Abstract: Luteolin (LUT) is a well-known flavonoid that exhibits a number of beneficial properties. Among these, it shows cardioprotective effects, as confirmed by numerous studies. However, its effect on mitochondrial potassium channels, the activation of which is related to cytoprotection, as well as on heart ischemia/reperfusion (I/R) damage prevention, has not yet been investigated. The large conductance calcium-regulated potassium channel (mitoBK_Ca) has been identified in both the mitochondria of the vascular endothelial cells, which plays a significant role in the functioning of the cardiovascular system under oxidative stress-related conditions, and in the mitochondria of cardiomyocytes, where it is deeply involved in cardiac protection against I/R injury. Therefore, the aim of this study was to explore the role of the mitoBK_Ca channel in luteolin-induced cytoprotection. A number of in vitro, in vivo, ex vivo and in silico studies have confirmed that luteolin activates this channel in the mitochondria of cardiomyocytes and endothelial cells, which in turn leads to the protection of the endothelium and a significant reduction in the extent of damage resulting from myocardial infarction, where this effect was partially abolished by the mitoBK_Ca channel blocker paxilline. In conclusion, these results suggest that luteolin has cardioprotective effects, at least in part, through the activation of the mitoBK_Ca channel, shedding light on a new putative mechanism of action.

中文翻译：

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木犀草素诱导的线粒体 BKCa 通道激活：未公开的细胞保护机制

摘要：木犀草素 (LUT ) 是一种众所周知的类黄酮，具有许多有益的特性。其中，它显示出心脏保护作用，正如许多研究所证实的那样。然而，尚未研究其对线粒体钾通道（其激活与细胞保护有关）以及对心脏缺血/再灌注 (I/R) 损伤预防的影响。大电导钙调节钾通道（mitoBK _Ca) 已在血管内皮细胞的线粒体（在氧化应激相关条件下对心血管系统的功能发挥重要作用）和心肌细胞的线粒体中被鉴定出来，其中它与心脏针对 I 的保护作用密切相关。 /R 伤害。因此，本研究的目的是探讨mitoBK _Ca通道在木犀草素诱导的细胞保护中的作用。许多体外、体内、离体和计算机_ _ _ 研究证实，木犀草素可激活心肌细胞和内皮细胞线粒体中的该通道，从而保护内皮并显着降低心肌梗塞造成的损伤程度，而这种作用被mitoBK部分消除_Ca通道阻滞剂桩。总之，这些结果表明，木犀草素具有心脏保护作用，至少部分是通过激活 mitoBK _Ca通道，揭示了一种新的推定作用机制。