Naringenin (NRG) was characterized for its ability to counteract mitochondrial dysfunction which is linked to cardiovascular diseases. The FF-ATPase can act as a molecular target of NRG. The interaction of NRG with this enzyme can avoid the energy transmission mechanism of ATP hydrolysis, especially in the presence of Ca cation used as cofactor. Indeed, NRG was a selective inhibitor of the hydrophilic F domain displaying a binding site overlapped with quercetin in the inside surface of an annulus made by the three α and the three β subunits arranged alternatively in a hexamer. The kinetic constant of inhibition suggested that NRG preferred the enzyme activated by Ca rather than the FF-ATPase activated by the natural cofactor Mg. From the inhibition type mechanism of NRG stemmed the possibility to speculate that NRG can prevent the activation of FF-ATPase by Ca. The event correlated to the protective role in the mitochondrial permeability transition pore opening by NRG as well as to the reduction of ROS production probably linked to the NRG chemical structure with antioxidant action. Moreover, in primary cerebral endothelial cells (ECs) obtained from stroke prone spontaneously hypertensive rats NRG had a protective effect on salt-induced injury by restoring cell viability and endothelial cell tube formation while also rescuing complex I activity.

中文翻译：

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柚皮素调节线粒体通透性转变作用于 F1FO-ATPase 并抵消盐水负荷诱导的 SHRSP 脑内皮细胞损伤的分子机制

柚皮素 (NRG) 的特点是能够对抗与心血管疾病相关的线粒体功能障碍。FF-ATPase 可以作为 NRG 的分子靶标。NRG 与该酶的相互作用可以避免 ATP 水解的能量传递机制，特别是在存在 Ca 阳离子作为辅助因子的情况下。事实上，NRG 是亲水性 F 结构域的选择性抑制剂，在由以六聚体交替排列的三个 α 和三个 β 亚基形成的环的内表面中显示与槲皮素重叠的结合位点。抑制动力学常数表明，NRG 更喜欢由 Ca 激活的酶，而不是由天然辅因子 Mg 激活的 FF-ATP 酶。从NRG的抑制型机制出发，推测NRG可以阻止Ca对FF-ATPase的激活。该事件与 NRG 对线粒体通透性转换孔打开的保护作用以及 ROS 产生的减少有关，可能与具有抗氧化作用的 NRG 化学结构有关。此外，在从易发生中风的自发性高血压大鼠中获得的原代脑内皮细胞（EC）中，NRG 通过恢复细胞活力和内皮细胞管形成同时还恢复复合物 I 活性，对盐诱导的损伤具有保护作用。