Integrating network pharmacology and pharmacological evaluation to reveal the therapeutic effects and potential mechanism of S-allylmercapto-N-acetylcysteine on acute respiratory distress syndrome.
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| Abstract |
In this research, we sought to examine the effectiveness of S-allylmercapto-N-acetylcysteine (ASSNAC) on LPS-provoked acute respiratory distress syndrome (ARDS) and its potential mechanism based on network pharmacology. To incorporate the effective targets of ASSNAC against ARDS, we firstly searched DisGeNET, TTD, GeneCards and OMIM databases. Then we used String database and Cytoscape program to create the protein-protein interaction network. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis both identified the potential pathways connected to genes. Cytoscape software was used to build the network of drug-targets-pathways and the SwissDock platform was applied to dock the molecule of ASSNAC with the key disease targets. Correspondingly, an ARDS model was established by instillation of LPS in mice to confirm the underlying action mechanism of ASSNAC on ARDS as indicated by the network pharmacology analysis. Results exhibited that 27 overlapping targets, including TLR4, ICAM1, HIF1A, MAPK1, NFKB1, and others, were filtered out. The in vivo experiments showed that ASSNAC alleviated LPS-induced lung injury by downregulating levels of pro-inflammatory mediators and lung dry-wet ratio. Also, ASSNAC attenuated oxidative stress evoked by LPS via diminishing MDA production and SOD consumption as well as upregulating HO-1 level through Nrf2 activation. Results from western blot, quantitative real-time PCR and immunohistochemistry suggested that ASSNAC developed its therapeutic effects by regulating TLR4/MyD88/NF-κB signaling pathway. In conclusion, our research presented the efficacy of ASSNAC against ARDS. Furthermore, the mechanism of ASSNAC on ARDS was clarified by combining network pharmacology prediction with experimental confirmation.
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| Authors | Jinglong Wang, Huatian Yang, Dandan Zheng, Yueyue Sun, Lulu An, Genju Li, Zhongxi Zhao |
| Journal | International immunopharmacology (Int Immunopharmacol) Vol. 121 Pg. 110516 (Aug 2023) ISSN: 1878-1705 [Electronic] Netherlands |
| PMID | 37369159 (Publication Type: Journal Article) |
| Copyright | Copyright © 2023 Elsevier B.V. All rights reserved. |
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