People's Hospital of Ningxia Hui Autonomous, Ningxia Medical University, Yinchuan 750002, China.
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
Bioorg Med Chem. 2024 Jun 15;108:117776. doi: 10.1016/j.bmc.2024.117776. Epub 2024 May 30.
Myocardial ischemia/reperfusion (MI/R) is a common cardiovascular disease that seriously affects the quality of life and prognosis of patients. In recent years, matrine has attracted widespread attention in the treatment of cardiovascular diseases. This study designed, synthesized, and characterized 20 new matrine derivatives and studied their protective effects on ischemia-reperfusion injury through in vivo and in vitro experiments. Based on cellular assays, most newly synthesized derivatives have a certain protective effect on Hypoxia/Reoxygenation (H/R) induced H9C2 cell damage, with compound 22 having the best activity and effectively reducing cell apoptosis and necrosis. In vitro experimental data shows that compound 22 can significantly reduce the infarct size of rat myocardium and improve cardiac function after MI/R injury. In summary, compound 22 is a new potential cardioprotective agent that can promote angiogenesis and enhance antioxidant activity by activating ADCY5, CREB3l4, and VEGFA, thereby protecting myocardial cell apoptosis and necrosis induced by MI/R.
心肌缺血/再灌注（MI/R）是一种常见的心血管疾病，严重影响患者的生活质量和预后。近年来，苦参碱在心血管疾病的治疗中引起了广泛关注。本研究通过体内和体外实验设计、合成和表征了 20 种新的苦参碱衍生物，并研究了它们对缺血再灌注损伤的保护作用。基于细胞实验，大多数新合成的衍生物对缺氧/复氧（H/R）诱导的 H9C2 细胞损伤具有一定的保护作用，其中化合物 22 活性最好，能有效减少细胞凋亡和坏死。体外实验数据表明，化合物 22 能显著减少大鼠心肌梗死面积，改善 MI/R 损伤后的心脏功能。综上所述，化合物 22 是一种新的潜在的心脏保护剂，可通过激活 ADCY5、CREB3l4 和 VEGFA 促进血管生成和增强抗氧化活性，从而保护 MI/R 诱导的心肌细胞凋亡和坏死。
