Systematic investigation of the pharmacological mechanism of Tanreqing injection in treating respiratory diseases by UHPLC/Q-TOF-MS/MS based on multiple in-house chemical libraries coupled with network pharmacology

Abstract

Tanreqing injection (TRQI), a drug approved by the National Drug Regulatory Authority of China (China SFDA, number: Z20030045), is widely used clinically to treat respiratory diseases. However, as a complex system, the pharmacological mechanism of TRQI for the treatment of respiratory diseases is still unclear. TRQI contains three Chinese medicines that make up the classic Chinese compound formulas Shuang-Huang-Lian (SHL). Moreover, it is known that SHL components are beneficial for characterizing the chemical compounds of TRQI. Therefore, in this study, we applied UHPLC/Q-TOF-MS/MS analysis based on multiple chemical compound libraries to identify the chemical profiles of TRQI and used network pharmacology to predict the potential targets of TRQI active compounds. First, three chemical libraries related to TRQI were created, including the TRQI in-house library, SHL in-house library, and targeted Metlin library. An integrated TRQI library was established by combining three chemical libraries for the identification and characterization of the chemical profiles of TRQI. Second, the potential targets of TRQI active compounds were predicted with the Swiss Target Prediction and TCMSP databases, and targets of respiratory disease were collected from the GeneCards database. Then, the network between the active compounds and common targets was established by Cytoscape 3.7.1. The common targets were imported into the STRING database to construct protein-protein interaction (PPI) networks and select core targets of TRQI against respiratory diseases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analyses of the core targets were performed by the Omicsbean analytic system and DAVID database, respectively. As a result, a total of 126 compounds were identified, and network pharmacological analysis showed that luteolin, wogonin, baicalein, chenodeoxycholic acid, l-serine, aspartic acid, oroxylin A, syringin, phenylalanine, and glutamic acid could be the active compounds of TRQI; GABBR1, MAPK3, GRM5, FOS, DRD2, GRM1, VEGFA, GRM3 and 92 other potential core targets for the treatment of respiratory diseases by modulating pathways in cancer, the calcium signaling pathway, cAMP signaling pathway, estrogen signaling pathway and TNF-α signaling pathway.

Keywords: In-house chemical library; Network pharmacology; Respiratory diseases; Tanreqing injection; UHPLC/Q-TOF-MS/MS analysis.