Ethnopharmacological relevance

Traditional Chinese medicine Leonurus japonicus Houtt. has a long history in the treatment of cardiovascular diseases. Stachydrine hydrochloride, the main bioactive ingredient extracted from Leonurus japonicus Houtt., has been shown to have cardioprotective effects. However, the underlying mechanisms of stachydrine hydrochloride haven't been comprehensively studied so far.

Aim of the study

The aim of this study was to investigate the protective role of stachydrine hydrochloride in heart failure and elucidate its possible mechanisms of action.

Materials and methods

In vivo, transverse aorta constriction was carried out in C57BL/6J mice, and thereafter, 7.2 mg/kg telmisartan (a selective AT1R antagonist as positive control) and 12 mg/kg stachydrine hydrochloride was administered daily intragastrically for 4 weeks. Cardiac function was evaluated by assessing morphological changes as well as echocardiographic and haemodynamic parameters. In vitro, neonatal rat cardiomyocytes or adult mice cardiomyocytes were treated with stachydrine hydrochloride and challenged with phenylephrine (α-AR agonist). Ventricular myocytes were isolated from the hearts of C57BL/6J mice by Langendorff crossflow perfusion system. Intracellular calcium was measured by an ion imaging system. The length and movement of sarcomere were traced to evaluate the systolic and diastolic function of single myocardial cells.

Results

Stachydrine hydrochloride improved the cardiac function and calcium transient amplitudes, and inhibited the SR leakage and the amount of sparks in cardiac myocytes isolated from TAC mice. We also demonstrated that stachydrine hydrochloride could ameliorated phenylephrine-induced enhance in sarcomere contraction, calcium transients and calcium sparks. Moreover, our data shown that stachydrine hydrochloride blocked the hyper-phosphorylation of CaMKII, RyR2, PLN, and prevented the disassociation of FKBP12.6 from RyR2.

Conclusion

Our results suggest that stachydrine hydrochloride exerts beneficial therapeutic effects against heart failure. These cardioprotective effects may be associated with the regulation of calcium handling by stachydrine hydrochloride through inhibiting the hyper-phosphorylation of CaMKII.

中文翻译：

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盐酸水苏碱减轻小鼠因压力超负荷引起的心力衰竭和钙处理不当

民族药理学意义

中药Leonurus japonicus Houtt。在心血管疾病的治疗方面历史悠久。盐酸水苏碱是从七叶忍冬中提取的主要生物活性成分，已显示具有心脏保护作用。但是，到目前为止，尚未对盐酸氢水苏碱的潜在机理进行全面的研究。

研究目的

这项研究的目的是调查盐酸水苏碱在心力衰竭中的保护作用，并阐明其可能的作用机制。

材料和方法

在体内，在C57BL / 6J小鼠中进行横动脉收缩，此后每天在胃内给药7.2 mg / kg替米沙坦（一种选择性的AT1R拮抗剂作为阳性对照）和12 mg / kg盐酸水苏醒。通过评估形态变化以及超声心动图和血流动力学参数来评估心脏功能。在体外，将新生大鼠心肌细胞或成年小鼠心肌细胞用盐酸水苏碱处理并用去氧肾上腺素（α-AR激动剂）攻击。通过Langendorff错流灌注系统从C57BL / 6J小鼠的心脏中分离出心室肌细胞。细胞内钙通过离子成像系统测量。追踪肌小节的长度和运动，以评估单个心肌细胞的收缩和舒张功能。

结果

盐酸水苏碱可改善心脏功能和钙瞬变幅度，并抑制从TAC小鼠分离的心肌细胞的SR泄漏和火花数量。我们还证明了盐酸水苏碱可以改善苯肾上腺素引起的肌节收缩，钙瞬变和钙火花的增强作用。此外，我们的数据表明，盐酸水苏碱可阻止CaMKII，RyR2，PLN的过度磷酸化，并阻止FKBP12.6与RyR2的解离。

结论

我们的结果表明，盐酸水苏碱对心力衰竭具有有益的治疗作用。这些心脏保护作用可能与通过抑制CaMKII的过度磷酸化来调节水苏碱盐酸盐对钙的处理有关。