Liu Jin-Cheng, Zhao Qing-Fei, Zhang Ling, Yu Bo-Yang, Li Fang, Kou Jun-Ping
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.
Am J Chin Med. 2023;51(7):1879-1904. doi: 10.1142/S0192415X23500830. Epub 2023 Aug 31.
Ruscogenin (RUS), a major effective steroidal sapogenin derived from , 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.
鲁斯可皂苷元（RUS）是一种从[植物名称未给出]中提取的主要有效甾体皂苷元，据报道它可以缓解心肌缺血（MI），但其心脏保护机制仍不完全清楚。在本研究中，我们观察到RUS显著减轻了MI诱导的心肌损伤，表现为梗死面积显著减小、生化标志物改善、心脏病理状况缓解、线粒体损伤减轻以及心肌细胞凋亡受到抑制。此外，RUS显著抑制了氧糖剥夺（OGD）引发的细胞损伤和凋亡。值得注意的是，RUS使肌球蛋白IIA与F-肌动蛋白之间的相互作用显著降低，同时恢复了线粒体融合与裂变的平衡。我们进一步使用小干扰RNA（siRNA）和过表达技术证实，RUS对MI的作用是由肌球蛋白IIA介导的。抑制肌球蛋白IIA导致线粒体融合与裂变失衡得到显著改善，同时抵消了RUS的有益作用。相反，肌球蛋白IIA的过表达加剧了线粒体融合与裂变之间的失衡，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的心脏保护作用中是必不可少的，甚至是关键的功能蛋白。总体而言，我们的研究结果阐明了一种尚未被发现的机制，即通过肌球蛋白IIA依赖的线粒体融合与裂变平衡来治疗MI。此外，我们的研究揭示了RUS保护作用背后的一种新机制。
