Chemical Space of Small Molecule Exploration for the Elucidation of Cough Suppressant Pharmacology of Ying Su Ke/Zi

Abstract

IntroductionChronic cough, a prevalent condition, lacks effective medical solutions. Traditionally, Ying Su Ke/Zi (derived from Papaver somniferum L.) has been used in certain ethnic herbal formulas to address cough. However, there is a notable absence of molecular-level exploration regarding their mechanism for treating cough. MethodsStarting with the chemical ingredients of Ying Su Ke/Zi, this study used principal component analysis to explore the chemical space of these compounds and set four rounds of screening criteria based on the chemical space distribution to quickly identify active compounds. Following that, their targets were predicted using the weighted ensemble system model, and target enrichment analysis was executed. ResultsIn total, 247 compounds in Ying Su Ke/Zi were data-mined from literature reports, based on which four rounds of screening yielded 88 potential active chemicals, mostly alkaloids. Besides, 168 target proteins, mostly G-protein-coupled receptors, were identified, and meanwhile the results of the enrichment analysis revealed that these target proteins are, mostly, localised at cell membranes, cell junctions, and cell projections, and they were primarily involved in biological processes ranging from stimulus response, signalling, and bioregulation, possessing molecular functions concerning altering molecular transduction activity and binding. Moreover, the key biological pathways covered by these target proteins are neuroactive receptor-ligand interaction pathway, serotonergic synapse pathway, etc. ConclusionsIntegrating the foregoing findings with the pathophysiological characteristics of cough, the current study reveals that Ying Su Ke/Zi exert their antitussive pharmacological effects primarily via opioidergic and serotonergic mechanisms.