Celastrol as a candidate drug for silicosis: From bioinformatics and network pharmacology to experimental validation.
Int Immunopharmacol
; 125(Pt B): 111068, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37948856
ABSTRACT
Silicosis, a highly lethal occupational respiratory disease characterized by irreversible pulmonary fibrosis, remains challenging to treat due to its unclear pathogenesis. In this study, bioinformatics, network pharmacology, and experimental validation were combined to explore potential mechanisms and therapeutic drugs for silicosis. First, the differentially expressed genesï¼DEGsï¼and pathway enrichment in pulmonary fibrosis were identified by GO and KEGG analysis. Next, the differential genes were submitted to cMap database for drug prediction and celastrol stood out as the most promising candidate drug. Then, network pharmacology analysis identified pharmacological targets of celastrol and demonstrated that celastrol could regulate JAK-STAT, MAPK, and Toll-like receptor signaling pathways. Finally, we verified the therapeutic role and mechanism of celastrol on silicosis. In vivo, celastrol significantly ameliorated CS-induced inflammation and fibrosis in silicosis mice, including inflammatory cell infiltration, collagen fiber and extracellular matrix deposition, fibroblast activation and related factor expression. Moreover, it dramatically improved lung respiratory function of silicosis mice. In vitro, celastrol suppressed CS-induced cytokine expression, apoptosis of macrophages and activation of Stat3 and Erk1/2 signals. Overall, our research identified and verified celastrol as a novel and promising candidate drug for silicosis.
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Base de dados:
MEDLINE
Assunto principal:
Fibrose Pulmonar
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Silicose
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article