Your browser doesn't support javascript.
loading
Oroxylin A alleviates myocardial ischemia-reperfusion injury by quelling ferroptosis via activating the DUSP10/MAPK-Nrf2 pathway.
Jin, Yifeng; Tan, Mingyue; Yin, Yunfei; Lin, Chen; Zhao, Yongjian; Zhang, Jun; Jiang, Tingbo; Li, Hongxia; He, Mingqing.
Afiliación
  • Jin Y; Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
  • Tan M; Department of General Practice, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
  • Yin Y; Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
  • Lin C; Department of Geriatrics, Southwest Hospital, The Third Military Medical University (Army Medical University), Chongqing, P. R. China.
  • Zhao Y; Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
  • Zhang J; Jinjihu Business District Squadron, Suzhou Industrial Park Food and Drug Safety Inspection Team, Suzhou, Jiangsu, P. R. China.
  • Jiang T; Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
  • Li H; Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
  • He M; Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
Phytother Res ; 2024 Sep 03.
Article en En | MEDLINE | ID: mdl-39225191
ABSTRACT
Reperfusion therapy is the primary treatment strategy for acute myocardial infarction (AMI). Paradoxically, it can lead to myocardial damage, namely myocardial ischemia/reperfusion injury (MIRI). This study explored whether oroxylin A (OA) protects the myocardium after MIRI by inhibiting ferroptosis and the underlying mechanism. In vivo, we established an MIRI model to investigate the protective effect of OA. In vitro, H9C2 cells were used to explore the regulation of ferroptosis by OA through immunofluorescence staining, western blotting, assay kits, etc. Additionally, RNA sequencing analysis (RNA-seq) and network pharmacology analyses were conducted to elucidate the molecular mechanisms. Our results showed that MIRI caused cardiac structural and functional damage in rats. MIRI promoted ferroptosis, which was consistently observed in vitro. However, pretreatment with OA reversed these effects. The mitogen-activated protein kinases (MAPK) signaling pathway participated in the MIRI process, with dual-specificity phosphatase 10 (DUSP10) found to regulate it. Further confirmation was provided by knocking down DUSP10 using small interfering RNA (siRNA), demonstrating the activation of the DUSP10/MAPK-Nrf2 pathway by OA to protect H9C2 cells from ferroptosis. Our research has demonstrated the mitigating effect of OA on MIRI and the improvement of myocardial function for the first time. The inhibition of ferroptosis has been identified as one of the mechanisms through which OA exerts its myocardial protective effects. Moreover, we have first unveiled that DUSP10 serves as an upstream target involved in mediating ferroptosis, and the regulation of the DUSP10/MAPK-Nrf2 pathway by OA is crucial in inhibiting ferroptosis to protect the myocardium.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Phytother Res Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Phytother Res Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido