Department of Cardiology, Key Laboratory of Panvascular Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Physical Medicine and Rehabilitation, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Int Immunopharmacol. 2024 Oct 25;140:112921. doi: 10.1016/j.intimp.2024.112921. Epub 2024 Aug 11.
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.
有效治疗心肌缺血再灌注（MIR）损伤仍然是未满足的临床需求。在这个阶段，心肌细胞凋亡很常见，这是一个重大的风险。补骨脂素是从补骨脂中提取的一种黄酮类化合物，已被证明具有抗炎、抗癌和抗动脉粥样硬化的特性。然而，补骨脂素是否以及如何影响 MIR 损伤尚不清楚。在这项研究中，我们使用体内和体外左前降支（LAD）冠状动脉结扎和氧葡萄糖剥夺再灌注（OGD/R）模型，探讨了补骨脂素作为一种有效的 MI/R 损伤治疗剂的机制。TUNEL、Annexin-V/PI 双染色、Ki67 免疫组化、western blot 分析和免疫荧光用于验证细胞凋亡水平和 Raf-1/ASK1 复合物活性。使用分子对接、补骨脂素-Raf-1 结合测定和共免疫沉淀（Co-IP）检测补骨脂素与 Raf-1/ASK1 复合物的相互作用。此外，还进行了 TTC 染色、超声心动图、HE 染色、Masson 三色染色和血清学检测，以评估补骨脂素在体内的心脏保护作用。这些发现表明，补骨脂素可减少 MIR 损伤诱导的心肌细胞凋亡，改善心脏功能。从机制上讲，补骨脂素可以与 Raf-1 相互作用并促进 Raf-1/ASK1 复合物的形成，从而抑制心肌细胞凋亡。总之，我们的结果表明，补骨脂素通过减少心肌细胞凋亡改善 MIR 损伤后的心脏功能障碍。
