Calenduloside E (CE) is a natural triterpenoid saponin isolated from Aralia elata (Miq.) Seem., a well-known traditional Chinese medicine. Our previous studies have shown that CE exerts cardiovascular protective effects both in vivo and in vitro. However, its role in myocardial ischemia/reperfusion injury (MIRI) and the mechanism involved are currently unknown. Mitochondrial dynamics play a key role in MIRI. This study investigated the effects of CE on mitochondrial dynamics and the signaling pathways involved in myocardial ischemia/reperfusion (MI/R). The MI/R rat model and the hypoxia/reoxygenation (H/R) cardiomyocyte model were established in this study. CE exerted significant cardioprotective effects in vivo and in vitro by improving cardiac function, decreasing myocardial infarct size, increasing cardiomyocyte viability, and inhibiting cardiomyocyte apoptosis associated with MI/R. Mechanistically, CE restored mitochondrial homeostasis against MI/R injury through improved mitochondrial ultrastructure, enhanced ATP content and mitochondrial membrane potential, and reduced mitochondrial permeability transition pore (MPTP) opening, while promoting mitochondrial fusion and preventing mitochondrial fission. However, genetic silencing of OPA1 by siRNA abolished the beneficial effects of CE on cardiomyocyte survival and mitochondrial dynamics. Moreover, we demonstrated that CE activated AMP-activated protein kinase (AMPK) and treatment with the AMPK inhibitor, compound C, abolished the protective effects of CE on OPA1 expression and mitochondrial function. Overall, this study demonstrates that CE is effective in mitigating MIRI by modulating AMPK activation-mediated OPA1-related mitochondrial fusion.

中文翻译：

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金盏花甙E通过调节AMPK和线粒体OPA1减轻心肌缺血/再灌注损伤。

Calenduloside E（CE）是一种天然三萜皂苷，从一种著名的中药Aralia elata（Miq。）Seem。中分离出来。我们以前的研究表明，CE在体内和体外均具有心血管保护作用。然而，目前尚不清楚其在心肌缺血/再灌注损伤（MIRI）中的作用及其涉及的机制。线粒体动力学在MIRI中起关键作用。这项研究调查了CE对线粒体动力学和心肌缺血/再灌注（MI / R）参与的信号通路的影响。本研究建立了MI / R大鼠模型和缺氧/复氧（H / R）心肌细胞模型。CE在体内和体内均具有显着的心脏保护作用体外通过改善心脏功能，减小心肌梗塞面积，增加心肌细胞活力并抑制与MI / R相关的心肌细胞凋亡。从机理上讲，CE通过改善线粒体的超微结构，增加ATP含量和线粒体膜电位，减少线粒体通透性过渡孔（MPTP）的开放来恢复针对MI / R损伤的线粒体稳态，同时促进线粒体融合并防止线粒体裂变。但是，siRNA对OPA1的基因沉默消除了CE对心肌细胞存活和线粒体动力学的有益作用。此外，我们证明了CE激活AMP激活的蛋白激酶（AMPK）并使用AMPK抑制剂化合物C消除了CE对OPA1表达和线粒体功能的保护作用。总体，