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1.
Mol Med Rep ; 24(5)2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34542166

RESUMEN

Cycloastragenol (CAG), a secondary metabolite from the roots of Astragalus zahlbruckneri, has been reported to exert anti­inflammatory effects in heart, skin and liver diseases. However, its role in asthma remains unclear. The present study aimed to investigate the effect of CAG on airway inflammation in an ovalbumin (OVA)­induced mouse asthma model. The current study evaluated the lung function and levels of inflammation and autophagy via measurement of airway hyperresponsiveness (AHR), lung histology examination, inflammatory cytokine measurement and western blotting, amongst other techniques. The results demonstrated that CAG attenuated OVA­induced AHR in vivo. In addition, the total number of leukocytes and eosinophils, as well as the secretion of inflammatory cytokines, including interleukin (IL)­5, IL­13 and immunoglobulin E were diminished in bronchoalveolar lavage fluid of the OVA­induced murine asthma model. Histological analysis revealed that CAG suppressed inflammatory cell infiltration and goblet cell secretion. Notably, based on molecular docking simulation, CAG was demonstrated to bind to the active site of autophagy­related gene 4­microtubule­associated proteins light chain 3 complex, which explains the reduced autophagic flux in asthma caused by CAG. The expression levels of proteins associated with autophagy pathways were inhibited following treatment with CAG. Taken together, the results of the present study suggest that CAG exerts an anti­inflammatory effect in asthma, and its role may be associated with the inhibition of autophagy in lung cells.


Asunto(s)
Antiasmáticos/farmacología , Asma/etiología , Autofagia/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Sapogeninas/farmacología , Animales , Asma/tratamiento farmacológico , Asma/metabolismo , Proteínas Relacionadas con la Autofagia/antagonistas & inhibidores , Proteínas Relacionadas con la Autofagia/química , Proteínas Relacionadas con la Autofagia/metabolismo , Biomarcadores , Biopsia , Hiperreactividad Bronquial/tratamiento farmacológico , Hiperreactividad Bronquial/etiología , Hiperreactividad Bronquial/metabolismo , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Manejo de la Enfermedad , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Femenino , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Inmunohistoquímica , Mediadores de Inflamación/metabolismo , Ratones , Proteínas Asociadas a Microtúbulos/antagonistas & inhibidores , Proteínas Asociadas a Microtúbulos/química , Proteínas Asociadas a Microtúbulos/metabolismo , Sapogeninas/química , Relación Estructura-Actividad
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