A strategy combining chemical analysis and network pharmacology to investigate the mechanism of Xiao’er Qingre Zhike Oral solution in cough

Abstract

AbstractXiao’er Qingre Zhike Oral Solution (XQZS) is a commonly used TCM formula to treat cough in children in China. Its complicated composition renders its chemical analysis and mechanism elucidation difficult. To evaluate the bioactive components and mechanism of XQZS against cough, we used a combination strategy of chemical analysis and network pharmacology. A UHPLC/Q‐Orbitrap–MS method was established for the identification and qualitative analysis of components of XQZS, and a total of 33 components were unambiguously identified. Aiming at identifying the components, network pharmacology revealed 107 potential targets related to cough. Using protein–protein interactions analysis, nine core targets were selected. Several cough‐related pathways were enriched using the Kyoto Encyclopedia of Genes and Genomes, including neuroactive ligand–receptor interaction, serotonergic synapse and dopaminergic synapse. The herb–compound–target–pathway network indicated that PTGS2 (COX‐2) was the core target of XQZS against cough. To demonstrate the inhibition effects of the major components against the key target, a COX‐2 inhibitor screening assay was used. Compounds P2, P4, P23 and P49 exhibited promising inhibition effects on COX‐2 at 20 μm, with inhibitory rates of 55.80–69.87%. In conclusion, this study demonstrates that XQZS may alleviate cough via the inhibition of PTGS2 (COX‐2) and the regulation of the serotonergic synapse pathway. The chemical analysis and network pharmacology integrated evaluation provided an efficient strategy for discovering the key pharmacological mechanism of XQZS.