Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Department of Cardiology and Medical Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Department of Cardiology and Medical Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Phytomedicine. 2023 Jan;108:154519. doi: 10.1016/j.phymed.2022.154519. Epub 2022 Oct 22.
Hypertension is a common risk factor for heart failure, and excessive angiotensin II (Ang II) leads to hypertensive cardiac alterations such as hypertrophy, cardiac fibrosis, remodeling, and dysfunction. Leonurine is the major active alkaloid compound obtained from the traditional Chinese herbal medicine, Leonurus japonicus Houtt. The effects of leonurine on Ang II-induced hypertensive cardiac injury remain unknown.
HYPOTHESIS/PURPOSE: In the present study, we investigated the cardioprotective effects of leonurine in Ang II-infused mice and explored the underlying mechanisms in cardiomyocytes.
Cardiac injury was induced by Ang II infusion in experimental mice with or without leonurine (at 10 or 20 mg/kg) treatment. H9c2 cells and neonatal rat primary cardiomyocytes were used to investigate the mechanisms through which leonurine exerts its protection effects.
The results showed that leonurine significantly alleviated Ang II-induced cardiac hypertrophy, fibrosis, and inflammation in both mice and cultured cardiomyocytes. Echocardiography revealed that leonurine preserved cardiac function in mice. Further investigations revealed that leonurine inhibited the activation of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways to reduce inflammatory response and injuries in Ang II-challenged cardiomyocytes. Inhibition of MAPKs and NF-κB in cardiomyocytes abolished the anti-inflammatory effects of leonurine.
Our study provides evidence that leonurine exerts protective effects against Ang II-induced hypertensive cardiac remodeling and dysfunction by inhibiting the MAPK and NF-κB pathways. Leonurine may be a promising agent for treating hypertensive heart failure.
高血压是心力衰竭的常见危险因素，过量的血管紧张素 II（Ang II）可导致高血压性心脏改变，如肥大、心脏纤维化、重构和功能障碍。益母草碱是从传统中药益母草中提取的主要活性生物碱化合物。益母草碱对 Ang II 诱导的高血压性心脏损伤的影响尚不清楚。
假说/目的：本研究旨在探讨益母草碱对 Ang II 输注小鼠的心脏保护作用，并在心肌细胞中探讨其潜在机制。
用 Ang II 输注诱导实验小鼠的心脏损伤，并用或不用益母草碱（10 或 20mg/kg）治疗。使用 H9c2 细胞和新生大鼠原代心肌细胞研究益母草碱发挥保护作用的机制。
结果表明，益母草碱可显著减轻 Ang II 诱导的小鼠和培养的心肌细胞中的心脏肥大、纤维化和炎症。超声心动图显示益母草碱可保护小鼠的心脏功能。进一步研究表明，益母草碱抑制丝裂原活化蛋白激酶（MAPK）和核因子 kappa B（NF-κB）通路的激活，以减少 Ang II 刺激的心肌细胞中的炎症反应和损伤。心肌细胞中 MAPKs 和 NF-κB 的抑制消除了益母草碱的抗炎作用。
本研究提供的证据表明，益母草碱通过抑制 MAPK 和 NF-κB 通路对 Ang II 诱导的高血压性心脏重构和功能障碍发挥保护作用。益母草碱可能是治疗高血压性心力衰竭的有前途的药物。
