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Int Immunopharmacol ; 98: 107913, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34218218

RESUMEN

The objective of this work was to study the effects and mechanisms of S-allylmercapto-N-acetylcysteine (ASSNAC) in the treatment of pulmonary emphysema based on network pharmacology analysis and other techniques. Firstly, the potential targets associated with ASSNAC and COPD were integrated using public databases. Then, a protein-protein interaction network was constructed using String database and Cytoscape software. The Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed on DAVID platform. The molecular docking of ASSNAC with some key disease targets was implemented on the SwissDock platform. To verify the results of the network pharmacology, a pulmonary emphysema mice model was established and treated with ASSNAC. Besides, the expressions of the predicted targets were detected by immunohistochemistry, Western blot analysis or enzyme-linked immunosorbent assay. Results showed that 33 overlapping targets are achieved, including CXCL8, ICAM1, MAP2K1, PTGS2, ACE and so on. The critical pathways of ASSNAC against COPD involved arachidonic acid metabolism, chemokine pathway, MAPK pathway, renin-angiotensin system, and others. Pharmacodynamic experiments demonstrated that ASSNAC decreased the pulmonary emphysema and inflammation in the pulmonary emphysema mice. Therefore, these results confirm the perspective of network pharmacology in the target verification, and indicate the treatment potential of ASSNAC against COPD.


Asunto(s)
Acetilcisteína/análogos & derivados , Compuestos Alílicos/farmacología , Antiinflamatorios/farmacología , Enfisema Pulmonar/tratamiento farmacológico , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Compuestos Alílicos/uso terapéutico , Animales , Antiinflamatorios/uso terapéutico , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Masculino , Ratones , Simulación del Acoplamiento Molecular , Farmacología en Red , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas/efectos de los fármacos , Mapas de Interacción de Proteínas/inmunología , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/inmunología , Enfisema Pulmonar/patología , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/inmunología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología
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