Activation of Nrf2 by Phloretin Attenuates Palmitic Acid-Induced Endothelial Cell Oxidative Stress via AMPK-Dependent Signaling.
J Agric Food Chem. 2019 Jan 9 ;67(1):120-131. Epub 2018 Dec 19. PMID: 30525573
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 Thrthrough activation of liver kinase B1. In conclusion, phloretin attenuates PA-induced oxidative stress in HUVECs via the AMPK/Nrf2 antioxidative pathway.