Abstract

Endothelial dysfunction is the pathological basis of atherosclerosis. Incomplete understanding of endothelial dysfunction etiology has impeded drug development for this devastating disease despite the currently available therapies. Floralozone, an aroma flavor, specifically exists in rabbit ear grass. Recently, floralozone has been demonstrated to inhibit atherosclerosis, but the underlying mechanisms are undefined. The present study was undertaken to explore whether floralozone pharmacologically targets endothelial dysfunction and therefore exerts therapeutic effects on atherosclerosis. The Na⁺/H⁺ exchanger 1 (NHE1), a channel protein, plays a vital role in atherosclerosis. Whether NHE1 is involved in the therapeutic effects of floralozone on endothelial dysfunction has yet to be further answered. By performing oil red staining and hematoxylin–eosin staining, vascular functional study, and oxidative stress monitoring, we found that floralozone not only reduced the size of carotid atherosclerotic plaque but also prevented endothelial dysfunction in atherosclerotic rats. NHE1 expression was upregulated in the inner membrane of carotid arteries and H₂O₂-induced primary rat aortic endothelial cells. Inspiringly, floralozone prevented the upregulation of NHE1 in vivo and in vitro. Notably, the administration of NHE1 activator LiCl significantly weakened the protective effect of floralozone on endothelial dysfunction in vivo and in vitro. Our study demonstrated that floralozone exerted its protective effect on endothelial dysfunction in atherosclerosis by ameliorating NHE1. NHE1 maybe a drug target for the treatment of atherosclerosis, and floralozone may be an effective drug to meet the urgent needs of atherosclerosis patients by dampening NHE1.

中文翻译：

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Floralozone 通过改善 NHE1 保护动脉粥样硬化中的内皮功能

 抽象的

内皮功能障碍是动脉粥样硬化的病理基础。尽管目前有可用的治疗方法，但对内皮功能障碍病因学的不完全了解阻碍了针对这种破坏性疾病的药物开发。 Floralozone是一种香气香料，专门存在于兔耳草中。最近，florozone已被证明可以抑制动脉粥样硬化，但其潜在机制尚不清楚。本研究旨在探讨弗洛洛酮是否在药理学上针对内皮功能障碍，从而对动脉粥样硬化发挥治疗作用。 Na ⁺ /H ⁺交换器 1 (NHE1) 是一种通道蛋白，在动脉粥样硬化中起着至关重要的作用。 NHE1是否参与了florozone对内皮功能障碍的治疗作用还有待进一步解答。通过油红染色和苏木精-伊红染色、血管功能研究和氧化应激监测，我们发现花洛酮不仅可以减少颈动脉粥样硬化斑块的大小，而且可以预防动脉粥样硬化大鼠的内皮功能障碍。 NHE1在颈动脉内膜和H ₂ O ₂诱导的原代大鼠主动脉内皮细胞中表达上调。令人鼓舞的是，florozone在体内和体外都阻止了 NHE1 的上调。值得注意的是，NHE1激活剂LiCl的施用显着削弱了florozone对体内和体外内皮功能障碍的保护作用。我们的研究表明，florozone 通过改善 NHE1 对动脉粥样硬化的内皮功能障碍发挥保护作用。 NHE1可能是治疗动脉粥样硬化的药物靶点，而花洛酮可能是通过抑制NHE1来满足动脉粥样硬化患者迫切需要的有效药物。