for quercetin, luteolin, eugalic acid, and kaempferol with hub proteins, suggesting potent multi-target interactions. MMP2/9 protein with quercetin, luteolin, and kaempferol complexes showed good stability during molecular dynamics (MD) simulations. Estimation of the binding free energy using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method validated the inhibitor potential of the identified compounds. These findings provide molecular evidence for the synergistic multi-pathway effects of the studied herbs, supporting their use as safe, affordable, and evidence-based complementary therapies for cough and cold.