Guan Sibin, Xin Yuanfeng, Ding Yagang, Zhang Qingliu, Han Wei
Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Chem Biodivers. 2023 Feb;20(2):e202200730. doi: 10.1002/cbdv.202200730. Epub 2023 Jan 24.
Adverse cardiac remodeling may lead to the development and progression of heart failure, which is lack of effective clinical treatment. Ginsenoside Rg1 (GRg1), a primary ingredient of Panax ginseng, protects against diverse cardiovascular disease, but its effects on cardiac remodeling remain unclear. Thus, we investigated the protective effect and mechanism of GRg1 on cardiac remodeling after myocardial infarction. GRg1 significantly ameliorated cardiac remodeling in mice with left anterior descending coronary artery ligation, reflected by reduced left ventricular dilation and decreased cardiac fibrosis, accompanied by improved cardiac function. Mechanistically, GRg1 considerably increased mitophagosomes formation, ameliorated cardiac mitochondria damage, and enhanced SIRT1/PINK1/Parkin-mediated mitophagy during cardiac remodeling. Consistently, GRg1 increased cell viability and attenuated apoptosis and fibrotic responses in H O -treated H9c2 cells by promoting the SIRT1/PINK1/Parkin axis. Furthermore, SIRT1-specific inhibitor (EX527) or the use of small interfering RNA against Parkin abolished the protective effect of GRg1 in vitro. These findings reveal a novel mechanism of GRg1 alleviating cardiac remodeling via enhancing SIRT1/PINK1/Parkin-mediated mitophagy.
不良心脏重塑可能导致心力衰竭的发生和发展，而心力衰竭缺乏有效的临床治疗方法。人参皂苷Rg1（GRg1）是人参的主要成分，可预防多种心血管疾病，但其对心脏重塑的影响尚不清楚。因此，我们研究了GRg1对心肌梗死后心脏重塑的保护作用及其机制。GRg1显著改善了左冠状动脉前降支结扎小鼠的心脏重塑，表现为左心室扩张减轻和心脏纤维化减少，并伴有心脏功能改善。机制上，GRg1在心脏重塑过程中显著增加了线粒体自噬体的形成，改善了心脏线粒体损伤，并增强了SIRT1/PINK1/Parkin介导的线粒体自噬。同样，GRg1通过促进SIRT1/PINK1/Parkin轴增加了过氧化氢处理的H9c2细胞的活力，减轻了细胞凋亡和纤维化反应。此外，SIRT1特异性抑制剂（EX527）或使用针对Parkin的小干扰RNA消除了GRg1在体外的保护作用。这些发现揭示了GRg1通过增强SIRT1/PINK1/Parkin介导的线粒体自噬减轻心脏重塑的新机制。
