ABSTRACT
BACKGROUND: The etiology and pathogenesis of cough are complex. As a Chinese patent medicine that has been on the market, ErtongKe (ETK) granules have a good effect in treating acute and chronic cough in children. The purpose of this research was to determine the bioactive components and possible action mechanisms of ETK in the treatment of cough using an integrated network pharmacology method. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Swiss target prediction databases were used to screen the potential components and associated targets of ETK. The Genecards database was then used to gather targets interacting with cough. An analysis of the signaling pathways associated with ETK for cough treatment was carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis methods. Cytoscape 3.8.1 was used to design the protein-protein interaction (PPI) and compound-target-pathway networks. Finally, the important genes and active components of ETK were confirmed using Auto Dock vina and Discovery studio software. RESULTS: Total 242 active components of ETK were screened, 1,173 potential targets related to the ingredients and 4,400 targets related to cough were collected separately. Moreover, 600 candidate targets and 39 signaling pathways were determined. We also screened out the following core components, including tuberostemonone, quercetin, kaempferol, praeruptorin E, stigmasterol, oroxylin A, and other potentially active ingredients. At the same time, 8 core targets, including JUN, PIK3CA, PIK3R1, MAPK14, EGFR, SRC, AKT1, and MAPK1, and 20 key pathways, including the cAMP signaling pathway, calcium signaling pathway, and PI3K-Akt signaling pathway among others, were also selected. All the 8 core targets were verified by molecular docking. CONCLUSIONS: This research established that ETK exerts anti-cough activity by modulating several targets and pathways through multiple components. Additionally, the pooled results shed light on ETK compounds being investigated as potential antitussives.