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Abstract
Quercetin (QR) has significant anti-respiratory syncytial virus (RSV) effects. However, its therapeutic mechanism has not been thoroughly explored. In this study, a lung inflammatory injury model caused by RSV was established in mice. Untargeted lung tissue metabolomics was used to identify differential metabolites and metabolic pathways. Network pharmacology was used to predict potential therapeutic targets of QR and analyze biological functions and pathways modulated by QR. By overlapping the results of the metabolomics and the network pharmacology analyses, the common targets of QR that were likely to be involved in the amelioration of RSV-induced lung inflammatory injury by QR were identified. Metabolomics analysis identified 52 differential metabolites and 244 corresponding targets, while network pharmacology analysis identified 126 potential targets of QR. By intersecting these 244 targets with the 126 targets, hypoxanthine–guanine phosphoribosyltransferase (HPRT1), thymidine phosphorylase (TYMP), lactoperoxidase (LPO), myeloperoxidase (MPO), and cytochrome P450 19A1 (CYP19A1) were identified as the common targets. The key targets, HPRT1, TYMP, LPO, and MPO, were components of purine metabolic pathways. The present study demonstrated that QR effectively ameliorated RSV-induced lung inflammatory injury in the established mouse model. Combining metabolomics and network pharmacology showed that the anti-RSV effect of QR was closely associated with purine metabolism pathways.
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1 Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Pediatrics, Nanjing, China (GRID:grid.410745.3) (ISNI:0000 0004 1765 1045); Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing, China (GRID:grid.410745.3) (ISNI:0000 0004 1765 1045)
2 Nanjing University of Chinese Medicine, Nanjing, China (GRID:grid.410745.3) (ISNI:0000 0004 1765 1045)
3 Henan University of Chinese Medicine, Zhengzhou, China (GRID:grid.256922.8) (ISNI:0000 0000 9139 560X)
4 Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Pediatrics, Nanjing, China (GRID:grid.410745.3) (ISNI:0000 0004 1765 1045)