Ruscogenin (RUS), a major effective steroidal sapogenin derived from Ophiopogon japonicas, has been reported to alleviate myocardial ischemia (MI), but its cardioprotective mechanism is still not completely clear. In this study, we observed that RUS markedly reduced MI-induced myocardial injury, as evidenced by notable reductions in infarct size, improvement in biochemical markers, alleviation of cardiac pathology, amelioration of mitochondrial damage, and inhibition of myocardial apoptosis. Moreover, RUS notably suppressed oxygen-glucose deprivation (OGD)-triggered cell injury and apoptosis. Notably, RUS demonstrated a considerable decrease of the interaction between myosin IIA and F-actin, along with the restoration of mitochondrial fusion and fission balance. We further confirmed that the effects of RUS on MI were mediated by myosin IIA using siRNA and overexpression techniques. The inhibition of myosin IIA resulted in a significant improvement of mitochondrial fusion and fission imbalance, while simultaneously counteracting the beneficial effects of RUS. By contrast, overexpression of myosin IIA aggravated the imbalance between mitochondrial fusion and fission and partially weakened the protection of RUS. These findings suggest that myosin IIA is essential or even a key functional protein in the cardioprotection of RUS. Overall, our results have elucidated an undiscovered mechanism involving myosin IIA-dependent mitochondrial fusion and fission balance for treating MI. Furthermore, our study has uncovered a novel mechanism underlying the protective effects of RUS.

中文翻译：

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Ruscogenin 通过肌球蛋白 IIA 依赖性线粒体融合和裂变平衡减轻心肌缺血。

Ruscogenin (RUS) 是一种源自麦冬的主要有效甾体皂苷元，据报道可以缓解心肌缺血 (MI)，但其心脏保护机制尚不完全清楚。在这项研究中，我们观察到 RUS 显着减少 MI 引起的心肌损伤，梗塞面积显着减小、生化标志物改善、心脏病理学缓解、线粒体损伤改善和心肌细胞凋亡抑制。此外，RUS 显着抑制氧糖剥夺 (OGD) 引发的细胞损伤和细胞凋亡。值得注意的是，RUS 证明肌球蛋白 IIA 和 F-肌动蛋白之间的相互作用显着减少，同时恢复了线粒体融合和裂变平衡。我们使用 siRNA 和过表达技术进一步证实 RUS 对 MI 的影响是由肌球蛋白 IIA 介导的。肌球蛋白 IIA 的抑制可显着改善线粒体融合和裂变失衡，同时抵消 RUS 的有益作用。相比之下，肌球蛋白IIA的过度表达加剧了线粒体融合与裂变之间的不平衡，并部分削弱了RUS的保护作用。这些发现表明，肌球蛋白 IIA 在 RUS 的心脏保护中是必需的，甚至是关键的功能蛋白。总体而言，我们的结果阐明了一种尚未发现的机制，涉及肌球蛋白 IIA 依赖性线粒体融合和裂变平衡治疗 MI。此外，我们的研究还发现了 RUS 保护作用的新机制。