Feng Ruiqi, Liu Jia, Wang Zhenhua, Zhang Jingwen, Cates Courtney, Rousselle Thomas, Meng Qingguo, Li Ji
Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China.
Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):556-568. doi: 10.1016/j.bbrc.2017.10.056. Epub 2017 Oct 13.
Ginsenosides have been studied extensively in recent years due to their therapeutic effects in cardiovascular diseases. While most studies examined the different ginsenosides individually, few studies compare the therapeutic effects among the different types. This study examined how effective protopanaxadiol, protopanaxatriol ginsenosides Rh2, Rg3, Rh1, and Rg2 of the ginsenoside family are in protecting H9c2 cardiomyocytes from damage caused by hypoxia/reoxygenation. In the current study, a model of myocardial ischemia and reperfusion was induced in H9c2 cardiomyocytes by oxygen deprivation via a hypoxia chamber followed by reoxygenation. Our data show that structures similar to that of protopanaxadiol, which lacked the hydroxide group at C6, were more effective in lowering apoptosis than structures similar to protopanaxatriol with a hydroxide group at C6. As the compounds increased in size and complexity, the cardioprotective effects diminished. In addition, the S enantiomer proved to be more effective in cardioprotection than the R enantiomer. Furthermore, the immunoblotting analysis demonstrated that ginsenosides activate AMPK but suppress JNK signaling pathways during hypoxia/reoxygenation. Thus, ginsenosides treatment attenuated hypoxia/reoxygenation-induced apoptosis via modulating cardioprotective AMPK and inflammation-related JNK signaling pathways.
近年来，人参皂苷因其对心血管疾病的治疗作用而受到广泛研究。虽然大多数研究分别考察了不同的人参皂苷，但很少有研究比较不同类型人参皂苷之间的治疗效果。本研究考察了人参皂苷家族中的原人参二醇、原人参三醇型人参皂苷Rh2、Rg3、Rh1和Rg2在保护H9c2心肌细胞免受缺氧/复氧损伤方面的效果如何。在本研究中，通过缺氧箱剥夺氧气，随后进行复氧，在H9c2心肌细胞中诱导心肌缺血再灌注模型。我们的数据表明，与原人参二醇结构相似、在C6位缺少羟基的结构，在降低细胞凋亡方面比在C6位带有羟基的原人参三醇结构更有效。随着化合物的尺寸和复杂性增加，心脏保护作用减弱。此外，S对映体在心脏保护方面比R对映体更有效。此外，免疫印迹分析表明，人参皂苷在缺氧/复氧过程中激活AMPK，但抑制JNK信号通路。因此，人参皂苷治疗通过调节心脏保护相关的AMPK和炎症相关的JNK信号通路，减轻缺氧/复氧诱导的细胞凋亡。
