Phloretin, a dihydrochalcone structural flavonoid compound, possesses antioxidant activity. In this study, we conducted studies to explore the function of phloretin on high palmitic acid-induced oxidative stress in human umbilical vein endothelial cells and investigated the potential mechanism using ribonucleic acid sequencing (RNA-Seq). Our findings reveal that phloretin significantly decreased the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione peroxidase-1 (Gpx-1) activity, and restored the loss of mitochondrial membrane potential (MMP). Next, whole transcriptome analysis was performed using RNA-Seq The results indicated more than 3000 differentially expressed genes (DEGs). Gene Ontology analysis revealed that the DEGs were categorized functionally, mainly by the biological processes, cell metabolism, and cellular response to chemical stimulus. The Kyoto Encyclopedia of Genes and Genomes indicated that they were mainly enriched in cAMP, apoptosis, and cytoskeletal regulation signaling pathways. Furthermore, on the basis of the results of RNA-Seq and Western blotting, our study verified that phloretin upregulated the expression of p-Nrf2 and HO-1 by promoting the phosphorylation of AMPK at Thr¹⁷² through activation of liver kinase B1. In conclusion, phloretin attenuates PA-induced oxidative stress in HUVECs via the AMPK/Nrf2 antioxidative pathway.

中文翻译：

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荧光素对Nrf2的激活通过依赖AMPK的信号减弱棕榈酸诱导的内皮细胞氧化应激

萤石素是一种二氢查耳酮结构的类黄酮化合物，具有抗氧化活性。在这项研究中，我们进行了研究，以研究伞菌素对高棕榈酸诱导的人脐静脉内皮细胞氧化应激的作用，并使用核糖核酸测序（RNA-Seq）研究了潜在的机制。我们的发现表明，芦丁显着降低了细胞内活性氧（ROS）和丙二醛（MDA）的水平，增加了超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶1（Gpx-1）的活性，并恢复了线粒体膜电位的丧失（ MMP）。接下来，使用RNA-Seq进行全转录组分析。结果表明，共有3000多个差异表达基因（DEG）。基因本体分析表明，DEGs按功能进行了分类，主要受生物过程，细胞代谢和细胞对化学刺激的反应的影响。《京都议定书》的基因与基因组百科全书指出，它们主要富含cAMP，细胞凋亡和细胞骨架调节信号通路。此外，基于RNA-Seq和Western印迹的结果，我们的研究证实，伞菌素通过促进AMPK在Thr的磷酸化上调了p-Nrf2和HO-1的表达。¹⁷²通过激活肝激酶B1。综上所述，促性腺激素释放素通过AMPK / Nrf2抗氧化途径减轻PAVE诱导的HUVECs氧化应激。