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Int Immunopharmacol ; 140: 112921, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39133953

RESUMO

Effective treatment of myocardial ischemia-reperfusion (MIR) injury remains an unmet clinical need. Cardiomyocyte apoptosis is common at this stage and poses a significant risk. Corylin, a flavonoid compound extracted from Psoralea corylifolia L., has been shown to have anti-inflammatory, anticancer, and antiatherosclerotic properties. However, whether and how corylin affects MIR injury remain unclear. In this study, we explored the mechanism of corylin as a potent therapeutic agent for MI/R injury, using a left anterior descending (LAD) coronary artery ligation and oxygen-glucose deprivation and reperfusion (OGD/R) model in vivo and in vitro. TUNEL, Annexin-V/PI double staining,Ki67 immunohistochemistry, western blot analysis, and immunofluorescence were used to validate cell apoptosis level and Raf-1/ASK1 complex activity. The interaction between corylin and Raf-1/ASK1 complex was detected using molecular docking, corylin-Raf-1 binding assays, and coimmunoprecipitation (Co-IP). Moreover, TTC staining, echocardiography, HE staining, Masson trichrome staining and serological testing were performed to assess the cardioprotective effects of corylin in vivo. These findings showed that corylin reduces MIR injury-induced cardiomyocyte apoptosis and improves cardiac function. Mechanistically, corylin can interact with Raf-1 and promote the formation of the Raf-1/ASK1 complex, thus inhibiting cardiomyocyte apoptosis. In conclusion, our results demonstrate that corylin ameliorated cardiac dysfunction after MIR injury by reducing myocardial apoptosis.


Assuntos
Apoptose , MAP Quinase Quinase Quinase 5 , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Proteínas Proto-Oncogênicas c-raf , Apoptose/efeitos dos fármacos , Animais , Proteínas Proto-Oncogênicas c-raf/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Camundongos Endogâmicos C57BL , Camundongos , Humanos , Psoralea/química , Modelos Animais de Doenças
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