Department of Cardiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Toxicology. 2019 Jun 15;422:1-13. doi: 10.1016/j.tox.2019.04.011. Epub 2019 Apr 18.
Myocarditis is a serious hazard to human life and is difficult to treat due to the proliferation of inflammatory lesions in the myocardium. Leonurine (LE) is a plant phenolic alkaloid extracted from Herba leonuri that has demonstrated cardioprotective effects in many preclinical experiments. However, whether LE can be used for myocarditis therapy has not been reported. We aimed to investigate the cardioprotective effects of LE on lipopolysaccharide (LPS)-induced myocarditis in vivo and vitro. The possible mechanism involved was also further elucidated. In vivo, C57BL/6 mice were exposed to LPS with or without LE. We found out that LE effectively improved cardiac function and attenuated cardiomyocyte apoptosis in mice with myocarditis. In addition, LPS-induced inflammatory and oxidative injuries in the myocardium were also reduced by LE administration. In vitro, LPS simultaneously induced apoptosis and reduced the H9c2 cells viability, followed by elevation of intracellular reactive oxygen species (ROS) generation. However, the abnormalities mentioned were preventable by LE pretreatment in a dose-dependent manner. Both in vivo and in vitro, LPS activated the nuclear factor kappa B (NF-кB) signaling pathway in myocarditis, and LE inhibited the increased expression of phosphorylated iκBα and p65 (p-iκBα, p-p65). Furthermore, the nuclear translocalization and nuclear protein expression of p65 in LPS-injured H9c2 cells were also suppressed by LE. Our results demonstrated that LE exerts potent cardioprotective effects against myocarditis via anti-inflammatory and antioxidative mechanisms, possibly through blocking the activation of NF-кB pathway.
心肌炎是一种严重危害人类生命的疾病，由于心肌内炎症病变的增殖，治疗起来很困难。益母草碱（LE）是从益母草中提取的植物酚类生物碱，在许多临床前实验中已显示出心脏保护作用。然而，LE 是否可用于心肌炎的治疗尚未有报道。我们旨在研究 LE 对体内和体外脂多糖（LPS）诱导的心肌炎的心脏保护作用，并进一步阐明其可能的机制。在体内，C57BL/6 小鼠用 LPS 加或不加 LE 处理。我们发现 LE 可有效改善心肌炎小鼠的心脏功能，减轻心肌细胞凋亡。此外，LE 还可减轻 LPS 诱导的心肌炎症和氧化损伤。在体外，LPS 同时诱导凋亡并降低 H9c2 细胞活力，随后导致细胞内活性氧（ROS）生成增加。然而，LE 预处理可呈剂量依赖性地预防这些异常。在体内和体外，LPS 均能激活心肌炎中的核因子 kappa B（NF-кB）信号通路，而 LE 则能抑制磷酸化 iκBα 和 p65（p-iκBα、p-p65）的表达增加。此外，LE 还能抑制 LPS 损伤的 H9c2 细胞中 p65 的核转位和核蛋白表达。我们的研究结果表明，LE 通过抗炎和抗氧化机制发挥强大的心脏保护作用，可能是通过阻断 NF-кB 通路的激活。
