Integration of UPLC-QE-MS/MS and network pharmacology to investigate the active components and action mechanisms of tea cake extract for treating cough

Abstract

The active components and mechanisms of tea cake extract (TCE) were investigated for treating cough. The components of TCE were tentatively identified by ultrahigh-performance liquid chromatography coupled with Q-Exactive MS/MS (UPLC-QE-MS/MS), whose targets were obtained from the Swiss Target Prediction database and the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. Cough-related targets were retrieved from the Gene Cards and Online Mendelian Inheritance in Man database. After the intersection targets had been obtained, enrichment analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined, and the protein-protein interaction network and active compound-intersection target-KEGG pathway network were constructed. Core active compounds and their targets were validated with molecular docking. A total of 78 compounds were identified from TCE, including 24 flavonoids, 17 phenolic acids, 10 alkaloids, seven organic acids, five triterpenes, five amino acids, five coumarins, three carbohydrates, one anthraquinone and one other. A total of 347 intersection targets were obtained. The top five GO terms with the most significant P-values were responses to oxygen-containing compounds and organic substances, chemical and cellular responses to chemical stimulus, and regulation of biological quality. The top five KEGG pathways with the most significant P-values were: the PI3K-Akt signaling pathway, lipids and atherosclerosis, human cytomegalovirus infection, fluid shear stress and atherosclerosis, and proteoglycans in cancer. The top five core active compounds were quercetin, genistein, luteolin, kaempferol and emodin. The top five core targets were protein kinase B (Akt1), prostaglandin-endoperoxide synthase 2 (PTGS2), mitogen-activated protein kinase 1/3 (MAPK1/3) and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1). The top five core active compounds could stably bind to their targets with LibDockScores higher than 100. Tea cake extract plays the antitussive role via multiple components and targets. Core targets (AKT1, MAPK1, MAPK3 and PIK3R1) and core components (quercetin, genistein, luteolin and kaempferol) involved in the PI3K-Akt signaling pathway are worth more attention in subsequent validation experiments.

Keywords: UPLC-QE-MS/MS; cough; network pharmacology; tea cake extract (TCE).